Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain

PubMed Central

2012-01-01

Background Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts. Results By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns. Conclusions Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function. PMID:22651826

Morphometric Analysis of Recognized Genes for Autism Spectrum Disorders and Obesity in Relationship to the Distribution of Protein-Coding Genes on Human Chromosomes.

PubMed

McGuire, Austen B; Rafi, Syed K; Manzardo, Ann M; Butler, Merlin G

2016-05-05

Mammalian chromosomes are comprised of complex chromatin architecture with the specific assembly and configuration of each chromosome influencing gene expression and function in yet undefined ways by varying degrees of heterochromatinization that result in Giemsa (G) negative euchromatic (light) bands and G-positive heterochromatic (dark) bands. We carried out morphometric measurements of high-resolution chromosome ideograms for the first time to characterize the total euchromatic and heterochromatic chromosome band length, distribution and localization of 20,145 known protein-coding genes, 790 recognized autism spectrum disorder (ASD) genes and 365 obesity genes. The individual lengths of G-negative euchromatin and G-positive heterochromatin chromosome bands were measured in millimeters and recorded from scaled and stacked digital images of 850-band high-resolution ideograms supplied by the International Society of Chromosome Nomenclature (ISCN) 2013. Our overall measurements followed established banding patterns based on chromosome size. G-negative euchromatic band regions contained 60% of protein-coding genes while the remaining 40% were distributed across the four heterochromatic dark band sub-types. ASD genes were disproportionately overrepresented in the darker heterochromatic sub-bands, while the obesity gene distribution pattern did not significantly differ from protein-coding genes. Our study supports recent trends implicating genes located in heterochromatin regions playing a role in biological processes including neurodevelopment and function, specifically genes associated with ASD.

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

PubMed

Javierre, Biola M; Burren, Oliver S; Wilder, Steven P; Kreuzhuber, Roman; Hill, Steven M; Sewitz, Sven; Cairns, Jonathan; Wingett, Steven W; Várnai, Csilla; Thiecke, Michiel J; Burden, Frances; Farrow, Samantha; Cutler, Antony J; Rehnström, Karola; Downes, Kate; Grassi, Luigi; Kostadima, Myrto; Freire-Pritchett, Paula; Wang, Fan; Stunnenberg, Hendrik G; Todd, John A; Zerbino, Daniel R; Stegle, Oliver; Ouwehand, Willem H; Frontini, Mattia; Wallace, Chris; Spivakov, Mikhail; Fraser, Peter

2016-11-17

Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Nuremberg Code: its history and implications.

PubMed

Kious, B M

2001-01-01

The Nuremberg Code is a foundational document in the ethics of medical research and human experimentation; the principle its authors espoused in 1946 have provided the framework for modern codes that address the same issues, and have received little challenge and only slight modification in decades since. By analyzing the Code's tragic genesis and its normative implications, it is possible to understand some of the essence of modern experimental ethics, as well as certain outstanding controversies that still plague medical science.

Correlation approach to identify coding regions in DNA sequences

NASA Technical Reports Server (NTRS)

Ossadnik, S. M.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Mantegna, R. N.; Peng, C. K.; Simons, M.; Stanley, H. E.

1994-01-01

Recently, it was observed that noncoding regions of DNA sequences possess long-range power-law correlations, whereas coding regions typically display only short-range correlations. We develop an algorithm based on this finding that enables investigators to perform a statistical analysis on long DNA sequences to locate possible coding regions. The algorithm is particularly successful in predicting the location of lengthy coding regions. For example, for the complete genome of yeast chromosome III (315,344 nucleotides), at least 82% of the predictions correspond to putative coding regions; the algorithm correctly identified all coding regions larger than 3000 nucleotides, 92% of coding regions between 2000 and 3000 nucleotides long, and 79% of coding regions between 1000 and 2000 nucleotides. The predictive ability of this new algorithm supports the claim that there is a fundamental difference in the correlation property between coding and noncoding sequences. This algorithm, which is not species-dependent, can be implemented with other techniques for rapidly and accurately locating relatively long coding regions in genomic sequences.

An imprinted non-coding genomic cluster at 14q32 defines clinically relevant molecular subtypes in osteosarcoma across multiple independent datasets.

PubMed

Hill, Katherine E; Kelly, Andrew D; Kuijjer, Marieke L; Barry, William; Rattani, Ahmed; Garbutt, Cassandra C; Kissick, Haydn; Janeway, Katherine; Perez-Atayde, Antonio; Goldsmith, Jeffrey; Gebhardt, Mark C; Arredouani, Mohamed S; Cote, Greg; Hornicek, Francis; Choy, Edwin; Duan, Zhenfeng; Quackenbush, John; Haibe-Kains, Benjamin; Spentzos, Dimitrios

2017-05-15

A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has been associated with outcome in osteosarcoma. We assessed the clinical utility of this miRNA set and their association with methylation status. We integrated coding and non-coding RNA data from three independent annotated clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and methylation data from one in vitro (19 cell lines) and one clinical (NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) osteosarcoma dataset, n = 80) dataset. We used time-dependent receiver operating characteristic (tdROC) analysis to evaluate the clinical value of candidate miRNA profiles and machine learning approaches to compare the coding and non-coding transcriptional programs of high- and low-risk osteosarcoma tumors and high- versus low-aggressiveness cell lines. In the cell line and TARGET datasets, we also studied the methylation patterns of the MEG3 imprinting control region on 14q32 and their association with miRNA expression and tumor aggressiveness. In the tdROC analysis, miRNA sets on 14q32 showed strong discriminatory power for recurrence and survival in the three clinical datasets. High- or low-risk tumor classification was robust to using different microRNA sets or classification methods. Machine learning approaches showed that genome-wide miRNA profiles and miRNA regulatory networks were quite different between the two outcome groups and mRNA profiles categorized the samples in a manner concordant with the miRNAs, suggesting potential molecular subtypes. Further, miRNA expression patterns were reproducible in comparing high-aggressiveness versus low-aggressiveness cell lines. Methylation patterns in the MEG3 differentially methylated region (DMR) also distinguished high-aggressiveness from low-aggressiveness cell lines and were associated with expression of several 14q32 miRNAs in both the cell lines and the large TARGET clinical dataset. Within the limits of available CpG array coverage, we observed a potential methylation-sensitive regulation of the non-coding RNA cluster by CTCF, a known enhancer-blocking factor. Loss of imprinting/methylation changes in the 14q32 non-coding region defines reproducible previously unrecognized osteosarcoma subtypes with distinct transcriptional programs and biologic and clinical behavior. Future studies will define the precise relationship between 14q32 imprinting, non-coding RNA expression, genomic enhancer binding, and tumor aggressiveness, with possible therapeutic implications for both early- and advanced-stage patients.

Simulation of inverse Compton scattering and its implications on the scattered linewidth

NASA Astrophysics Data System (ADS)

Ranjan, N.; Terzić, B.; Krafft, G. A.; Petrillo, V.; Drebot, I.; Serafini, L.

2018-03-01

Rising interest in inverse Compton sources has increased the need for efficient models that properly quantify the behavior of scattered radiation given a set of interaction parameters. The current state-of-the-art simulations rely on Monte Carlo-based methods, which, while properly expressing scattering behavior in high-probability regions of the produced spectra, may not correctly simulate such behavior in low-probability regions (e.g. tails of spectra). Moreover, sampling may take an inordinate amount of time for the desired accuracy to be achieved. In this paper, we present an analytic derivation of the expression describing the scattered radiation linewidth and propose a model to describe the effects of horizontal and vertical emittance on the properties of the scattered radiation. We also present an improved version of the code initially reported in Krafft et al. [Phys. Rev. Accel. Beams 19, 121302 (2016), 10.1103/PhysRevAccelBeams.19.121302], that can perform the same simulations as those present in cain and give accurate results in low-probability regions by integrating over the emissions of the electrons. Finally, we use these codes to carry out simulations that closely verify the behavior predicted by the analytically derived scaling law.

Simulation of inverse Compton scattering and its implications on the scattered linewidth

DOE PAGES

Ranjan, N.; Terzić, B.; Krafft, G. A.; ...

2018-03-06

Rising interest in inverse Compton sources has increased the need for efficient models that properly quantify the behavior of scattered radiation given a set of interaction parameters. The current state-of-the-art simulations rely on Monte Carlo-based methods, which, while properly expressing scattering behavior in high-probability regions of the produced spectra, may not correctly simulate such behavior in low-probability regions (e.g. tails of spectra). Moreover, sampling may take an inordinate amount of time for the desired accuracy to be achieved. Here in this article, we present an analytic derivation of the expression describing the scattered radiation linewidth and propose a model tomore » describe the effects of horizontal and vertical emittance on the properties of the scattered radiation. We also present an improved version of the code initially reported in Krafft et al. [Phys. Rev. Accel. Beams 19, 121302 (2016)], that can perform the same simulations as those present in cain and give accurate results in low-probability regions by integrating over the emissions of the electrons. Finally, we use these codes to carry out simulations that closely verify the behavior predicted by the analytically derived scaling law.« less

MHC class I-associated peptides derive from selective regions of the human genome.

PubMed

Pearson, Hillary; Daouda, Tariq; Granados, Diana Paola; Durette, Chantal; Bonneil, Eric; Courcelles, Mathieu; Rodenbrock, Anja; Laverdure, Jean-Philippe; Côté, Caroline; Mader, Sylvie; Lemieux, Sébastien; Thibault, Pierre; Perreault, Claude

2016-12-01

MHC class I-associated peptides (MAPs) define the immune self for CD8+ T lymphocytes and are key targets of cancer immunosurveillance. Here, the goals of our work were to determine whether the entire set of protein-coding genes could generate MAPs and whether specific features influence the ability of discrete genes to generate MAPs. Using proteogenomics, we have identified 25,270 MAPs isolated from the B lymphocytes of 18 individuals who collectively expressed 27 high-frequency HLA-A,B allotypes. The entire MAP repertoire presented by these 27 allotypes covered only 10% of the exomic sequences expressed in B lymphocytes. Indeed, 41% of expressed protein-coding genes generated no MAPs, while 59% of genes generated up to 64 MAPs, often derived from adjacent regions and presented by different allotypes. We next identified several features of transcripts and proteins associated with efficient MAP production. From these data, we built a logistic regression model that predicts with good accuracy whether a gene generates MAPs. Our results show preferential selection of MAPs from a limited repertoire of proteins with distinctive features. The notion that the MHC class I immunopeptidome presents only a small fraction of the protein-coding genome for monitoring by the immune system has profound implications in autoimmunity and cancer immunology.

MHC class I–associated peptides derive from selective regions of the human genome

PubMed Central

Pearson, Hillary; Granados, Diana Paola; Durette, Chantal; Bonneil, Eric; Courcelles, Mathieu; Rodenbrock, Anja; Laverdure, Jean-Philippe; Côté, Caroline; Thibault, Pierre

2016-01-01

MHC class I–associated peptides (MAPs) define the immune self for CD8+ T lymphocytes and are key targets of cancer immunosurveillance. Here, the goals of our work were to determine whether the entire set of protein-coding genes could generate MAPs and whether specific features influence the ability of discrete genes to generate MAPs. Using proteogenomics, we have identified 25,270 MAPs isolated from the B lymphocytes of 18 individuals who collectively expressed 27 high-frequency HLA-A,B allotypes. The entire MAP repertoire presented by these 27 allotypes covered only 10% of the exomic sequences expressed in B lymphocytes. Indeed, 41% of expressed protein-coding genes generated no MAPs, while 59% of genes generated up to 64 MAPs, often derived from adjacent regions and presented by different allotypes. We next identified several features of transcripts and proteins associated with efficient MAP production. From these data, we built a logistic regression model that predicts with good accuracy whether a gene generates MAPs. Our results show preferential selection of MAPs from a limited repertoire of proteins with distinctive features. The notion that the MHC class I immunopeptidome presents only a small fraction of the protein-coding genome for monitoring by the immune system has profound implications in autoimmunity and cancer immunology. PMID:27841757

Methodology for fast detection of false sharing in threaded scientific codes

DOEpatents

Chung, I-Hsin; Cong, Guojing; Murata, Hiroki; Negishi, Yasushi; Wen, Hui-Fang

2014-11-25

A profiling tool identifies a code region with a false sharing potential. A static analysis tool classifies variables and arrays in the identified code region. A mapping detection library correlates memory access instructions in the identified code region with variables and arrays in the identified code region while a processor is running the identified code region. The mapping detection library identifies one or more instructions at risk, in the identified code region, which are subject to an analysis by a false sharing detection library. A false sharing detection library performs a run-time analysis of the one or more instructions at risk while the processor is re-running the identified code region. The false sharing detection library determines, based on the performed run-time analysis, whether two different portions of the cache memory line are accessed by the generated binary code.

A Novel Multi-Scale Domain Overlapping CFD/STH Coupling Methodology for Multi-Dimensional Flows Relevant to Nuclear Applications

NASA Astrophysics Data System (ADS)

Grunloh, Timothy P.

The objective of this dissertation is to develop a 3-D domain-overlapping coupling method that leverages the superior flow field resolution of the Computational Fluid Dynamics (CFD) code STAR-CCM+ and the fast execution of the System Thermal Hydraulic (STH) code TRACE to efficiently and accurately model thermal hydraulic transport properties in nuclear power plants under complex conditions of regulatory and economic importance. The primary contribution is the novel Stabilized Inertial Domain Overlapping (SIDO) coupling method, which allows for on-the-fly correction of TRACE solutions for local pressures and velocity profiles inside multi-dimensional regions based on the results of the CFD simulation. The method is found to outperform the more frequently-used domain decomposition coupling methods. An STH code such as TRACE is designed to simulate large, diverse component networks, requiring simplifications to the fluid flow equations for reasonable execution times. Empirical correlations are therefore required for many sub-grid processes. The coarse grids used by TRACE diminish sensitivity to small scale geometric details such as Reactor Pressure Vessel (RPV) internals. A CFD code such as STAR-CCM+ uses much finer computational meshes that are sensitive to the geometric details of reactor internals. In turbulent flows, it is infeasible to fully resolve the flow solution, but the correlations used to model turbulence are at a low level. The CFD code can therefore resolve smaller scale flow processes. The development of a 3-D coupling method was carried out with the intention of improving predictive capabilities of transport properties in the downcomer and lower plenum regions of an RPV in reactor safety calculations. These regions are responsible for the multi-dimensional mixing effects that determine the distribution at the core inlet of quantities with reactivity implications, such as fluid temperature and dissolved neutron absorber concentration.

2-D Structure of the A Region of Xist RNA and Its Implication for PRC2 Association

PubMed Central

Maenner, Sylvain; Blaud, Magali; Fouillen, Laetitia; Savoye, Anne; Marchand, Virginie; Dubois, Agnès; Sanglier-Cianférani, Sarah; Van Dorsselaer, Alain; Clerc, Philippe; Avner, Philip; Visvikis, Athanase; Branlant, Christiane

2010-01-01

In placental mammals, inactivation of one of the X chromosomes in female cells ensures sex chromosome dosage compensation. The 17 kb non-coding Xist RNA is crucial to this process and accumulates on the future inactive X chromosome. The most conserved Xist RNA region, the A region, contains eight or nine repeats separated by U-rich spacers. It is implicated in the recruitment of late inactivated X genes to the silencing compartment and likely in the recruitment of complex PRC2. Little is known about the structure of the A region and more generally about Xist RNA structure. Knowledge of its structure is restricted to an NMR study of a single A repeat element. Our study is the first experimental analysis of the structure of the entire A region in solution. By the use of chemical and enzymatic probes and FRET experiments, using oligonucleotides carrying fluorescent dyes, we resolved problems linked to sequence redundancies and established a 2-D structure for the A region that contains two long stem-loop structures each including four repeats. Interactions formed between repeats and between repeats and spacers stabilize these structures. Conservation of the spacer terminal sequences allows formation of such structures in all sequenced Xist RNAs. By combination of RNP affinity chromatography, immunoprecipitation assays, mass spectrometry, and Western blot analysis, we demonstrate that the A region can associate with components of the PRC2 complex in mouse ES cell nuclear extracts. Whilst a single four-repeat motif is able to associate with components of this complex, recruitment of Suz12 is clearly more efficient when the entire A region is present. Our data with their emphasis on the importance of inter-repeat pairing change fundamentally our conception of the 2-D structure of the A region of Xist RNA and support its possible implication in recruitment of the PRC2 complex. PMID:20052282

Mutation spectrum of the Norrie disease pseudoglioma (NDP) gene in Indian patients with FEVR.

PubMed

Musada, Ganeswara Rao; Jalali, Subhadra; Hussain, Anjli; Chururu, Anupama Reddy; Gaddam, Pramod Reddy; Chakrabarti, Subhabrata; Kaur, Inderjeet

2016-01-01

Mutations in the Norrie disease pseudoglioma (NDP; Xp11.3) gene have been involved in retinal blood vessel formation and neural differentiation and are implicated in familial exudative vitreoretinopathy (FEVR) cases. However, the role of the gene has not been explored in the Indian context. Thus, this study was designed to understand the involvement of NDP among Indian patients with FEVR. The study cohort comprised 225 subjects, including unrelated patients with FEVR (n = 110) and ethnically matched healthy subjects (n = 115) recruited from a tertiary eye care center in India. The entire coding regions, intron-exon boundaries, along with the 5' and 3' untranslated regions of NDP were screened with resequencing following standard protocols. The spectrum of the observed variants was analyzed in conjunction with data available from other populations. Eight potentially pathogenic mutations (p.His4ArgfsX21, p.Asp23GlufsX9, p.Ile48ValfsX55, p.His50Asp, p.Ser57*, p.Gly113Asp, p.Arg121Gln, and p.Cys126Arg, including five novel ones), were observed in the coding region of the NDP gene in ten unrelated FEVR probands (9%). The novel changes were not observed in the control subjects and were unavailable in the dbSNP, ESP5400, NIEHS95, and ExAC databases. All probands with NDP mutations exhibited classical features of the disease as observed among patients with FEVR worldwide. This is perhaps the first study to demonstrate the involvement of NDP among patients with Indian FEVR that further expands its mutation spectrum. The data generated could have broad implications in genetic counseling, disease management, and early intervention for a better prognosis in FEVR.

Mutation spectrum of the Norrie disease pseudoglioma (NDP) gene in Indian patients with FEVR

PubMed Central

Musada, Ganeswara Rao; Jalali, Subhadra; Hussain, Anjli; Chururu, Anupama Reddy; Gaddam, Pramod Reddy; Chakrabarti, Subhabrata

2016-01-01

Purpose Mutations in the Norrie disease pseudoglioma (NDP; Xp11.3) gene have been involved in retinal blood vessel formation and neural differentiation and are implicated in familial exudative vitreoretinopathy (FEVR) cases. However, the role of the gene has not been explored in the Indian context. Thus, this study was designed to understand the involvement of NDP among Indian patients with FEVR. Methods The study cohort comprised 225 subjects, including unrelated patients with FEVR (n = 110) and ethnically matched healthy subjects (n = 115) recruited from a tertiary eye care center in India. The entire coding regions, intron–exon boundaries, along with the 5′ and 3′ untranslated regions of NDP were screened with resequencing following standard protocols. The spectrum of the observed variants was analyzed in conjunction with data available from other populations. Results Eight potentially pathogenic mutations (p.His4ArgfsX21, p.Asp23GlufsX9, p.Ile48ValfsX55, p.His50Asp, p.Ser57*, p.Gly113Asp, p.Arg121Gln, and p.Cys126Arg, including five novel ones), were observed in the coding region of the NDP gene in ten unrelated FEVR probands (9%). The novel changes were not observed in the control subjects and were unavailable in the dbSNP, ESP5400, NIEHS95, and ExAC databases. All probands with NDP mutations exhibited classical features of the disease as observed among patients with FEVR worldwide. Conclusions This is perhaps the first study to demonstrate the involvement of NDP among patients with Indian FEVR that further expands its mutation spectrum. The data generated could have broad implications in genetic counseling, disease management, and early intervention for a better prognosis in FEVR. PMID:27217716

Advanced simulation of mixed-material erosion/evolution and application to low and high-Z containing plasma facing components

NASA Astrophysics Data System (ADS)

Brooks, J. N.; Hassanein, A.; Sizyuk, T.

2013-07-01

Plasma interactions with mixed-material surfaces are being analyzed using advanced modeling of time-dependent surface evolution/erosion. Simulations use the REDEP/WBC erosion/redeposition code package coupled to the HEIGHTS package ITMC-DYN mixed-material formation/response code, with plasma parameter input from codes and data. We report here on analysis for a DIII-D Mo/C containing tokamak divertor. A DIII-D/DiMES probe experiment simulation predicts that sputtered molybdenum from a 1 cm diameter central spot quickly saturates (˜4 s) in the 5 cm diameter surrounding carbon probe surface, with subsequent re-sputtering and transport to off-probe divertor regions, and with high (˜50%) redeposition on the Mo spot. Predicted Mo content in the carbon agrees well with post-exposure probe data. We discuss implications and mixed-material analysis issues for Be/W mixing at the ITER outer divertor, and Li, C, Mo mixing at an NSTX divertor.

Global variation in CYP2C8–CYP2C9 functional haplotypes

PubMed Central

Speed, William C; Kang, Soonmo Peter; Tuck, David P; Harris, Lyndsay N; Kidd, Kenneth K

2009-01-01

We have studied the global frequency distributions of 10 single nucleotide polymorphisms (SNPs) across 132 kb of CYP2C8 and CYP2C9 in ∼2500 individuals representing 45 populations. Five of the SNPs were in noncoding sequences; the other five involved the more common missense variants (four in CYP2C8, one in CYP2C9) that change amino acids in the gene products. One haplotype containing two CYP2C8 coding variants and one CYP2C9 coding variant reaches an average frequency of 10% in Europe; a set of haplotypes with a different CYP2C8 coding variant reaches 17% in Africa. In both cases these haplotypes are found in other regions of the world at <1%. This considerable geographic variation in haplotype frequencies impacts the interpretation of CYP2C8/CYP2C9 association studies, and has pharmacogenomic implications for drug interactions. PMID:19381162

Universal evolutionary selection for high dimensional silent patterns of information hidden in the redundancy of viral genetic code.

PubMed

Goz, Eli; Zafrir, Zohar; Tuller, Tamir

2018-04-30

Understanding how viruses co-evolve with their hosts and adapt various genomic level strategies in order to ensure their fitness may have essential implications in unveiling the secrets of viral evolution, and in developing new vaccines and therapeutic approaches. Here, based on a novel genomic analysis of 2,625 different viruses and 439 corresponding host organisms, we provide evidence of universal evolutionary selection for high dimensional 'silent' patterns of information hidden in the redundancy of viral genetic code. Our model suggests that long substrings of nucleotides in the coding regions of viruses from all classes, often also repeat in the corresponding viral hosts from all domains of life. Selection for these substrings cannot be explained only by such phenomena as codon usage bias, horizontal gene transfer, and the encoded proteins. Genes encoding structural proteins responsible for building the core of the viral particles were found to include more host-repeating substrings, and these substrings tend to appear in the middle parts of the viral coding regions. In addition, in human viruses these substrings tend to be enriched with motives related to transcription factors and RNA binding proteins. The host-repeating substrings are possibly related to the evolutionary pressure on the viruses to effectively interact with host's intracellular factors and to efficiently escape from the host's immune system. tamirtul@post.tau.ac.il (TT). Supplementary data are available at Bioinformatics online.

Emotional Complexity and the Neural Representation of Emotion in Motion

PubMed Central

Barnard, Philip J.; Lawrence, Andrew D.

2011-01-01

According to theories of emotional complexity, individuals low in emotional complexity encode and represent emotions in visceral or action-oriented terms, whereas individuals high in emotional complexity encode and represent emotions in a differentiated way, using multiple emotion concepts. During functional magnetic resonance imaging, participants viewed valenced animated scenarios of simple ball-like figures attending either to social or spatial aspects of the interactions. Participant’s emotional complexity was assessed using the Levels of Emotional Awareness Scale. We found a distributed set of brain regions previously implicated in processing emotion from facial, vocal and bodily cues, in processing social intentions, and in emotional response, were sensitive to emotion conveyed by motion alone. Attention to social meaning amplified the influence of emotion in a subset of these regions. Critically, increased emotional complexity correlated with enhanced processing in a left temporal polar region implicated in detailed semantic knowledge; with a diminished effect of social attention; and with increased differentiation of brain activity between films of differing valence. Decreased emotional complexity was associated with increased activity in regions of pre-motor cortex. Thus, neural coding of emotion in semantic vs action systems varies as a function of emotional complexity, helping reconcile puzzling inconsistencies in neuropsychological investigations of emotion recognition. PMID:20207691

In the nose of the beholder: are olfactory influences on human mate choice driven by variation in immune system genes or sex hormone levels?

PubMed

Roberts, Thomas; Roiser, Jonathan P

2010-11-01

The human leukocyte antigen (HLA) is the most polymorphic region of the genome, coding for proteins that mediate human immune response. This polymorphism may be maintained by balancing selection and certain populations show deviations from expected gene frequencies. Supporting this hypothesis, studies into olfactory preferences have suggested that females prefer the scent of males with dissimilar HLA to their own. However, it has also been proposed that androstenones play a role in female mate choice, and as these molecules inhibit the immune system, this has implications for the theory of HLA-driven mate preference. This review will critically analyze the findings of studies investigating olfactory preference in humans, and their implications for these two contrasting theories of mate choice.

Electron holes appear to trigger cancer-implicated mutations

NASA Astrophysics Data System (ADS)

Miller, John; Villagran, Martha

Malignant tumors are caused by mutations, which also affect their subsequent growth and evolution. We use a novel approach, computational DNA hole spectroscopy [M.Y. Suarez-Villagran & J.H. Miller, Sci. Rep. 5, 13571 (2015)], to compute spectra of enhanced hole probability based on actual sequence data. A hole is a mobile site of positive charge created when an electron is removed, for example by radiation or contact with a mutagenic agent. Peaks in the hole spectrum depict sites where holes tend to localize and potentially trigger a base pair mismatch during replication. Our studies of reveal a correlation between hole spectrum peaks and spikes in human mutation frequencies. Importantly, we also find that hole peak positions that do not coincide with large variant frequencies often coincide with cancer-implicated mutations and/or (for coding DNA) encoded conserved amino acids. This enables combining hole spectra with variant data to identify critical base pairs and potential cancer `driver' mutations. Such integration of DNA hole and variance spectra could also prove invaluable for pinpointing critical regions, and sites of driver mutations, in the vast non-protein-coding genome. Supported by the State of Texas through the Texas Ctr. for Superconductivity.

The expanding regulatory universe of p53 in gastrointestinal cancer.

PubMed

Fesler, Andrew; Zhang, Ning; Ju, Jingfang

2016-01-01

Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

Lessons learned from the initial sequencing of the pig genome: comparative analysis of an 8 Mb region of pig chromosome 17

PubMed Central

Hart, Elizabeth A; Caccamo, Mario; Harrow, Jennifer L; Humphray, Sean J; Gilbert, James GR; Trevanion, Steve; Hubbard, Tim; Rogers, Jane; Rothschild, Max F

2007-01-01

Background We describe here the sequencing, annotation and comparative analysis of an 8 Mb region of pig chromosome 17, which provides a useful test region to assess coverage and quality for the pig genome sequencing project. We report our findings comparing the annotation of draft sequence assembled at different depths of coverage. Results Within this region we annotated 71 loci, of which 53 are orthologous to human known coding genes. When compared to the syntenic regions in human (20q13.13-q13.33) and mouse (chromosome 2, 167.5 Mb-178.3 Mb), this region was found to be highly conserved with respect to gene order. The most notable difference between the three species is the presence of a large expansion of zinc finger coding genes and pseudogenes on mouse chromosome 2 between Edn3 and Phactr3 that is absent from pig and human. All of our annotation has been made publicly available in the Vertebrate Genome Annotation browser, VEGA. We assessed the impact of coverage on sequence assembly across this region and found, as expected, that increased sequence depth resulted in fewer, longer contigs. One-third of our annotated loci could not be fully re-aligned back to the low coverage version of the sequence, principally because the transcripts are fragmented over several contigs. Conclusion We have demonstrated the considerable advantages of sequencing at increased read depths and discuss the implications that lower coverage sequence may have on subsequent comparative and functional studies, particularly those involving complex loci such as GNAS. PMID:17705864

The full mitochondrial genome sequence of Raillietina tetragona from chicken (Cestoda: Davaineidae).

PubMed

Liang, Jian-Ying; Lin, Rui-Qing

2016-11-01

In the present study, the complete mitochondrial DNA (mtDNA) sequence of Raillietina tetragona was sequenced and its gene contents and genome organizations was compared with that of other tapeworm. The complete mt genome sequence of R. tetragona is 14,444 bp in length. It contains 12 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and two non-coding region. All genes are transcribed in the same direction and have a nucleotide composition high in A and T. The contents of A + T of the complete mt genome are 71.4% for R. tetragona. The R. tetragona mt genome sequence provides novel mtDNA marker for studying the molecular epidemiology and population genetics of Raillietina and has implications for the molecular diagnosis of chicken cestodosis caused by Raillietina.

First Mitochondrial Genome from Nemouridae (Plecoptera) Reveals Novel Features of the Elongated Control Region and Phylogenetic Implications

PubMed Central

Chen, Zhi-Teng; Du, Yu-Zhou

2017-01-01

The complete mitochondrial genome (mitogenome) of Nemoura nankinensis (Plecoptera: Nemouridae) was sequenced as the first reported mitogenome from the family Nemouridae. The N. nankinensis mitogenome was the longest (16,602 bp) among reported plecopteran mitogenomes, and it contains 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes and two ribosomal RNA (rRNA) genes. Most PCGs used standard ATN as start codons, and TAN as termination codons. All tRNA genes of N. nankinensis could fold into the cloverleaf secondary structures except for trnSer (AGN), whose dihydrouridine (DHU) arm was reduced to a small loop. There was also a large non-coding region (control region, CR) in the N. nankinensis mitogenome. The 1751 bp CR was the longest and had the highest A+T content (81.8%) among stoneflies. A large tandem repeat region, five potential stem-loop (SL) structures, four tRNA-like structures and four conserved sequence blocks (CSBs) were detected in the elongated CR. The presence of these tRNA-like structures in the CR has never been reported in other plecopteran mitogenomes. These novel features of the elongated CR in N. nankinensis may have functions associated with the process of replication and transcription. Finally, phylogenetic reconstruction suggested that Nemouridae was the sister-group of Capniidae. PMID:28475163

First Mitochondrial Genome from Nemouridae (Plecoptera) Reveals Novel Features of the Elongated Control Region and Phylogenetic Implications.

PubMed

Chen, Zhi-Teng; Du, Yu-Zhou

2017-05-05

The complete mitochondrial genome (mitogenome) of Nemoura nankinensis (Plecoptera: Nemouridae) was sequenced as the first reported mitogenome from the family Nemouridae. The N. nankinensis mitogenome was the longest (16,602 bp) among reported plecopteran mitogenomes, and it contains 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes and two ribosomal RNA (rRNA) genes. Most PCGs used standard ATN as start codons, and TAN as termination codons. All tRNA genes of N. nankinensis could fold into the cloverleaf secondary structures except for trnSer ( AGN ), whose dihydrouridine (DHU) arm was reduced to a small loop. There was also a large non-coding region (control region, CR) in the N. nankinensis mitogenome. The 1751 bp CR was the longest and had the highest A+T content (81.8%) among stoneflies. A large tandem repeat region, five potential stem-loop (SL) structures, four tRNA-like structures and four conserved sequence blocks (CSBs) were detected in the elongated CR. The presence of these tRNA-like structures in the CR has never been reported in other plecopteran mitogenomes. These novel features of the elongated CR in N. nankinensis may have functions associated with the process of replication and transcription. Finally, phylogenetic reconstruction suggested that Nemouridae was the sister-group of Capniidae.

Oscillatory networks of high-level mental alignment: A perspective-taking MEG study.

PubMed

Seymour, R A; Wang, H; Rippon, G; Kessler, K

2018-08-15

Mentally imagining another's perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al. (2016) showed that theta-band (3-7 Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a similar paradigm, we set out to unravel the extended functional brain network in detail. Increasing the angle between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral prefrontal cortex (PFC) and right anterior cingulate cortex (ACC). Using Granger-causality, we showed that lateral PFC and ACC exert top-down influence over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling in relation to the rTPJ. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a 'hub' to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations. Copyright © 2018 Elsevier Inc. All rights reserved.

Misregulation effect of a novel allelic variant in the Z promoter region found in cis with the CYP21A2 p.P482S mutation: implications for 21-hydroxylase deficiency.

PubMed

Fernández, Cecilia S; Bruque, Carlos D; Taboas, Melisa; Buzzalino, Noemí D; Espeche, Lucia D; Pasqualini, Titania; Charreau, Eduardo H; Alba, Liliana G; Ghiringhelli, Pablo D; Dain, Liliana

2015-09-01

The aim of the current study was to search for the presence of genetic variants in the CYP21A2 Z promoter regulatory region in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Screening of the 10 most frequent pseudogene-derived mutations was followed by direct sequencing of the entire coding sequence, the proximal promoter, and a distal regulatory region in DNA samples from patients with at least one non-determined allele. We report three non-classical patients that presented a novel genetic variant-g.15626A>G-within the Z promoter regulatory region. In all the patients, the novel variant was found in cis with the mild, less frequent, p.P482S mutation located in the exon 10 of the CYP21A2 gene. The putative pathogenic implication of the novel variant was assessed by in silico analyses and in vitro assays. Topological analyses showed differences in the curvature and bendability of the DNA region bearing the novel variant. By performing functional studies, a significantly decreased activity of a reporter gene placed downstream from the regulatory region was found by the G transition. Our results may suggest that the activity of an allele bearing the p.P482S mutation may be influenced by the misregulated CYP21A2 transcriptional activity exerted by the Z promoter A>G variation.

Accuracy of clinical coding for procedures in oral and maxillofacial surgery.

PubMed

Khurram, S A; Warner, C; Henry, A M; Kumar, A; Mohammed-Ali, R I

2016-10-01

Clinical coding has important financial implications, and discrepancies in the assigned codes can directly affect the funding of a department and hospital. Over the last few years, numerous oversights have been noticed in the coding of oral and maxillofacial (OMF) procedures. To establish the accuracy and completeness of coding, we retrospectively analysed the records of patients during two time periods: March to May 2009 (324 patients), and January to March 2014 (200 patients). Two investigators independently collected and analysed the data to ensure accuracy and remove bias. A large proportion of operations were not assigned all the relevant codes, and only 32% - 33% were correct in both cycles. To our knowledge, this is the first reported audit of clinical coding in OMFS, and it highlights serious shortcomings that have substantial financial implications. Better input by the surgical team and improved communication between the surgical and coding departments will improve accuracy. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase

PubMed Central

Hawkins, Vivian N; Auliff, Alyson; Prajapati, Surendra Kumar; Rungsihirunrat, Kanchana; Hapuarachchi, Hapuarachchige C; Maestre, Amanda; O'Neil, Michael T; Cheng, Qin; Joshi, Hema; Na-Bangchang, Kesara; Sibley, Carol Hopkins

2008-01-01

Background In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. Methods The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Results Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. Conclusion It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy. PMID:18442404

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase.

PubMed

Hawkins, Vivian N; Auliff, Alyson; Prajapati, Surendra Kumar; Rungsihirunrat, Kanchana; Hapuarachchi, Hapuarachchige C; Maestre, Amanda; O'Neil, Michael T; Cheng, Qin; Joshi, Hema; Na-Bangchang, Kesara; Sibley, Carol Hopkins

2008-04-28

In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy.

Human heavy chain disease protein WIS: implications for the organization of immunoglobulin genes.

PubMed Central

Franklin, E C; Prelli, F; Frangione, B

1979-01-01

Protein WIS is a human gamma3 heavy (H) chain disease immunoglobulin variant whose amino acid sequence is most readily interpreted by postulating that three residues of the amino terminus are followed by a deletion of most of the variable (VH) domain, which ends at the variable-constant (VC) joining region. Then there is a stretch of eight residues, three of which are unusual, while the other five have striking homology to the VC junction sequence. This is followed by a second deletion, which ends at the beginning of the quadruplicated hinge region. These findings are consistent with mutations resulting in deletions of most of the gene coding for the V region and CH1 domain followed by splicing at the VC joining region and at the hinge. These structural features fit well the notion of genetic discontinuity between V and C genes and also suggest similar mechanisms of excision and splicing in the interdomain regions of the C gene of the heavy chain. PMID:106391

Increasing the Yield in Targeted Next-Generation Sequencing by Implicating CNV Analysis, Non-Coding Exons and the Overall Variant Load: The Example of Retinal Dystrophies

PubMed Central

Eisenberger, Tobias; Neuhaus, Christine; Khan, Arif O.; Decker, Christian; Preising, Markus N.; Friedburg, Christoph; Bieg, Anika; Gliem, Martin; Issa, Peter Charbel; Holz, Frank G.; Baig, Shahid M.; Hellenbroich, Yorck; Galvez, Alberto; Platzer, Konrad; Wollnik, Bernd; Laddach, Nadja; Ghaffari, Saeed Reza; Rafati, Maryam; Botzenhart, Elke; Tinschert, Sigrid; Börger, Doris; Bohring, Axel; Schreml, Julia; Körtge-Jung, Stefani; Schell-Apacik, Chayim; Bakur, Khadijah; Al-Aama, Jumana Y.; Neuhann, Teresa; Herkenrath, Peter; Nürnberg, Gudrun; Nürnberg, Peter; Davis, John S.; Gal, Andreas; Bergmann, Carsten; Lorenz, Birgit; Bolz, Hanno J.

2013-01-01

Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are major causes of blindness. They result from mutations in many genes which has long hampered comprehensive genetic analysis. Recently, targeted next-generation sequencing (NGS) has proven useful to overcome this limitation. To uncover “hidden mutations” such as copy number variations (CNVs) and mutations in non-coding regions, we extended the use of NGS data by quantitative readout for the exons of 55 RP and LCA genes in 126 patients, and by including non-coding 5′ exons. We detected several causative CNVs which were key to the diagnosis in hitherto unsolved constellations, e.g. hemizygous point mutations in consanguineous families, and CNVs complemented apparently monoallelic recessive alleles. Mutations of non-coding exon 1 of EYS revealed its contribution to disease. In view of the high carrier frequency for retinal disease gene mutations in the general population, we considered the overall variant load in each patient to assess if a mutation was causative or reflected accidental carriership in patients with mutations in several genes or with single recessive alleles. For example, truncating mutations in RP1, a gene implicated in both recessive and dominant RP, were causative in biallelic constellations, unrelated to disease when heterozygous on a biallelic mutation background of another gene, or even non-pathogenic if close to the C-terminus. Patients with mutations in several loci were common, but without evidence for di- or oligogenic inheritance. Although the number of targeted genes was low compared to previous studies, the mutation detection rate was highest (70%) which likely results from completeness and depth of coverage, and quantitative data analysis. CNV analysis should routinely be applied in targeted NGS, and mutations in non-coding exons give reason to systematically include 5′-UTRs in disease gene or exome panels. Consideration of all variants is indispensable because even truncating mutations may be misleading. PMID:24265693

Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies.

PubMed

Eisenberger, Tobias; Neuhaus, Christine; Khan, Arif O; Decker, Christian; Preising, Markus N; Friedburg, Christoph; Bieg, Anika; Gliem, Martin; Charbel Issa, Peter; Holz, Frank G; Baig, Shahid M; Hellenbroich, Yorck; Galvez, Alberto; Platzer, Konrad; Wollnik, Bernd; Laddach, Nadja; Ghaffari, Saeed Reza; Rafati, Maryam; Botzenhart, Elke; Tinschert, Sigrid; Börger, Doris; Bohring, Axel; Schreml, Julia; Körtge-Jung, Stefani; Schell-Apacik, Chayim; Bakur, Khadijah; Al-Aama, Jumana Y; Neuhann, Teresa; Herkenrath, Peter; Nürnberg, Gudrun; Nürnberg, Peter; Davis, John S; Gal, Andreas; Bergmann, Carsten; Lorenz, Birgit; Bolz, Hanno J

2013-01-01

Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are major causes of blindness. They result from mutations in many genes which has long hampered comprehensive genetic analysis. Recently, targeted next-generation sequencing (NGS) has proven useful to overcome this limitation. To uncover "hidden mutations" such as copy number variations (CNVs) and mutations in non-coding regions, we extended the use of NGS data by quantitative readout for the exons of 55 RP and LCA genes in 126 patients, and by including non-coding 5' exons. We detected several causative CNVs which were key to the diagnosis in hitherto unsolved constellations, e.g. hemizygous point mutations in consanguineous families, and CNVs complemented apparently monoallelic recessive alleles. Mutations of non-coding exon 1 of EYS revealed its contribution to disease. In view of the high carrier frequency for retinal disease gene mutations in the general population, we considered the overall variant load in each patient to assess if a mutation was causative or reflected accidental carriership in patients with mutations in several genes or with single recessive alleles. For example, truncating mutations in RP1, a gene implicated in both recessive and dominant RP, were causative in biallelic constellations, unrelated to disease when heterozygous on a biallelic mutation background of another gene, or even non-pathogenic if close to the C-terminus. Patients with mutations in several loci were common, but without evidence for di- or oligogenic inheritance. Although the number of targeted genes was low compared to previous studies, the mutation detection rate was highest (70%) which likely results from completeness and depth of coverage, and quantitative data analysis. CNV analysis should routinely be applied in targeted NGS, and mutations in non-coding exons give reason to systematically include 5'-UTRs in disease gene or exome panels. Consideration of all variants is indispensable because even truncating mutations may be misleading.

Presence of tannins in sorghum grains is conditioned by different natural alleles of Tannin1

PubMed Central

Wu, Yuye; Li, Xianran; Xiang, Wenwen; Zhu, Chengsong; Lin, Zhongwei; Wu, Yun; Li, Jiarui; Pandravada, Satchidanand; Ridder, Dustan D.; Bai, Guihua; Wang, Ming L.; Trick, Harold N.; Bean, Scott R.; Tuinstra, Mitchell R.; Tesso, Tesfaye T.; Yu, Jianming

2012-01-01

Sorghum, an ancient old-world cereal grass, is the dietary staple of over 500 million people in more than 30 countries in the tropics and semitropics. Its C4 photosynthesis, drought resistance, wide adaptation, and high nutritional value hold the promise to alleviate hunger in Africa. Not present in other major cereals, such as rice, wheat, and maize, condensed tannins (proanthocyanidins) in the pigmented testa of some sorghum cultivars have been implicated in reducing protein digestibility but recently have been shown to promote human health because of their high antioxidant capacity and ability to fight obesity through reduced digestion. Combining quantitative trait locus mapping, meta-quantitative trait locus fine-mapping, and association mapping, we showed that the nucleotide polymorphisms in the Tan1 gene, coding a WD40 protein, control the tannin biosynthesis in sorghum. A 1-bp G deletion in the coding region, causing a frame shift and a premature stop codon, led to a nonfunctional allele, tan1-a. Likewise, a different 10-bp insertion resulted in a second nonfunctional allele, tan1-b. Transforming the sorghum Tan1 ORF into a nontannin Arabidopsis mutant restored the tannin phenotype. In addition, reduction in nucleotide diversity from wild sorghum accessions to landraces and cultivars was found at the region that codes the highly conserved WD40 repeat domains and the C-terminal region of the protein. Genetic research in crops, coupled with nutritional and medical research, could open the possibility of producing different levels and combinations of phenolic compounds to promote human health. PMID:22699509

Translation attenuation via 3′ terminal codon usage in bovine csn1s2 is responsible for the difference in αs2- and β-casein profile in milk

PubMed Central

Kim, Julie J; Yu, Jaeju; Bag, Jnanankur; Bakovic, Marica; Cant, John P

2015-01-01

The rate of secretion of αs2-casein into bovine milk is approximately 25% of that of β-casein, yet mammary expression of their respective mRNA transcripts (csn1s2 and csn2) is not different. Our objective was to identify molecular mechanisms that explain the difference in translation efficiency between csn1s2 and csn2. Cell-free translational efficiency of csn2 was 5 times that of csn1s2. Transcripts of csn1s2 distributed into heavier polysomes than csn2 transcripts, indicating an attenuation of elongation and/or termination. Stimulatory and inhibitory effects of the 5′ and 3′ UTRs on translational efficiency were different with luciferase and casein sequences in the coding regions. Substituting the 5′ and 3′ UTRs from csn2 into csn1s2 did not improve csn1s2 translation, implicating the coding region itself in the translation difference. Deletion of a 28-codon fragment from the 3′ terminus of the csn1s2 coding region, which displays codons with low correlations to cell fitness, increased translation to a par with csn2. We conclude that the usage of the last 28 codons of csn1s2 is the main regulatory element that attenuates its expression and is responsible for the differential translational expression of csn1s2 and csn2. PMID:25826667

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

PubMed

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

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

Kerr, J.M.; Fisher, L.W.; Termine, J.D.

The authors have isolated and partially sequenced the human bone sialoprotein gene (IBSP). IBSP has been sublocalized by in situ hybridization to chromosome 4q38-q31 and is composed of six small exons (51 to 159 bp) and 1 large exon ([approximately]2.6 kb). The intron/exon junctions defined by sequence analysis are of class O, retaining an intact coding triplet. Sequence analysis of the 5[prime] upstream region revealed a TATAA (nucleotides -30 to-25 from the transcriptional start point) and a CCAAT (nucleotides -56 to-52) box, both in the reverse orientation. Intron 1 contains interesting structural elements composed of polypyrimidine repeats followed by amore » poly(AC)[sub n] tract. Both types of structural elements have been detected in promoter regions of other genes and have been implicated in transcriptional regulation. Several differences between the previously published cDNA sequence and the authors' sequence have been identified, most of which are contained within the untranslated exon 1. Three base revisions in the coding region include a G to T (Gly to Val, amino acid 195), T to C (Val to Ala, amino acid 268), and T to A (Glu to Asp, amino acid 270). In conclusion, the genomic organization and potential regulatory elements of human IBSP have been elucidated. 42 refs., 4 figs., 1 tab.« less

Crises Management in the Oil and Gas Industry: The Niger Delta Experience

NASA Astrophysics Data System (ADS)

Odemene, Glory C.

The Niger Delta crises escalated beyond the borders of the Nigerian nation to become an issue that affected individuals and corporations around the world. This study led to the discovery of how the local crises escalated with international implications. This discovery was accomplished by addressing how the Niger Delta crises escalated from villages to international scenes, with notable impacts on the environment, health, safety, security, and financial segments of local, international, private, and corporate entities. Using Sweeny's crisis decision theory and Lazarus and Folkman's coping theory, the study considered the coping strategies of community members, the decisions, and actions they took in response to the management approaches of the government and the oil and gas companies (OGCs). This qualitative study utilized historical narrative to collect data by interviewing 4 participants who lived and worked in the region during the crises. NVivo was used for manual and automatic coding of data, as well as for categorization and connection of codes. Content analysis of identified codes and categories revealed the themes and trends in the experiences narrated by participants. Findings include the root causes, trend of escalation, and management strategies of the government and the OGCs that influenced the crises. These findings will help to influence policies and practices in the region and enhance effective management of current and emerging conflicts, with possibilities of restoring stability and security in the areas and in the nation at large.

Convergence of the Critical Cooling Rate for Protoplanetary Disk Fragmentation Achieved: The Key Role of Numerical Dissipation of Angular Momentum

NASA Astrophysics Data System (ADS)

Deng, Hongping; Mayer, Lucio; Meru, Farzana

2017-09-01

We carry out simulations of gravitationally unstable disks using smoothed particle hydrodynamics (SPH) and the novel Lagrangian meshless finite mass (MFM) scheme in the GIZMO code. Our aim is to understand the cause of the nonconvergence of the cooling boundary for fragmentation reported in the literature. We run SPH simulations with two different artificial viscosity implementations and compare them with MFM, which does not employ any artificial viscosity. With MFM we demonstrate convergence of the critical cooling timescale for fragmentation at {β }{crit}≈ 3. Nonconvergence persists in SPH codes. We show how the nonconvergence problem is caused by artificial fragmentation triggered by excessive dissipation of angular momentum in domains with large velocity derivatives. With increased resolution, such domains become more prominent. Vorticity lags behind density, due to numerical viscous dissipation in these regions, promoting collapse with longer cooling times. Such effect is shown to be dominant over the competing tendency of artificial viscosity to diminish with increasing resolution. When the initial conditions are first relaxed for several orbits, the flow is more regular, with lower shear and vorticity in nonaxisymmetric regions, aiding convergence. Yet MFM is the only method that converges exactly. Our findings are of general interest, as numerical dissipation via artificial viscosity or advection errors can also occur in grid-based codes. Indeed, for the FARGO code values of {β }{crit} significantly higher than our converged estimate have been reported in the literature. Finally, we discuss implications for giant planet formation via disk instability.

Focus Group Research on the Implications of Adopting the Unified English Braille Code

ERIC Educational Resources Information Center

Wetzel, Robin; Knowlton, Marie

2006-01-01

Five focus groups explored concerns about adopting the Unified English Braille Code. The consensus was that while the proposed changes to the literary braille code would be minor, those to the mathematics braille code would be much more extensive. The participants emphasized that "any code that reduces the number of individuals who can access…

Quantized phase coding and connected region labeling for absolute phase retrieval.

PubMed

Chen, Xiangcheng; Wang, Yuwei; Wang, Yajun; Ma, Mengchao; Zeng, Chunnian

2016-12-12

This paper proposes an absolute phase retrieval method for complex object measurement based on quantized phase-coding and connected region labeling. A specific code sequence is embedded into quantized phase of three coded fringes. Connected regions of different codes are labeled and assigned with 3-digit-codes combining the current period and its neighbors. Wrapped phase, more than 36 periods, can be restored with reference to the code sequence. Experimental results verify the capability of the proposed method to measure multiple isolated objects.

One Speaker, Two Languages. Cross-Disciplinary Perspectives on Code-Switching.

ERIC Educational Resources Information Center

Milroy, Lesley, Ed.; Muysken, Pieter, Ed.

Fifteen articles review code-switching in the four major areas: policy implications in specific institutional and community settings; perspectives of social theory of code-switching as a form of speech behavior in particular social contexts; the grammatical analysis of code-switching, including factors that constrain switching even within a…

Non-White, No More: Effect Coding as an Alternative to Dummy Coding with Implications for Higher Education Researchers

ERIC Educational Resources Information Center

Mayhew, Matthew J.; Simonoff, Jeffrey S.

2015-01-01

The purpose of this article is to describe effect coding as an alternative quantitative practice for analyzing and interpreting categorical, race-based independent variables in higher education research. Unlike indicator (dummy) codes that imply that one group will be a reference group, effect codes use average responses as a means for…

Numerical Prediction of SERN Performance using WIND code

NASA Technical Reports Server (NTRS)

Engblom, W. A.

2003-01-01

Computational results are presented for the performance and flow behavior of single-expansion ramp nozzles (SERNs) during overexpanded operation and transonic flight. Three-dimensional Reynolds-Averaged Navier Stokes (RANS) results are obtained for two vehicle configurations, including the NASP Model 5B and ISTAR RBCC (a variant of X-43B) using the WIND code. Numerical predictions for nozzle integrated forces and pitch moments are directly compared to experimental data for the NASP Model 5B, and adequate-to-excellent agreement is found. The sensitivity of SERN performance and separation phenomena to freestream static pressure and Mach number is demonstrated via a matrix of cases for both vehicles. 3-D separation regions are shown to be induced by either lateral (e.g., sidewall) shocks or vertical (e.g., cowl trailing edge) shocks. Finally, the implications of this work to future preliminary design efforts involving SERNs are discussed.

Mammalian Comparative Genomics Reveals Genetic and Epigenetic Features Associated with Genome Reshuffling in Rodentia

PubMed Central

Capilla, Laia; Sánchez-Guillén, Rosa Ana; Farré, Marta; Paytuví-Gallart, Andreu; Malinverni, Roberto; Ventura, Jacint; Larkin, Denis M.

2016-01-01

Abstract Understanding how mammalian genomes have been reshuffled through structural changes is fundamental to the dynamics of its composition, evolutionary relationships between species and, in the long run, speciation. In this work, we reveal the evolutionary genomic landscape in Rodentia, the most diverse and speciose mammalian order, by whole-genome comparisons of six rodent species and six representative outgroup mammalian species. The reconstruction of the evolutionary breakpoint regions across rodent phylogeny shows an increased rate of genome reshuffling that is approximately two orders of magnitude greater than in other mammalian species here considered. We identified novel lineage and clade-specific breakpoint regions within Rodentia and analyzed their gene content, recombination rates and their relationship with constitutive lamina genomic associated domains, DNase I hypersensitivity sites and chromatin modifications. We detected an accumulation of protein-coding genes in evolutionary breakpoint regions, especially genes implicated in reproduction and pheromone detection and mating. Moreover, we found an association of the evolutionary breakpoint regions with active chromatin state landscapes, most probably related to gene enrichment. Our results have two important implications for understanding the mechanisms that govern and constrain mammalian genome evolution. The first is that the presence of genes related to species-specific phenotypes in evolutionary breakpoint regions reinforces the adaptive value of genome reshuffling. Second, that chromatin conformation, an aspect that has been often overlooked in comparative genomic studies, might play a role in modeling the genomic distribution of evolutionary breakpoints. PMID:28175287

Mammalian Comparative Genomics Reveals Genetic and Epigenetic Features Associated with Genome Reshuffling in Rodentia.

PubMed

Capilla, Laia; Sánchez-Guillén, Rosa Ana; Farré, Marta; Paytuví-Gallart, Andreu; Malinverni, Roberto; Ventura, Jacint; Larkin, Denis M; Ruiz-Herrera, Aurora

2016-12-01

Understanding how mammalian genomes have been reshuffled through structural changes is fundamental to the dynamics of its composition, evolutionary relationships between species and, in the long run, speciation. In this work, we reveal the evolutionary genomic landscape in Rodentia, the most diverse and speciose mammalian order, by whole-genome comparisons of six rodent species and six representative outgroup mammalian species. The reconstruction of the evolutionary breakpoint regions across rodent phylogeny shows an increased rate of genome reshuffling that is approximately two orders of magnitude greater than in other mammalian species here considered. We identified novel lineage and clade-specific breakpoint regions within Rodentia and analyzed their gene content, recombination rates and their relationship with constitutive lamina genomic associated domains, DNase I hypersensitivity sites and chromatin modifications. We detected an accumulation of protein-coding genes in evolutionary breakpoint regions, especially genes implicated in reproduction and pheromone detection and mating. Moreover, we found an association of the evolutionary breakpoint regions with active chromatin state landscapes, most probably related to gene enrichment. Our results have two important implications for understanding the mechanisms that govern and constrain mammalian genome evolution. The first is that the presence of genes related to species-specific phenotypes in evolutionary breakpoint regions reinforces the adaptive value of genome reshuffling. Second, that chromatin conformation, an aspect that has been often overlooked in comparative genomic studies, might play a role in modeling the genomic distribution of evolutionary breakpoints.

Pitch-Responsive Cortical Regions in Congenital Amusia.

PubMed

Norman-Haignere, Sam V; Albouy, Philippe; Caclin, Anne; McDermott, Josh H; Kanwisher, Nancy G; Tillmann, Barbara

2016-03-09

Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work. Copyright © 2016 the authors 0270-6474/16/362986-09$15.00/0.

The role of ethical principles in health care and the implications for ethical codes.

PubMed Central

Limentani, A E

1999-01-01

A common ethical code for everybody involved in health care is desirable, but there are important limitations to the role such a code could play. In order to understand these limitations the approach to ethics using principles and their application to medicine is discussed, and in particular the implications of their being prima facie. The expectation of what an ethical code can do changes depending on how ethical properties in general are understood. The difficulties encountered when ethical values are applied reactively to an objective world can be avoided by seeing them as a more integral part of our understanding of the world. It is concluded that an ethical code can establish important values and describe a common ethical context for health care but is of limited use in solving new and complex ethical problems. PMID:10536764

The Influence of Building Codes on Recreation Facility Design.

ERIC Educational Resources Information Center

Morrison, Thomas A.

1989-01-01

Implications of building codes upon design and construction of recreation facilities are investigated (national building codes, recreation facility standards, and misperceptions of design requirements). Recreation professionals can influence architectural designers to correct past deficiencies, but they must understand architectural and…

Evaluation of seismic design spectrum based on UHS implementing fourth-generation seismic hazard maps of Canada

NASA Astrophysics Data System (ADS)

Ahmed, Ali; Hasan, Rafiq; Pekau, Oscar A.

2016-12-01

Two recent developments have come into the forefront with reference to updating the seismic design provisions for codes: (1) publication of new seismic hazard maps for Canada by the Geological Survey of Canada, and (2) emergence of the concept of new spectral format outdating the conventional standardized spectral format. The fourth -generation seismic hazard maps are based on enriched seismic data, enhanced knowledge of regional seismicity and improved seismic hazard modeling techniques. Therefore, the new maps are more accurate and need to incorporate into the Canadian Highway Bridge Design Code (CHBDC) for its next edition similar to its building counterpart National Building Code of Canada (NBCC). In fact, the code writers expressed similar intentions with comments in the commentary of CHBCD 2006. During the process of updating codes, NBCC, and AASHTO Guide Specifications for LRFD Seismic Bridge Design, American Association of State Highway and Transportation Officials, Washington (2009) lowered the probability level from 10 to 2% and 10 to 5%, respectively. This study has brought five sets of hazard maps corresponding to 2%, 5% and 10% probability of exceedance in 50 years developed by the GSC under investigation. To have a sound statistical inference, 389 Canadian cities are selected. This study shows the implications of the changes of new hazard maps on the design process (i.e., extent of magnification or reduction of the design forces).

Analytical Solutions for Radiative Transfer: Implications for Giant Planet Formation by Disk Instability

NASA Astrophysics Data System (ADS)

Boss, Alan P.

2009-03-01

The disk instability mechanism for giant planet formation is based on the formation of clumps in a marginally gravitationally unstable protoplanetary disk, which must lose thermal energy through a combination of convection and radiative cooling if they are to survive and contract to become giant protoplanets. While there is good observational support for forming at least some giant planets by disk instability, the mechanism has become theoretically contentious, with different three-dimensional radiative hydrodynamics codes often yielding different results. Rigorous code testing is required to make further progress. Here we present two new analytical solutions for radiative transfer in spherical coordinates, suitable for testing the code employed in all of the Boss disk instability calculations. The testing shows that the Boss code radiative transfer routines do an excellent job of relaxing to and maintaining the analytical results for the radial temperature and radiative flux profiles for a spherical cloud with high or moderate optical depths, including the transition from optically thick to optically thin regions. These radial test results are independent of whether the Eddington approximation, diffusion approximation, or flux-limited diffusion approximation routines are employed. The Boss code does an equally excellent job of relaxing to and maintaining the analytical results for the vertical (θ) temperature and radiative flux profiles for a disk with a height proportional to the radial distance. These tests strongly support the disk instability mechanism for forming giant planets.

Functional Characterization of the Human Speech Articulation Network.

PubMed

Basilakos, Alexandra; Smith, Kimberly G; Fillmore, Paul; Fridriksson, Julius; Fedorenko, Evelina

2018-05-01

A number of brain regions have been implicated in articulation, but their precise computations remain debated. Using functional magnetic resonance imaging, we examine the degree of functional specificity of articulation-responsive brain regions to constrain hypotheses about their contributions to speech production. We find that articulation-responsive regions (1) are sensitive to articulatory complexity, but (2) are largely nonoverlapping with nearby domain-general regions that support diverse goal-directed behaviors. Furthermore, premotor articulation regions show selectivity for speech production over some related tasks (respiration control), but not others (nonspeech oral-motor [NSO] movements). This overlap between speech and nonspeech movements concords with electrocorticographic evidence that these regions encode articulators and their states, and with patient evidence whereby articulatory deficits are often accompanied by oral-motor deficits. In contrast, the superior temporal regions show strong selectivity for articulation relative to nonspeech movements, suggesting that these regions play a specific role in speech planning/production. Finally, articulation-responsive portions of posterior inferior frontal gyrus show some selectivity for articulation, in line with the hypothesis that this region prepares an articulatory code that is passed to the premotor cortex. Taken together, these results inform the architecture of the human articulation system.

Geographically varying effects of weather on tobacco consumption: implications for health marketing initiatives.

PubMed

Govind, Rahul; Garg, Nitika; Sun, Wenbin

2014-01-01

Weather and its fluctuations have been found to influence the consumption of negative hedonic goods. However, such findings are of limited use to health marketers who cannot control the weather, and hence, its effects. The current research utilizes data obtained at the zip-code level to study geographical variations in the effect of weather on tobacco consumption across the entire continental United States. The results allow health marketers to identify areas that will be most responsive to marketing efforts aimed at curtailing negative hedonic consumption and thus implement more effective, region-specific initiatives.

Fingerprints of resistant Escherichia coli O157:H7 from vegetables and environmental samples.

PubMed

Abakpa, Grace Onyukwo; Umoh, Veronica J; Kamaruzaman, Sijam; Ibekwe, Mark

2018-01-01

Some routes of transmission of Escherichia coli O157:H7 to fresh produce include contaminated irrigation water and manure polluted soils. The aim of the present study was to determine the genetic relationships of E. coli O157:H7 isolated from some produce growing region in Nigeria using enterobacterial repetitive intergenic consensus (ERIC) DNA fingerprinting analysis. A total of 440 samples comprising leafy greens, irrigation water, manure and soil were obtained from vegetable producing regions in Kano and Plateau States, Nigeria. Genes coding for the quinolone resistance-determinant (gyrA) and plasmid (pCT) coding for multidrug resistance (MDR) were determined using polymerase chain reaction (PCR) in 16 isolates that showed MDR. Cluster analysis of the ERIC-PCR profiles based on band sizes revealed six main clusters from the sixteen isolates analysed. The largest cluster (cluster 3) grouped isolates from vegetables and manure at a similarity coefficient of 0.72. The present study provides data that support the potential transmission of resistant strains of E. coli O157:H7 from vegetables and environmental sources to humans with potential public health implications, especially in developing countries. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Comparative Mitogenomics of the Assassin Bug Genus Peirates (Hemiptera: Reduviidae: Peiratinae) Reveal Conserved Mitochondrial Genome Organization of P. atromaculatus, P. fulvescens and P. turpis

PubMed Central

Zhao, Guangyu; Li, Hu; Zhao, Ping; Cai, Wanzhi

2015-01-01

In this study, we sequenced four new mitochondrial genomes and presented comparative mitogenomic analyses of five species in the genus Peirates (Hemiptera: Reduviidae). Mitochondrial genomes of these five assassin bugs had a typical set of 37 genes and retained the ancestral gene arrangement of insects. The A+T content, AT- and GC-skews were similar to the common base composition biases of insect mtDNA. Genomic size ranges from 15,702 bp to 16,314 bp and most of the size variation was due to length and copy number of the repeat unit in the putative control region. All of the control region sequences included large tandem repeats present in two or more copies. Our result revealed similarity in mitochondrial genomes of P. atromaculatus, P. fulvescens and P. turpis, as well as the highly conserved genomic-level characteristics of these three species, e.g., the same start and stop codons of protein-coding genes, conserved secondary structure of tRNAs, identical location and length of non-coding and overlapping regions, and conservation of structural elements and tandem repeat unit in control region. Phylogenetic analyses also supported a close relationship between P. atromaculatus, P. fulvescens and P. turpis, which might be recently diverged species. The present study indicates that mitochondrial genome has important implications on phylogenetics, population genetics and speciation in the genus Peirates. PMID:25689825

Phonological Coding Abilities: Identification of Impairments Related to Phonologically Based Reading Problems.

ERIC Educational Resources Information Center

Swank, Linda K.

1994-01-01

Relationships between phonological coding abilities and reading outcomes have implications for differential diagnosis of language-based reading problems. The theoretical construct of specific phonological coding ability is explained, including phonological encoding, phonological awareness and metaphonology, lexical access, working memory, and…

RRE: a tool for the extraction of non-coding regions surrounding annotated genes from genomic datasets.

PubMed

Lazzarato, F; Franceschinis, G; Botta, M; Cordero, F; Calogero, R A

2004-11-01

RRE allows the extraction of non-coding regions surrounding a coding sequence [i.e. gene upstream region, 5'-untranslated region (5'-UTR), introns, 3'-UTR, downstream region] from annotated genomic datasets available at NCBI. RRE parser and web-based interface are accessible at http://www.bioinformatica.unito.it/bioinformatics/rre/rre.html

A comparison of complete mitochondrial genomes of silver carp hypophthalmichthys molitrix and bighead carp hypophthalmichthys nobilis: Implications for their taxonomic relationship and phylogeny

USGS Publications Warehouse

Li, S.-F.; Xu, J.-W.; Yang, Q.-L.; Wang, C.H.; Chen, Q.; Chapman, D.C.; Lu, G.

2009-01-01

Based upon morphological characters, Silver carp Hypophthalmichthys molitrix and bighead carp Hypophthalmichthys nobilis (or Aristichthys nobilis) have been classified into either the same genus or two distinct genera. Consequently, the taxonomic relationship of the two species at the generic level remains equivocal. This issue is addressed by sequencing complete mitochondrial genomes of H. molitrix and H. nobilis, comparing their mitogenome organization, structure and sequence similarity, and conducting a comprehensive phylogenetic analysis of cyprinid species. As with other cyprinid fishes, the mitogenomes of the two species were structurally conserved, containing 37 genes including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA (tRNAs) genes and a putative control region (D-loop). Sequence similarity between the two mitogenomes varied in different genes or regions, being highest in the tRNA genes (98??8%), lowest in the control region (89??4%) and intermediate in the protein-coding genes (94??2%). Analyses of the sequence comparison and phylogeny using concatenated protein sequences support the view that the two species belong to the genus Hypophthalmichthys. Further studies using nuclear markers and involving more closely related species, and the systematic combination of traditional biology and molecular biology are needed in order to confirm this conclusion. ?? 2009 The Fisheries Society of the British Isles.

The Use and Effectiveness of Triple Multiplex System for Coding Region Single Nucleotide Polymorphism in Mitochondrial DNA Typing of Archaeologically Obtained Human Skeletons from Premodern Joseon Tombs of Korea

PubMed Central

Oh, Chang Seok; Lee, Soong Deok; Kim, Yi-Suk; Shin, Dong Hoon

2015-01-01

Previous study showed that East Asian mtDNA haplogroups, especially those of Koreans, could be successfully assigned by the coupled use of analyses on coding region SNP markers and control region mutation motifs. In this study, we tried to see if the same triple multiplex analysis for coding regions SNPs could be also applicable to ancient samples from East Asia as the complementation for sequence analysis of mtDNA control region. By the study on Joseon skeleton samples, we know that mtDNA haplogroup determined by coding region SNP markers successfully falls within the same haplogroup that sequence analysis on control region can assign. Considering that ancient samples in previous studies make no small number of errors in control region mtDNA sequencing, coding region SNP analysis can be used as good complimentary to the conventional haplogroup determination, especially of archaeological human bone samples buried underground over long periods. PMID:26345190

On fuzzy semantic similarity measure for DNA coding.

PubMed

Ahmad, Muneer; Jung, Low Tang; Bhuiyan, Md Al-Amin

2016-02-01

A coding measure scheme numerically translates the DNA sequence to a time domain signal for protein coding regions identification. A number of coding measure schemes based on numerology, geometry, fixed mapping, statistical characteristics and chemical attributes of nucleotides have been proposed in recent decades. Such coding measure schemes lack the biologically meaningful aspects of nucleotide data and hence do not significantly discriminate coding regions from non-coding regions. This paper presents a novel fuzzy semantic similarity measure (FSSM) coding scheme centering on FSSM codons׳ clustering and genetic code context of nucleotides. Certain natural characteristics of nucleotides i.e. appearance as a unique combination of triplets, preserving special structure and occurrence, and ability to own and share density distributions in codons have been exploited in FSSM. The nucleotides׳ fuzzy behaviors, semantic similarities and defuzzification based on the center of gravity of nucleotides revealed a strong correlation between nucleotides in codons. The proposed FSSM coding scheme attains a significant enhancement in coding regions identification i.e. 36-133% as compared to other existing coding measure schemes tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark matter' un-annotated RNA.

PubMed

Kapranov, Philipp; St Laurent, Georges; Raz, Tal; Ozsolak, Fatih; Reynolds, C Patrick; Sorensen, Poul H B; Reaman, Gregory; Milos, Patrice; Arceci, Robert J; Thompson, John F; Triche, Timothy J

2010-12-21

Discovery that the transcriptional output of the human genome is far more complex than predicted by the current set of protein-coding annotations and that most RNAs produced do not appear to encode proteins has transformed our understanding of genome complexity and suggests new paradigms of genome regulation. However, the fraction of all cellular RNA whose function we do not understand and the fraction of the genome that is utilized to produce that RNA remain controversial. This is not simply a bookkeeping issue because the degree to which this un-annotated transcription is present has important implications with respect to its biologic function and to the general architecture of genome regulation. For example, efforts to elucidate how non-coding RNAs (ncRNAs) regulate genome function will be compromised if that class of RNAs is dismissed as simply 'transcriptional noise'. We show that the relative mass of RNA whose function and/or structure we do not understand (the so called 'dark matter' RNAs), as a proportion of all non-ribosomal, non-mitochondrial human RNA (mt-RNA), can be greater than that of protein-encoding transcripts. This observation is obscured in studies that focus only on polyA-selected RNA, a method that enriches for protein coding RNAs and at the same time discards the vast majority of RNA prior to analysis. We further show the presence of a large number of very long, abundantly-transcribed regions (100's of kb) in intergenic space and further show that expression of these regions is associated with neoplastic transformation. These overlap some regions found previously in normal human embryonic tissues and raises an interesting hypothesis as to the function of these ncRNAs in both early development and neoplastic transformation. We conclude that 'dark matter' RNA can constitute the majority of non-ribosomal, non-mitochondrial-RNA and a significant fraction arises from numerous very long, intergenic transcribed regions that could be involved in neoplastic transformation.

Quantifying Low Energy Proton Damage in Multijunction Solar Cells

NASA Technical Reports Server (NTRS)

Messenger, Scott R.; Burke, Edward A.; Walters, Robert J.; Warner, Jeffrey H.; Summers, Geoffrey P.; Lorentzen, Justin R.; Morton, Thomas L.; Taylor, Steven J.

2007-01-01

An analysis of the effects of low energy proton irradiation on the electrical performance of triple junction (3J) InGaP2/GaAs/Ge solar cells is presented. The Monte Carlo ion transport code (SRIM) is used to simulate the damage profile induced in a 3J solar cell under the conditions of typical ground testing and that of the space environment. The results are used to present a quantitative analysis of the defect, and hence damage, distribution induced in the cell active region by the different radiation conditions. The modelling results show that, in the space environment, the solar cell will experience a uniform damage distribution through the active region of the cell. Through an application of the displacement damage dose analysis methodology, the implications of this result on mission performance predictions are investigated.

Design and System Implications of a Family of Wideband HF Data Waveforms

DTIC Science & Technology

2010-09-01

code rates (i.e. 8/9, 9/10) will be used to attain the highest data rates for surface wave links. Very high puncturing of convolutional codes can...Communication Links”, Edition 1, North Atlantic Treaty Organization, 2009. [14] Yasuda, Y., Kashiki, K., Hirata, Y. “High- Rate Punctured Convolutional Codes ...length 7 convolutional code that has been used for over two decades in 110A. In addition, repetition coding and puncturing was

Statistical properties of DNA sequences

NASA Technical Reports Server (NTRS)

Peng, C. K.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Mantegna, R. N.; Simons, M.; Stanley, H. E.

1995-01-01

We review evidence supporting the idea that the DNA sequence in genes containing non-coding regions is correlated, and that the correlation is remarkably long range--indeed, nucleotides thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationarity" feature of the sequence of base pairs by applying a new algorithm called detrended fluctuation analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and non-coding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to every DNA sequence (33301 coding and 29453 non-coding) in the entire GenBank database. Finally, we describe briefly some recent work showing that the non-coding sequences have certain statistical features in common with natural and artificial languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts. These statistical properties of non-coding sequences support the possibility that non-coding regions of DNA may carry biological information.

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications

PubMed Central

Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

2017-01-01

Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lncRNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). Certain lncRNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lncRNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lncRNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC. PMID:28932078

On the error probability of general tree and trellis codes with applications to sequential decoding

NASA Technical Reports Server (NTRS)

Johannesson, R.

1973-01-01

An upper bound on the average error probability for maximum-likelihood decoding of the ensemble of random binary tree codes is derived and shown to be independent of the length of the tree. An upper bound on the average error probability for maximum-likelihood decoding of the ensemble of random L-branch binary trellis codes of rate R = 1/n is derived which separates the effects of the tail length T and the memory length M of the code. It is shown that the bound is independent of the length L of the information sequence. This implication is investigated by computer simulations of sequential decoding utilizing the stack algorithm. These simulations confirm the implication and further suggest an empirical formula for the true undetected decoding error probability with sequential decoding.

Integrating Bar-Code Medication Administration Competencies in the Curriculum: Implications for Nursing Education and Interprofessional Collaboration.

PubMed

Angel, Vini M; Friedman, Marvin H; Friedman, Andrea L

This article describes an innovative project involving the integration of bar-code medication administration technology competencies in the nursing curriculum through interprofessional collaboration among nursing, pharmacy, and computer science disciplines. A description of the bar-code medication administration technology project and lessons learned are presented.

Coding and Comprehension in Skilled Reading and Implications for Reading Instruction.

ERIC Educational Resources Information Center

Perfetti, Charles A.; Lesgold, Alan M.

A view of skilled reading is suggested that emphasizes an intimate connection between coding and comprehension. It is suggested that skilled comprehension depends on a highly refined facility for generating and manipulating language codes, especially at the phonetic/articulatory level. The argument is developed that decoding expertise should be a…

Utilization of recently developed codes for high power Brayton and Rankine cycle power systems

NASA Technical Reports Server (NTRS)

Doherty, Michael P.

1993-01-01

Two recently developed FORTRAN computer codes for high power Brayton and Rankine thermodynamic cycle analysis for space power applications are presented. The codes were written in support of an effort to develop a series of subsystem models for multimegawatt Nuclear Electric Propulsion, but their use is not limited just to nuclear heat sources or to electric propulsion. Code development background, a description of the codes, some sample input/output from one of the codes, and state future plans/implications for the use of these codes by NASA's Lewis Research Center are provided.

Simultaneous perception of a spoken and a signed language: The brain basis of ASL-English code-blends

PubMed Central

Weisberg, Jill; McCullough, Stephen; Emmorey, Karen

2018-01-01

Code-blends (simultaneous words and signs) are a unique characteristic of bimodal bilingual communication. Using fMRI, we investigated code-blend comprehension in hearing native ASL-English bilinguals who made a semantic decision (edible?) about signs, audiovisual words, and semantically equivalent code-blends. English and ASL recruited a similar fronto-temporal network with expected modality differences: stronger activation for English in auditory regions of bilateral superior temporal cortex, and stronger activation for ASL in bilateral occipitotemporal visual regions and left parietal cortex. Code-blend comprehension elicited activity in a combination of these regions, and no cognitive control regions were additionally recruited. Furthermore, code-blends elicited reduced activation relative to ASL presented alone in bilateral prefrontal and visual extrastriate cortices, and relative to English alone in auditory association cortex. Consistent with behavioral facilitation observed during semantic decisions, the findings suggest that redundant semantic content induces more efficient neural processing in language and sensory regions during bimodal language integration. PMID:26177161

The complete mitochondrial genome of lesser long-tailed Hamster Cricetulus longicaudatus (Milne-Edwards, 1867) and phylogenetic implications.

PubMed

Zhang, Ziqi; Sun, Tong; Kang, Chunlan; Liu, Yang; Liu, Shaoying; Yue, Bisong; Zeng, Tao

2016-01-01

The complete mitochondrial genome sequence of Cricetulus longicaudatus (Rodentia Cricetidae: Cricetinae) was determined and was deposited in GenBank (GenBank accession no. KM067270). The mitochondrial genome of C. longicaudatus was 16,302 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region, with an identical order to that of other rodents' mitochondrial genomes. The phylogenetic analysis was performed with Bayesian inference based on the concatenated nucleotide sequence of 12 protein-coding genes on the heavy strand. The result showed that these species from Cricetidae and its two subfamilies (Cricetinae and Arvicolines) formed solid monophyletic group, respectively. The Cricetulus had close phylogenetic relationship with Tscherskia among three genera (Cricetulus, Cricetulus and Mesocricetus). Neodon irene and Myodes regulus were embedded in Microtus and Eothenomys, respectively. The unusual phylogenetic positions of Neodon irene and Myodes regulus remain further study in the future.

Preserving Envelope Efficiency in Performance Based Code Compliance

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

Thornton, Brian A.; Sullivan, Greg P.; Rosenberg, Michael I.

2015-06-20

The City of Seattle 2012 Energy Code (Seattle 2014), one of the most progressive in the country, is under revision for its 2015 edition. Additionally, city personnel participate in the development of the next generation of the Washington State Energy Code and the International Energy Code. Seattle has pledged carbon neutrality by 2050 including buildings, transportation and other sectors. The United States Department of Energy (DOE), through Pacific Northwest National Laboratory (PNNL) provided technical assistance to Seattle in order to understand the implications of one potential direction for its code development, limiting trade-offs of long-lived building envelope components less stringentmore » than the prescriptive code envelope requirements by using better-than-code but shorter-lived lighting and heating, ventilation, and air-conditioning (HVAC) components through the total building performance modeled energy compliance path. Weaker building envelopes can permanently limit building energy performance even as lighting and HVAC components are upgraded over time, because retrofitting the envelope is less likely and more expensive. Weaker building envelopes may also increase the required size, cost and complexity of HVAC systems and may adversely affect occupant comfort. This report presents the results of this technical assistance. The use of modeled energy code compliance to trade-off envelope components with shorter-lived building components is not unique to Seattle and the lessons and possible solutions described in this report have implications for other jurisdictions and energy codes.« less

The first complete mitochondrial genome of Bactrocera tsuneonis (Miyake) (Diptera: Tephritidae) by next-generation sequencing and its phylogenetic implications.

PubMed

Zhang, Yue; Feng, Shiqian; Zeng, Yiying; Ning, Hong; Liu, Lijun; Zhao, Zihua; Jiang, Fan; Li, Zhihong

2018-06-23

Bactrocera tsuneonis (Miyake), generally known as the Japanese orange fly, is considered to be a major pest of commercial citrus crops. It has a limited distribution in China, Japan and Vietnam, but it has the potential to invade areas outside of Asia. More genetic information of B. tsuneonis should be obtained in order to develop effective methodologies for rapid and accurate molecular identification due to the difficulty of distinguishing it from Bactrocera minax based on morphological features. We report here the whole mitochondrial genome of B. tsuneonis sequenced by next-generation sequencing. This mitogenome sequence had a total length of 15,865 bp, a typical circular molecule comprising 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding region (A + T-rich control region). The structure and organization of the molecule were typical and similar compared with the published homologous sequences of other fruit flies in Tephritidae. The phylogenetic analyses based on the mitochondrial genome data presented a close genetic relationship between B. tsuneonis and B. minax. This is the first report of the complete mitochondrial genome of B. tsuneonis, and it can be used in further studies of species diagnosis, evolutionary biology, prevention and control. Copyright © 2018. Published by Elsevier B.V.

LncSubpathway: a novel approach for identifying dysfunctional subpathways associated with risk lncRNAs by integrating lncRNA and mRNA expression profiles and pathway topologies.

PubMed

Xu, Yanjun; Li, Feng; Wu, Tan; Xu, Yingqi; Yang, Haixiu; Dong, Qun; Zheng, Meiyu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Li, Xia

2017-02-28

Long non-coding RNAs (lncRNAs) play important roles in various biological processes, including the development of many diseases. Pathway analysis is a valuable aid for understanding the cellular functions of these transcripts. We have developed and characterized LncSubpathway, a novel method that integrates lncRNA and protein coding gene (PCG) expression with interactome data to identify disease risk subpathways that functionally associated with risk lncRNAs. LncSubpathway identifies the most relevance regions which are related with risk lncRNA set and implicated with study conditions through simultaneously considering the dysregulation extent of lncRNAs, PCGs and their correlations. Simulation studies demonstrated that the sensitivity and false positive rates of LncSubpathway were within acceptable ranges, and that LncSubpathway could accurately identify dysregulated regions that related with disease risk lncRNAs within pathways. When LncSubpathway was applied to colorectal carcinoma and breast cancer subtype datasets, it identified cancer type- and breast cancer subtype-related meaningful subpathways. Further, analysis of its robustness and reproducibility indicated that LncSubpathway was a reliable means of identifying subpathways that functionally associated with lncRNAs. LncSubpathway is freely available at http://www.bio-bigdata.com/lncSubpathway/.

LncSubpathway: a novel approach for identifying dysfunctional subpathways associated with risk lncRNAs by integrating lncRNA and mRNA expression profiles and pathway topologies

PubMed Central

Wu, Tan; Xu, Yingqi; Yang, Haixiu; Dong, Qun; Zheng, Meiyu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Li, Xia

2017-01-01

Long non-coding RNAs (lncRNAs) play important roles in various biological processes, including the development of many diseases. Pathway analysis is a valuable aid for understanding the cellular functions of these transcripts. We have developed and characterized LncSubpathway, a novel method that integrates lncRNA and protein coding gene (PCG) expression with interactome data to identify disease risk subpathways that functionally associated with risk lncRNAs. LncSubpathway identifies the most relevance regions which are related with risk lncRNA set and implicated with study conditions through simultaneously considering the dysregulation extent of lncRNAs, PCGs and their correlations. Simulation studies demonstrated that the sensitivity and false positive rates of LncSubpathway were within acceptable ranges, and that LncSubpathway could accurately identify dysregulated regions that related with disease risk lncRNAs within pathways. When LncSubpathway was applied to colorectal carcinoma and breast cancer subtype datasets, it identified cancer type- and breast cancer subtype-related meaningful subpathways. Further, analysis of its robustness and reproducibility indicated that LncSubpathway was a reliable means of identifying subpathways that functionally associated with lncRNAs. LncSubpathway is freely available at http://www.bio-bigdata.com/lncSubpathway/. PMID:28152521

Pickup ion processes associated with spacecraft thrusters: Implications for solar probe plus

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

Clemens, Adam, E-mail: a.j.clemens@qmul.ac.uk; Burgess, David

2016-03-15

Chemical thrusters are widely used in spacecraft for attitude control and orbital manoeuvres. They create an exhaust plume of neutral gas which produces ions via photoionization and charge exchange. Measurements of local plasma properties will be affected by perturbations caused by the coupling between the newborn ions and the plasma. A model of neutral expansion has been used in conjunction with a fully three-dimensional hybrid code to study the evolution and ionization over time of the neutral cloud produced by the firing of a mono-propellant hydrazine thruster as well as the interactions of the resulting ion cloud with the ambientmore » solar wind. Results are presented which show that the plasma in the region near to the spacecraft will be perturbed for an extended period of time with the formation of an interaction region around the spacecraft, a moderate amplitude density bow wave bounding the interaction region and evidence of an instability at the forefront of the interaction region which causes clumps of ions to be ejected from the main ion cloud quasi-periodically.« less

Particle-In-Cell Simulations of the Solar Wind Interaction with Lunar Crustal Magnetic Anomalies: Magnetic Cusp Regions

NASA Technical Reports Server (NTRS)

Poppe, A. R.; Halekas, J. S.; Delory, G. T.; Farrell, W. M.

2012-01-01

As the solar wind is incident upon the lunar surface, it will occasionally encounter lunar crustal remanent magnetic fields. These magnetic fields are small-scale, highly non-dipolar, have strengths up to hundreds of nanotesla, and typically interact with the solar wind in a kinetic fashion. Simulations, theoretical analyses, and spacecraft observations have shown that crustal fields can reflect solar wind protons via a combination of magnetic and electrostatic reflection; however, analyses of surface properties have suggested that protons may still access the lunar surface in the cusp regions of crustal magnetic fields. In this first report from a planned series of studies, we use a 1 1/2-dimensional, electrostatic particle-in-cell code to model the self-consistent interaction between the solar wind, the cusp regions of lunar crustal remanent magnetic fields, and the lunar surface. We describe the self-consistent electrostatic environment within crustal cusp regions and discuss the implications of this work for the role that crustal fields may play regulating space weathering of the lunar surface via proton bombardment.

A code of ethics for health care ethics consultants: journey to the present and implications for the field.

PubMed

Tarzian, Anita J; Wocial, Lucia D

2015-01-01

For decades a debate has played out in the literature about who bioethicists are, what they do, whether they can be considered professionals qua bioethicists, and, if so, what professional responsibilities they are called to uphold. Health care ethics consultants are bioethicists who work in health care settings. They have been seeking guidance documents that speak to their special relationships/duties toward those they serve. By approving a Code of Ethics and Professional Responsibilities for Health Care Ethics Consultants, the American Society for Bioethics and Humanities (ASBH) has moved the professionalization debate forward in a significant way. This first code of ethics focuses on individuals who provide health care ethics consultation (HCEC) in clinical settings. The evolution of the code's development, implications for the field of HCEC and bioethics, and considerations for future directions are presented here.

Figuring Out Gas in Galaxies In Enzo (FOGGIE): Resolving the Inner Circumgalactic Medium

NASA Astrophysics Data System (ADS)

Corlies, Lauren; Peeples, Molly; Tumlinson, Jason; O'Shea, Brian; Smith, Britton

2018-01-01

Cosmological hydrodynamical simulations using every common numerical method have struggled to reproduce the multiphase nature of the circumgalactic medium (CGM) revealed by recent observations. However, to date, resolution in these simulations has been aimed at dense regions — the galactic disk and in-falling satellites — while the diffuse CGM never reaches comparable levels of refinement. Taking advantage of the flexible grid structure of the adaptive mesh refinement code Enzo, we force refinement in a region of the CGM of a Milky Way-like galaxy to the same spatial resolution as that of the disk. In this talk, I will present how the physical and structural distributions of the circumgalactic gas change dramatically as a function of the resolution alone. I will also show the implications these changes have for the observational properties of the gas in the context of the observations.

Regional 3D Numerical Modeling of the Lithosphere-Mantle System: Implications for Continental Rift-Parallel Surface Velocities

NASA Astrophysics Data System (ADS)

Stamps, S.; Bangerth, W.; Hager, B. H.

2014-12-01

The East African Rift System (EARS) is an active divergent plate boundary with slow, approximately E-W extension rates ranging from <1-6 mm/yr. Previous work using thin-sheet modeling indicates lithospheric buoyancy dominates the force balance driving large-scale Nubia-Somalia divergence, however GPS observations within the Western Branch of the EARS show along-rift motions that contradict this simple model. Here, we test the role of mantle flow at the rift-scale using our new, regional 3D numerical model based on the open-source code ASPECT. We define a thermal lithosphere with thicknesses that are systematically changed for generic models or based on geophysical constraints in the Western branch (e.g. melting depths, xenoliths, seismic tomography). Preliminary results suggest existing variations in lithospheric thicknesses along-rift in the Western Branch can drive upper mantle flow that is consistent with geodetic observations.

"There are too many, but never enough": qualitative case study investigating routine coding of clinical information in depression.

PubMed

Cresswell, Kathrin; Morrison, Zoe; Kalra, Dipak; Sheikh, Aziz

2012-01-01

We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned. Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care. Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding. There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined.

Functional annotation of HOT regions in the human genome: implications for human disease and cancer

PubMed Central

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-01-01

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy. PMID:26113264

Functional annotation of HOT regions in the human genome: implications for human disease and cancer.

PubMed

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-06-26

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy.

On the Biological Plausibility of Grandmother Cells: Implications for Neural Network Theories in Psychology and Neuroscience

ERIC Educational Resources Information Center

Bowers, Jeffrey S.

2009-01-01

A fundamental claim associated with parallel distributed processing (PDP) theories of cognition is that knowledge is coded in a distributed manner in mind and brain. This approach rejects the claim that knowledge is coded in a localist fashion, with words, objects, and simple concepts (e.g. "dog"), that is, coded with their own dedicated…

Regional and temporal variations in coding of hospital diagnoses referring to upper gastrointestinal and oesophageal bleeding in Germany.

PubMed

Langner, Ingo; Mikolajczyk, Rafael; Garbe, Edeltraut

2011-08-17

Health insurance claims data are increasingly used for health services research in Germany. Hospital diagnoses in these data are coded according to the International Classification of Diseases, German modification (ICD-10-GM). Due to the historical division into West and East Germany, different coding practices might persist in both former parts. Additionally, the introduction of Diagnosis Related Groups (DRGs) in Germany in 2003/2004 might have changed the coding. The aim of this study was to investigate regional and temporal variations in coding of hospitalisation diagnoses in Germany. We analysed hospitalisation diagnoses for oesophageal bleeding (OB) and upper gastrointestinal bleeding (UGIB) from the official German Hospital Statistics provided by the Federal Statistical Office. Bleeding diagnoses were classified as "specific" (origin of bleeding provided) or "unspecific" (origin of bleeding not provided) coding. We studied regional (former East versus West Germany) differences in incidence of hospitalisations with specific or unspecific coding for OB and UGIB and temporal variations between 2000 and 2005. For each year, incidence ratios of hospitalisations for former East versus West Germany were estimated with log-linear regression models adjusting for age, gender and population density. Significant differences in specific and unspecific coding between East and West Germany and over time were found for both, OB and UGIB hospitalisation diagnoses, respectively. For example in 2002, incidence ratios of hospitalisations for East versus West Germany were 1.24 (95% CI 1.16-1.32) for specific and 0.67 (95% CI 0.60-0.74) for unspecific OB diagnoses and 1.43 (95% CI 1.36-1.51) for specific and 0.83 (95% CI 0.80-0.87) for unspecific UGIB. Regional differences nearly disappeared and time trends were less marked when using combined specific and unspecific diagnoses of OB or UGIB, respectively. During the study period, there were substantial regional and temporal variations in the coding of OB and UGIB diagnoses in hospitalised patients. Possible explanations for the observed regional variations are different coding preferences, further influenced by changes in coding and reimbursement rules. Analysing groups of diagnoses including specific and unspecific codes reduces the influence of varying coding practices.

Implementation of the International Code of Marketing of Breastmilk Substitutes in the Eastern Mediterranean Region.

PubMed

Al Jawaldeh, Ayoub; Sayed, Ghada

2018-04-05

Optimal breastfeeding practices and appropriate complementary feeding improve child health, survival and development. The countries of the Eastern Mediterranean Region have made significant strides in formulation and implementation of legislation to protect and promote breastfeeding based on The International Code of Marketing of Breast-milk Substitutes (the Code) and subsequent relevant World Health Assembly resolutions. To assess the implementation of the Code in the Region. Assessment was conducted by the World Health Organization (WHO) Regional Office for the Eastern Mediterranean using a WHO standard questionnaire. Seventeen countries in the Region have enacted legislation to protect breastfeeding. Only 6 countries have comprehensive legislation or other legal measures reflecting all or most provisions of the Code; 4 countries have legal measures incorporating many provisions of the Code; 7 countries have legal measures that contain a few provisions of the Code; 4 countries are currently studying the issue; and only 1 country has no measures in place. Further analysis of the legislation found that the text of articles in the laws fully reflected the Code articles in only 6 countries. Most countries need to revisit and amend existing national legislation to implement fully the Code and relevant World Health Assembly resolutions, supported by systematic monitoring and reporting. Copyright © World Health Organization (WHO) 2018. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).

The Legal Implication of Cultural Bias in the Intelligence Testing of Disadvantaged School Children

ERIC Educational Resources Information Center

Georgetown Law Journal, 1973

1973-01-01

The court cases and legal codes cited in this article include: Brown v. Board of Education, 1954; Hobson v. Hansen, 1967; Diana v. State Board of Education (Calif.), 1970; and, California Education Code, 1972. (SF)

Living off-grid in an arid environment without a well : can residential and commercial/industrial water harvesting help solve water supply problems?

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

Axness, Carl L.; Ferrando, Ana

2010-08-01

Our family of three lives comfortably off-grid without a well in an arid region ({approx}9 in/yr, average). This year we expect to achieve water sustainability with harvested or grey water supporting all of our needs (including a garden and trees), except drinking water (about 7 gallons/week). We discuss our implementation and the implication that for an investment of a few thousand dollars, many single family homes could supply a large portion of their own water needs, significantly reducing municipal water demand. Generally, harvested water is very low in minerals and pollutants, but may need treatment for microbes in order tomore » be potable. This may be addressed via filters, UV light irradiation or through chemical treatment (bleach). Looking further into the possibility of commercial water harvesting from malls, big box stores and factories, we ask whether water harvesting could supply a significant portion of potable water by looking at two cities with water supply problems. We look at the implications of separate municipal water lines for potable and clean non-potable uses. Implications on changes to future building codes are explored.« less

Improving the sensitivity and specificity of the abbreviated injury scale coding system.

PubMed Central

Kramer, C F; Barancik, J I; Thode, H C

1990-01-01

The Abbreviated Injury Scale with Epidemiologic Modifications (AIS 85-EM) was developed to make it possible to code information about anatomic injury types and locations that, although generally available from medical records, is not codable under the standard Abbreviated Injury Scale, published by the American Association for Automotive Medicine in 1985 (AIS 85). In a population-based sample of 3,223 motor vehicle trauma cases, 68 percent of the patients had one or more injuries that were coded to the AIS 85 body region nonspecific category external. When the same patients' injuries were coded using the AIS 85-EM coding procedure, only 15 percent of the patients had injuries that could not be coded to a specific body region. With AIS 85-EM, the proportion of codable head injury cases increased from 16 percent to 37 percent, thereby improving the potential for identifying cases with head and threshold brain injury. The data suggest that body region coding of all injuries is necessary to draw valid and reliable conclusions about changes in injury patterns and their sequelae. The increased specificity of body region coding improves assessments of the efficacy of injury intervention strategies and countermeasure programs using epidemiologic methodology. PMID:2116633

25 CFR 900.125 - What shall a construction contract proposal contain?

Code of Federal Regulations, 2012 CFR

2012-04-01

... tribal building codes and engineering standards; (4) Structural integrity; (5) Accountability of funds..., standards and methods (including national, regional, state, or tribal building codes or construction... methods (including national, regional, state, or tribal building codes or construction industry standards...

25 CFR 900.125 - What shall a construction contract proposal contain?

Code of Federal Regulations, 2014 CFR

2014-04-01

... tribal building codes and engineering standards; (4) Structural integrity; (5) Accountability of funds..., standards and methods (including national, regional, state, or tribal building codes or construction... methods (including national, regional, state, or tribal building codes or construction industry standards...

25 CFR 900.125 - What shall a construction contract proposal contain?

Code of Federal Regulations, 2013 CFR

2013-04-01

... tribal building codes and engineering standards; (4) Structural integrity; (5) Accountability of funds..., standards and methods (including national, regional, state, or tribal building codes or construction... methods (including national, regional, state, or tribal building codes or construction industry standards...

25 CFR 900.125 - What shall a construction contract proposal contain?

Code of Federal Regulations, 2011 CFR

2011-04-01

... tribal building codes and engineering standards; (4) Structural integrity; (5) Accountability of funds..., standards and methods (including national, regional, state, or tribal building codes or construction... methods (including national, regional, state, or tribal building codes or construction industry standards...

25 CFR 900.125 - What shall a construction contract proposal contain?

Code of Federal Regulations, 2010 CFR

2010-04-01

... tribal building codes and engineering standards; (4) Structural integrity; (5) Accountability of funds..., standards and methods (including national, regional, state, or tribal building codes or construction... methods (including national, regional, state, or tribal building codes or construction industry standards...

A common class of transcripts with 5'-intron depletion, distinct early coding sequence features, and N1-methyladenosine modification.

PubMed

Cenik, Can; Chua, Hon Nian; Singh, Guramrit; Akef, Abdalla; Snyder, Michael P; Palazzo, Alexander F; Moore, Melissa J; Roth, Frederick P

2017-03-01

Introns are found in 5' untranslated regions (5'UTRs) for 35% of all human transcripts. These 5'UTR introns are not randomly distributed: Genes that encode secreted, membrane-bound and mitochondrial proteins are less likely to have them. Curiously, transcripts lacking 5'UTR introns tend to harbor specific RNA sequence elements in their early coding regions. To model and understand the connection between coding-region sequence and 5'UTR intron status, we developed a classifier that can predict 5'UTR intron status with >80% accuracy using only sequence features in the early coding region. Thus, the classifier identifies transcripts with 5 ' proximal- i ntron- m inus-like-coding regions ("5IM" transcripts). Unexpectedly, we found that the early coding sequence features defining 5IM transcripts are widespread, appearing in 21% of all human RefSeq transcripts. The 5IM class of transcripts is enriched for non-AUG start codons, more extensive secondary structure both preceding the start codon and near the 5' cap, greater dependence on eIF4E for translation, and association with ER-proximal ribosomes. 5IM transcripts are bound by the exon junction complex (EJC) at noncanonical 5' proximal positions. Finally, N 1 -methyladenosines are specifically enriched in the early coding regions of 5IM transcripts. Taken together, our analyses point to the existence of a distinct 5IM class comprising ∼20% of human transcripts. This class is defined by depletion of 5' proximal introns, presence of specific RNA sequence features associated with low translation efficiency, N 1 -methyladenosines in the early coding region, and enrichment for noncanonical binding by the EJC. © 2017 Cenik et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Determining coding CpG islands by identifying regions significant for pattern statistics on Markov chains.

PubMed

Singer, Meromit; Engström, Alexander; Schönhuth, Alexander; Pachter, Lior

2011-09-23

Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.

Important role of endocannabinoid signaling in the development of functional vision and locomotion in zebrafish.

PubMed

Martella, Andrea; Sepe, Rosa M; Silvestri, Cristoforo; Zang, Jingjing; Fasano, Giulia; Carnevali, Oliana; De Girolamo, Paolo; Neuhauss, Stephan C F; Sordino, Paolo; Di Marzo, Vincenzo

2016-12-01

The developmental role of the endocannabinoid system still remains to be fully understood. Here, we report the presence of a complete endocannabinoid system during zebrafish development and show that the genes that code for enzymes that catalyze the anabolism and catabolism (mgll and dagla) of the endocannabinoid, 2-AG (2-arachidonoylglycerol), as well as 2-AG main receptor in the brain, cannabinoid receptor type 1, are coexpressed in defined regions of axonal growth. By using morpholino-induced transient knockdown of the zebrafish Daglα homolog and its pharmacologic rescue, we suggest that synthesis of 2-AG is implicated in the control of axon formation in the midbrain-hindbrain region and that animals that lack Daglα display abnormal physiological behaviors in tests that measure stereotyped movement and motion perception. Our results suggest that the well-established role for 2-AG in axonal outgrowth has implications for the control of vision and movement in zebrafish and, thus, is likely common to all vertebrates.-Martella, A., Sepe, R. M., Silvestri, C., Zang, J., Fasano, G., Carnevali, O., De Girolamo, P., Neuhauss, S. C. F., Sordino, P., Di Marzo, V. Important role of endocannabinoid signaling in the development of functional vision and locomotion in zebrafish. © FASEB.

A Network Based Method for Analysis of lncRNA-Disease Associations and Prediction of lncRNAs Implicated in Diseases

PubMed Central

Yang, Xiaofei; Gao, Lin; Guo, Xingli; Shi, Xinghua; Wu, Hao; Song, Fei; Wang, Bingbo

2014-01-01

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer's disease, pancreatic cancer, and gastric cancer were verified by other independent studies. PMID:24498199

Protein functional features are reflected in the patterns of mRNA translation speed.

PubMed

López, Daniel; Pazos, Florencio

2015-07-09

The degeneracy of the genetic code makes it possible for the same amino acid string to be coded by different messenger RNA (mRNA) sequences. These "synonymous mRNAs" may differ largely in a number of aspects related to their overall translational efficiency, such as secondary structure content and availability of the encoded transfer RNAs (tRNAs). Consequently, they may render different yields of the translated polypeptides. These mRNA features related to translation efficiency are also playing a role locally, resulting in a non-uniform translation speed along the mRNA, which has been previously related to some protein structural features and also used to explain some dramatic effects of "silent" single-nucleotide-polymorphisms (SNPs). In this work we perform the first large scale analysis of the relationship between three experimental proxies of mRNA local translation efficiency and the local features of the corresponding encoded proteins. We found that a number of protein functional and structural features are reflected in the patterns of ribosome occupancy, secondary structure and tRNA availability along the mRNA. One or more of these proxies of translation speed have distinctive patterns around the mRNA regions coding for certain protein local features. In some cases the three patterns follow a similar trend. We also show specific examples where these patterns of translation speed point to the protein's important structural and functional features. This support the idea that the genome not only codes the protein functional features as sequences of amino acids, but also as subtle patterns of mRNA properties which, probably through local effects on the translation speed, have some consequence on the final polypeptide. These results open the possibility of predicting a protein's functional regions based on a single genomic sequence, and have implications for heterologous protein expression and fine-tuning protein function.

The first mitochondrial genome for the butterfly family Riodinidae (Abisara fylloides) and its systematic implications.

PubMed

Zhao, Fang; Huang, Dun-Yuan; Sun, Xiao-Yan; Shi, Qing-Hui; Hao, Jia-Sheng; Zhang, Lan-Lan; Yang, Qun

2013-10-01

The Riodinidae is one of the lepidopteran butterfly families. This study describes the complete mitochondrial genome of the butterfly species Abisara fylloides, the first mitochondrial genome of the Riodinidae family. The results show that the entire mitochondrial genome of A. fylloides is 15 301 bp in length, and contains 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a 423 bp A+T-rich region. The gene content, orientation and order are identical to the majority of other lepidopteran insects. Phylogenetic reconstruction was conducted using the concatenated 13 protein-coding gene (PCG) sequences of 19 available butterfly species covering all the five butterfly families (Papilionidae, Nymphalidae, Peridae, Lycaenidae and Riodinidae). Both maximum likelihood and Bayesian inference analyses highly supported the monophyly of Lycaenidae+Riodinidae, which was standing as the sister of Nymphalidae. In addition, we propose that the riodinids be categorized into the family Lycaenidae as a subfamilial taxon. The Riodinidae is one of the lepidopteran butterfly families. This study describes the complete mitochondrial genome of the butterfly species Abisara fylloides , the first mitochondrial genome of the Riodinidae family. The results show that the entire mitochondrial genome of A. fylloides is 15 301 bp in length, and contains 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a 423 bp A+T-rich region. The gene content, orientation and order are identical to the majority of other lepidopteran insects. Phylogenetic reconstruction was conducted using the concatenated 13 protein-coding gene (PCG) sequences of 19 available butterfly species covering all the five butterfly families (Papilionidae, Nymphalidae, Peridae, Lycaenidae and Riodinidae). Both maximum likelihood and Bayesian inference analyses highly supported the monophyly of Lycaenidae+Riodinidae, which was standing as the sister of Nymphalidae. In addition, we propose that the riodinids be categorized into the family Lycaenidae as a subfamilial taxon.

Chromatin accessibility prediction via a hybrid deep convolutional neural network.

PubMed

Liu, Qiao; Xia, Fei; Yin, Qijin; Jiang, Rui

2018-03-01

A majority of known genetic variants associated with human-inherited diseases lie in non-coding regions that lack adequate interpretation, making it indispensable to systematically discover functional sites at the whole genome level and precisely decipher their implications in a comprehensive manner. Although computational approaches have been complementing high-throughput biological experiments towards the annotation of the human genome, it still remains a big challenge to accurately annotate regulatory elements in the context of a specific cell type via automatic learning of the DNA sequence code from large-scale sequencing data. Indeed, the development of an accurate and interpretable model to learn the DNA sequence signature and further enable the identification of causative genetic variants has become essential in both genomic and genetic studies. We proposed Deopen, a hybrid framework mainly based on a deep convolutional neural network, to automatically learn the regulatory code of DNA sequences and predict chromatin accessibility. In a series of comparison with existing methods, we show the superior performance of our model in not only the classification of accessible regions against background sequences sampled at random, but also the regression of DNase-seq signals. Besides, we further visualize the convolutional kernels and show the match of identified sequence signatures and known motifs. We finally demonstrate the sensitivity of our model in finding causative noncoding variants in the analysis of a breast cancer dataset. We expect to see wide applications of Deopen with either public or in-house chromatin accessibility data in the annotation of the human genome and the identification of non-coding variants associated with diseases. Deopen is freely available at https://github.com/kimmo1019/Deopen. ruijiang@tsinghua.edu.cn. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A motion compensation technique using sliced blocks and its application to hybrid video coding

NASA Astrophysics Data System (ADS)

Kondo, Satoshi; Sasai, Hisao

2005-07-01

This paper proposes a new motion compensation method using "sliced blocks" in DCT-based hybrid video coding. In H.264 ? MPEG-4 Advance Video Coding, a brand-new international video coding standard, motion compensation can be performed by splitting macroblocks into multiple square or rectangular regions. In the proposed method, on the other hand, macroblocks or sub-macroblocks are divided into two regions (sliced blocks) by an arbitrary line segment. The result is that the shapes of the segmented regions are not limited to squares or rectangles, allowing the shapes of the segmented regions to better match the boundaries between moving objects. Thus, the proposed method can improve the performance of the motion compensation. In addition, adaptive prediction of the shape according to the region shape of the surrounding macroblocks can reduce overheads to describe shape information in the bitstream. The proposed method also has the advantage that conventional coding techniques such as mode decision using rate-distortion optimization can be utilized, since coding processes such as frequency transform and quantization are performed on a macroblock basis, similar to the conventional coding methods. The proposed method is implemented in an H.264-based P-picture codec and an improvement in bit rate of 5% is confirmed in comparison with H.264.

Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains.

PubMed

Dumas, Laura; Dickens, C Michael; Anderson, Nathan; Davis, Jonathan; Bennett, Beth; Radcliffe, Richard A; Sikela, James M

2014-06-01

It has been well documented that genetic factors can influence predisposition to develop alcoholism. While the underlying genomic changes may be of several types, two of the most common and disease associated are copy number variations (CNVs) and sequence alterations of protein coding regions. The goal of this study was to identify CNVs and single-nucleotide polymorphisms that occur in gene coding regions that may play a role in influencing the risk of an individual developing alcoholism. Toward this end, two mouse strains were used that have been selectively bred based on their differential sensitivity to alcohol: the Inbred long sleep (ILS) and Inbred short sleep (ISS) mouse strains. Differences in initial response to alcohol have been linked to risk for alcoholism, and the ILS/ISS strains are used to investigate the genetics of initial sensitivity to alcohol. Array comparative genomic hybridization (arrayCGH) and exome sequencing were conducted to identify CNVs and gene coding sequence differences, respectively, between ILS and ISS mice. Mouse arrayCGH was performed using catalog Agilent 1 × 244 k mouse arrays. Subsequently, exome sequencing was carried out using an Illumina HiSeq 2000 instrument. ArrayCGH detected 74 CNVs that were strain-specific (38 ILS/36 ISS), including several ISS-specific deletions that contained genes implicated in brain function and neurotransmitter release. Among several interesting coding variations detected by exome sequencing was the gain of a premature stop codon in the alpha-amylase 2B (AMY2B) gene specifically in the ILS strain. In total, exome sequencing detected 2,597 and 1,768 strain-specific exonic gene variants in the ILS and ISS mice, respectively. This study represents the most comprehensive and detailed genomic comparison of ILS and ISS mouse strains to date. The two complementary genome-wide approaches identified strain-specific CNVs and gene coding sequence variations that should provide strong candidates to contribute to the alcohol-related phenotypic differences associated with these strains.

Utilization of an Academic Nursing Center.

ERIC Educational Resources Information Center

Cole, Frank L.; Mackey, Thomas

1996-01-01

Using data from an academic nursing center that cared for 3,263 patients over eight months, diseases were classified using International Classification of Diseases codes, and procedures were classified using Current Procedural Terminology codes. Patterns of health care emerged, with implications for clinical teaching. (SK)

Effects of target fragmentation on evaluation of LET spectra from space radiations: implications for space radiation protection studies

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Shinn, J. L.; Badavi, F. F.; Badhwar, G. D.

1996-01-01

We present calculations of linear energy transfer (LET) spectra in low earth orbit from galactic cosmic rays and trapped protons using the HZETRN/BRYNTRN computer code. The emphasis of our calculations is on the analysis of the effects of secondary nuclei produced through target fragmentation in the spacecraft shield or detectors. Recent improvements in the HZETRN/BRYNTRN radiation transport computer code are described. Calculations show that at large values of LET (> 100 keV/micrometer) the LET spectra seen in free space and low earth orbit (LEO) are dominated by target fragments and not the primary nuclei. Although the evaluation of microdosimetric spectra is not considered here, calculations of LET spectra support that the large lineal energy (y) events are dominated by the target fragments. Finally, we discuss the situation for interplanetary exposures to galactic cosmic rays and show that current radiation transport codes predict that in the region of high LET values the LET spectra at significant shield depths (> 10 g/cm2 of Al) is greatly modified by target fragments. These results suggest that studies of track structure and biological response of space radiation should place emphasis on short tracks of medium charge fragments produced in the human body by high energy protons and neutrons.

Scaling features of noncoding DNA

NASA Technical Reports Server (NTRS)

Stanley, H. E.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Peng, C. K.; Simons, M.

1999-01-01

We review evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene, and utilize this fact to build a Coding Sequence Finder Algorithm, which uses statistical ideas to locate the coding regions of an unknown DNA sequence. Finally, we describe briefly some recent work adapting to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function, and reporting that noncoding regions in eukaryotes display a larger redundancy than coding regions. Specifically, we consider the possibility that this result is solely a consequence of nucleotide concentration differences as first noted by Bonhoeffer and his collaborators. We find that cytosine-guanine (CG) concentration does have a strong "background" effect on redundancy. However, we find that for the purine-pyrimidine binary mapping rule, which is not affected by the difference in CG concentration, the Shannon redundancy for the set of analyzed sequences is larger for noncoding regions compared to coding regions.

“There Are Too Many, but Never Enough": Qualitative Case Study Investigating Routine Coding of Clinical Information in Depression

PubMed Central

Cresswell, Kathrin; Morrison, Zoe; Sheikh, Aziz; Kalra, Dipak

2012-01-01

Background We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned. Materials and Methods Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care. Results Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding. Conclusions There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined. PMID:22937106

Competitive region orientation code for palmprint verification and identification

NASA Astrophysics Data System (ADS)

Tang, Wenliang

2015-11-01

Orientation features of the palmprint have been widely investigated in coding-based palmprint-recognition methods. Conventional orientation-based coding methods usually used discrete filters to extract the orientation feature of palmprint. However, in real operations, the orientations of the filter usually are not consistent with the lines of the palmprint. We thus propose a competitive region orientation-based coding method. Furthermore, an effective weighted balance scheme is proposed to improve the accuracy of the extracted region orientation. Compared with conventional methods, the region orientation of the palmprint extracted using the proposed method can precisely and robustly describe the orientation feature of the palmprint. Extensive experiments on the baseline PolyU and multispectral palmprint databases are performed and the results show that the proposed method achieves a promising performance in comparison to conventional state-of-the-art orientation-based coding methods in both palmprint verification and identification.

Nucleotide sequence determination of guinea-pig casein B mRNA reveals homology with bovine and rat alpha s1 caseins and conservation of the non-coding regions of the mRNA.

PubMed Central

Hall, L; Laird, J E; Craig, R K

1984-01-01

Nucleotide sequence analysis of cloned guinea-pig casein B cDNA sequences has identified two casein B variants related to the bovine and rat alpha s1 caseins. Amino acid homology was largely confined to the known bovine or predicted rat phosphorylation sites and within the 'signal' precursor sequence. Comparison of the deduced nucleotide sequence of the guinea-pig and rat alpha s1 casein mRNA species showed greater sequence conservation in the non-coding than in the coding regions, suggesting a functional and possibly regulatory role for the non-coding regions of casein mRNA. The results provide insight into the evolution of the casein genes, and raise questions as to the role of conserved nucleotide sequences within the non-coding regions of mRNA species. Images Fig. 1. PMID:6548375

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers

PubMed Central

Latgé, Guillaume; Poulet, Christophe; Bours, Vincent; Jerusalem, Guy

2018-01-01

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers. PMID:29301303

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.

PubMed

Latgé, Guillaume; Poulet, Christophe; Bours, Vincent; Josse, Claire; Jerusalem, Guy

2018-01-02

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers.

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity

PubMed Central

Turcot, Valérie; Lu, Yingchang; Highland, Heather M; Schurmann, Claudia; Justice, Anne E; Fine, Rebecca S; Bradfield, Jonathan P; Esko, Tõnu; Giri, Ayush; Graff, Mariaelisa; Guo, Xiuqing; Hendricks, Audrey E; Karaderi, Tugce; Lempradl, Adelheid; Locke, Adam E; Mahajan, Anubha; Marouli, Eirini; Sivapalaratnam, Suthesh; Young, Kristin L; Alfred, Tamuno; Feitosa, Mary F; Masca, Nicholas GD; Manning, Alisa K; Medina-Gomez, Carolina; Mudgal, Poorva; Ng, Maggie CY; Reiner, Alex P; Vedantam, Sailaja; Willems, Sara M; Winkler, Thomas W; Abecasis, Goncalo; Aben, Katja K; Alam, Dewan S; Alharthi, Sameer E; Allison, Matthew; Amouyel, Philippe; Asselbergs, Folkert W; Auer, Paul L; Balkau, Beverley; Bang, Lia E; Barroso, Inês; Bastarache, Lisa; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F; Blüher, Matthias; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A; Bork-Jensen, Jette; Bots, Michiel L; Bottinger, Erwin P; Bowden, Donald W; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H; Broer, Linda; Brumat, Marco; Burt, Amber A; Butterworth, Adam S; Campbell, Peter T; Cappellani, Stefania; Carey, David J; Catamo, Eulalia; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Cocca, Massimiliano; Collins, Francis S; Cook, James P; Corley, Janie; Galbany, Jordi Corominas; Cox, Amanda J; Crosslin, David S; Cuellar-Partida, Gabriel; D'Eustacchio, Angela; Danesh, John; Davies, Gail; de Bakker, Paul IW; de Groot, Mark CH; de Mutsert, Renée; Deary, Ian J; Dedoussis, George; Demerath, Ellen W; den Heijer, Martin; den Hollander, Anneke I; den Ruijter, Hester M; Dennis, Joe G; Denny, Josh C; Di Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dubé, Marie-Pierre; Dunning, Alison M; Easton, Douglas F; Edwards, Todd L; Ellinghaus, David; Ellinor, Patrick T; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Farooqi, I. Sadaf; Faul, Jessica D; Fauser, Sascha; Feng, Shuang; Ferrannini, Ele; Ferrieres, Jean; Florez, Jose C; Ford, Ian; Fornage, Myriam; Franco, Oscar H; Franke, Andre; Franks, Paul W; Friedrich, Nele; Frikke-Schmidt, Ruth; Galesloot, Tessel E.; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Gibson, Jane; Giedraitis, Vilmantas; Gjesing, Anette P; Gordon-Larsen, Penny; Gorski, Mathias; Grabe, Hans-Jörgen; Grant, Struan FA; Grarup, Niels; Griffiths, Helen L; Grove, Megan L; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeff; Hakonarson, Hakon; Hammerschlag, Anke R; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B; Hattersley, Andrew T; Have, Christian T; Hayward, Caroline; He, Liang; Heard-Costa, Nancy L; Heath, Andrew C; Heid, Iris M; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W; Holmen, Oddgeir L; Hovingh, G Kees; Howson, Joanna MM; Hu, Yao; Huang, Paul L; Huffman, Jennifer E; Ikram, M Arfan; Ingelsson, Erik; Jackson, Anne U; Jansson, Jan-Håkan; Jarvik, Gail P; Jensen, Gorm B; Jia, Yucheng; Johansson, Stefan; Jørgensen, Marit E; Jørgensen, Torben; Jukema, J Wouter; Kahali, Bratati; Kahn, René S; Kähönen, Mika; Kamstrup, Pia R; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon LR; Karpe, Fredrik; Kathiresan, Sekar; Kee, Frank; Kiemeney, Lambertus A; Kim, Eric; Kitajima, Hidetoshi; Komulainen, Pirjo; Kooner, Jaspal S; Kooperberg, Charles; Korhonen, Tellervo; Kovacs, Peter; Kuivaniemi, Helena; Kutalik, Zoltán; Kuulasmaa, Kari; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A; Lamparter, David; Lange, Ethan M; Lange, Leslie A; Langenberg, Claudia; Larson, Eric B; Lee, Nanette R; Lehtimäki, Terho; Lewis, Cora E; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Keng-Hung; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Ching-Ti; Liu, Dajiang J; Liu, Yongmei; Lo, Ken Sin; Lophatananon, Artitaya; Lotery, Andrew J; Loukola, Anu; Luan, Jian'an; Lubitz, Steven A; Lyytikäinen, Leo-Pekka; Männistö, Satu; Marenne, Gaëlle; Mazul, Angela L; McCarthy, Mark I; McKean-Cowdin, Roberta; Medland, Sarah E; Meidtner, Karina; Milani, Lili; Mistry, Vanisha; Mitchell, Paul; Mohlke, Karen L; Moilanen, Leena; Moitry, Marie; Montgomery, Grant W; Mook-Kanamori, Dennis O; Moore, Carmel; Mori, Trevor A; Morris, Andrew D; Morris, Andrew P; Müller-Nurasyid, Martina; Munroe, Patricia B; Nalls, Mike A; Narisu, Narisu; Nelson, Christopher P; Neville, Matt; Nielsen, Sune F; Nikus, Kjell; Njølstad, Pål R; Nordestgaard, Børge G; Nyholt, Dale R; O'Connel, Jeffrey R; O’Donoghue, Michelle L.; Olde Loohuis, Loes M; Ophoff, Roel A; Owen, Katharine R; Packard, Chris J; Padmanabhan, Sandosh; Palmer, Colin NA; Palmer, Nicholette D; Pasterkamp, Gerard; Patel, Aniruddh P; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L; Peloso, Gina M; Pennell, Craig E; Perola, Markus; Perry, James A; Perry, John RB; Pers, Tune H; Person, Thomas N; Peters, Annette; Petersen, Eva RB; Peyser, Patricia A; Pirie, Ailith; Polasek, Ozren; Polderman, Tinca J; Puolijoki, Hannu; Raitakari, Olli T; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F; Renström, Frida; Rheinberger, Myriam; Ridker, Paul M; Rioux, John D; Rivas, Manuel A; Roberts, David J; Robertson, Neil R; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J; Sapkota, Yadav; Sattar, Naveed; Schoen, Robert E; Schreiner, Pamela J; Schulze, Matthias B; Scott, Robert A; Segura-Lepe, Marcelo P; Shah, Svati H; Sheu, Wayne H-H; Sim, Xueling; Slater, Andrew J; Small, Kerrin S; Smith, Albert Vernon; Southam, Lorraine; Spector, Timothy D; Speliotes, Elizabeth K; Starr, John M; Stefansson, Kari; Steinthorsdottir, Valgerdur; Stirrups, Kathleen E; Strauch, Konstantin; Stringham, Heather M; Stumvoll, Michael; Sun, Liang; Surendran, Praveen; Swift, Amy J; Tada, Hayato; Tansey, Katherine E; Tardif, Jean-Claude; Taylor, Kent D; Teumer, Alexander; Thompson, Deborah J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Thuesen, Betina H; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P; Uher, Rudolf; Uitterlinden, André G; Uusitupa, Matti; van der Laan, Sander W; van Duijn, Cornelia M; van Leeuwen, Nienke; van Setten, Jessica; Vanhala, Mauno; Varbo, Anette; Varga, Tibor V; Varma, Rohit; Velez Edwards, Digna R; Vermeulen, Sita H; Veronesi, Giovanni; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F; Völker, Uwe; Vuckovic, Dragana; Wagenknecht, Lynne E; Walker, Mark; Wallentin, Lars; Wang, Feijie; Wang, Carol A; Wang, Shuai; Wang, Yiqin; Ware, Erin B; Wareham, Nicholas J; Warren, Helen R; Waterworth, Dawn M; Wessel, Jennifer; White, Harvey D; Willer, Cristen J; Wilson, James G; Witte, Daniel R; Wood, Andrew R; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhao, Wei; Zhou, Wei; Zondervan, Krina T; Rotter, Jerome I; Pospisilik, John A; Rivadeneira, Fernando; Borecki, Ingrid B; Deloukas, Panos; Frayling, Timothy M; Lettre, Guillaume; North, Kari E; Lindgren, Cecilia M; Hirschhorn, Joel N; Loos, Ruth JF

2018-01-01

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, non-coding variants from which pinpointing causal genes remains challenging. Here, we combined data from 718,734 individuals to discover rare and low-frequency (MAF<5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which eight in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, ZNF169) newly implicated in human obesity, two (MC4R, KSR2) previously observed in extreme obesity, and two variants in GIPR. Effect sizes of rare variants are ~10 times larger than of common variants, with the largest effect observed in carriers of an MC4R stop-codon (p.Tyr35Ter, MAF=0.01%), weighing ~7kg more than non-carriers. Pathway analyses confirmed enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically-supported therapeutic targets to treat obesity. PMID:29273807

Nurses' knowledge of the code for nurses.

PubMed

Miller, B K; Beck, L; Adams, D

1991-01-01

"Investigation of Professionalism in Nursing Behaviors" was funded by the Beta Upsilon Chapter of Sigma Theta Tau International and the College of Nursing, Arizona State University. Researchers asked 514 nurses in eight western states if they had a copy of the Code For Nurses. Most respondents did not have a copy of the Code; however, they indicated that adherence to the Code was essential to the professional nurse. Years of practice, educational background, participation in autonomous activities, and present position were variables used to determine those respondents most likely to possess a copy of the Code. Implications for continuing educators are discussed.

Detecting the borders between coding and non-coding DNA regions in prokaryotes based on recursive segmentation and nucleotide doublets statistics

PubMed Central

2012-01-01

Background Detecting the borders between coding and non-coding regions is an essential step in the genome annotation. And information entropy measures are useful for describing the signals in genome sequence. However, the accuracies of previous methods of finding borders based on entropy segmentation method still need to be improved. Methods In this study, we first applied a new recursive entropic segmentation method on DNA sequences to get preliminary significant cuts. A 22-symbol alphabet is used to capture the differential composition of nucleotide doublets and stop codon patterns along three phases in both DNA strands. This process requires no prior training datasets. Results Comparing with the previous segmentation methods, the experimental results on three bacteria genomes, Rickettsia prowazekii, Borrelia burgdorferi and E.coli, show that our approach improves the accuracy for finding the borders between coding and non-coding regions in DNA sequences. Conclusions This paper presents a new segmentation method in prokaryotes based on Jensen-Rényi divergence with a 22-symbol alphabet. For three bacteria genomes, comparing to A12_JR method, our method raised the accuracy of finding the borders between protein coding and non-coding regions in DNA sequences. PMID:23282225

The HayWired earthquake scenario—Engineering implications

USGS Publications Warehouse

Detweiler, Shane T.; Wein, Anne M.

2018-04-18

The HayWired Earthquake Scenario—Engineering Implications is the second volume of U.S. Geological Survey (USGS) Scientific Investigations Report 2017–5013, which describes the HayWired scenario, developed by USGS and its partners. The scenario is a hypothetical yet scientifically realistic earthquake sequence that is being used to better understand hazards for the San Francisco Bay region during and after a magnitude-7 earthquake (mainshock) on the Hayward Fault and its aftershocks.Analyses in this volume suggest that (1) 800 deaths and 16,000 nonfatal injuries result from shaking alone, plus property and direct business interruption losses of more than $82 billion from shaking, liquefaction, and landslides; (2) the building code is designed to protect lives, but even if all buildings in the region complied with current building codes, 0.4 percent could collapse, 5 percent could be unsafe to occupy, and 19 percent could have restricted use; (3) people expect, prefer, and would be willing to pay for greater resilience of buildings; (4) more than 22,000 people could require extrication from stalled elevators, and more than 2,400 people could require rescue from collapsed buildings; (5) the average east-bay resident could lose water service for 6 weeks, some for as long as 6 months; (6) older steel-frame high-rise office buildings and new reinforced-concrete residential buildings in downtown San Francisco and Oakland could be unusable for as long as 10 months; (7) about 450 large fires could result in a loss of residential and commercial building floor area equivalent to more than 52,000 single-family homes and cause property (building and content) losses approaching $30 billion; and (8) combining earthquake early warning (ShakeAlert) with “drop, cover, and hold on” actions could prevent as many as 1,500 nonfatal injuries out of 18,000 total estimated nonfatal injuries from shaking and liquefaction hazards.

Brief surgical procedure code lists for outcomes measurement and quality improvement in resource-limited settings.

PubMed

Liu, Charles; Kayima, Peter; Riesel, Johanna; Situma, Martin; Chang, David; Firth, Paul

2017-11-01

The lack of a classification system for surgical procedures in resource-limited settings hinders outcomes measurement and reporting. Existing procedure coding systems are prohibitively large and expensive to implement. We describe the creation and prospective validation of 3 brief procedure code lists applicable in low-resource settings, based on analysis of surgical procedures performed at Mbarara Regional Referral Hospital, Uganda's second largest public hospital. We reviewed operating room logbooks to identify all surgical operations performed at Mbarara Regional Referral Hospital during 2014. Based on the documented indication for surgery and procedure(s) performed, we assigned each operation up to 4 procedure codes from the International Classification of Diseases, 9th Revision, Clinical Modification. Coding of procedures was performed by 2 investigators, and a random 20% of procedures were coded by both investigators. These codes were aggregated to generate procedure code lists. During 2014, 6,464 surgical procedures were performed at Mbarara Regional Referral Hospital, to which we assigned 435 unique procedure codes. Substantial inter-rater reliability was achieved (κ = 0.7037). The 111 most common procedure codes accounted for 90% of all codes assigned, 180 accounted for 95%, and 278 accounted for 98%. We considered these sets of codes as 3 procedure code lists. In a prospective validation, we found that these lists described 83.2%, 89.2%, and 92.6% of surgical procedures performed at Mbarara Regional Referral Hospital during August to September of 2015, respectively. Empirically generated brief procedure code lists based on International Classification of Diseases, 9th Revision, Clinical Modification can be used to classify almost all surgical procedures performed at a Ugandan referral hospital. Such a standardized procedure coding system may enable better surgical data collection for administration, research, and quality improvement in resource-limited settings. Copyright © 2017 Elsevier Inc. All rights reserved.

Both the stroma and thylakoid lumen of tobacco chloroplasts are competent for the formation of disulphide bonds in recombinant proteins.

PubMed

Bally, Julia; Paget, Eric; Droux, Michel; Job, Claudette; Job, Dominique; Dubald, Manuel

2008-01-01

Plant chloroplasts are promising vehicles for recombinant protein production, but the process of protein folding in these organelles is not well understood in comparison with that in prokaryotic systems, such as Escherichia coli. This is particularly true for disulphide bond formation which is crucial for the biological activity of many therapeutic proteins. We have investigated the capacity of tobacco (Nicotiana tabacum) chloroplasts to efficiently form disulphide bonds in proteins by expressing in this plant cell organelle a well-known bacterial enzyme, alkaline phosphatase, whose activity and stability strictly depend on the correct formation of two intramolecular disulphide bonds. Plastid transformants have been generated that express either the mature enzyme, localized in the stroma, or the full-length coding region, including its signal peptide. The latter has the potential to direct the recombinant alkaline phosphatase into the lumen of thylakoids, giving access to this even less well-characterized organellar compartment. We show that the chloroplast stroma supports the formation of an active enzyme, unlike a normal bacterial cytosol. Sorting of alkaline phosphatase to the thylakoid lumen occurs in the plastid transformants translating the full-length coding region, and leads to larger amounts and more active enzyme. These results are compared with those obtained in bacteria. The implications of these findings on protein folding properties and competency of chloroplasts for disulphide bond formation are discussed.

The Complete Mitochondrial Genome of Ctenoptilum vasava (Lepidoptera: Hesperiidae: Pyrginae) and Its Phylogenetic Implication

PubMed Central

Hao, Jiasheng; Sun, Qianqian; Zhao, Huabin; Sun, Xiaoyan; Gai, Yonghua; Yang, Qun

2012-01-01

We here report the first complete mitochondrial (mt) genome of a skipper, Ctenoptilum vasava Moore, 1865 (Lepidoptera: Hesperiidae: Pyrginae). The mt genome of the skipper is a circular molecule of 15,468 bp, containing 2 ribosomal RNA genes, 24 putative transfer RNA (tRNA), genes including an extra copy of trnS (AGN) and a tRNA-like insertion trnL (UUR), 13 protein-coding genes and an AT-rich region. All protein-coding genes (PCGs) are initiated by ATN codons and terminated by the typical stop codon TAA or TAG, except for COII which ends with a single T. The intergenic spacer sequence between trnS (AGN) and ND1 genes also contains the ATACTAA motif. The AT-rich region of 429 bp is comprised of nonrepetitive sequences, including the motif ATAGA followed by an 19 bp poly-T stretch, a microsatellite-like (AT)3 (TA)9 element next to the ATTTA motif, an 11 bp poly-A adjacent to tRNAs. Phylogenetic analyses (ML and BI methods) showed that Papilionoidea is not a natural group, and Hesperioidea is placed within the Papilionoidea as a sister to ((Pieridae + Lycaenidae) + Nymphalidae) while Papilionoidae is paraphyletic to Hesperioidea. This result is remarkably different from the traditional view where Papilionoidea and Hesperioidea are considered as two distinct superfamilies. PMID:22577351

Sperm Bindin Divergence under Sexual Selection and Concerted Evolution in Sea Stars.

PubMed

Patiño, Susana; Keever, Carson C; Sunday, Jennifer M; Popovic, Iva; Byrne, Maria; Hart, Michael W

2016-08-01

Selection associated with competition among males or sexual conflict between mates can create positive selection for high rates of molecular evolution of gamete recognition genes and lead to reproductive isolation between species. We analyzed coding sequence and repetitive domain variation in the gene encoding the sperm acrosomal protein bindin in 13 diverse sea star species. We found that bindin has a conserved coding sequence domain structure in all 13 species, with several repeated motifs in a large central region that is similar among all sea stars in organization but highly divergent among genera in nucleotide and predicted amino acid sequence. More bindin codons and lineages showed positive selection for high relative rates of amino acid substitution in genera with gonochoric outcrossing adults (and greater expected strength of sexual selection) than in selfing hermaphrodites. That difference is consistent with the expectation that selfing (a highly derived mating system) may moderate the strength of sexual selection and limit the accumulation of bindin amino acid differences. The results implicate both positive selection on single codons and concerted evolution within the repetitive region in bindin divergence, and suggest that both single amino acid differences and repeat differences may affect sperm-egg binding and reproductive compatibility. © The Author 2016. 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.

Identification of long non-coding RNAs in two anthozoan species and their possible implications for coral bleaching.

PubMed

Huang, Chen; Morlighem, Jean-Étienne R L; Cai, Jing; Liao, Qiwen; Perez, Carlos Daniel; Gomes, Paula Braga; Guo, Min; Rádis-Baptista, Gandhi; Lee, Simon Ming-Yuen

2017-07-13

Long non-coding RNAs (lncRNAs) have been shown to play regulatory roles in a diverse range of biological processes and are associated with the outcomes of various diseases. The majority of studies about lncRNAs focus on model organisms, with lessened investigation in non-model organisms to date. Herein, we have undertaken an investigation on lncRNA in two zoanthids (cnidarian): Protolpalythoa varibilis and Palythoa caribaeorum. A total of 11,206 and 13,240 lncRNAs were detected in P. variabilis and P. caribaeorum transcriptome, respectively. Comparison using NONCODE database indicated that the majority of these lncRNAs is taxonomically species-restricted with no identifiable orthologs. Even so, we found cases in which short regions of P. caribaeorum's lncRNAs were similar to vertebrate species' lncRNAs, and could be associated with lncRNA conserved regulatory functions. Consequently, some high-confidence lncRNA-mRNA interactions were predicted based on such conserved regions, therefore revealing possible involvement of lncRNAs in posttranscriptional processing and regulation in anthozoans. Moreover, investigation of differentially expressed lncRNAs, in healthy colonies and colonial individuals undergoing natural bleaching, indicated that some up-regulated lncRNAs in P. caribaeorum could posttranscriptionally regulate the mRNAs encoding proteins of Ras-mediated signal transduction pathway and components of innate immune-system, which could contribute to the molecular response of coral bleaching.

Concreteness Effects in Text Recall: Dual Coding or Context Availability?

ERIC Educational Resources Information Center

Sadoski, Mark; And Others

1995-01-01

Extends an earlier study by using different materials, ratings for familiarity, and more stringent experimental controls. Finds concreteness effects in two experiments using undergraduate students. Suggests that familiarity and concreteness contribute separately to recall. Supports a dual coding theory. Discusses implications for text design. (RS)

Phylogenetic Network for European mtDNA

PubMed Central

Finnilä, Saara; Lehtonen, Mervi S.; Majamaa, Kari

2001-01-01

The sequence in the first hypervariable segment (HVS-I) of the control region has been used as a source of evolutionary information in most phylogenetic analyses of mtDNA. Population genetic inference would benefit from a better understanding of the variation in the mtDNA coding region, but, thus far, complete mtDNA sequences have been rare. We determined the nucleotide sequence in the coding region of mtDNA from 121 Finns, by conformation-sensitive gel electrophoresis and subsequent sequencing and by direct sequencing of the D loop. Furthermore, 71 sequences from our previous reports were included, so that the samples represented all the mtDNA haplogroups present in the Finnish population. We found a total of 297 variable sites in the coding region, which allowed the compilation of unambiguous phylogenetic networks. The D loop harbored 104 variable sites, and, in most cases, these could be localized within the coding-region networks, without discrepancies. Interestingly, many homoplasies were detected in the coding region. Nucleotide variation in the rRNA and tRNA genes was 6%, and that in the third nucleotide positions of structural genes amounted to 22% of that in the HVS-I. The complete networks enabled the relationships between the mtDNA haplogroups to be analyzed. Phylogenetic networks based on the entire coding-region sequence in mtDNA provide a rich source for further population genetic studies, and complete sequences make it easier to differentiate between disease-causing mutations and rare polymorphisms. PMID:11349229

Systematic analysis of coding and noncoding DNA sequences using methods of statistical linguistics

NASA Technical Reports Server (NTRS)

Mantegna, R. N.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Peng, C. K.; Simons, M.; Stanley, H. E.

1995-01-01

We compare the statistical properties of coding and noncoding regions in eukaryotic and viral DNA sequences by adapting two tests developed for the analysis of natural languages and symbolic sequences. The data set comprises all 30 sequences of length above 50 000 base pairs in GenBank Release No. 81.0, as well as the recently published sequences of C. elegans chromosome III (2.2 Mbp) and yeast chromosome XI (661 Kbp). We find that for the three chromosomes we studied the statistical properties of noncoding regions appear to be closer to those observed in natural languages than those of coding regions. In particular, (i) a n-tuple Zipf analysis of noncoding regions reveals a regime close to power-law behavior while the coding regions show logarithmic behavior over a wide interval, while (ii) an n-gram entropy measurement shows that the noncoding regions have a lower n-gram entropy (and hence a larger "n-gram redundancy") than the coding regions. In contrast to the three chromosomes, we find that for vertebrates such as primates and rodents and for viral DNA, the difference between the statistical properties of coding and noncoding regions is not pronounced and therefore the results of the analyses of the investigated sequences are less conclusive. After noting the intrinsic limitations of the n-gram redundancy analysis, we also briefly discuss the failure of the zeroth- and first-order Markovian models or simple nucleotide repeats to account fully for these "linguistic" features of DNA. Finally, we emphasize that our results by no means prove the existence of a "language" in noncoding DNA.

Sensitivity to perception level differentiates two subnetworks within the mirror neuron system.

PubMed

Simon, Shiri; Mukamel, Roy

2017-05-01

Mirror neurons are a subset of brain cells that discharge during action execution and passive observation of similar actions. An open question concerns the functional role of their ability to match observed and executed actions. Since understanding of goals requires conscious perception of actions, we expect that mirror neurons potentially involved in action goal coding, will be modulated by changes in action perception level. Here, we manipulated perception level of action videos depicting short hand movements and measured the corresponding fMRI BOLD responses in mirror regions. Our results show that activity levels within a network of regions, including the sensorimotor cortex, primary motor cortex, dorsal premotor cortex and posterior superior temporal sulcus, are sensitive to changes in action perception level, whereas activity levels in the inferior frontal gyrus, ventral premotor cortex, supplementary motor area and superior parietal lobule are invariant to such changes. In addition, this parcellation to two sub-networks manifest as smaller functional distances within each group of regions during task and resting state. Our results point to functional differences between regions within the mirror neurons system which may have implications with respect to their possible role in action understanding. © The Author (2017). Published by Oxford University Press.

Constant time worker thread allocation via configuration caching

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

Eichenberger, Alexandre E; O'Brien, John K. P.

Mechanisms are provided for allocating threads for execution of a parallel region of code. A request for allocation of worker threads to execute the parallel region of code is received from a master thread. Cached thread allocation information identifying prior thread allocations that have been performed for the master thread are accessed. Worker threads are allocated to the master thread based on the cached thread allocation information. The parallel region of code is executed using the allocated worker threads.

SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes

PubMed Central

Mix, Heiko; Lobanov, Alexey V.; Gladyshev, Vadim N.

2007-01-01

Expression of selenocysteine (Sec)-containing proteins requires the presence of a cis-acting mRNA structure, called selenocysteine insertion sequence (SECIS) element. In bacteria, this structure is located in the coding region immediately downstream of the Sec-encoding UGA codon, whereas in eukaryotes a completely different SECIS element has evolved in the 3′-untranslated region. Here, we report that SECIS elements in the coding regions of selenoprotein mRNAs support Sec insertion in higher eukaryotes. Comprehensive computational analysis of all available viral genomes revealed a SECIS element within the ORF of a naturally occurring selenoprotein homolog of glutathione peroxidase 4 in fowlpox virus. The fowlpox SECIS element supported Sec insertion when expressed in mammalian cells as part of the coding region of viral or mammalian selenoproteins. In addition, readthrough at UGA was observed when the viral SECIS element was located upstream of the Sec codon. We also demonstrate successful de novo design of a functional SECIS element in the coding region of a mammalian selenoprotein. Our data provide evidence that the location of the SECIS element in the untranslated region is not a functional necessity but rather is an evolutionary adaptation to enable a more efficient synthesis of selenoproteins. PMID:17169995

Coded Cooperation for Multiway Relaying in Wireless Sensor Networks †

PubMed Central

Si, Zhongwei; Ma, Junyang; Thobaben, Ragnar

2015-01-01

Wireless sensor networks have been considered as an enabling technology for constructing smart cities. One important feature of wireless sensor networks is that the sensor nodes collaborate in some manner for communications. In this manuscript, we focus on the model of multiway relaying with full data exchange where each user wants to transmit and receive data to and from all other users in the network. We derive the capacity region for this specific model and propose a coding strategy through coset encoding. To obtain good performance with practical codes, we choose spatially-coupled LDPC (SC-LDPC) codes for the coded cooperation. In particular, for the message broadcasting from the relay, we construct multi-edge-type (MET) SC-LDPC codes by repeatedly applying coset encoding. Due to the capacity-achieving property of the SC-LDPC codes, we prove that the capacity region can theoretically be achieved by the proposed MET SC-LDPC codes. Numerical results with finite node degrees are provided, which show that the achievable rates approach the boundary of the capacity region in both binary erasure channels and additive white Gaussian channels. PMID:26131675

Coded Cooperation for Multiway Relaying in Wireless Sensor Networks.

PubMed

Si, Zhongwei; Ma, Junyang; Thobaben, Ragnar

2015-06-29

Wireless sensor networks have been considered as an enabling technology for constructing smart cities. One important feature of wireless sensor networks is that the sensor nodes collaborate in some manner for communications. In this manuscript, we focus on the model of multiway relaying with full data exchange where each user wants to transmit and receive data to and from all other users in the network. We derive the capacity region for this specific model and propose a coding strategy through coset encoding. To obtain good performance with practical codes, we choose spatially-coupled LDPC (SC-LDPC) codes for the coded cooperation. In particular, for the message broadcasting from the relay, we construct multi-edge-type (MET) SC-LDPC codes by repeatedly applying coset encoding. Due to the capacity-achieving property of the SC-LDPC codes, we prove that the capacity region can theoretically be achieved by the proposed MET SC-LDPC codes. Numerical results with finite node degrees are provided, which show that the achievable rates approach the boundary of the capacity region in both binary erasure channels and additive white Gaussian channels.

Transient Ejector Analysis (TEA) code user's guide

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1993-01-01

A FORTRAN computer program for the semi analytic prediction of unsteady thrust augmenting ejector performance has been developed, based on a theoretical analysis for ejectors. That analysis blends classic self-similar turbulent jet descriptions with control-volume mixing region elements. Division of the ejector into an inlet, diffuser, and mixing region allowed flexibility in the modeling of the physics for each region. In particular, the inlet and diffuser analyses are simplified by a quasi-steady-analysis, justified by the assumption that pressure is the forcing function in those regions. Only the mixing region is assumed to be dominated by viscous effects. The present work provides an overview of the code structure, a description of the required input and output data file formats, and the results for a test case. Since there are limitations to the code for applications outside the bounds of the test case, the user should consider TEA as a research code (not as a production code), designed specifically as an implementation of the proposed ejector theory. Program error flags are discussed, and some diagnostic routines are presented.

Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

PubMed

Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

2016-11-29

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

Clinical directors' views of centralisation and commissioning of cleft services in the U.K.

PubMed

Searle, Aidan; Scott, Julia K; Sandy, Jonathan; Ness, Andrew; Waylen, Andrea

2015-01-22

To determine the views of Clinical Directors working in the United Kingdom (U.K.) Cleft Service with regard to centralisation, commissioning and impact on cleft service provision. In-depth qualitative interviews were conducted with 11 Clinical Directors representing regional cleft services. Interviews were transcribed verbatim, a coding frame was developed by two researchers and transcripts were coded using a thematic, 'interpretive' approach. Clinical Directors perceived the commissioning of cleft services in the U.K. to be dependent upon historical agreements and individual negotiation despite service centralisation. Furthermore, Clinical Directors perceived unfairness in the commissioning and funding of cleft services and reported inconsistencies in funding models and service costs that have implications for delivering an equitable cleft service with an effective Multidisciplinary Team. National Health Service (NHS) commissioning bodies can learn lessons from the centralisation of cleft care. Clinical Directors' accounts of their relationships with specialist commissioning bodies and their perspectives of funding cleft services may serve to increase parity and improve the commissioning of cleft services in the U.K.

Bilingual First Language Acquisition: Exploring the Limits of the Language Faculty.

ERIC Educational Resources Information Center

Genesee, Fred

2001-01-01

Reviews current research in three domains of bilingual acquisition: pragmatic features of bilingual code mixing, grammatical constraints on child bilingual code mixing, and bilingual syntactic development. Examines implications from these domains for the understanding of the limits of the mental faculty to acquire language. (Author/VWL)

[Population density, age distribution and urbanisation as factors influencing the frequency of home visits--an analysis for Mecklenburg-West Pomerania].

PubMed

Heymann, R; Weitmann, K; Weiss, S; Thierfelder, D; Flessa, S; Hoffmann, W

2009-07-01

This study examines and compares the frequency of home visits by general practitioners in regions with a lower population density and regions with a higher population density. The discussion centres on the hypothesis whether the number of home visits in rural and remote areas with a low population density is, in fact, higher than in urbanised areas with a higher population density. The average age of the population has been considered in both cases. The communities of Mecklenburg West-Pomerania were aggregated into postal code regions. The analysis is based on these postal code regions. The average frequency of home visits per 100 inhabitants/km2 has been calculated via a bivariate, linear regression model with the population density and the average age for the postal code region as independent variables. The results are based on billing data of the year 2006 as provided by the Association of Statutory Health Insurance Physicians of Mecklenburg-Western Pomerania. In a second step a variable which clustered the postal codes of urbanised areas was added to a multivariate model. The hypothesis of a negative correlation between the frequency of home visits and the population density of the areas examined cannot be confirmed for Mecklenburg-Western Pomerania. Following the dichotomisation of the postal code regions into sparsely and densely populated areas, only the very sparsely populated postal code regions (less than 100 inhabitants/km2) show a tendency towards a higher frequency of home visits. Overall, the frequency of home visits in sparsely populated postal code regions is 28.9% higher than in the densely populated postal code regions (more than 100 inhabitants/km2), although the number of general practitioners is approximately the same in both groups. In part this association seems to be confirmed by a positive correlation between the average age in the individual postal code regions and the number of home visits carried out in the area. As calculated on the basis of the data at hand, only the very sparsely populated areas with a still gradually decreasing population show a tendency towards a higher frequency of home visits. According to the data of 2006, the number of home visits remains high in sparsely populated areas. It may increase in the near future as the number of general practitioners in these areas will gradually decrease while the number of immobile and older inhabitants will increase.

An automatic and efficient pipeline for disease gene identification through utilizing family-based sequencing data.

PubMed

Song, Dandan; Li, Ning; Liao, Lejian

2015-01-01

Due to the generation of enormous amounts of data at both lower costs as well as in shorter times, whole-exome sequencing technologies provide dramatic opportunities for identifying disease genes implicated in Mendelian disorders. Since upwards of thousands genomic variants can be sequenced in each exome, it is challenging to filter pathogenic variants in protein coding regions and reduce the number of missing true variants. Therefore, an automatic and efficient pipeline for finding disease variants in Mendelian disorders is designed by exploiting a combination of variants filtering steps to analyze the family-based exome sequencing approach. Recent studies on the Freeman-Sheldon disease are revisited and show that the proposed method outperforms other existing candidate gene identification methods.

Detection and Characterization of the Photospheric and Coronal Magnetic Fields of Sunspot Groups: Implications for Flare Forecasting

DTIC Science & Technology

2015-05-25

Techniques & Data used.    For this project data was used primarily from two instruments, HMI and AIA onboard SDO...automatically using SMART­DF code (shown in  circles) using  HMI  data (left side). The same region observed in high resolution using  1m­Swedish Solar Telescope...simultaneous measurements of continuum  intensity and LOS magnetic field to segment ARs into umbrae, penumbrae and plage. Data  from the  HMI  instrument

Mitochondrial genome evolution in the Saccharomyces sensu stricto complex.

PubMed

Ruan, Jiangxing; Cheng, Jian; Zhang, Tongcun; Jiang, Huifeng

2017-01-01

Exploring the evolutionary patterns of mitochondrial genomes is important for our understanding of the Saccharomyces sensu stricto (SSS) group, which is a model system for genomic evolution and ecological analysis. In this study, we first obtained the complete mitochondrial sequences of two important species, Saccharomyces mikatae and Saccharomyces kudriavzevii. We then compared the mitochondrial genomes in the SSS group with those of close relatives, and found that the non-coding regions evolved rapidly, including dramatic expansion of intergenic regions, fast evolution of introns and almost 20-fold higher rearrangement rates than those of the nuclear genomes. However, the coding regions, and especially the protein-coding genes, are more conserved than those in the nuclear genomes of the SSS group. The different evolutionary patterns of coding and non-coding regions in the mitochondrial and nuclear genomes may be related to the origin of the aerobic fermentation lifestyle in this group. Our analysis thus provides novel insights into the evolution of mitochondrial genomes.

Novel variants of the 5S rRNA genes in Eruca sativa.

PubMed

Singh, K; Bhatia, S; Lakshmikumaran, M

1994-02-01

The 5S ribosomal RNA (rRNA) genes of Eruca sativa were cloned and characterized. They are organized into clusters of tandemly repeated units. Each repeat unit consists of a 119-bp coding region followed by a noncoding spacer region that separates it from the coding region of the next repeat unit. Our study reports novel gene variants of the 5S rRNA genes in plants. Two families of the 5S rDNA, the 0.5-kb size family and the 1-kb size family, coexist in the E. sativa genome. The 0.5-kb size family consists of the 5S rRNA genes (S4) that have coding regions similar to those of other reported plant 5S rDNA sequences, whereas the 1-kb size family consists of the 5S rRNA gene variants (S1) that exist as 1-kb BamHI tandem repeats. S1 is made up of two variant units (V1 and V2) of 5S rDNA where the BamHI site between the two units is mutated. Sequence heterogeneity among S4, V1, and V2 units exists throughout the sequence and is not limited to the noncoding spacer region only. The coding regions of V1 and V2 show approximately 20% dissimilarity to the coding regions of S4 and other reported plant 5S rDNA sequences. Such a large variation in the coding regions of the 5S rDNA units within the same plant species has been observed for the first time. Restriction site variation is observed between the two size classes of 5S rDNA in E. sativa.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.

PubMed

Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R

2009-10-01

Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.

78 FR 18321 - International Code Council: The Update Process for the International Codes and Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... for Residential Construction in High Wind Regions. ICC 700: National Green Building Standard The..., coordinated, and necessary to regulate the built environment. Federal agencies frequently use these codes and... International Codes and Standards consist of the following: ICC Codes International Building Code. International...

Palindromic repetitive DNA elements with coding potential in Methanocaldococcus jannaschii.

PubMed

Suyama, Mikita; Lathe, Warren C; Bork, Peer

2005-10-10

We have identified 141 novel palindromic repetitive elements in the genome of euryarchaeon Methanocaldococcus jannaschii. The total length of these elements is 14.3kb, which corresponds to 0.9% of the total genomic sequence and 6.3% of all extragenic regions. The elements can be divided into three groups (MJRE1-3) based on the sequence similarity. The low sequence identity within each of the groups suggests rather old origin of these elements in M. jannaschii. Three MJRE2 elements were located within the protein coding regions without disrupting the coding potential of the host genes, indicating that insertion of repeats might be a widespread mechanism to enhance sequence diversity in coding regions.

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection.

PubMed

Mendes-Junior, C T; Castelli, E C; Meyer, D; Simões, A L; Donadi, E A

2013-12-01

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3'UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.

Using the NCBI Genome Databases to Compare the Genes for Human & Chimpanzee Beta Hemoglobin

ERIC Educational Resources Information Center

Offner, Susan

2010-01-01

The beta hemoglobin protein is identical in humans and chimpanzees. In this tutorial, students see that even though the proteins are identical, the genes that code for them are not. There are many more differences in the introns than in the exons, which indicates that coding regions of DNA are more highly conserved than non-coding regions.

36 CFR 1234.20 - What rules apply if there is a conflict between NARA standards and other regulatory standards...

Code of Federal Regulations, 2014 CFR

2014-07-01

... regional building codes, the following rules of precedence apply: (1) Between differing levels of fire... cannot be reconciled with a requirement of this part, the local or regional code applies. (b) If any of... require documentation of the mandatory nature of the conflicting code and the inability to reconcile that...

36 CFR 1234.20 - What rules apply if there is a conflict between NARA standards and other regulatory standards...

Code of Federal Regulations, 2012 CFR

2012-07-01

... regional building codes, the following rules of precedence apply: (1) Between differing levels of fire... cannot be reconciled with a requirement of this part, the local or regional code applies. (b) If any of... require documentation of the mandatory nature of the conflicting code and the inability to reconcile that...

36 CFR 1234.20 - What rules apply if there is a conflict between NARA standards and other regulatory standards...

Code of Federal Regulations, 2011 CFR

2011-07-01

... regional building codes, the following rules of precedence apply: (1) Between differing levels of fire... cannot be reconciled with a requirement of this part, the local or regional code applies. (b) If any of... require documentation of the mandatory nature of the conflicting code and the inability to reconcile that...

36 CFR § 1234.20 - What rules apply if there is a conflict between NARA standards and other regulatory standards...

Code of Federal Regulations, 2013 CFR

2013-07-01

... regional building codes, the following rules of precedence apply: (1) Between differing levels of fire... cannot be reconciled with a requirement of this part, the local or regional code applies. (b) If any of... require documentation of the mandatory nature of the conflicting code and the inability to reconcile that...

Basic biology and therapeutic implications of lncRNA.

PubMed

Khorkova, O; Hsiao, J; Wahlestedt, C

2015-06-29

Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation. Here we will briefly review the recent studies in the field of lncRNA biology focusing mostly on mammalian species and discuss their therapeutic implications. Copyright © 2015 Elsevier B.V. All rights reserved.

Loss of heterozygosity at 7q22 and mutation analysis of the CDP gene in human epithelial ovarian tumors.

PubMed

Neville, P J; Thomas, N; Campbell, I G

2001-02-01

Many tumor types including that of the ovary show loss of heterozygosity (LOH) on chromosome arm 7q, which suggests the existence of at least one tumor suppressor gene (TSG) on this chromosome arm. We have studied the region surrounding the putative tumor suppressor gene CUTL1 at 7q22 in 127 epithelial ovarian tumors. LOH was found across 7q22 in 31% of malignant and 14% of benign ovarian tumors. In 16% of the tumors the LOH appeared to be centered on the CUTL1 gene. This gene has been implicated previously as a TSG in both uterine leiomyomas and breast carcinoma. However, mutation analysis of the CUTL1 gene in 47 tumors with 7q22 LOH failed to identify any somatic alterations in the coding regions. This finding suggests that CUTL1 may not be the target of the 7q22 LOH in ovarian cancers.

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness

PubMed Central

Russell, Theron A.; Blizinsky, Katherine D.; Cobia, Derin J.; Cahill, Michael; Xie, Zhong; Sweet, Robert A.; Duan, Jubao; Gejman, Pablo V.; Wang, Lei; Csernansky, John G.; Penzes, Peter

2014-01-01

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability catalyze the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homolog of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex. PMID:25224588

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness.

PubMed

Russell, Theron A; Blizinsky, Katherine D; Cobia, Derin J; Cahill, Michael E; Xie, Zhong; Sweet, Robert A; Duan, Jubao; Gejman, Pablo V; Wang, Lei; Csernansky, John G; Penzes, Peter

2014-09-16

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability to catalyse the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homologue of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex.

Staufen1 senses overall transcript secondary structure to regulate translation

PubMed Central

Ricci, Emiliano P; Kucukural, Alper; Cenik, Can; Mercier, Blandine C; Singh, Guramrit; Heyer, Erin E; Ashar-Patel, Ami; Peng, Lingtao; Moore, Melissa J

2015-01-01

Human Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein implicated in multiple post-transcriptional gene-regulatory processes. Here we combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting, formaldehyde cross-linking, sonication-mediated RNA fragmentation and deep sequencing to map Staufen1-binding sites transcriptome wide. We find that Stau1 binds complex secondary structures containing multiple short helices, many of which are formed by inverted Alu elements in annotated 3′ untranslated regions (UTRs) or in ‘strongly distal’ 3′ UTRs. Stau1 also interacts with actively translating ribosomes and with mRNA coding sequences (CDSs) and 3′ UTRs in proportion to their GC content and propensity to form internal secondary structure. On mRNAs with high CDS GC content, higher Stau1 levels lead to greater ribosome densities, thus suggesting a general role for Stau1 in modulating translation elongation through structured CDS regions. Our results also indicate that Stau1 regulates translation of transcription-regulatory proteins. PMID:24336223

The 3D Structure of the Immunoglobulin Heavy-Chain Locus: Implications for Long-Range Genomic Interactions

PubMed Central

Jhunjhunwala, Suchit; van Zelm, Menno C.; Peak, Mandy M.; Cutchin, Steve; Riblet, Roy; van Dongen, Jacques J.M.; Grosveld, Frank G.; Knoch, Tobias A.; Murre, Cornelis

2009-01-01

SUMMARY The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (VH), diversity (DH), joining (JH) and constant (CH) coding elements. How the Igh locus is structured in 3D space is unknown. To probe the topography of the Igh locus, spatial distance distributions were determined between 12 genomic markers that span the entire Igh locus. Comparison of the distance distributions to computer simulations of alternative chromatin arrangements predicted that the Igh locus is organized into compartments containing clusters of loops separated by linkers. Trilateration and triple-point angle measurements indicated the mean relative 3D positions of the VH, DH, JH, and CH elements, showed compartmentalization and striking conformational changes involving VH and DH-JH elements during early B cell development. In pro-B cells, the entire repertoire of VH regions (2 Mbp) appeared to have merged and juxtaposed to the DH elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency. PMID:18423198

Genealogical analyses of rabies virus strains from Brazil based on N gene alleles.

PubMed Central

Heinemann, M. B.; Fernandes-Matioli, F. M. C.; Cortez, A.; Soares, R. M.; Sakamoto, S. M.; Bernardi, F.; Ito, F. H.; Madeira, A. M. B. N.; Richtzenhain, L. J.

2002-01-01

Thirty rabies virus isolates from cows and vampire bats from different regions of São Paulo State, Southeastern Brazil and three rabies vaccines were studied genetically. The analysis was based on direct sequencing of PCR-amplified products of 600 nucleotides coding for the amino terminus of nucleoprotein gene. The sequences were checked to verify their genealogical and evolutionary relationships and possible implication for health programmes. Statistical data indicated that there were no significant genetic differences between samples isolated from distinct hosts, from different geographical regions and between samples collected in the last two decades. According to the HKA test, the variability observed in the sequences is probably due to genetic drift. Since changes in genetic material may produce modifications in the protein responsible for immunogenicity of virus, which may eventually cause vaccine failure in herds, we suggest that continuous efforts in monitoring genetic diversity in rabies virus field strains, in relation to vaccine strains, must be conducted. PMID:12113496

A fetus with an X;1 balanced reciprocal translocation and eye disease.

PubMed Central

Seller, M J; Pal, K; Horsley, S; Davies, A F; Berry, A C; Meredith, R; McCartney, A C

1995-01-01

A 19 week female fetus is described with a de novo X;1 reciprocal balanced translocation, with the breakpoint on the X chromosome at Xp11.4, and eye pathology consistent with the early stages of Norrie disease. The fetus seems to be an example of a female manifesting an X linked recessive disease, and it was shown that the normal X chromosome was completely inactivated in all cells examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ hybridisation studies showed that the Norrie disease gene had not obviously been disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of the coding region of the gene. Several eye disease genes map to the same region of the X chromosome, but are excluded on grounds of pathology. One possibility is that this fetus has a Norrie-like eye disease caused by the mutation of another gene located at Xp11.4. If this is so, there are implications for prenatal diagnosis. Images PMID:7562972

The Atmospheric Dynamics of Alpha Tau (K5 III) -- Clues to Understanding the Magnetic Dynamo

NASA Technical Reports Server (NTRS)

Carpenter Kenneth G.

2008-01-01

Using HST/GHRS, HST/STIS and FUSE archival data for (alpha) Tau and the CHIANTI spectroscopic code, we have derived line shifts, volumetric emission measures, and plasma density estimates, and calculated filling factors for a number of UV lines forming between 10,000 K and 300,000 K in the outer atmosphere of this red giant star. The data suggest the presence of low-temperature extended regions and high-temperature compact regions, associated with magnetically open and closed structures in the stellar atmosphere, respectively. The signatures of UV lines from Alpha Tau can be consistently understood via a model of upward-traveling Alfven waves in a gravitationally stratified atmosphere. These wakes cause non-thermal broadening in UV lines due to unresolved wave motions and downward plasma motions in compact magnetic loops heated by resonant .4lf\\en wave heating. We discuss implications of this interpretation for understanding the nature of magnetic dynamos operating in late-type giants.

Outbreak of poliomyelitis in Finland in 1984-85 - Re-analysis of viral sequences using the current standard approach.

PubMed

Simonen, Marja-Leena; Roivainen, Merja; Iber, Jane; Burns, Cara; Hovi, Tapani

2010-01-01

In 1984, a wild type 3 poliovirus (PV3/FIN84) spread all over Finland causing nine cases of paralytic poliomyelitis and one case of aseptic meningitis. The outbreak was ended in 1985 with an intensive vaccination campaign. By limited sequence comparison with previously isolated PV3 strains, closest relatives of PV3/FIN84 were found among strains circulating in the Mediterranean region. Now we wanted to reanalyse the relationships using approaches currently exploited in poliovirus surveillance. Cell lysates of 22 strains isolated during the outbreak and stored frozen were subjected to RT-PCR amplification in three genomic regions without prior subculture. Sequences of the entire VP1 coding region, 150 nucleotides in the VP1-2A junction, most of the 5' non-coding region, partial sequences of the 3D RNA polymerase coding region and partial 3' non-coding region were compared within the outbreak and with sequences available in data banks. In addition, complete nucleotide sequences were obtained for 2 strains isolated from two different cases of disease during the outbreak. The results confirmed the previously described wide intraepidemic variation of the strains, including amino acid substitutions in antigenic sites, as well as the likely Mediterranean region origin of the strains. Simplot and bootscanning analyses of the complete genomes indicated complicated evolutionary history of the non-capsid coding regions of the genome suggesting several recombinations with different HEV-C viruses in the past.

Impact of Concreteness on Comprehensibility, Interest, and Memory for Text: Implications for Dual Coding Theory and Text Design.

ERIC Educational Resources Information Center

Sadoski, Mark; And Others

1993-01-01

The comprehensibility, interestingness, familiarity, and memorability of concrete and abstract instructional texts were studied in 4 experiments involving 221 college students. Results indicate that concreteness (ease of imagery) is the variable overwhelmingly most related to comprehensibility and recall. Dual coding theory and schema theory are…

Domain Organization and Evolution of the Highly Divergent 5′ Coding Region of Genomes of Arteriviruses, Including the Novel Possum Nidovirus

PubMed Central

Gulyaeva, Anastasia; Hoogendoorn, Erik; Giles, Julia; Samborskiy, Dmitry

2017-01-01

ABSTRACT In five experimentally characterized arterivirus species, the 5′-end genome coding region encodes the most divergent nonstructural proteins (nsp's), nsp1 and nsp2, which include papain-like proteases (PLPs) and other poorly characterized domains. These are involved in regulation of transcription, polyprotein processing, and virus-host interaction. Here we present results of a bioinformatics analysis of this region of 14 arterivirus species, including that of the most distantly related virus, wobbly possum disease virus (WPDV), determined by a modified 5′ rapid amplification of cDNA ends (RACE) protocol. By combining profile-profile comparisons and phylogeny reconstruction, we identified an association of the four distinct domain layouts of nsp1-nsp2 with major phylogenetic lineages, implicating domain gain, including duplication, and loss in the early nsp1 evolution. Specifically, WPDV encodes highly divergent homologs of PLP1a, PLP1b, PLP1c, and PLP2, with PLP1a lacking the catalytic Cys residue, but does not encode nsp1 Zn finger (ZnF) and “nuclease” domains, which are conserved in other arteriviruses. Unexpectedly, our analysis revealed that the only catalytically active nsp1 PLP of equine arteritis virus (EAV), known as PLP1b, is most similar to PLP1c and thus is likely to be a PLP1b paralog. In all non-WPDV arteriviruses, PLP1b/c and PLP1a show contrasting patterns of conservation, with the N- and C-terminal subdomains, respectively, being enriched with conserved residues, which is indicative of different functional specializations. The least conserved domain of nsp2, the hypervariable region (HVR), has its size varied 5-fold and includes up to four copies of a novel PxPxPR motif that is potentially recognized by SH3 domain-containing proteins. Apparently, only EAV lacks the signal that directs −2 ribosomal frameshifting in the nsp2 coding region. IMPORTANCE Arteriviruses comprise a family of mammalian enveloped positive-strand RNA viruses that include some of the most economically important pathogens of swine. Most of our knowledge about this family has been obtained through characterization of viruses from five species: Equine arteritis virus, Simian hemorrhagic fever virus, Lactate dehydrogenase-elevating virus, Porcine respiratory and reproductive syndrome virus 1, and Porcine respiratory and reproductive syndrome virus 2. Here we present the results of comparative genomics analyses of viruses from all known 14 arterivirus species, including the most distantly related virus, WPDV, whose genome sequence was completed in this study. Our analysis focused on the multifunctional 5′-end genome coding region that encodes multidomain nonstructural proteins 1 and 2. Using diverse bioinformatics techniques, we identified many patterns of evolutionary conservation that are specific to members of distinct arterivirus species, both characterized and novel, or their groups. They are likely associated with structural and functional determinants important for virus replication and virus-host interaction. PMID:28053107

The mitochondrial genome of the phytopathogenic basidiomycete Moniliophthora perniciosa is 109 kb in size and contains a stable integrated plasmid.

PubMed

Formighieri, Eduardo F; Tiburcio, Ricardo A; Armas, Eduardo D; Medrano, Francisco J; Shimo, Hugo; Carels, Nicolas; Góes-Neto, Aristóteles; Cotomacci, Carolina; Carazzolle, Marcelo F; Sardinha-Pinto, Naiara; Thomazella, Daniela P T; Rincones, Johana; Digiampietri, Luciano; Carraro, Dirce M; Azeredo-Espin, Ana M; Reis, Sérgio F; Deckmann, Ana C; Gramacho, Karina; Gonçalves, Marilda S; Moura Neto, José P; Barbosa, Luciana V; Meinhardt, Lyndel W; Cascardo, Júlio C M; Pereira, Gonçalo A G

2008-10-01

We present here the sequence of the mitochondrial genome of the basidiomycete phytopathogenic hemibiotrophic fungus Moniliophthora perniciosa, causal agent of the Witches' Broom Disease in Theobroma cacao. The DNA is a circular molecule of 109,103 base pairs, with 31.9% GC, and is the largest sequenced so far. This size is due essentially to the presence of numerous non-conserved hypothetical ORFs. It contains the 14 genes coding for proteins involved in the oxidative phosphorylation, the two rRNA genes, one ORF coding for a ribosomal protein (rps3), and a set of 26 tRNA genes that recognize codons for all amino acids. Seven homing endonucleases are located inside introns. Except atp8, all conserved known genes are in the same orientation. Phylogenetic analysis based on the cox genes agrees with the commonly accepted fungal taxonomy. An uncommon feature of this mitochondrial genome is the presence of a region that contains a set of four, relatively small, nested, inverted repeats enclosing two genes coding for polymerases with an invertron-type structure and three conserved hypothetical genes interpreted as the stable integration of a mitochondrial linear plasmid. The integration of this plasmid seems to be a recent evolutionary event that could have implications in fungal biology. This sequence is available under GenBank accession number AY376688.

Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening

PubMed Central

Dostie, Josée; Lemire, Edmond; Bouchard, Philippe; Field, Michael; Jones, Kristie; Lorenz, Birgit; Menten, Björn; Buysse, Karen; Pattyn, Filip; Friedli, Marc; Ucla, Catherine; Rossier, Colette; Wyss, Carine; Speleman, Frank; De Paepe, Anne; Dekker, Job; Antonarakis, Stylianos E.; De Baere, Elfride

2009-01-01

To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5′ to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular. PMID:19543368

A global view of the nonprotein-coding transcriptome in Plasmodium falciparum

PubMed Central

Raabe, Carsten A.; Sanchez, Cecilia P.; Randau, Gerrit; Robeck, Thomas; Skryabin, Boris V.; Chinni, Suresh V.; Kube, Michael; Reinhardt, Richard; Ng, Guey Hooi; Manickam, Ravichandran; Kuryshev, Vladimir Y.; Lanzer, Michael; Brosius, Juergen; Tang, Thean Hock; Rozhdestvensky, Timofey S.

2010-01-01

Nonprotein-coding RNAs (npcRNAs) represent an important class of regulatory molecules that act in many cellular pathways. Here, we describe the experimental identification and validation of the small npcRNA transcriptome of the human malaria parasite Plasmodium falciparum. We identified 630 novel npcRNA candidates. Based on sequence and structural motifs, 43 of them belong to the C/D and H/ACA-box subclasses of small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs). We further observed the exonization of a functional H/ACA snoRNA gene, which might contribute to the regulation of ribosomal protein L7a gene expression. Some of the small npcRNA candidates are from telomeric and subtelomeric repetitive regions, suggesting their potential involvement in maintaining telomeric integrity and subtelomeric gene silencing. We also detected 328 cis-encoded antisense npcRNAs (asRNAs) complementary to P. falciparum protein-coding genes of a wide range of biochemical pathways, including determinants of virulence and pathology. All cis-encoded asRNA genes tested exhibit lifecycle-specific expression profiles. For all but one of the respective sense–antisense pairs, we deduced concordant patterns of expression. Our findings have important implications for a better understanding of gene regulatory mechanisms in P. falciparum, revealing an extended and sophisticated npcRNA network that may control the expression of housekeeping genes and virulence factors. PMID:19864253

A global view of the nonprotein-coding transcriptome in Plasmodium falciparum.

PubMed

Raabe, Carsten A; Sanchez, Cecilia P; Randau, Gerrit; Robeck, Thomas; Skryabin, Boris V; Chinni, Suresh V; Kube, Michael; Reinhardt, Richard; Ng, Guey Hooi; Manickam, Ravichandran; Kuryshev, Vladimir Y; Lanzer, Michael; Brosius, Juergen; Tang, Thean Hock; Rozhdestvensky, Timofey S

2010-01-01

Nonprotein-coding RNAs (npcRNAs) represent an important class of regulatory molecules that act in many cellular pathways. Here, we describe the experimental identification and validation of the small npcRNA transcriptome of the human malaria parasite Plasmodium falciparum. We identified 630 novel npcRNA candidates. Based on sequence and structural motifs, 43 of them belong to the C/D and H/ACA-box subclasses of small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs). We further observed the exonization of a functional H/ACA snoRNA gene, which might contribute to the regulation of ribosomal protein L7a gene expression. Some of the small npcRNA candidates are from telomeric and subtelomeric repetitive regions, suggesting their potential involvement in maintaining telomeric integrity and subtelomeric gene silencing. We also detected 328 cis-encoded antisense npcRNAs (asRNAs) complementary to P. falciparum protein-coding genes of a wide range of biochemical pathways, including determinants of virulence and pathology. All cis-encoded asRNA genes tested exhibit lifecycle-specific expression profiles. For all but one of the respective sense-antisense pairs, we deduced concordant patterns of expression. Our findings have important implications for a better understanding of gene regulatory mechanisms in P. falciparum, revealing an extended and sophisticated npcRNA network that may control the expression of housekeeping genes and virulence factors.

Error-Rate Bounds for Coded PPM on a Poisson Channel

NASA Technical Reports Server (NTRS)

Moision, Bruce; Hamkins, Jon

2009-01-01

Equations for computing tight bounds on error rates for coded pulse-position modulation (PPM) on a Poisson channel at high signal-to-noise ratio have been derived. These equations and elements of the underlying theory are expected to be especially useful in designing codes for PPM optical communication systems. The equations and the underlying theory apply, more specifically, to a case in which a) At the transmitter, a linear outer code is concatenated with an inner code that includes an accumulator and a bit-to-PPM-symbol mapping (see figure) [this concatenation is known in the art as "accumulate-PPM" (abbreviated "APPM")]; b) The transmitted signal propagates on a memoryless binary-input Poisson channel; and c) At the receiver, near-maximum-likelihood (ML) decoding is effected through an iterative process. Such a coding/modulation/decoding scheme is a variation on the concept of turbo codes, which have complex structures, such that an exact analytical expression for the performance of a particular code is intractable. However, techniques for accurately estimating the performances of turbo codes have been developed. The performance of a typical turbo code includes (1) a "waterfall" region consisting of a steep decrease of error rate with increasing signal-to-noise ratio (SNR) at low to moderate SNR, and (2) an "error floor" region with a less steep decrease of error rate with increasing SNR at moderate to high SNR. The techniques used heretofore for estimating performance in the waterfall region have differed from those used for estimating performance in the error-floor region. For coded PPM, prior to the present derivations, equations for accurate prediction of the performance of coded PPM at high SNR did not exist, so that it was necessary to resort to time-consuming simulations in order to make such predictions. The present derivation makes it unnecessary to perform such time-consuming simulations.

Recurrent and functional regulatory mutations in breast cancer.

PubMed

Rheinbay, Esther; Parasuraman, Prasanna; Grimsby, Jonna; Tiao, Grace; Engreitz, Jesse M; Kim, Jaegil; Lawrence, Michael S; Taylor-Weiner, Amaro; Rodriguez-Cuevas, Sergio; Rosenberg, Mara; Hess, Julian; Stewart, Chip; Maruvka, Yosef E; Stojanov, Petar; Cortes, Maria L; Seepo, Sara; Cibulskis, Carrie; Tracy, Adam; Pugh, Trevor J; Lee, Jesse; Zheng, Zongli; Ellisen, Leif W; Iafrate, A John; Boehm, Jesse S; Gabriel, Stacey B; Meyerson, Matthew; Golub, Todd R; Baselga, Jose; Hidalgo-Miranda, Alfredo; Shioda, Toshi; Bernards, Andre; Lander, Eric S; Getz, Gad

2017-07-06

Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.

The (Missed) Potential of the Patient-centered Medical Home for Disparities.

PubMed

Reibling, Nadine; Rosenthal, Meredith B

2016-01-01

Disparities in health care and health outcomes are a significant problem in the United States. Delivery system reforms such as the patient-centered medical home (PCMH) could have important implications for disparities. To investigate what role disparities play in current PCMH initiatives and how their set-up might impact on disparities. We selected 4 state-based PCMH initiatives (Colorado, Massachusetts, Pennsylvania, and Rhode Island), 1 regional initiative in New Orleans, and 1 multistate initiative. We interviewed 30 key actors in these initiatives and 3 health policy experts on disparities in the context of PCMH. Interview data were coded using the constant comparative method. We find that disparities are not an explicit priority in PCMH initiatives. Nevertheless, many policymakers, providers, and initiative leaders believe that the model has the potential to reduce disparities. However, because of the funding structure of initiatives and the lack of adjustment of quality metrics, health policy experts do not share this optimism and safety-net providers report concerns and frustration. Even though disparities are currently not a priority in the PCMH community, the design of initiatives has important implications for disparities.

Second-generation sequencing of entire mitochondrial coding-regions (∼15.4 kb) holds promise for study of the phylogeny and taxonomy of human body lice and head lice.

PubMed

Xiong, H; Campelo, D; Pollack, R J; Raoult, D; Shao, R; Alem, M; Ali, J; Bilcha, K; Barker, S C

2014-08-01

The Illumina Hiseq platform was used to sequence the entire mitochondrial coding-regions of 20 body lice, Pediculus humanus Linnaeus, and head lice, P. capitis De Geer (Phthiraptera: Pediculidae), from eight towns and cities in five countries: Ethiopia, France, China, Australia and the U.S.A. These data (∼310 kb) were used to see how much more informative entire mitochondrial coding-region sequences were than partial mitochondrial coding-region sequences, and thus to guide the design of future studies of the phylogeny, origin, evolution and taxonomy of body lice and head lice. Phylogenies were compared from entire coding-region sequences (∼15.4 kb), entire cox1 (∼1.5 kb), partial cox1 (∼700 bp) and partial cytb (∼600 bp) sequences. On the one hand, phylogenies from entire mitochondrial coding-region sequences (∼15.4 kb) were much more informative than phylogenies from entire cox1 sequences (∼1.5 kb) and partial gene sequences (∼600 to ∼700 bp). For example, 19 branches had > 95% bootstrap support in our maximum likelihood tree from the entire mitochondrial coding-regions (∼15.4 kb) whereas the tree from 700 bp cox1 had only two branches with bootstrap support > 95%. Yet, by contrast, partial cytb (∼600 bp) and partial cox1 (∼486 bp) sequences were sufficient to genotype lice to Clade A, B or C. The sequences of the mitochondrial genomes of the P. humanus, P. capitis and P. schaeffi Fahrenholz studied are in NCBI GenBank under the accession numbers KC660761-800, KC685631-6330, KC241882-97, EU219988-95, HM241895-8 and JX080388-407. © 2014 The Royal Entomological Society.

Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment

PubMed Central

Nudel, R; Simpson, N H; Baird, G; O’Hare, A; Conti-Ramsden, G; Bolton, P F; Hennessy, E R; Ring, S M; Davey Smith, G; Francks, C; Paracchini, S; Monaco, A P; Fisher, S E; Newbury, D F

2014-01-01

Specific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 (P = 3.74 × 10−8) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10−7). A subsequent targeted association of six single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers’ genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders. PMID:24571439

Accurate coding in sepsis: clinical significance and financial implications.

PubMed

Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

2016-09-01

Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone. Copyright © 2016 The Healthcare Infection Society. All rights reserved.

Regulation of mammalian cell differentiation by long non-coding RNAs

PubMed Central

Hu, Wenqian; Alvarez-Dominguez, Juan R; Lodish, Harvey F

2012-01-01

Differentiation of specialized cell types from stem and progenitor cells is tightly regulated at several levels, both during development and during somatic tissue homeostasis. Many long non-coding RNAs have been recognized as an additional layer of regulation in the specification of cellular identities; these non-coding species can modulate gene-expression programmes in various biological contexts through diverse mechanisms at the transcriptional, translational or messenger RNA stability levels. Here, we summarize findings that implicate long non-coding RNAs in the control of mammalian cell differentiation. We focus on several representative differentiation systems and discuss how specific long non-coding RNAs contribute to the regulation of mammalian development. PMID:23070366

GBS: Global 3D simulation of tokamak edge region

NASA Astrophysics Data System (ADS)

Zhu, Ben; Fisher, Dustin; Rogers, Barrett; Ricci, Paolo

2012-10-01

A 3D two-fluid global code, namely Global Braginskii Solver (GBS), is being developed to explore the physics of turbulent transport, confinement, self-consistent profile formation, pedestal scaling and related phenomena in the edge region of tokamaks. Aimed at solving drift-reduced Braginskii equations [1] in complex magnetic geometry, the GBS is used for turbulence simulation in SOL region. In the recent upgrade, the simulation domain is expanded into close flux region with twist-shift boundary conditions. Hence, the new GBS code is able to explore global transport physics in an annular full-torus domain from the top of the pedestal into the far SOL. We are in the process of identifying and analyzing the linear and nonlinear instabilities in the system using the new GBS code. Preliminary results will be presented and compared with other codes if possible.[4pt] [1] A. Zeiler, J. F. Drake and B. Rogers, Phys. Plasmas 4, 2134 (1997)

Analysis and recognition of 5′ UTR intron splice sites in human pre-mRNA

PubMed Central

Eden, E.; Brunak, S.

2004-01-01

Prediction of splice sites in non-coding regions of genes is one of the most challenging aspects of gene structure recognition. We perform a rigorous analysis of such splice sites embedded in human 5′ untranslated regions (UTRs), and investigate correlations between this class of splice sites and other features found in the adjacent exons and introns. By restricting the training of neural network algorithms to ‘pure’ UTRs (not extending partially into protein coding regions), we for the first time investigate the predictive power of the splicing signal proper, in contrast to conventional splice site prediction, which typically relies on the change in sequence at the transition from protein coding to non-coding. By doing so, the algorithms were able to pick up subtler splicing signals that were otherwise masked by ‘coding’ noise, thus enhancing significantly the prediction of 5′ UTR splice sites. For example, the non-coding splice site predicting networks pick up compositional and positional bias in the 3′ ends of non-coding exons and 5′ non-coding intron ends, where cytosine and guanine are over-represented. This compositional bias at the true UTR donor sites is also visible in the synaptic weights of the neural networks trained to identify UTR donor sites. Conventional splice site prediction methods perform poorly in UTRs because the reading frame pattern is absent. The NetUTR method presented here performs 2–3-fold better compared with NetGene2 and GenScan in 5′ UTRs. We also tested the 5′ UTR trained method on protein coding regions, and discovered, surprisingly, that it works quite well (although it cannot compete with NetGene2). This indicates that the local splicing pattern in UTRs and coding regions is largely the same. The NetUTR method is made publicly available at www.cbs.dtu.dk/services/NetUTR. PMID:14960723

Epigenetics: a new frontier in dentistry.

PubMed

Williams, S D; Hughes, T E; Adler, C J; Brook, A H; Townsend, G C

2014-06-01

In 2007, only four years after the completion of the Human Genome Project, the journal Science announced that epigenetics was the 'breakthrough of the year'. Time magazine placed it second in the top 10 discoveries of 2009. While our genetic code (i.e. our DNA) contains all of the information to produce the elements we require to function, our epigenetic code determines when and where genes in the genetic code are expressed. Without the epigenetic code, the genetic code is like an orchestra without a conductor. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression during development and subsequently potentially influencing oral disease susceptibility. This paper provides a review of the field of epigenetics aimed specifically at oral health professionals. It defines epigenetics, addresses the underlying concepts and provides details about specific epigenetic molecular mechanisms. Further, we discuss some of the key areas where epigenetics is implicated, and review the literature on epigenetics research in dentistry, including its relevance to clinical disciplines. This review considers some implications of epigenetics for the future of dental practice, including a 'personalized medicine' approach to the management of common oral diseases. © 2014 Australian Dental Association.

Variability and transmission by Aphis glycines of North American and Asian Soybean mosaic virus isolates.

PubMed

Domier, L L; Latorre, I J; Steinlage, T A; McCoppin, N; Hartman, G L

2003-10-01

The variability of North American and Asian strains and isolates of Soybean mosaic virus was investigated. First, polymerase chain reaction (PCR) products representing the coat protein (CP)-coding regions of 38 SMVs were analyzed for restriction fragment length polymorphisms (RFLP). Second, the nucleotide and predicted amino acid sequence variability of the P1-coding region of 18 SMVs and the helper component/protease (HC/Pro) and CP-coding regions of 25 SMVs were assessed. The CP nucleotide and predicted amino acid sequences were the most similar and predicted phylogenetic relationships similar to those obtained from RFLP analysis. Neither RFLP nor sequence analyses of the CP-coding regions grouped the SMVs by geographical origin. The P1 and HC/Pro sequences were more variable and separated the North American and Asian SMV isolates into two groups similar to previously reported differences in pathogenic diversity of the two sets of SMV isolates. The P1 region was the most informative of the three regions analyzed. To assess the biological relevance of the sequence differences in the HC/Pro and CP coding regions, the transmissibility of 14 SMV isolates by Aphis glycines was tested. All field isolates of SMV were transmitted efficiently by A. glycines, but the laboratory isolates analyzed were transmitted poorly. The amino acid sequences from most, but not all, of the poorly transmitted isolates contained mutations in the aphid transmission-associated DAG and/or KLSC amino acid sequence motifs of CP and HC/Pro, respectively.

Ways with Data: Understanding Coding as Writing

ERIC Educational Resources Information Center

Lindgren, Chris

2017-01-01

In this dissertation, I report findings from an exploratory case-study about Ray, a web developer, who works on a data-driven news team that finds and tells compelling stories with large sets of data. I implicate this case of Ray's coding on a data team in a writing studies epistemology, which is guided by the following question: "What might…

The Pluralisation of Family Life: Implications for Preschool Education

ERIC Educational Resources Information Center

Šebart, Mojca Kovac; Kuhar, Roman

2017-01-01

The article takes as its starting point the public debate about the newly proposed Family Code in Slovenia in 2009. Inter alia, the Code introduced a new, inclusive definition of the family in accordance with the contemporary pluralisation of family life. This raised a number of questions about how--if at all--various families are addressed in the…

A Theoretical Analysis of Learning with Graphics--Implications for Computer Graphics Design.

ERIC Educational Resources Information Center

ChanLin, Lih-Juan

This paper reviews the literature pertinent to learning with graphics. The dual coding theory provides explanation about how graphics are stored and precessed in semantic memory. The level of processing theory suggests how graphics can be employed in learning to encourage deeper processing. In addition to dual coding theory and level of processing…

Using a Corporate Code of Ethics to Assess Students' Ethicality: Implications for Business Education

ERIC Educational Resources Information Center

Persons, Obeua

2009-01-01

The author used a corporate code of ethics as a roadmap to create 18 scenarios for assessing business students' ethicality as measured by their behavioral intention. Using a logistic regression analysis, the author also examined 8 factors that could potentially influence students' ethicality. Results indicate 6 scenarios related to 5 areas of the…

Studies of Braille Reading Rates and Implications for the Unified English Braille Code

ERIC Educational Resources Information Center

Wetzel, Robin; Knowlton, Marie

2006-01-01

Reading rate data was collected from both print and braille readers in the areas of mathematics and literary braille. Literary braille data was collected for contracted and uncontracted braille text with dropped whole-word contractions and part-word contractions as they would appear in the Unified English Braille Code. No significant differences…

78 FR 52477 - Promulgation of State Implementation Plan Revisions; Revision to Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

...), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver, Colorado 80202-1129. Hand Delivery: Director, Air Program, Environmental Protection Agency (EPA), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver... Agency (EPA), Region 8, 1595 Wynkoop Street, Denver, Colorado 80202-1129. EPA requests that if at all...

Novel mutations of TCOF1 gene in European patients with treacher Collins syndrome

PubMed Central

2011-01-01

Background Treacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phospho-protein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases. Methods In this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication. Results Fifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein. Conclusion This study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein. PMID:21951868

Novel mutations of TCOF1 gene in European patients with Treacher Collins syndrome.

PubMed

Conte, Chiara; D'Apice, Maria Rosaria; Rinaldi, Fabrizio; Gambardella, Stefano; Sangiuolo, Federica; Novelli, Giuseppe

2011-09-27

Treacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phospho-protein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases. In this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication. Fifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein. This study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein.

Extinction probabilities and stationary distributions of mobile genetic elements in prokaryotes: The birth-death-diversification model.

PubMed

Drakos, Nicole E; Wahl, Lindi M

2015-12-01

Theoretical approaches are essential to our understanding of the complex dynamics of mobile genetic elements (MGEs) within genomes. Recently, the birth-death-diversification model was developed to describe the dynamics of mobile promoters (MPs), a particular class of MGEs in prokaryotes. A unique feature of this model is that genetic diversification of elements was included. To explore the implications of diversification on the longterm fate of MGE lineages, in this contribution we analyze the extinction probabilities, extinction times and equilibrium solutions of the birth-death-diversification model. We find that diversification increases both the survival and growth rate of MGE families, but the strength of this effect depends on the rate of horizontal gene transfer (HGT). We also find that the distribution of MGE families per genome is not necessarily monotonically decreasing, as observed for MPs, but may have a peak in the distribution that is related to the HGT rate. For MPs specifically, we find that new families have a high extinction probability, and predict that the number of MPs is increasing, albeit at a very slow rate. Additionally, we develop an extension of the birth-death-diversification model which allows MGEs in different regions of the genome, for example coding and non-coding, to be described by different rates. This extension may offer a potential explanation as to why the majority of MPs are located in non-promoter regions of the genome. Copyright © 2015 Elsevier Inc. All rights reserved.

Population genetic implications from sequence variation in four Y chromosome genes.

PubMed

Shen, P; Wang, F; Underhill, P A; Franco, C; Yang, W H; Roxas, A; Sung, R; Lin, A A; Hyman, R W; Vollrath, D; Davis, R W; Cavalli-Sforza, L L; Oefner, P J

2000-06-20

Some insight into human evolution has been gained from the sequencing of four Y chromosome genes. Primary genomic sequencing determined gene SMCY to be composed of 27 exons that comprise 4,620 bp of coding sequence. The unfinished sequencing of the 5' portion of gene UTY1 was completed by primer walking, and a total of 20 exons were found. By using denaturing HPLC, these two genes, as well as DBY and DFFRY, were screened for polymorphic sites in 53-72 representatives of the five continents. A total of 98 variants were found, yielding nucleotide diversity estimates of 2.45 x 10(-5), 5. 07 x 10(-5), and 8.54 x 10(-5) for the coding regions of SMCY, DFFRY, and UTY1, respectively, with no variant having been observed in DBY. In agreement with most autosomal genes, diversity estimates for the noncoding regions were about 2- to 3-fold higher and ranged from 9. 16 x 10(-5) to 14.2 x 10(-5) for the four genes. Analysis of the frequencies of derived alleles for all four genes showed that they more closely fit the expectation of a Luria-Delbrück distribution than a distribution expected under a constant population size model, providing evidence for exponential population growth. Pairwise nucleotide mismatch distributions date the occurrence of population expansion to approximately 28,000 years ago. This estimate is in accord with the spread of Aurignacian technology and the disappearance of the Neanderthals.

Differentiation of the glucocerebrosidase gene from pseudogene by long-template PCR: Implications for Gaucher disease

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

Tayebi, N.; Cushner, S.; Sidransky, E.

1996-09-01

We describe the use of long-template PCR to differentiate the glucocerebrosidase gene from its pseudogene, which will simplify molecular diagnostic testing and the detection of known and new mutations in patients with Gaucher disease. Gaucher disease results from the inherited deficiency of the lysosomal enzyme, glucocerebrosidase. Sixteen kilobases downstream of the glucocerebrosidase gene is a pseudogene, which is {approximately}2 kb shorter and has >96% identity to the coding regions of the functional gene. Many mutations encountered in Gaucher patients are identical to sequences ordinarily found only in the pseudogene, and some result from recombination between the gene and pseudogene. Thus,more » for diagnostic purposes it is essential to differentiate between sequences from the gene and pseudogene. 9 refs., 1 fig.« less

Molecular Dissection of a Major Gene Effect on a Quantitative Trait: The Level of Alcohol Dehydrogenase Expression in Drosophila Melanogaster

PubMed Central

Stam, L. F.; Laurie, C. C.

1996-01-01

A molecular mapping experiment shows that a major gene effect on a quantitative trait, the level of alcohol dehydrogenase expression in Drosophila melanogaster, is due to multiple polymorphisms within the Adh gene. These polymorphisms are located in an intron, the coding sequence, and the 3' untranslated region. Because of nonrandom associations among polymorphisms at different sites, the individual effects combine (in some cases epistatically) to produce ``superalleles'' with large effect. These results have implications for the interpretation of major gene effects detected by quantitative trait locus mapping methods. They show that large effects due to a single locus may be due to multiple associated polymorphisms (or sequential fixations in isolated populations) rather than individual mutations of large effect. PMID:8978044

Consequences of narrow cyclotron emission from Hercules X-1

NASA Technical Reports Server (NTRS)

Weaver, R. P.

1978-01-01

The implications of the recent observations of a narrow cyclotron line in the hard X-ray spectrum of Hercules X-1 are studied. A Monte Carlo code is used to simulate the X-ray transfer of an intrinsically narrow feature at approximately 56 keV through an opaque, cold magnetospheric shell. The results of this study indicate that if a narrow line can be emitted by the source region, then only about 10% of the photons remain in a narrow feature after scattering through the shell. The remaining photons are scattered into a broad feature (FWHM approximately 30 keV) that peaks near 20 keV. Thus, these calculations indicate that the intrinsic source luminosity of the cyclotron line is at least an order of magnitude greater than the observed luminosity.

Systems implications of L-band fade data statistics for LEO mobile systems

NASA Technical Reports Server (NTRS)

Devieux, Carrie L.

1993-01-01

This paper examines and analyzes research data on the role of foliage attenuation in signal fading between a satellite transmitter and a terrestrial vehicle-mounted receiver. The frequency band of measurement, called L-Band, includes the region 1610.0 to 1626.5 MHz. Data from tests involving various combinations of foliage and vehicle movement conditions clearly show evidence of fast fading (in excess of 0.5 dB per millisecond) and fade depths as great or greater than 16 dB. As a result, the design of a communications link power control that provides the level of accuracy necessary for power sensitive systems could be significantly impacted. Specific examples of this include the communications links that employ Code Division Multiple Access (CDMA) as a modulation technique.

A novel de novo POGZ mutation in a patient with intellectual disability.

PubMed

Tan, Bo; Zou, Yongyi; Zhang, Yue; Zhang, Rui; Ou, Jianjun; Shen, Yidong; Zhao, Jingping; Luo, Xiaomei; Guo, Jing; Zeng, Lanlan; Hu, Yiqiao; Zheng, Yu; Pan, Qian; Liang, Desheng; Wu, Lingqian

2016-04-01

POGZ, the gene encoding pogo transposable element-derived protein with zinc-finger domain, has been implicated in autism spectrum disorder and it is widely expressed in the human tissues, including the brain. Intellectual disability (ID) is highly heterogeneous neurodevelopment disorder and affects ~2-3% of the general population. Here we report the identification of a novel frameshift mutation in the coding region of the POGZ gene (c.1277_1278insC), which occurred de novo in a Chinese patient with ID. In silico analysis and western blotting revealed this frameshift mutation generating truncated protein in peripheral blood lymphocytes, and this may disrupt several important domains of POGZ gene. Our finding broadens the spectrum of POGZ mutations and may help to understand the molecular basis of ID and aid genetic counseling.

Systems implications of L-band fade data statistics for LEO mobile systems

NASA Astrophysics Data System (ADS)

Devieux, Carrie L.

This paper examines and analyzes research data on the role of foliage attenuation in signal fading between a satellite transmitter and a terrestrial vehicle-mounted receiver. The frequency band of measurement, called L-Band, includes the region 1610.0 to 1626.5 MHz. Data from tests involving various combinations of foliage and vehicle movement conditions clearly show evidence of fast fading (in excess of 0.5 dB per millisecond) and fade depths as great or greater than 16 dB. As a result, the design of a communications link power control that provides the level of accuracy necessary for power sensitive systems could be significantly impacted. Specific examples of this include the communications links that employ Code Division Multiple Access (CDMA) as a modulation technique.

Neurodevelopmental Delay Diagnosis Rates Are Increased in a Region with Aerial Pesticide Application.

PubMed

Hicks, Steven D; Wang, Ming; Fry, Katherine; Doraiswamy, Vignesh; Wohlford, Eric M

2017-01-01

A number of studies have implicated pesticides in childhood developmental delay (DD) and autism spectrum disorder (ASD). The influence of the route of pesticide exposure on neurodevelopmental delay is not well defined. To study this factor, we examined ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis. The aim of this study was to determine if areas with aerial pesticide exposure had higher rates of ASD/DD diagnoses. This regional study identified higher rates of ASD/DD diagnoses in an area with aerial pesticides application. Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD (adjusted RR = 1.37, 95% CI = 1.06-1.78, p  = 0.02). A Poisson regression model controlling for regional characteristics (poverty, pesticide use, population density, and distance to medical center), subject characteristics (race and sex), and local birth characteristics (prematurity, low birthweight, and birth rates) identified a significant relationship between aerial pesticide use and ASD/DD rates. The relationship between pesticide application and human neurodevelopment deserves additional study to develop safe and effective methods of mosquito prevention, particularly as communities develop plans for Zika virus control.

Implications of Sino-American Strategic Competition on Southeast Asia’s Post-Cold War Regional Order

DTIC Science & Technology

2003-12-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS IMPLICATIONS OF SINO-AMERICAN STRATEGIC COMPETITION ON SOUTHEAST ASIA’S...Implications of Sino-American Strategic Competition on Southeast Asia’s Post-Cold War Regional Order 5. FUNDING NUMBERS 6. AUTHOR Sidharto R...IMPLICATIONS OF SINO-AMERICAN STRATEGIC COMPETITION ON SOUTHEAST ASIA’S POST-COLD WAR REGIONAL ORDER Sidharto R. Suryodipuro Civilian, Foreign

Identification of common, unique and polymorphic microsatellites among 73 cyanobacterial genomes.

PubMed

Kabra, Ritika; Kapil, Aditi; Attarwala, Kherunnisa; Rai, Piyush Kant; Shanker, Asheesh

2016-04-01

Microsatellites also known as Simple Sequence Repeats are short tandem repeats of 1-6 nucleotides. These repeats are found in coding as well as non-coding regions of both prokaryotic and eukaryotic genomes and play a significant role in the study of gene regulation, genetic mapping, DNA fingerprinting and evolutionary studies. The availability of 73 complete genome sequences of cyanobacteria enabled us to mine and statistically analyze microsatellites in these genomes. The cyanobacterial microsatellites identified through bioinformatics analysis were stored in a user-friendly database named CyanoSat, which is an efficient data representation and query system designed using ASP.net. The information in CyanoSat comprises of perfect, imperfect and compound microsatellites found in coding, non-coding and coding-non-coding regions. Moreover, it contains PCR primers with 200 nucleotides long flanking region. The mined cyanobacterial microsatellites can be freely accessed at www.compubio.in/CyanoSat/home.aspx. In addition to this 82 polymorphic, 13,866 unique and 2390 common microsatellites were also detected. These microsatellites will be useful in strain identification and genetic diversity studies of cyanobacteria.

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory.

PubMed

Hasselmo, Michael E; Giocomo, Lisa M; Brandon, Mark P; Yoshida, Motoharu

2010-12-31

Understanding the mechanisms of episodic memory requires linking behavioral data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. Copyright © 2010 Elsevier B.V. All rights reserved.

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory

PubMed Central

Hasselmo, Michael E.; Giocomo, Lisa M.; Yoshida, Motoharu

2010-01-01

Understanding the mechanisms of episodic memory requires linking behavioural data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within these brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. PMID:20018213

Effects of photophoresis on the dust distribution in a 3D protoplanetary disc

NASA Astrophysics Data System (ADS)

Cuello, N.; Gonzalez, J.-F.; Pignatale, F. C.

2016-05-01

Photophoresis is a physical process based on momentum exchange between an illuminated dust particle and its gaseous environment. Its net effect in protoplanetary discs (PPD) is the outward transport of solid bodies from hot to cold regions. This process naturally leads to the formation of ring-shaped features where dust piles up. In this work, we study the dynamical effects of photophoresis in PPD by including the photophoretic force in the two-fluid (gas+dust) smoothed particle hydrodynamics (SPH) code developed by Barrière-Fouchet et al. (2005). We find that the conditions of pressure and temperature encountered in the inner regions of PPD result in important photophoretic forces, which dramatically affect the radial motion of solid bodies. Moreover, dust particles have different equilibrium locations in the disc depending on their size and their intrinsic density. The radial transport towards the outer parts of the disc is more efficient for silicates than for iron particles, which has important implications for meteoritic composition. Our results indicate that photophoresis must be taken into account in the inner regions of PPD to fully understand the dynamics and the evolution of the dust composition.

Synonymous deoptimization of the foot-and-mouth disease virus P1 coding region causes attenuation in vivo while inducing a strong neutralizing antibody response

USDA-ARS?s Scientific Manuscript database

Codon bias deoptimization has been previously used to successfully attenuate human pathogens including polio, respiratory syncytial and influenza viruses. We have applied a similar technology to deoptimize the capsid coding region (P1 region) of the cDNA infectious clone of foot-and-mouth disease vi...

The Code of the Street and Romantic Relationships: A dyadic analysis

PubMed Central

Barr, Ashley B.; Simons, Ronald L.; Stewart, Eric A.

2012-01-01

Since its publication, Elijah Anderson’s (1999) code of the street thesis has found support in studies connecting disadvantage to the internalization of street-oriented values and an associated lifestyle of violent/deviant behavior. This primary emphasis on deviance in public arenas has precluded researchers from examining the implications of the code of the street for less public arenas, like intimate relationships. In an effort to understand if and how the endorsement of the street code may infiltrate such relationships, the present study examines the associations between the code of the street and relationship satisfaction and commitment among young adults involved in heterosexual romantic relationships. Using a dyadic approach, we find that street code orientation, in general, negatively predicts satisfaction and commitment, in part due to increased relationship hostility/conflict associated with the internalization of the code. Gender differences in these associations are considered and discussed at length. PMID:23504000

Advancing methods for reliably assessing motivational interviewing fidelity using the Motivational Interviewing Skills Code

PubMed Central

Lord, Sarah Peregrine; Can, Doğan; Yi, Michael; Marin, Rebeca; Dunn, Christopher W.; Imel, Zac E.; Georgiou, Panayiotis; Narayanan, Shrikanth; Steyvers, Mark; Atkins, David C.

2014-01-01

The current paper presents novel methods for collecting MISC data and accurately assessing reliability of behavior codes at the level of the utterance. The MISC 2.1 was used to rate MI interviews from five randomized trials targeting alcohol and drug use. Sessions were coded at the utterance-level. Utterance-based coding reliability was estimated using three methods and compared to traditional reliability estimates of session tallies. Session-level reliability was generally higher compared to reliability using utterance-based codes, suggesting that typical methods for MISC reliability may be biased. These novel methods in MI fidelity data collection and reliability assessment provided rich data for therapist feedback and further analyses. Beyond implications for fidelity coding, utterance-level coding schemes may elucidate important elements in the counselor-client interaction that could inform theories of change and the practice of MI. PMID:25242192

Advancing methods for reliably assessing motivational interviewing fidelity using the motivational interviewing skills code.

PubMed

Lord, Sarah Peregrine; Can, Doğan; Yi, Michael; Marin, Rebeca; Dunn, Christopher W; Imel, Zac E; Georgiou, Panayiotis; Narayanan, Shrikanth; Steyvers, Mark; Atkins, David C

2015-02-01

The current paper presents novel methods for collecting MISC data and accurately assessing reliability of behavior codes at the level of the utterance. The MISC 2.1 was used to rate MI interviews from five randomized trials targeting alcohol and drug use. Sessions were coded at the utterance-level. Utterance-based coding reliability was estimated using three methods and compared to traditional reliability estimates of session tallies. Session-level reliability was generally higher compared to reliability using utterance-based codes, suggesting that typical methods for MISC reliability may be biased. These novel methods in MI fidelity data collection and reliability assessment provided rich data for therapist feedback and further analyses. Beyond implications for fidelity coding, utterance-level coding schemes may elucidate important elements in the counselor-client interaction that could inform theories of change and the practice of MI. Copyright © 2015 Elsevier Inc. All rights reserved.

Iraq’s Debt Relief: Procedure and Potential Implications for International Debt Relief

DTIC Science & Technology

2008-10-02

Order Code RL33376 Iraq’s Debt Relief: Procedure and Potential Implications for International Debt Relief Updated October 2, 2008 Martin A. Weiss...4. TITLE AND SUBTITLE Iraq?s Debt Relief: Procedure and Potential Implications for International Debt Relief 5a. CONTRACT NUMBER 5b. GRANT NUMBER...b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Iraq’s Debt Relief: Procedure

Single-nucleotide polymorphisms in the SEPTIN12 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

PubMed

Miyakawa, Hiroe; Miyamoto, Toshinobu; Koh, Eitetsu; Tsujimura, Akira; Miyagawa, Yasushi; Saijo, Yasuaki; Namiki, Mikio; Sengoku, Kazuo

2012-01-01

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis, including human SEPTIN12, were identified by expression microarray analysis of human testicular tissue. Septin12 is a member of the septin family of conserved cytoskeletal GTPases that form heteropolymeric filamentous structures in interphase cells. It is expressed specifically in the testis. Therefore, we hypothesized that mutation or polymorphisms of SEPTIN12 participate in male infertility, especially Sertoli cell-only syndrome (SCOS). To investigate whether SEPTIN12 gene defects are associated with azoospermia caused by SCOS, mutational analysis was performed in 100 Japanese patients by direct sequencing of coding regions. Statistical analysis was performed in patients with SCOS and in 140 healthy control men. No mutations were found in SEPTIN12 ; however, 8 coding single-nucleotide polymorphisms (SNP1-SNP8) could be detected in the patients with SCOS. The genotype and allele frequencies in SNP3, SNP4, and SNP6 were notably higher in the SCOS group than in the control group (P < .001). These results suggest that SEPTIN12 might play a critical role in human spermatogenesis.

Computational DNA hole spectroscopy: A new tool to predict mutation hotspots, critical base pairs, and disease ‘driver’ mutations

PubMed Central

Suárez, Martha Y.; Villagrán; Miller, John H.

2015-01-01

We report on a new technique, computational DNA hole spectroscopy, which creates spectra of electron hole probabilities vs. nucleotide position. A hole is a site of positive charge created when an electron is removed. Peaks in the hole spectrum depict sites where holes tend to localize and potentially trigger a base pair mismatch during replication. Our studies of mitochondrial DNA reveal a correlation between L-strand hole spectrum peaks and spikes in the human mutation spectrum. Importantly, we also find that hole peak positions that do not coincide with large variant frequencies often coincide with disease-implicated mutations and/or (for coding DNA) encoded conserved amino acids. This enables combining hole spectra with variant data to identify critical base pairs and potential disease ‘driver’ mutations. Such integration of DNA hole and variance spectra could ultimately prove invaluable for pinpointing critical regions of the vast non-protein-coding genome. An observed asymmetry in correlations, between the spectrum of human mtDNA variations and the L- and H-strand hole spectra, is attributed to asymmetric DNA replication processes that occur for the leading and lagging strands. PMID:26310834

Computational DNA hole spectroscopy: A new tool to predict mutation hotspots, critical base pairs, and disease 'driver' mutations.

PubMed

Villagrán, Martha Y Suárez; Miller, John H

2015-08-27

We report on a new technique, computational DNA hole spectroscopy, which creates spectra of electron hole probabilities vs. nucleotide position. A hole is a site of positive charge created when an electron is removed. Peaks in the hole spectrum depict sites where holes tend to localize and potentially trigger a base pair mismatch during replication. Our studies of mitochondrial DNA reveal a correlation between L-strand hole spectrum peaks and spikes in the human mutation spectrum. Importantly, we also find that hole peak positions that do not coincide with large variant frequencies often coincide with disease-implicated mutations and/or (for coding DNA) encoded conserved amino acids. This enables combining hole spectra with variant data to identify critical base pairs and potential disease 'driver' mutations. Such integration of DNA hole and variance spectra could ultimately prove invaluable for pinpointing critical regions of the vast non-protein-coding genome. An observed asymmetry in correlations, between the spectrum of human mtDNA variations and the L- and H-strand hole spectra, is attributed to asymmetric DNA replication processes that occur for the leading and lagging strands.

A structural variant in the 5’-flanking region of the TWIST2 gene affects melanocyte development in belted cattle

PubMed Central

Drögemüller, Cord; Jagannathan, Vidhya; Keller, Irene; Wüthrich, Daniel; Bruggmann, Rémy; Schütz, Ekkehard; Demmel, Steffi; Moser, Simon; Signer-Hasler, Heidi; Pieńkowska-Schelling, Aldona; Schelling, Claude; Sande, Marcos; Rongen, Ronald

2017-01-01

Belted cattle have a circular belt of unpigmented hair and skin around their midsection. The belt is inherited as a monogenic autosomal dominant trait. We mapped the causative variant to a 37 kb segment on bovine chromosome 3. Whole genome sequence data of 2 belted and 130 control cattle yielded only one private genetic variant in the critical interval in the two belted animals. The belt-associated variant was a copy number variant (CNV) involving the quadruplication of a 6 kb non-coding sequence located approximately 16 kb upstream of the TWIST2 gene. Increased copy numbers at this CNV were strongly associated with the belt phenotype in a cohort of 333 cases and 1322 controls. We hypothesized that the CNV causes aberrant expression of TWIST2 during neural crest development, which might negatively affect melanoblasts. Functional studies showed that ectopic expression of bovine TWIST2 in neural crest in transgenic zebrafish led to a decrease in melanocyte numbers. Our results thus implicate an unsuspected involvement of TWIST2 in regulating pigmentation and reveal a non-coding CNV underlying a captivating Mendelian character. PMID:28658273

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

PubMed Central

Adoue, Veronique; Schiavi, Alicia; Light, Nicholas; Almlöf, Jonas Carlsson; Lundmark, Per; Ge, Bing; Kwan, Tony; Caron, Maxime; Rönnblom, Lars; Wang, Chuan; Chen, Shu-Huang; Goodall, Alison H; Cambien, Francois; Deloukas, Panos; Ouwehand, Willem H; Syvänen, Ann-Christine; Pastinen, Tomi

2014-01-01

Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40–60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor–SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. PMID:25326100

Complete chloroplast genome sequences of Drimys, Liriodendron, andPiper: Implications for the phylogeny of magnoliids and the evolution ofGC content

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

Zhengqiu, C.; Penaflor, C.; Kuehl, J.V.

2006-06-01

The magnoliids represent the largest basal angiosperm clade with four orders, 19 families and 8,500 species. Although several recent angiosperm molecular phylogenies have supported the monophyly of magnoliids and suggested relationships among the orders, the limited number of genes examined resulted in only weak support, and these issues remain controversial. Furthermore, considerable incongruence has resulted in phylogenies supporting three different sets of relationships among magnoliids and the two large angiosperm clades, monocots and eudicots. This is one of the most important remaining issues concerning relationships among basal angiosperms. We sequenced the chloroplast genomes of three magnoliids, Drimys (Canellales), Liriodendron (Magnoliales),more » and Piper (Piperales), and used these data in combination with 32 other completed angiosperm chloroplast genomes to assess phylogenetic relationships among magnoliids. The Drimys and Piper chloroplast genomes are nearly identical in size at 160,606 and 160,624 bp, respectively. The genomes include a pair of inverted repeats of 26,649 bp (Drimys) and 27,039 (Piper), separated by a small single copy region of 18,621 (Drimys) and 18,878 (Piper) and a large single copy region of 88,685 bp (Drimys) and 87,666 bp (Piper). The gene order of both taxa is nearly identical to many other unrearranged angiosperm chloroplast genomes, including Calycanthus, the other published magnoliid genome. Comparisons of angiosperm chloroplast genomes indicate that GC content is not uniformly distributed across the genome. Overall GC content ranges from 34-39%, and coding regions have a substantially higher GC content than non-coding regions (both intergenic spacers and introns). Among protein-coding genes, GC content varies by codon position with 1st codon > 2nd codon > 3rd codon, and it varies by functional group with photosynthetic genes having the highest percentage and NADH genes the lowest. Across the genome, GC content is highest in the inverted repeat due to the presence of rRNA genes and lowest in the small single copy region where most NADH genes are located. Phylogenetic analyses using maximum parsimony and maximum likelihood methods were performed on DNA sequences of 61 protein-coding genes. Trees from both analyses provided strong support for the monophyly of magnoliids and two strongly supported groups were identified, the Canellales/Piperales and the Laurales/Magnoliales. The phylogenies also provided moderate to strong support for the basal position of Amborella, and a sister relationship of magnoliids to a clade that includes monocots and eudicots. The complete sequences of three magnoliid chloroplast genomes provide new data from the largest basal angiosperm clade. Evolutionary comparisons of these new genome sequences, combined with other published angiosperm genome, confirm that GC content is unevenly distributed across the genome by location, codon position, and functional group. Furthermore, phylogenetic analyses provide the strongest support so far for the hypothesis that the magnoliids are sister to a large clade that includes both monocots and eudicots.« less

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome

PubMed Central

Ferlaino, Michael; Rogers, Mark F.; Shihab, Hashem A.; Mort, Matthew; Cooper, David N.; Gaunt, Tom R.; Campbell, Colin

2018-01-01

Background Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. Results We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. Conclusions FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome. PMID:28985712

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.

PubMed

Ferlaino, Michael; Rogers, Mark F; Shihab, Hashem A; Mort, Matthew; Cooper, David N; Gaunt, Tom R; Campbell, Colin

2017-10-06

Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.

[Relevance of long non-coding RNAs in tumour biology].

PubMed

Nagy, Zoltán; Szabó, Diána Rita; Zsippai, Adrienn; Falus, András; Rácz, Károly; Igaz, Péter

2012-09-23

The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is transcribed. Beside small RNAs (including microRNAs) more and more data are disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length that are implicated in the regulation of several basic molecular processes (cell proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of these long non-coding RNAs have been associated with human tumours, including H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in various neoplasms relative to healthy tissues. Long non-coding RNAs may represent novel markers of molecular diagnostics and they might even turn out to be targets of therapeutic intervention.

Topographical and geological amplification: case studies and engineering implications

USGS Publications Warehouse

Celebi, M.

1991-01-01

Topographical and geological amplification that occurred during past earthquakes are quantified using spectral ratios of recorded motions. Several cases are presented from the 1985 Chilean and Mexican earthquakes as well as the 1983 Coalinga (California) and 1987 Supersition Hills (California) earthquake. The strong motions recorded in Mexico City during the 1985 Michoacan earthquake are supplemented by ambient motions recorded within Mexico City to quantify the now well known resonating frequencies of the Mexico City lakebed. Topographical amplification in Canal Beagle (Chile), Coalinga and Superstition Hills (California) are quantified using the ratios derived from the aftershocks following the earthquakes. A special dense array was deployed to record the aftershocks in each case. The implications of both geological and topographical amplification are discussed in light of current code provisions. The observed geological amplifications has already influenced the code provisions. Suggestions are made to the effect that the codes should include further provisions to take the amplification due to topography into account. ?? 1991.

The nucleotide composition of microbial genomes indicates differential patterns of selection on core and accessory genomes.

PubMed

Bohlin, Jon; Eldholm, Vegard; Pettersson, John H O; Brynildsrud, Ola; Snipen, Lars

2017-02-10

The core genome consists of genes shared by the vast majority of a species and is therefore assumed to have been subjected to substantially stronger purifying selection than the more mobile elements of the genome, also known as the accessory genome. Here we examine intragenic base composition differences in core genomes and corresponding accessory genomes in 36 species, represented by the genomes of 731 bacterial strains, to assess the impact of selective forces on base composition in microbes. We also explore, in turn, how these results compare with findings for whole genome intragenic regions. We found that GC content in coding regions is significantly higher in core genomes than accessory genomes and whole genomes. Likewise, GC content variation within coding regions was significantly lower in core genomes than in accessory genomes and whole genomes. Relative entropy in coding regions, measured as the difference between observed and expected trinucleotide frequencies estimated from mononucleotide frequencies, was significantly higher in the core genomes than in accessory and whole genomes. Relative entropy was positively associated with coding region GC content within the accessory genomes, but not within the corresponding coding regions of core or whole genomes. The higher intragenic GC content and relative entropy, as well as the lower GC content variation, observed in the core genomes is most likely associated with selective constraints. It is unclear whether the positive association between GC content and relative entropy in the more mobile accessory genomes constitutes signatures of selection or selective neutral processes.

Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.

PubMed

Bassett, Anne S; Lowther, Chelsea; Merico, Daniele; Costain, Gregory; Chow, Eva W C; van Amelsvoort, Therese; McDonald-McGinn, Donna; Gur, Raquel E; Swillen, Ann; Van den Bree, Marianne; Murphy, Kieran; Gothelf, Doron; Bearden, Carrie E; Eliez, Stephan; Kates, Wendy; Philip, Nicole; Sashi, Vandana; Campbell, Linda; Vorstman, Jacob; Cubells, Joseph; Repetto, Gabriela M; Simon, Tony; Boot, Erik; Heung, Tracy; Evers, Rens; Vingerhoets, Claudia; van Duin, Esther; Zackai, Elaine; Vergaelen, Elfi; Devriendt, Koen; Vermeesch, Joris R; Owen, Michael; Murphy, Clodagh; Michaelovosky, Elena; Kushan, Leila; Schneider, Maude; Fremont, Wanda; Busa, Tiffany; Hooper, Stephen; McCabe, Kathryn; Duijff, Sasja; Isaev, Karin; Pellecchia, Giovanna; Wei, John; Gazzellone, Matthew J; Scherer, Stephen W; Emanuel, Beverly S; Guo, Tingwei; Morrow, Bernice E; Marshall, Christian R

2017-11-01

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.

Nonsyndromic cleft lip with or without cleft palate: Increased burden of rare variants within Gremlin-1, a component of the bone morphogenetic protein 4 pathway.

PubMed

Al Chawa, Taofik; Ludwig, Kerstin U; Fier, Heide; Pötzsch, Bernd; Reich, Rudolf H; Schmidt, Gül; Braumann, Bert; Daratsianos, Nikolaos; Böhmer, Anne C; Schuencke, Hannah; Alblas, Margrieta; Fricker, Nadine; Hoffmann, Per; Knapp, Michael; Lange, Christoph; Nöthen, Markus M; Mangold, Elisabeth

2014-06-01

The genes Gremlin-1 (GREM1) and Noggin (NOG) are components of the bone morphogenetic protein 4 pathway, which has been implicated in craniofacial development. Both genes map to recently identified susceptibility loci (chromosomal region 15q13, 17q22) for nonsyndromic cleft lip with or without cleft palate (nsCL/P). The aim of the present study was to determine whether rare variants in either gene are implicated in nsCL/P etiology. The complete coding regions, untranslated regions, and splice sites of GREM1 and NOG were sequenced in 96 nsCL/P patients and 96 controls of Central European ethnicity. Three burden and four nonburden tests were performed. Statistically significant results were followed up in a second case-control sample (n = 96, respectively). For rare variants observed in cases, segregation analyses were performed. In NOG, four rare sequence variants (minor allele frequency < 1%) were identified. Here, burden and nonburden analyses generated nonsignificant results. In GREM1, 33 variants were identified, 15 of which were rare. Of these, five were novel. Significant p-values were generated in three nonburden analyses. Segregation analyses revealed incomplete penetrance for all variants investigated. Our study did not provide support for NOG being the causal gene at 17q22. However, the observation of a significant excess of rare variants in GREM1 supports the hypothesis that this is the causal gene at chr. 15q13. Because no single causal variant was identified, future sequencing analyses of GREM1 should involve larger samples and the investigation of regulatory elements. © 2014 Wiley Periodicals, Inc.

Identifying acute myocardial infarction: effects on treatment and mortality, and implications for National Service Framework audit.

PubMed

Sapsford, R J; Lawrance, R A; Dorsch, M F; Das, R; Jackson, B M; Morrell, C; Robinson, M B; Hall, A S

2003-03-01

The National Service Framework (NSF) for Coronary Heart Disease requires annual clinical audit of the care of patients with myocardial infarction, with little guidance on how to achieve these standards and monitor practice. To assess which method of identification of acute myocardial infarction (AMI) cases is most suitable for NSF audit, and to determine the effect of the definition of AMI on the assessment of quality of care. Observational study. Over a 3-month period, 2153 consecutive patients from 20 hospitals across the Yorkshire region, with confirmed AMI, were identified from coronary care registers, biochemistry records and hospital coding systems. The sensitivity and positive predictive value of AMI patient identification using clinical coding, biochemistry and coronary care registers were compared to a 'gold standard' (the combination of all three methods). Of 3685 possible cases of AMI singled out by one or more methods, 2153 patients were identified as having a final diagnosis of AMI. Hospital coding revealed 1668 (77.5%) cases, with a demographic profile similar to that of the total cohort. Secondary preventative measures required for inclusion in NSF were also of broadly similar distribution. The sensitivities and positive predictive values for patient identification were substantially less in the cohorts identified through biochemistry and coronary care unit register. Patients fulfilling WHO criteria (n=1391) had a 30-day mortality of 15.9%, vs. 24.2% for the total cohort. Hospital coding misses a substantial proportion (22.5%) of AMI cases, but without any apparent systematic bias, and thus provides a suitably representative and robust basis for NSF-related audit. Better still would be the routine use of multiple methods of case identification.

Long Non-Coding RNAs Differentially Expressed between Normal versus Primary Breast Tumor Tissues Disclose Converse Changes to Breast Cancer-Related Protein-Coding Genes

PubMed Central

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U.; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N.; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O.

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes. PMID:25264628

Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

PubMed

Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O

2014-01-01

Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

NASA Astrophysics Data System (ADS)

Duan, Aiying; Jiang, Chaowei; Hu, Qiang; Zhang, Huai; Gary, G. Allen; Wu, S. T.; Cao, Jinbin

2017-06-01

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE-MHD-NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from the region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO/AIA. It is found that the CESE-MHD-NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ˜10°. This suggests that the CESE-MHD-NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (˜30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

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

Duan, Aiying; Zhang, Huai; Jiang, Chaowei

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE–MHD–NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from themore » region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO /AIA. It is found that the CESE–MHD–NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ∼10°. This suggests that the CESE–MHD–NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (∼30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.« less

Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder

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

Altemus, M.; Murphy, D.L.; Greenberg, B.

1996-07-26

Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a rolemore » for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. 27 refs.« less

A hybrid LBG/lattice vector quantizer for high quality image coding

NASA Technical Reports Server (NTRS)

Ramamoorthy, V.; Sayood, K.; Arikan, E. (Editor)

1991-01-01

It is well known that a vector quantizer is an efficient coder offering a good trade-off between quantization distortion and bit rate. The performance of a vector quantizer asymptotically approaches the optimum bound with increasing dimensionality. A vector quantized image suffers from the following types of degradations: (1) edge regions in the coded image contain staircase effects, (2) quasi-constant or slowly varying regions suffer from contouring effects, and (3) textured regions lose details and suffer from granular noise. All three of these degradations are due to the finite size of the code book, the distortion measures used in the design, and due to the finite training procedure involved in the construction of the code book. In this paper, we present an adaptive technique which attempts to ameliorate the edge distortion and contouring effects.

The complete mitochondrial genome of Chrysopa pallens (Insecta, Neuroptera, Chrysopidae).

PubMed

He, Kun; Chen, Zhe; Yu, Dan-Na; Zhang, Jia-Yong

2012-10-01

The complete mitochondrial genome of Chrysopa pallens (Neuroptera, Chrysopidae) was sequenced. It consists of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA (rRNA) genes, and a control region (AT-rich region). The total length of C. pallens mitogenome is 16,723 bp with 79.5% AT content, and the length of control region is 1905 bp with 89.1% AT content. The non-coding regions of C. pallens include control region between 12S rRNA and trnI genes, and a 75-bp space region between trnI and trnQ genes.

A-to-I editing of coding and non-coding RNAs by ADARs

PubMed Central

Nishikura, Kazuko

2016-01-01

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. This A-to-I editing occurs not only in protein-coding regions of mRNAs, but also frequently in non-coding regions that contain inverted Alu repeats. Editing of coding sequences can result in the expression of functionally altered proteins that are not encoded in the genome, whereas the significance of Alu editing remains largely unknown. Certain microRNA (miRNA) precursors are also edited, leading to reduced expression or altered function of mature miRNAs. Conversely, recent studies indicate that ADAR1 forms a complex with Dicer to promote miRNA processing, revealing a new function of ADAR1 in the regulation of RNA interference. PMID:26648264

Implementation of generalized quantum measurements: Superadditive quantum coding, accessible information extraction, and classical capacity limit

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

Takeoka, Masahiro; Fujiwara, Mikio; Mizuno, Jun

2004-05-01

Quantum-information theory predicts that when the transmission resource is doubled in quantum channels, the amount of information transmitted can be increased more than twice by quantum-channel coding technique, whereas the increase is at most twice in classical information theory. This remarkable feature, the superadditive quantum-coding gain, can be implemented by appropriate choices of code words and corresponding quantum decoding which requires a collective quantum measurement. Recently, an experimental demonstration was reported [M. Fujiwara et al., Phys. Rev. Lett. 90, 167906 (2003)]. The purpose of this paper is to describe our experiment in detail. Particularly, a design strategy of quantum-collective decodingmore » in physical quantum circuits is emphasized. We also address the practical implication of the gain on communication performance by introducing the quantum-classical hybrid coding scheme. We show how the superadditive quantum-coding gain, even in a small code length, can boost the communication performance of conventional coding techniques.« less

MKHITAR GOSH'S MEDIEVAL LAW CODE AND ITS IMPLICATIONS FOR ARMENIAN COMMUNITIES ABROAD.

PubMed

Davtyan, Susanna; Khachatryan, Mikayel; Johrian, Ara; Ghazaryan, Karen

2014-07-01

The Law Book of the medieval Armenian legal and economic thought is an exceptional work that encompasses valuable information of the Armenian nation's domestic life. Mkhitar Gosh was considered to be one of the most outstanding figures and lawyers (lawmakers) of all times. Armenian Law Code after Mkhitar Gosh is writhed at 12 century. One of the primary sources for the law code was Armenian customary law. This Code became moral code for guiding for hall Armenians over the world because of high moral spirit reflecting Armenian mentality. This article presents the brief history of extension of legal rules setting out in the Law Code. The Law Code was established and widely used not only in Armenia but also in a number of Armenian communities abroad (Russian, Poland, Georgia, Latvia, India etc.). Law Code was accepted by all Armenians. Moreover, it served for the development of legislation for a number of civilized European and Asian countries.

Mutation spectrum of fork-head transcriptional factor gene (FOXL2) in Indian Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) patients.

PubMed

Kaur, Inderjeet; Hussain, Avid; Naik, Milind N; Murthy, Ramesh; Honavar, Santosh G

2011-06-01

The fork-head transcription factor gene (FOXL2) gene has been implicated in Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) type I and type II. The authors aimed to evaluate the involvement of FOXL2 in familial and sporadic cases of BPES in an Indian cohort. The present cohort comprised clinically well-characterised BPES cases that included six affected families, two sporadic cases and 60 unaffected normal controls. The 5' untranslated and coding region of FOXL2 was screened by resequencing and confirmed by restriction digestion. Further, genotype-phenotype correlations were done to understand the implications of the observed mutation. Six mutations were observed in eight cases (87.5%). These included a novel deletion (c.860delC), three previously reported duplications (c.663-692dup 30, c.672-701dup30 and c.843-859dup17), a frame shift (c.804dupC) and a homozygous missense mutation (p.E69K). The p.E69k mutation was seen in both heterozygous and homozygous form in a large four-generational family, and disease severity was found to be directly linked to the allelic dosage. Two SNPs (c.501C→T, c.536C→G) were also noted. An unusual coexistence of polycystic ovarian disease (PCOD) with BPES was also seen in one of the families. Mutations in the region downstream of the fork-head domain were predominantly responsible for BPES among Indian patients.

A Comparison of Athletic Movement Among Talent-Identified Juniors From Different Football Codes in Australia: Implications for Talent Development.

PubMed

Woods, Carl T; Keller, Brad S; McKeown, Ian; Robertson, Sam

2016-09-01

Woods, CT, Keller, BS, McKeown, I, and Robertson, S. A comparison of athletic movement among talent-identified juniors from different football codes in Australia: implications for talent development. J Strength Cond Res 30(9): 2440-2445, 2016-This study aimed to compare the athletic movement skill of talent-identified (TID) junior Australian Rules football (ARF) and soccer players. The athletic movement skill of 17 TID junior ARF players (17.5-18.3 years) was compared against 17 TID junior soccer players (17.9-18.7 years). Players in both groups were members of an elite junior talent development program within their respective football codes. All players performed an athletic movement assessment that included an overhead squat, double lunge, single-leg Romanian deadlift (both movements performed on right and left legs), a push-up, and a chin-up. Each movement was scored across 3 essential assessment criteria using a 3-point scale. The total score for each movement (maximum of 9) and the overall total score (maximum of 63) were used as the criterion variables for analysis. A multivariate analysis of variance tested the main effect of football code (2 levels) on the criterion variables, whereas a 1-way analysis of variance identified where differences occurred. A significant effect was noted, with the TID junior ARF players outscoring their soccer counterparts when performing the overhead squat and push-up. No other criterions significantly differed according to the main effect. Practitioners should be aware that specific sporting requirements may incur slight differences in athletic movement skill among TID juniors from different football codes. However, given the low athletic movement skill noted in both football codes, developmental coaches should address the underlying movement skill capabilities of juniors when prescribing physical training in both codes.

Performance and Scalability of Discriminative Metrics for Comparative Gene Identification in 12 Drosophila Genomes

PubMed Central

Lin, Michael F.; Deoras, Ameya N.; Rasmussen, Matthew D.; Kellis, Manolis

2008-01-01

Comparative genomics of multiple related species is a powerful methodology for the discovery of functional genomic elements, and its power should increase with the number of species compared. Here, we use 12 Drosophila genomes to study the power of comparative genomics metrics to distinguish between protein-coding and non-coding regions. First, we study the relative power of different comparative metrics and their relationship to single-species metrics. We find that even relatively simple multi-species metrics robustly outperform advanced single-species metrics, especially for shorter exons (≤240 nt), which are common in animal genomes. Moreover, the two capture largely independent features of protein-coding genes, with different sensitivity/specificity trade-offs, such that their combinations lead to even greater discriminatory power. In addition, we study how discovery power scales with the number and phylogenetic distance of the genomes compared. We find that species at a broad range of distances are comparably effective informants for pairwise comparative gene identification, but that these are surpassed by multi-species comparisons at similar evolutionary divergence. In particular, while pairwise discovery power plateaued at larger distances and never outperformed the most advanced single-species metrics, multi-species comparisons continued to benefit even from the most distant species with no apparent saturation. Last, we find that genes in functional categories typically considered fast-evolving can nonetheless be recovered at very high rates using comparative methods. Our results have implications for comparative genomics analyses in any species, including the human. PMID:18421375

A Working Model for the System Alumina-Magnesia.

DTIC Science & Technology

1983-05-01

Several regions in the resulting diagram appear rather uncertain: the liquidus ’National bureau of StandaTds. JANAF Thermochemical Tables, by D. R. Stull ...Code 131) 1 Naval Ordnance Station, Indian Head (Technical Library) 29 Naval Postgraduate School. Monterey Code 012, Dean of Research (1) Code 06... Dean of Science and Engineering (1) Code 1424. Library - Technical Reports (2) Code 33. Weapons Engineering Program Office (1) Code 61. Chairman

Processing deficits in monitoring analog and digital displays: Implications for attentional theory and mental-state estimation research

NASA Technical Reports Server (NTRS)

Payne, David G.; Gunther, Virginia A. L.

1988-01-01

Subjects performed short term memory tasks, involving both spatial and verbal components, and a visual monitoring task involving either analog or digital display formats. These two tasks (memory vs. monitoring) were performed both singly and in conjunction. Contrary to expectations derived from multiple resource theories of attentional processes, there was no evidence that when the two tasks involved the same cognitive codes (i.e., either both spatial or both verbal/linguistics) there was more of a dual task performance decrement than when the two tasks employed different cognitive codes/processes. These results are discussed in terms of their implications for theories of attentional processes and also for research in mental state estimation.

A comparison of cosmological hydrodynamic codes

NASA Technical Reports Server (NTRS)

Kang, Hyesung; Ostriker, Jeremiah P.; Cen, Renyue; Ryu, Dongsu; Hernquist, Lars; Evrard, August E.; Bryan, Greg L.; Norman, Michael L.

1994-01-01

We present a detailed comparison of the simulation results of various hydrodynamic codes. Starting with identical initial conditions based on the cold dark matter scenario for the growth of structure, with parameters h = 0.5 Omega = Omega(sub b) = 1, and sigma(sub 8) = 1, we integrate from redshift z = 20 to z = O to determine the physical state within a representative volume of size L(exp 3) where L = 64 h(exp -1) Mpc. Five indenpendent codes are compared: three of them Eulerian mesh-based and two variants of the smooth particle hydrodynamics 'SPH' Lagrangian approach. The Eulerian codes were run at N(exp 3) = (32(exp 3), 64(exp 3), 128(exp 3), and 256(exp 3)) cells, the SPH codes at N(exp 3) = 32(exp 3) and 64(exp 3) particles. Results were then rebinned to a 16(exp 3) grid with the exception that the rebinned data should converge, by all techniques, to a common and correct result as N approaches infinity. We find that global averages of various physical quantities do, as expected, tend to converge in the rebinned model, but that uncertainites in even primitive quantities such as (T), (rho(exp 2))(exp 1/2) persists at the 3%-17% level achieve comparable and satisfactory accuracy for comparable computer time in their treatment of the high-density, high-temeprature regions as measured in the rebinned data; the variance among the five codes (at highest resolution) for the mean temperature (as weighted by rho(exp 2) is only 4.5%. Examined at high resolution we suspect that the density resolution is better in the SPH codes and the thermal accuracy in low-density regions better in the Eulerian codes. In the low-density, low-temperature regions the SPH codes have poor accuracy due to statiscal effects, and the Jameson code gives the temperatures which are too high, due to overuse of artificial viscosity in these high Mach number regions. Overall the comparison allows us to better estimate errors; it points to ways of improving this current generation ofhydrodynamic codes and of suiting their use to problems which exploit their best individual features.

Informed Consent and Clinical Research Involving Children and Adolescents: Implications of the Revised APA Ethics Code and HIPAA

ERIC Educational Resources Information Center

Fisher, Celia B.

2004-01-01

In 2003, 2 new sets of rules and regulations affecting the conduct of clinical research involving children and adolescents went into effect: the revised American Psychological Association's (APA) Ethical Principles of Psychologists and Code of Conduct (APA, 2002; effective June 1, 2003) and the Privacy Rule (45 CFR Part 160 and A and E of Part…

3DFEMWATER/3DLEWASTE: NUMERICAL CODES FOR DELINEATING WELLHEAD PROTECTION AREAS IN AGRICULTURAL REGIONS BASED ON THE ASSIMILATIVE CAPACITY CRITERION

EPA Science Inventory

Two related numerical codes, 3DFEMWATER and 3DLEWASTE, are presented sed to delineate wellhead protection areas in agricultural regions using the assimilative capacity criterion. DFEMWATER (Three-dimensional Finite Element Model of Water Flow Through Saturated-Unsaturated Media) ...

3D-PDR: Three-dimensional photodissociation region code

NASA Astrophysics Data System (ADS)

Bisbas, T. G.; Bell, T. A.; Viti, S.; Yates, J.; Barlow, M. J.

2018-03-01

3D-PDR is a three-dimensional photodissociation region code written in Fortran. It uses the Sundials package (written in C) to solve the set of ordinary differential equations and it is the successor of the one-dimensional PDR code UCL_PDR (ascl:1303.004). Using the HEALpix ray-tracing scheme (ascl:1107.018), 3D-PDR solves a three-dimensional escape probability routine and evaluates the attenuation of the far-ultraviolet radiation in the PDR and the propagation of FIR/submm emission lines out of the PDR. The code is parallelized (OpenMP) and can be applied to 1D and 3D problems.

Dual coding theory, word abstractness, and emotion: a critical review of Kousta et al. (2011).

PubMed

Paivio, Allan

2013-02-01

Kousta, Vigliocco, Del Campo, Vinson, and Andrews (2011) questioned the adequacy of dual coding theory and the context availability model as explanations of representational and processing differences between concrete and abstract words. They proposed an alternative approach that focuses on the role of emotional content in the processing of abstract concepts. Their dual coding critique is, however, based on impoverished and, in some respects, incorrect interpretations of the theory and its implications. This response corrects those gaps and misinterpretations and summarizes research findings that show predicted variations in the effects of dual coding variables in different tasks and contexts. Especially emphasized is an empirically supported dual coding theory of emotion that goes beyond the Kousta et al. emphasis on emotion in abstract semantics. 2013 APA, all rights reserved

Becoming Inclusive: A Code of Conduct for Inclusion and Diversity.

PubMed

Schmidt, Bonnie J; MacWilliams, Brent R; Neal-Boylan, Leslie

There are increasing concerns about exclusionary behaviors and lack of diversity in the nursing profession. Exclusionary behaviors, which may include incivility, bullying, and workplace violence, discriminate and isolate individuals and groups who are different, whereas inclusive behaviors encourage diversity. To address inclusion and diversity in nursing, this article offers a code of conduct. This code of conduct builds on existing nursing codes of ethics and applies to nursing students and nurses in both educational and practice settings. Inclusive behaviors that are demonstrated in nurses' relationships with patients, colleagues, the profession, and society are described. This code of conduct provides a basis for measureable change, empowerment, and unification of the profession. Recommendations, implications, and a pledge to action are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Polymorphism at the defensin gene in the Anopheles gambiae complex: testing different selection hypotheses

PubMed Central

Simard, Frédéric; Licht, Monica; Besansky, Nora J.; Lehmann, Tovi

2007-01-01

Genetic variation in defensin, a gene encoding a major effector molecule of insects immune response was analyzed within and between populations of three members of the Anopheles gambiae complex. The species selected included the two anthropophilic species, An. gambiae and An. arabiensis and the most zoophilic species of the complex, An. quadriannulatus. The first species was represented by four populations spanning its extreme genetic and geographical ranges, whereas each of the other two species was represented by a single population. We found (i) reduced overall polymorphism in the mature peptide region and in the total coding region, together with specific reductions in rare and moderately frequent mutations (sites) in the coding region compared with non coding regions, (ii) markedly reduced rate of nonsynonymous diversity compared with synonymous variation in the mature peptide and virtually identical mature peptide across the three species, and (iii) increased divergence between species in the mature peptide together with reduced differentiation between populations of An. gambiae in the same DNA region. These patterns suggest a strong purifying selection on the mature peptide and probably the whole coding region. Because An. quadriannulatus is not exposed to human pathogens, identical mature peptide and similar pattern of polymorphism across species implies that human pathogens played no role as selective agents on this peptide. PMID:17161659

A Combinatorial Geometry Target Description of the High Mobility Multipurpose Wheeled Vehicle (HMMWV)

DTIC Science & Technology

1985-10-01

NOTE3 1W. KFY OORDS (Continwo =n reverse aide If necesesar aid ldwttlfy by" block ntmber) •JW7 Regions, COM-EOM Region Ident• fication GIFT Material...technique of mobna.tcri• i Geometr- (Com-Geom). The Com-Gem data is used as input to the Geometric Inf• •cation for Targets ( GIFT ) computer code to... GIFT ) 2 3 computer code. This report documents the combinatorial geometry (Com-Geom) target description data which is the input data for the GIFT code

What the success of brain imaging implies about the neural code.

PubMed

Guest, Olivia; Love, Bradley C

2017-01-19

The success of fMRI places constraints on the nature of the neural code. The fact that researchers can infer similarities between neural representations, despite fMRI's limitations, implies that certain neural coding schemes are more likely than others. For fMRI to succeed given its low temporal and spatial resolution, the neural code must be smooth at the voxel and functional level such that similar stimuli engender similar internal representations. Through proof and simulation, we determine which coding schemes are plausible given both fMRI's successes and its limitations in measuring neural activity. Deep neural network approaches, which have been forwarded as computational accounts of the ventral stream, are consistent with the success of fMRI, though functional smoothness breaks down in the later network layers. These results have implications for the nature of the neural code and ventral stream, as well as what can be successfully investigated with fMRI.

TWANG-PIC, a novel gyro-averaged one-dimensional particle-in-cell code for interpretation of gyrotron experiments

NASA Astrophysics Data System (ADS)

Braunmueller, F.; Tran, T. M.; Vuillemin, Q.; Alberti, S.; Genoud, J.; Hogge, J.-Ph.; Tran, M. Q.

2015-06-01

A new gyrotron simulation code for simulating the beam-wave interaction using a monomode time-dependent self-consistent model is presented. The new code TWANG-PIC is derived from the trajectory-based code TWANG by describing the electron motion in a gyro-averaged one-dimensional Particle-In-Cell (PIC) approach. In comparison to common PIC-codes, it is distinguished by its computation speed, which makes its use in parameter scans and in experiment interpretation possible. A benchmark of the new code is presented as well as a comparative study between the two codes. This study shows that the inclusion of a time-dependence in the electron equations, as it is the case in the PIC-approach, is mandatory for simulating any kind of non-stationary oscillations in gyrotrons. Finally, the new code is compared with experimental results and some implications of the violated model assumptions in the TWANG code are disclosed for a gyrotron experiment in which non-stationary regimes have been observed and for a critical case that is of interest in high power gyrotron development.

TWANG-PIC, a novel gyro-averaged one-dimensional particle-in-cell code for interpretation of gyrotron experiments

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

Braunmueller, F., E-mail: falk.braunmueller@epfl.ch; Tran, T. M.; Alberti, S.

A new gyrotron simulation code for simulating the beam-wave interaction using a monomode time-dependent self-consistent model is presented. The new code TWANG-PIC is derived from the trajectory-based code TWANG by describing the electron motion in a gyro-averaged one-dimensional Particle-In-Cell (PIC) approach. In comparison to common PIC-codes, it is distinguished by its computation speed, which makes its use in parameter scans and in experiment interpretation possible. A benchmark of the new code is presented as well as a comparative study between the two codes. This study shows that the inclusion of a time-dependence in the electron equations, as it is themore » case in the PIC-approach, is mandatory for simulating any kind of non-stationary oscillations in gyrotrons. Finally, the new code is compared with experimental results and some implications of the violated model assumptions in the TWANG code are disclosed for a gyrotron experiment in which non-stationary regimes have been observed and for a critical case that is of interest in high power gyrotron development.« less

East Asian mtDNA haplogroup determination in Koreans: haplogroup-level coding region SNP analysis and subhaplogroup-level control region sequence analysis.

PubMed

Lee, Hwan Young; Yoo, Ji-Eun; Park, Myung Jin; Chung, Ukhee; Kim, Chong-Youl; Shin, Kyoung-Jin

2006-11-01

The present study analyzed 21 coding region SNP markers and one deletion motif for the determination of East Asian mitochondrial DNA (mtDNA) haplogroups by designing three multiplex systems which apply single base extension methods. Using two multiplex systems, all 593 Korean mtDNAs were allocated into 15 haplogroups: M, D, D4, D5, G, M7, M8, M9, M10, M11, R, R9, B, A, and N9. As the D4 haplotypes occurred most frequently in Koreans, the third multiplex system was used to further define D4 subhaplogroups: D4a, D4b, D4e, D4g, D4h, and D4j. This method allowed the complementation of coding region information with control region mutation motifs and the resultant findings also suggest reliable control region mutation motifs for the assignment of East Asian mtDNA haplogroups. These three multiplex systems produce good results in degraded samples as they contain small PCR products (101-154 bp) for single base extension reactions. SNP scoring was performed in 101 old skeletal remains using these three systems to prove their utility in degraded samples. The sequence analysis of mtDNA control region with high incidence of haplogroup-specific mutations and the selective scoring of highly informative coding region SNPs using the three multiplex systems are useful tools for most applications involving East Asian mtDNA haplogroup determination and haplogroup-directed stringent quality control.

Functional interrogation of non-coding DNA through CRISPR genome editing

PubMed Central

Canver, Matthew C.; Bauer, Daniel E.; Orkin, Stuart H.

2017-01-01

Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. PMID:28288828

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes

PubMed Central

Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A.

2015-01-01

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. PMID:25491206

Current Impact, Future Prospects and Implications of Mobile Healthcare in India

PubMed Central

Kappal, Rishi; Mehndiratta, Amit; Anandaraj, Prabu; Tsanas, Athanasios

2014-01-01

India has a diverse geographical landscape and predominately rural population. Telemedicine is identified as one of the technological pillars to support healthcare services in this region, but is associated with high cost and complex infrastructure, thus restricting its wider use. Mobile-based healthcare (m-Health) services may provide a practical, promising alternative approach to support healthcare facilities. India has a high mobile user base, both in cities and in rural regions. The appropriate identification of mobile data transmission technology for healthcare services is vital to optimally use the available technology. In this article, we review current telecommunication systemsin India, specifically the evolving consensus on the need for CDMA (Code Division Multiple Access - a wireless technology used by leading international and national operators. This technology is deployed in 800MHz band making it economically viable and far reaching with high quality of services) to continue its operations in India along with mobile healthcare services. We also discuss how healthcare services may be extended using m-Health technologies, given the availability of telecommunications and related services. PMID:29755887

The Genetics of the Thyroid Stimulating Hormone Receptor: History and Relevance

PubMed Central

Yin, Xiaoming; Latif, Rauf

2010-01-01

Background The thyroid stimulating hormone receptor (TSHR) is the key regulator of thyrocyte function. The gene for the TSHR on chromosome 14q31 has been implicated as coding for the major autoantigen in the autoimmune hyperthyroidism of Graves' disease (GD) to which T cells and autoantibodies are directed. Summary The TSHR is a seven-transmembrane domain receptor that undergoes complex posttranslational processing. In this brief review, we look at the genetics of this important autoantigen and its influence on a variety of tissue functions in addition to its role in the induction of GD. Conclusions There is convincing evidence that the TSH receptor gene confers increased susceptibility for GD, but not Hashimoto's thyroiditis. GD is associated with polymorphisms in the intron 1 gene region. How such noncoding nucleotide changes influence disease susceptibility remains uncertain, but is likely to involve TSHR splicing variants and/or microRNAs arising from this gene region. Whether such influences are confined to the thyroid gland or whether they influence cell function in the many extrathyroidal sites of TSHR expression remains unknown. PMID:20578897

Simultaneous mutation and copy number variation (CNV) detection by multiplex PCR-based GS-FLX sequencing.

PubMed

Goossens, Dirk; Moens, Lotte N; Nelis, Eva; Lenaerts, An-Sofie; Glassee, Wim; Kalbe, Andreas; Frey, Bruno; Kopal, Guido; De Jonghe, Peter; De Rijk, Peter; Del-Favero, Jurgen

2009-03-01

We evaluated multiplex PCR amplification as a front-end for high-throughput sequencing, to widen the applicability of massive parallel sequencers for the detailed analysis of complex genomes. Using multiplex PCR reactions, we sequenced the complete coding regions of seven genes implicated in peripheral neuropathies in 40 individuals on a GS-FLX genome sequencer (Roche). The resulting dataset showed highly specific and uniform amplification. Comparison of the GS-FLX sequencing data with the dataset generated by Sanger sequencing confirmed the detection of all variants present and proved the sensitivity of the method for mutation detection. In addition, we showed that we could exploit the multiplexed PCR amplicons to determine individual copy number variation (CNV), increasing the spectrum of detected variations to both genetic and genomic variants. We conclude that our straightforward procedure substantially expands the applicability of the massive parallel sequencers for sequencing projects of a moderate number of amplicons (50-500) with typical applications in resequencing exons in positional or functional candidate regions and molecular genetic diagnostics. 2008 Wiley-Liss, Inc.

Epigenetic Regulation of Transcription in Trypanosomatid Protozoa.

PubMed

Martínez-Calvillo, Santiago; Romero-Meza, Gabriela; Vizuet-de-Rueda, Juan C; Florencio-Martínez, Luis E; Manning-Cela, Rebeca; Nepomuceno-Mejía, Tomás

2018-02-01

The Trypanosomatid family includes flagellated parasites that cause fatal human diseases. Remarkably, protein-coding genes in these organisms are positioned in long tandem arrays that are transcribed polycistronically. However, the knowledge about regulation of transcription initiation and termination in trypanosomatids is scarce. The importance of epigenetic regulation in these processes has become evident in the last years, as distinctive histone modifications and histone variants have been found in transcription initiation and termination regions. Moreover, multiple chromatin-related proteins have been identified and characterized in trypanosomatids, including histone-modifying enzymes, effector complexes, chromatin-remodelling enzymes and histone chaperones. Notably, base J, a modified thymine residue present in the nuclear DNA of trypanosomatids, has been implicated in transcriptional regulation. Here we review the current knowledge on epigenetic control of transcription by all three RNA polymerases in this group of early-diverged eukaryotes.

Molecular cloning and evolutionary analysis of the calcium-modulated contractile protein, centrin, in green algae and land plants.

PubMed

Bhattacharya, D; Steinkötter, J; Melkonian, M

1993-12-01

Centrin (= caltractin) is a ubiquitous, cytoskeletal protein which is a member of the EF-hand superfamily of calcium-binding proteins. A centrin-coding cDNA was isolated and characterized from the prasinophyte green alga Scherffelia dubia. Centrin PCR amplification primers were used to isolate partial, homologous cDNA sequences from the green algae Tetraselmis striata and Spermatozopsis similis. Annealing analyses suggested that centrin is a single-copy-coding region in T. striata and S. similis and other green algae studied. Centrin-coding regions from S. dubia, S. similis and T. striata encode four colinear EF-hand domains which putatively bind calcium. Phylogenetic analyses, including homologous sequences from Chlamydomonas reinhardtii and the land plant Atriplex nummularia, demonstrate that the domains of centrins are congruent and arose from the two-fold duplication of an ancestral EF hand with Domains 1+3 and Domains 2+4 clustering. The domains of centrins are also congruent with those of calmodulins demonstrating that, like calmodulin, centrin is an ancient protein which arose within the ancestor of all eukaryotes via gene duplication. Phylogenetic relationships inferred from centrin-coding region comparisons mirror results of small subunit ribosomal RNA sequence analyses suggesting that centrin-coding regions are useful evolutionary markers within the green algae.

Combined actions of multiple hairpin loop structures and sites of rate-limiting endonucleolytic cleavage determine differential degradation rates of individual segments within polycistronic puf operon mRNA.

PubMed Central

Klug, G; Cohen, S N

1990-01-01

Differential expression of the genes within the puf operon of Rhodobacter capsulatus is accomplished in part by differences in the rate of degradation of different segments of the puf transcript. We report here that decay of puf mRNA sequences specifying the light-harvesting I (LHI) and reaction center (RC) photosynthetic membrane peptides is initiated endoribonucleolytically within a discrete 1.4-kilobase segment of the RC-coding region. Deletion of this segment increased the half-life of the RC-coding region from 8 to 20 min while not affecting decay of LHI-coding sequences upstream from an intercistronic hairpin loop structure shown previously to impede 3'-to-5' degradation. Prolongation of RC segment half-life was dependent on the presence of other hairpin structures 3' to the RC region. Inserting the endonuclease-sensitive sites into the LHI-coding segment markedly accelerated its degradation. Our results suggest that differential degradation of the RC- and LHI-coding segments of puf mRNA is accomplished at least in part by the combined actions of RC region-specific endonuclease(s), one or more exonucleases, and several strategically located exonuclease-impeding hairpins. Images PMID:2394682

Cloning & sequence identification of Hsp27 gene and expression analysis of the protein on thermal stress in Lucilia cuprina.

PubMed

Singh, Manish K; Tiwari, Pramod K

2016-08-01

Hsp27, a highly conserved small molecular weight heat shock protein, is widely known to be developmentally regulated and heat inducible. Its role in thermotolerance is also implicated. This study is a sequel of our earlier studies to understand the molecular organization of heat shock genes/proteins and their role in development and thermal adaptation in a sheep pest, Lucilia cuprina (blowfly), which exhibits unusually high adaptability to a variety of environmental stresses, including heat and chemicals. In this report our aim was to understand the evolutionary relationship of Lucilia hsp27 gene/protein with those of other species and its role in thermal adaptation. We sequence characterized the Lchsp27 gene (coding region) and analyzed its expression in various larval and adult tissues under normal as well as heat shock conditions. The nucleotide sequence analysis of 678 bps long-coding region of Lchsp27 exhibited closest evolutionary proximity with Drosophila (90.09%), which belongs to the same order, Diptera. Heat shock caused significant enhancement in the expression of Lchsp27 gene in all the larval and adult tissues examined, however, in a tissue specific manner. Significantly, in Malpighian tubules, while the heat-induced level of hsp27 transcript (mRNA) appeared increased as compared to control, the protein level remained unaltered and nuclear localized. We infer that Lchsp27 may have significant role in the maintenance of cellular homeostasis, particularly, during summer months, when the fly remains exposed to high heat in its natural habitat. © 2015 Institute of Zoology, Chinese Academy of Sciences.

A fresh look at the male-specific region of the human Y chromosome.

PubMed

Jangravi, Zohreh; Alikhani, Mehdi; Arefnezhad, Babak; Sharifi Tabar, Mehdi; Taleahmad, Sara; Karamzadeh, Razieh; Jadaliha, Mahdieh; Mousavi, Seyed Ahmad; Ahmadi Rastegar, Diba; Parsamatin, Pouria; Vakilian, Haghighat; Mirshahvaladi, Shahab; Sabbaghian, Marjan; Mohseni Meybodi, Anahita; Mirzaei, Mehdi; Shahhoseini, Maryam; Ebrahimi, Marzieh; Piryaei, Abbas; Moosavi-Movahedi, Ali Akbar; Haynes, Paul A; Goodchild, Ann K; Nasr-Esfahani, Mohammad Hossein; Jabbari, Esmaiel; Baharvand, Hossein; Sedighi Gilani, Mohammad Ali; Gourabi, Hamid; Salekdeh, Ghasem Hosseini

2013-01-04

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome's length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein-protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping.

Implication of common and disease specific variants in CLU, CR1, and PICALM.

PubMed

Ferrari, Raffaele; Moreno, Jorge H; Minhajuddin, Abu T; O'Bryant, Sid E; Reisch, Joan S; Barber, Robert C; Momeni, Parastoo

2012-08-01

Two recent genome-wide association studies (GWAS) for late onset Alzheimer's disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects. We confirmed the association of rs3851179 (PICALM) (p = 7.4 × 10(-3)) with the disease status. Through sequencing we identified 18 variants in CLU, 3 of which were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only found in patients and the 16 variants identified in PICALM gene were present in both patients and controls. In silico analysis of the variants in PICALM did not predict any damaging effect on the protein. The haplotype analysis of the variants in each gene predicted a common haplotype when the 3 single nucleotide polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), respectively, were included. For each gene the haplotype structure and size differed between patients and controls. In conclusion, we confirmed association of CLU, CR1, and PICALM genes with the disease status in our cohort through identification of a number of disease-specific variants among patients through the sequencing of the coding region of these genes. Published by Elsevier Inc.

HIV1 V3 loop hypermutability is enhanced by the guanine usage bias in the part of env gene coding for it.

PubMed

Khrustalev, Vladislav Victorovich

2009-01-01

Guanine is the most mutable nucleotide in HIV genes because of frequently occurring G to A transitions, which are caused by cytosine deamination in viral DNA minus strands catalyzed by APOBEC enzymes. Distribution of guanine between three codon positions should influence the probability for G to A mutation to be nonsynonymous (to occur in first or second codon position). We discovered that nucleotide sequences of env genes coding for third variable regions (V3 loops) of gp120 from HIV1 and HIV2 have different kinds of guanine usage biases. In the HIV1 reference strain and 100 additionally analyzed HIV1 strains the guanine usage bias in V3 loop coding regions (2G>1G>3G) should lead to elevated nonsynonymous G to A transitions occurrence rates. In the HIV2 reference strain and 100 other HIV2 strains guanine usage bias in V3 loop coding regions (3G>2G>1G) should protect V3 loops from hypermutability. According to the HIV1 and HIV2 V3 alignment, insertion of the sequence enriched with 2G (21 codons in length) occurred during the evolution of HIV1 predecessor, while insertion of the different sequence enriched with 3G (19 codons in length) occurred during the evolution of HIV2 predecessor. The higher is the level of 3G in the V3 coding region, the lower should be the immune escaping mutation occurrence rates. This hypothesis was tested in this study by comparing the guanine usage in V3 loop coding regions from HIV1 fast and slow progressors. All calculations have been performed by our algorithms "VVK In length", "VVK Dinucleotides" and "VVK Consensus" (www.barkovsky.hotmail.ru).

The Mitochondrial Cytochrome Oxidase Subunit I Gene Occurs on a Minichromosome with Extensive Heteroplasmy in Two Species of Chewing Lice, Geomydoecus aurei and Thomomydoecus minor

PubMed Central

Pietan, Lucas L.; Spradling, Theresa A.

2016-01-01

In animals, mitochondrial DNA (mtDNA) typically occurs as a single circular chromosome with 13 protein-coding genes and 22 tRNA genes. The various species of lice examined previously, however, have shown mitochondrial genome rearrangements with a range of chromosome sizes and numbers. Our research demonstrates that the mitochondrial genomes of two species of chewing lice found on pocket gophers, Geomydoecus aurei and Thomomydoecus minor, are fragmented with the 1,536 base-pair (bp) cytochrome-oxidase subunit I (cox1) gene occurring as the only protein-coding gene on a 1,916–1,964 bp minicircular chromosome in the two species, respectively. The cox1 gene of T. minor begins with an atypical start codon, while that of G. aurei does not. Components of the non-protein coding sequence of G. aurei and T. minor include a tRNA (isoleucine) gene, inverted repeat sequences consistent with origins of replication, and an additional non-coding region that is smaller than the non-coding sequence of other lice with such fragmented mitochondrial genomes. Sequences of cox1 minichromosome clones for each species reveal extensive length and sequence heteroplasmy in both coding and noncoding regions. The highly variable non-gene regions of G. aurei and T. minor have little sequence similarity with one another except for a 19-bp region of phylogenetically conserved sequence with unknown function. PMID:27589589

The 1985 Army Experience Survey: Tabular Descriptions of First-Term Attritees. Volume 2

DTIC Science & Technology

1986-01-01

survey receipt control and sample management systems . Data were also keyed, edited, coded, and weighted. The coding schemes developed to classify... R136 REGION OF RESIDENCE WHEN YOU JOINED ARMY. .. ................. 272-273 049 El37 U TERMS OF ACTIVE ENLISTMENT .. ........ ................ 274...272 R136 -- REGION OF RESIDENCE WHEN YOU JOINED ARMY RECODED - WHAT STATE WERE YOU LIVING IN WHEN YOU JOINED THE ARMY! (RECODED TO REGION OF RSID) I

The 1985 Army Experience Survey: Tabular Descriptions of Enlisted Retirees. Volume 1

DTIC Science & Technology

1986-01-01

processed through survey receipt control and sample management systems . Data were also keyed, edited, coded, and weighted. The coding schemes...222-223 047A R135 AGE OF OLDEST CHILD .............-.-.-.-.-.-.-.-.-.-.-.-... . 224-225 048 R136 REGION OF RESIDENCE WHEN... R136 -- REGION OF RESIDENCE WHEN YOU JOINED ARMY 7 RECODED - WHAT STATE WERE YOU LIVING IN WHEN YOU JOItNED THE ARMY? (RECODED TO REGION OF RSID) I

RNAcode: Robust discrimination of coding and noncoding regions in comparative sequence data

PubMed Central

Washietl, Stefan; Findeiß, Sven; Müller, Stephan A.; Kalkhof, Stefan; von Bergen, Martin; Hofacker, Ivo L.; Stadler, Peter F.; Goldman, Nick

2011-01-01

With the availability of genome-wide transcription data and massive comparative sequencing, the discrimination of coding from noncoding RNAs and the assessment of coding potential in evolutionarily conserved regions arose as a core analysis task. Here we present RNAcode, a program to detect coding regions in multiple sequence alignments that is optimized for emerging applications not covered by current protein gene-finding software. Our algorithm combines information from nucleotide substitution and gap patterns in a unified framework and also deals with real-life issues such as alignment and sequencing errors. It uses an explicit statistical model with no machine learning component and can therefore be applied “out of the box,” without any training, to data from all domains of life. We describe the RNAcode method and apply it in combination with mass spectrometry experiments to predict and confirm seven novel short peptides in Escherichia coli and to analyze the coding potential of RNAs previously annotated as “noncoding.” RNAcode is open source software and available for all major platforms at http://wash.github.com/rnacode. PMID:21357752

RNAcode: robust discrimination of coding and noncoding regions in comparative sequence data.

PubMed

Washietl, Stefan; Findeiss, Sven; Müller, Stephan A; Kalkhof, Stefan; von Bergen, Martin; Hofacker, Ivo L; Stadler, Peter F; Goldman, Nick

2011-04-01

With the availability of genome-wide transcription data and massive comparative sequencing, the discrimination of coding from noncoding RNAs and the assessment of coding potential in evolutionarily conserved regions arose as a core analysis task. Here we present RNAcode, a program to detect coding regions in multiple sequence alignments that is optimized for emerging applications not covered by current protein gene-finding software. Our algorithm combines information from nucleotide substitution and gap patterns in a unified framework and also deals with real-life issues such as alignment and sequencing errors. It uses an explicit statistical model with no machine learning component and can therefore be applied "out of the box," without any training, to data from all domains of life. We describe the RNAcode method and apply it in combination with mass spectrometry experiments to predict and confirm seven novel short peptides in Escherichia coli and to analyze the coding potential of RNAs previously annotated as "noncoding." RNAcode is open source software and available for all major platforms at http://wash.github.com/rnacode.

Extension of the XGC code for global gyrokinetic simulations in stellarator geometry

NASA Astrophysics Data System (ADS)

Cole, Michael; Moritaka, Toseo; White, Roscoe; Hager, Robert; Ku, Seung-Hoe; Chang, Choong-Seock

2017-10-01

In this work, the total-f, gyrokinetic particle-in-cell code XGC is extended to treat stellarator geometries. Improvements to meshing tools and the code itself have enabled the first physics studies, including single particle tracing and flux surface mapping in the magnetic geometry of the heliotron LHD and quasi-isodynamic stellarator Wendelstein 7-X. These have provided the first successful test cases for our approach. XGC is uniquely placed to model the complex edge physics of stellarators. A roadmap to such a global confinement modeling capability will be presented. Single particle studies will include the physics of energetic particles' global stochastic motions and their effect on confinement. Good confinement of energetic particles is vital for a successful stellarator reactor design. These results can be compared in the core region with those of other codes, such as ORBIT3d. In subsequent work, neoclassical transport and turbulence can then be considered and compared to results from codes such as EUTERPE and GENE. After sufficient verification in the core region, XGC will move into the stellarator edge region including the material wall and neutral particle recycling.

30 CFR 250.1495 - How do I demonstrate financial solvency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 99503-5823, jeffrey,[email protected], (907) 334-5300. (2) For Gulf of Mexico and Atlantic OCS: Joshua Joyce, Regional FARM Program Coordinator, BOEMRE Gulf of Mexico OCS Region, 1201 Elmwood Park Boulevard... provision of the U.S. Bankruptcy Code (Title 11 of the United States Code), or BOEMRE notifies you that you...

30 CFR 250.1495 - How do I demonstrate financial solvency?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., [email protected], (907) 334-5300. (2) For Gulf of Mexico and Atlantic OCS: Joshua Joyce, Regional FARM Program Coordinator, BOEM Gulf of Mexico OCS Region, 1201 Elmwood Park Boulevard New Orleans, LA.... Bankruptcy Code (Title 11 of the United States Code), or BSEE notifies you that you must redemonstrate...

30 CFR 250.1495 - How do I demonstrate financial solvency?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., [email protected], (907) 334-5300. (2) For Gulf of Mexico and Atlantic OCS: Joshua Joyce, Regional FARM Program Coordinator, BOEM Gulf of Mexico OCS Region, 1201 Elmwood Park Boulevard New Orleans, LA.... Bankruptcy Code (Title 11 of the United States Code), or BSEE notifies you that you must redemonstrate...

30 CFR 250.1495 - How do I demonstrate financial solvency?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., [email protected], (907) 334-5300. (2) For Gulf of Mexico and Atlantic OCS: Joshua Joyce, Regional FARM Program Coordinator, BOEM Gulf of Mexico OCS Region, 1201 Elmwood Park Boulevard New Orleans, LA.... Bankruptcy Code (Title 11 of the United States Code), or BSEE notifies you that you must redemonstrate...

Expressed gene sequence of the IFN-gamma-response chemokine CXCL9 of cattle, horses, and swine

USDA-ARS?s Scientific Manuscript database

This report describes the cloning and characterization of expressed gene sequences of bovine, equine, and swine CXCL9 from RNA obtained from peripheral blood mononuclear cell (PBMC) or other tissues. The bovine coding region was 378 nucleotides in length, while the equine and swine coding regions w...

A Partial Least Squares Based Procedure for Upstream Sequence Classification in Prokaryotes.

PubMed

Mehmood, Tahir; Bohlin, Jon; Snipen, Lars

2015-01-01

The upstream region of coding genes is important for several reasons, for instance locating transcription factor, binding sites, and start site initiation in genomic DNA. Motivated by a recently conducted study, where multivariate approach was successfully applied to coding sequence modeling, we have introduced a partial least squares (PLS) based procedure for the classification of true upstream prokaryotic sequence from background upstream sequence. The upstream sequences of conserved coding genes over genomes were considered in analysis, where conserved coding genes were found by using pan-genomics concept for each considered prokaryotic species. PLS uses position specific scoring matrix (PSSM) to study the characteristics of upstream region. Results obtained by PLS based method were compared with Gini importance of random forest (RF) and support vector machine (SVM), which is much used method for sequence classification. The upstream sequence classification performance was evaluated by using cross validation, and suggested approach identifies prokaryotic upstream region significantly better to RF (p-value < 0.01) and SVM (p-value < 0.01). Further, the proposed method also produced results that concurred with known biological characteristics of the upstream region.

Association of Amine-Receptor DNA Sequence Variants with Associative Learning in the Honeybee.

PubMed

Lagisz, Malgorzata; Mercer, Alison R; de Mouzon, Charlotte; Santos, Luana L S; Nakagawa, Shinichi

2016-03-01

Octopamine- and dopamine-based neuromodulatory systems play a critical role in learning and learning-related behaviour in insects. To further our understanding of these systems and resulting phenotypes, we quantified DNA sequence variations at six loci coding octopamine-and dopamine-receptors and their association with aversive and appetitive learning traits in a population of honeybees. We identified 79 polymorphic sequence markers (mostly SNPs and a few insertions/deletions) located within or close to six candidate genes. Intriguingly, we found that levels of sequence variation in the protein-coding regions studied were low, indicating that sequence variation in the coding regions of receptor genes critical to learning and memory is strongly selected against. Non-coding and upstream regions of the same genes, however, were less conserved and sequence variations in these regions were weakly associated with between-individual differences in learning-related traits. While these associations do not directly imply a specific molecular mechanism, they suggest that the cross-talk between dopamine and octopamine signalling pathways may influence olfactory learning and memory in the honeybee.

The effect of cost construction based on either DRG or ICD-9 codes or risk group stratification on the resulting cost-effectiveness ratios.

PubMed

Chumney, Elinor C G; Biddle, Andrea K; Simpson, Kit N; Weinberger, Morris; Magruder, Kathryn M; Zelman, William N

2004-01-01

As cost-effectiveness analyses (CEAs) are increasingly used to inform policy decisions, there is a need for more information on how different cost determination methods affect cost estimates and the degree to which the resulting cost-effectiveness ratios (CERs) may be affected. The lack of specificity of diagnosis-related groups (DRGs) could mean that they are ill-suited for costing applications in CEAs. Yet, the implications of using International Classification of Diseases-9th edition (ICD-9) codes or a form of disease-specific risk group stratification instead of DRGs has yet to be clearly documented. To demonstrate the implications of different disease coding mechanisms on costs and the magnitude of error that could be introduced in head-to-head comparisons of resulting CERs. We based our analyses on a previously published Markov model for HIV/AIDS therapies. We used the Healthcare Cost and Utilisation Project Nationwide Inpatient Sample (HCUP-NIS) data release 6, which contains all-payer data on hospital inpatient stays from selected states. We added costs for the mean number of hospitalisations, derived from analyses based on either DRG or ICD-9 codes or risk group stratification cost weights, to the standard outpatient and prescription drug costs to yield an estimate of total charges for each AIDS-defining illness (ADI). Finally, we estimated the Markov model three times with the appropriate ADI cost weights to obtain CERs specific to the use of either DRG or ICD-9 codes or risk group. Contrary to expectations, we found that the choice of coding/grouping assumptions that are disease-specific by either DRG codes, ICD-9 codes or risk group resulted in very similar CER estimates for highly active antiretroviral therapy. The large variations in the specific ADI cost weights across the three different coding approaches was especially interesting. However, because no one approach produced consistently higher estimates than the others, the Markov model's weighted cost per event and resulting CERs were remarkably close in value to one another. Although DRG codes are based on broader categories and contain less information than ICD-9 codes, in practice the choice of whether to use DRGs or ICD-9 codes may have little effect on the CEA results in heterogeneous conditions such as HIV/AIDS.

Lossy to lossless object-based coding of 3-D MRI data.

PubMed

Menegaz, Gloria; Thiran, Jean-Philippe

2002-01-01

We propose a fully three-dimensional (3-D) object-based coding system exploiting the diagnostic relevance of the different regions of the volumetric data for rate allocation. The data are first decorrelated via a 3-D discrete wavelet transform. The implementation via the lifting steps scheme allows to map integer-to-integer values, enabling lossless coding, and facilitates the definition of the object-based inverse transform. The coding process assigns disjoint segments of the bitstream to the different objects, which can be independently accessed and reconstructed at any up-to-lossless quality. Two fully 3-D coding strategies are considered: embedded zerotree coding (EZW-3D) and multidimensional layered zero coding (MLZC), both generalized for region of interest (ROI)-based processing. In order to avoid artifacts along region boundaries, some extra coefficients must be encoded for each object. This gives rise to an overheading of the bitstream with respect to the case where the volume is encoded as a whole. The amount of such extra information depends on both the filter length and the decomposition depth. The system is characterized on a set of head magnetic resonance images. Results show that MLZC and EZW-3D have competitive performances. In particular, the best MLZC mode outperforms the others state-of-the-art techniques on one of the datasets for which results are available in the literature.

DoD STINFO Manager Training Course STINFO Documentation

DTIC Science & Technology

2002-05-01

nawcws2.wsmr.army.mil PENNSYLVANIA ONR Manufacturing Technology Det Carderock Div NAVSURFWARCEN Attn: Philip M. Broudy (Code 20) John Bozewicz (Code 911...Available NTIS; 91N33013.) AD-A252 069 11 Pinelli, Thomas E.; Madeline Henderson; Ann P. Bishop; and Philip Doty. Chronology of Selected Literature...Mindy L Kotler . "Japanese Tech- nological Innovation: Implications for Large Commercial Aircraft and Knowledge Diffusion." Paper presented at the

Implications for Language Diversity in Instruction in the Context of Target Language Classrooms: Development of a Preliminary Model of the Effectiveness of Teacher Code-Switching

ERIC Educational Resources Information Center

Lee, Jang Ho

2012-01-01

This paper concerns the conceptual and pedagogical issues that revolve around target language (TL) only instruction and teacher code-switching in the context of TL classrooms. To this end, I first examine four intertwined ideas (that is, monolingualism, naturalism, native-speakerism, and absolutism) that run through the monolingual approach to TL…

Understanding the Code: acting in a patient's best interests.

PubMed

Griffith, Richard

2015-09-01

The revised Code of the Nursing and Midwifery Council (NMC), the statutory professional regulator for registered district nurses, makes clear that while district nurses can interpret the values and principles for use in community settings, the standards are not negotiable or discretionary. They must be applied or the district nurse's fitness to practice will be called into question. In this article in the continuing series analysing the legal implications of the Code on district nurse practice, the author considers the fourth standard that requires district nurses to act in the best interests of people at all times.

A computational and theoretical analysis of falling frequency VLF emissions

NASA Astrophysics Data System (ADS)

Nunn, David; Omura, Yoshiharu

2012-08-01

Recently much progress has been made in the simulation and theoretical understanding of rising frequency triggered emissions and rising chorus. Both PIC and Vlasov VHS codes produce risers in the region downstream from the equator toward which the VLF waves are traveling. The VHS code only produces fallers or downward hooks with difficulty due to the coherent nature of wave particle interaction across the equator. With the VHS code we now confine the interaction region to be the region upstream from the equator, where inhomogeneity factor S is positive. This suppresses correlated wave particle interaction effects across the equator and the tendency of the code to trigger risers, and permits the formation of a proper falling tone generation region. The VHS code now easily and reproducibly triggers falling tones. The evolution of resonant particle current JE in space and time shows a generation point at -5224 km and the wavefield undergoes amplification of some 25 dB in traversing the nonlinear generation region. The current component parallel to wave magnetic field (JB) is positive, whereas it is negative for risers. The resonant particle trap shows an enhanced distribution function or `hill', whereas risers have a `hole'. According to recent theory (Omura et al., 2008, 2009) sweeping frequency is due primarily to the advective term. The nonlinear frequency shift term is now negative (˜-12 Hz) and the sweep rate of -800 Hz/s is approximately nonlinear frequency shift divided by TN, the transition time, of the order of a trapping time.

Categorical encoding of color in the brain.

PubMed

Bird, Chris M; Berens, Samuel C; Horner, Aidan J; Franklin, Anna

2014-03-25

The areas of the brain that encode color categorically have not yet been reliably identified. Here, we used functional MRI adaptation to identify neuronal populations that represent color categories irrespective of metric differences in color. Two colors were successively presented within a block of trials. The two colors were either from the same or different categories (e.g., "blue 1 and blue 2" or "blue 1 and green 1"), and the size of the hue difference was varied. Participants performed a target detection task unrelated to the difference in color. In the middle frontal gyrus of both hemispheres and to a lesser extent, the cerebellum, blood-oxygen level-dependent response was greater for colors from different categories relative to colors from the same category. Importantly, activation in these regions was not modulated by the size of the hue difference, suggesting that neurons in these regions represent color categorically, regardless of metric color difference. Representational similarity analyses, which investigated the similarity of the pattern of activity across local groups of voxels, identified other regions of the brain (including the visual cortex), which responded to metric but not categorical color differences. Therefore, categorical and metric hue differences appear to be coded in qualitatively different ways and in different brain regions. These findings have implications for the long-standing debate on the origin and nature of color categories, and also further our understanding of how color is processed by the brain.

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

Strauss, H.R.

This paper describes the code FEMHD, an adaptive finite element MHD code, which is applied in a number of different manners to model MHD behavior and edge plasma phenomena on a diverted tokamak. The code uses an unstructured triangular mesh in 2D and wedge shaped mesh elements in 3D. The code has been adapted to look at neutral and charged particle dynamics in the plasma scrape off region, and into a full MHD-particle code.

Unfiltered Talk--A Challenge to Categories.

ERIC Educational Resources Information Center

McCormick, Kay

A study investigated how and why code switching and mixing occurs between English and Afrikaans in a region of South Africa. In District Six, non-standard Afrikaans seems to be a mixed code, and it is unclear whether non-standard English is a mixed code. Consequently, it is unclear when codes are being switched or mixed. The analysis looks at…

A Catalogue of Putative cis-Regulatory Interactions Between Long Non-coding RNAs and Proximal Coding Genes Based on Correlative Analysis Across Diverse Human Tumors.

PubMed

Basu, Swaraj; Larsson, Erik

2018-05-31

Antisense transcripts and other long non-coding RNAs are pervasive in mammalian cells, and some of these molecules have been proposed to regulate proximal protein-coding genes in cis For example, non-coding transcription can contribute to inactivation of tumor suppressor genes in cancer, and antisense transcripts have been implicated in the epigenetic inactivation of imprinted genes. However, our knowledge is still limited and more such regulatory interactions likely await discovery. Here, we make use of available gene expression data from a large compendium of human tumors to generate hypotheses regarding non-coding-to-coding cis -regulatory relationships with emphasis on negative associations, as these are less likely to arise for reasons other than cis -regulation. We document a large number of possible regulatory interactions, including 193 coding/non-coding pairs that show expression patterns compatible with negative cis -regulation. Importantly, by this approach we capture several known cases, and many of the involved coding genes have known roles in cancer. Our study provides a large catalog of putative non-coding/coding cis -regulatory pairs that may serve as a basis for further experimental validation and characterization. Copyright © 2018 Basu and Larsson.

Functional interrogation of non-coding DNA through CRISPR genome editing.

PubMed

Canver, Matthew C; Bauer, Daniel E; Orkin, Stuart H

2017-05-15

Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of code expanding optimizations on instruction cache design

NASA Technical Reports Server (NTRS)

Chen, William Y.; Chang, Pohua P.; Conte, Thomas M.; Hwu, Wen-Mei W.

1991-01-01

It is shown that code expanding optimizations have strong and non-intuitive implications on instruction cache design. Three types of code expanding optimizations are studied: instruction placement, function inline expansion, and superscalar optimizations. Overall, instruction placement reduces the miss ratio of small caches. Function inline expansion improves the performance for small cache sizes, but degrades the performance of medium caches. Superscalar optimizations increases the cache size required for a given miss ratio. On the other hand, they also increase the sequentiality of instruction access so that a simple load-forward scheme effectively cancels the negative effects. Overall, it is shown that with load forwarding, the three types of code expanding optimizations jointly improve the performance of small caches and have little effect on large caches.

Do plant cell walls have a code?

PubMed

Tavares, Eveline Q P; Buckeridge, Marcos S

2015-12-01

A code is a set of rules that establish correspondence between two worlds, signs (consisting of encrypted information) and meaning (of the decrypted message). A third element, the adaptor, connects both worlds, assigning meaning to a code. We propose that a Glycomic Code exists in plant cell walls where signs are represented by monosaccharides and phenylpropanoids and meaning is cell wall architecture with its highly complex association of polymers. Cell wall biosynthetic mechanisms, structure, architecture and properties are addressed according to Code Biology perspective, focusing on how they oppose to cell wall deconstruction. Cell wall hydrolysis is mainly focused as a mechanism of decryption of the Glycomic Code. Evidence for encoded information in cell wall polymers fine structure is highlighted and the implications of the existence of the Glycomic Code are discussed. Aspects related to fine structure are responsible for polysaccharide packing and polymer-polymer interactions, affecting the final cell wall architecture. The question whether polymers assembly within a wall display similar properties as other biological macromolecules (i.e. proteins, DNA, histones) is addressed, i.e. do they display a code? Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Different evolutionary patterns of SNPs between domains and unassigned regions in human protein-coding sequences.

PubMed

Pang, Erli; Wu, Xiaomei; Lin, Kui

2016-06-01

Protein evolution plays an important role in the evolution of each genome. Because of their functional nature, in general, most of their parts or sites are differently constrained selectively, particularly by purifying selection. Most previous studies on protein evolution considered individual proteins in their entirety or compared protein-coding sequences with non-coding sequences. Less attention has been paid to the evolution of different parts within each protein of a given genome. To this end, based on PfamA annotation of all human proteins, each protein sequence can be split into two parts: domains or unassigned regions. Using this rationale, single nucleotide polymorphisms (SNPs) in protein-coding sequences from the 1000 Genomes Project were mapped according to two classifications: SNPs occurring within protein domains and those within unassigned regions. With these classifications, we found: the density of synonymous SNPs within domains is significantly greater than that of synonymous SNPs within unassigned regions; however, the density of non-synonymous SNPs shows the opposite pattern. We also found there are signatures of purifying selection on both the domain and unassigned regions. Furthermore, the selective strength on domains is significantly greater than that on unassigned regions. In addition, among all of the human protein sequences, there are 117 PfamA domains in which no SNPs are found. Our results highlight an important aspect of protein domains and may contribute to our understanding of protein evolution.

Statistical and linguistic features of DNA sequences

NASA Technical Reports Server (NTRS)

Havlin, S.; Buldyrev, S. V.; Goldberger, A. L.; Mantegna, R. N.; Peng, C. K.; Simons, M.; Stanley, H. E.

1995-01-01

We present evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationary" feature of the sequence of base pairs by applying a new algorithm called Detrended Fluctuation Analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and noncoding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to all eukaryotic DNA sequences (33 301 coding and 29 453 noncoding) in the entire GenBank database. We describe a simple model to account for the presence of long-range power-law correlations which is based upon a generalization of the classic Levy walk. Finally, we describe briefly some recent work showing that the noncoding sequences have certain statistical features in common with natural languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function. We suggest that noncoding regions in plants and invertebrates may display a smaller entropy and larger redundancy than coding regions, further supporting the possibility that noncoding regions of DNA may carry biological information.

76 FR 27622 - Approval and Promulgation of State Implementation Plan Revisions; Infrastructure Requirements for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-12

...), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver, Colorado 80202-1129. Hand Delivery: Director, Air Program, Environmental Protection Agency (EPA), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver..., Denver, Colorado 80202-1129. EPA requests that if at all possible, you contact the individual listed in...

A biological inspired fuzzy adaptive window median filter (FAWMF) for enhancing DNA signal processing.

PubMed

Ahmad, Muneer; Jung, Low Tan; Bhuiyan, Al-Amin

2017-10-01

Digital signal processing techniques commonly employ fixed length window filters to process the signal contents. DNA signals differ in characteristics from common digital signals since they carry nucleotides as contents. The nucleotides own genetic code context and fuzzy behaviors due to their special structure and order in DNA strand. Employing conventional fixed length window filters for DNA signal processing produce spectral leakage and hence results in signal noise. A biological context aware adaptive window filter is required to process the DNA signals. This paper introduces a biological inspired fuzzy adaptive window median filter (FAWMF) which computes the fuzzy membership strength of nucleotides in each slide of window and filters nucleotides based on median filtering with a combination of s-shaped and z-shaped filters. Since coding regions cause 3-base periodicity by an unbalanced nucleotides' distribution producing a relatively high bias for nucleotides' usage, such fundamental characteristic of nucleotides has been exploited in FAWMF to suppress the signal noise. Along with adaptive response of FAWMF, a strong correlation between median nucleotides and the Π shaped filter was observed which produced enhanced discrimination between coding and non-coding regions contrary to fixed length conventional window filters. The proposed FAWMF attains a significant enhancement in coding regions identification i.e. 40% to 125% as compared to other conventional window filters tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms. This study proves that conventional fixed length window filters applied to DNA signals do not achieve significant results since the nucleotides carry genetic code context. The proposed FAWMF algorithm is adaptive and outperforms significantly to process DNA signal contents. The algorithm applied to variety of DNA datasets produced noteworthy discrimination between coding and non-coding regions contrary to fixed window length conventional filters. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations

PubMed Central

Araya, Carlos L.; Cenik, Can; Reuter, Jason A.; Kiss, Gert; Pande, Vijay S.; Snyder, Michael P.; Greenleaf, William J.

2015-01-01

Cancer sequencing studies have primarily identified cancer-driver genes by the accumulation of protein-altering mutations. An improved method would be annotation-independent, sensitive to unknown distributions of functions within proteins, and inclusive of non-coding drivers. We employed density-based clustering methods in 21 tumor types to detect variably-sized significantly mutated regions (SMRs). SMRs reveal recurrent alterations across a spectrum of coding and non-coding elements, including transcription factor binding sites and untranslated regions mutated in up to ∼15% of specific tumor types. SMRs reveal spatial clustering of mutations at molecular domains and interfaces, often with associated changes in signaling. Mutation frequencies in SMRs demonstrate that distinct protein regions are differentially mutated among tumor types, as exemplified by a linker region of PIK3CA in which biophysical simulations suggest mutations affect regulatory interactions. The functional diversity of SMRs underscores both the varied mechanisms of oncogenic misregulation and the advantage of functionally-agnostic driver identification. PMID:26691984

Ethanol-BDNF interactions: Still More Questions than Answers

PubMed Central

Davis, Margaret I.

2008-01-01

Brain Derived Neurotrophic Factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through decreased expression of BDNF or through inability of the receptor to transduce signals in the presence of ethanol. In contrast, recent studies implicate region-specific up-regulation of BDNF and associated signaling pathways in anxiety, addiction and homeostasis after ethanol exposure. Anxiety and depression are precipitating factors for substance abuse and these disorders also involve region-specific changes in BDNF in both pathogenesis and response to pharmacotherapy. Polymorphisms in the genes coding for BDNF and its receptor TrkB are linked to affective, substance abuse and appetitive disorders and therefore may play a role in the development of alcoholism. This review summarizes historical and pre-clinical data on BDNF and TrkB as it relates to ethanol toxicity and addiction. Many unresolved questions about region-specific changes in BDNF expression and the precise role of BDNF in neuropsychiatric disorders and addiction remain to be elucidated. Resolution of these questions will require significant integration of the literature on addiction and comorbid psychiatric disorders that contribute to the development of alcoholism. PMID:18394710

GUMAP: A GUPIXWIN-compatible code for extracting regional spectra from nuclear microbeam list mode files

NASA Astrophysics Data System (ADS)

Russell, John L.; Campbell, John L.; Boyd, Nicholas I.; Dias, Johnny F.

2018-02-01

The newly developed GUMAP software creates element maps from OMDAQ list mode files, displays these maps individually or collectively, and facilitates on-screen definitions of specified regions from which a PIXE spectrum can be built. These include a free-hand region defined by moving the cursor. The regional charge is entered automatically into the spectrum file in a new GUPIXWIN-compatible format, enabling a GUPIXWIN analysis of the spectrum. The code defaults to the OMDAQ dead time treatment but also facilitates two other methods for dead time correction in sample regions with count rates different from the average.

A two-locus global DNA barcode for land plants: the coding rbcL gene complements the non-coding trnH-psbA spacer region.

PubMed

Kress, W John; Erickson, David L

2007-06-06

A useful DNA barcode requires sufficient sequence variation to distinguish between species and ease of application across a broad range of taxa. Discovery of a DNA barcode for land plants has been limited by intrinsically lower rates of sequence evolution in plant genomes than that observed in animals. This low rate has complicated the trade-off in finding a locus that is universal and readily sequenced and has sufficiently high sequence divergence at the species-level. Here, a global plant DNA barcode system is evaluated by comparing universal application and degree of sequence divergence for nine putative barcode loci, including coding and non-coding regions, singly and in pairs across a phylogenetically diverse set of 48 genera (two species per genus). No single locus could discriminate among species in a pair in more than 79% of genera, whereas discrimination increased to nearly 88% when the non-coding trnH-psbA spacer was paired with one of three coding loci, including rbcL. In silico trials were conducted in which DNA sequences from GenBank were used to further evaluate the discriminatory power of a subset of these loci. These trials supported the earlier observation that trnH-psbA coupled with rbcL can correctly identify and discriminate among related species. A combination of the non-coding trnH-psbA spacer region and a portion of the coding rbcL gene is recommended as a two-locus global land plant barcode that provides the necessary universality and species discrimination.

Theory-based model for the pedestal, edge stability and ELMs in tokamaks

NASA Astrophysics Data System (ADS)

Pankin, A. Y.; Bateman, G.; Brennan, D. P.; Schnack, D. D.; Snyder, P. B.; Voitsekhovitch, I.; Kritz, A. H.; Janeschitz, G.; Kruger, S.; Onjun, T.; Pacher, G. W.; Pacher, H. D.

2006-04-01

An improved model for triggering edge localized mode (ELM) crashes is developed for use within integrated modelling simulations of the pedestal and ELM cycles at the edge of H-mode tokamak plasmas. The new model is developed by using the BALOO, DCON and ELITE ideal MHD stability codes to derive parametric expressions for the ELM triggering threshold. The whole toroidal mode number spectrum is studied with these codes. The DCON code applies to low mode numbers, while the BALOO code applies to only high mode numbers and the ELITE code applies to intermediate and high mode numbers. The variables used in the parametric stability expressions are the normalized pressure gradient and the parallel current density, which drive ballooning and peeling modes. Two equilibria motivated by DIII-D geometry with different plasma triangularities are studied. It is found that the stable region in the high triangularity discharge covers a much larger region of parameter space than the corresponding stability region in the low triangularity discharge. The new ELM trigger model is used together with a previously developed model for pedestal formation and ELM crashes in the ASTRA integrated modelling code to follow the time evolution of the temperature profiles during ELM cycles. The ELM frequencies obtained in the simulations of low and high triangularity discharges are observed to increase with increasing heating power. There is a transition from second stability to first ballooning mode stability as the heating power is increased in the high triangularity simulations. The results from the ideal MHD stability codes are compared with results from the resistive MHD stability code NIMROD.

XGC developments for a more efficient XGC-GENE code coupling

NASA Astrophysics Data System (ADS)

Dominski, Julien; Hager, Robert; Ku, Seung-Hoe; Chang, Cs

2017-10-01

In the Exascale Computing Program, the High-Fidelity Whole Device Modeling project initially aims at delivering a tightly-coupled simulation of plasma neoclassical and turbulence dynamics from the core to the edge of the tokamak. To permit such simulations, the gyrokinetic codes GENE and XGC will be coupled together. Numerical efforts are made to improve the numerical schemes agreement in the coupling region. One of the difficulties of coupling those codes together is the incompatibility of their grids. GENE is a continuum grid-based code and XGC is a Particle-In-Cell code using unstructured triangular mesh. A field-aligned filter is thus implemented in XGC. Even if XGC originally had an approximately field-following mesh, this field-aligned filter permits to have a perturbation discretization closer to the one solved in the field-aligned code GENE. Additionally, new XGC gyro-averaging matrices are implemented on a velocity grid adapted to the plasma properties, thus ensuring same accuracy from the core to the edge regions.

Network perturbation by recurrent regulatory variants in cancer

PubMed Central

Cho, Ara; Lee, Insuk; Choi, Jung Kyoon

2017-01-01

Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes. PMID:28333928

Snake mitochondrial genomes: phylogenetic relationships and implications of extended taxon sampling for interpretations of mitogenomic evolution

PubMed Central

2010-01-01

Background Snake mitochondrial genomes are of great interest in understanding mitogenomic evolution because of gene duplications and rearrangements and the fast evolutionary rate of their genes compared to other vertebrates. Mitochondrial gene sequences have also played an important role in attempts to resolve the contentious phylogenetic relationships of especially the early divergences among alethinophidian snakes. Two recent innovative studies found dramatic gene- and branch-specific relative acceleration in snake protein-coding gene evolution, particularly along internal branches leading to Serpentes and Alethinophidia. It has been hypothesized that some of these rate shifts are temporally (and possibly causally) associated with control region duplication and/or major changes in ecology and anatomy. Results The near-complete mitochondrial (mt) genomes of three henophidian snakes were sequenced: Anilius scytale, Rhinophis philippinus, and Charina trivirgata. All three genomes share a duplicated control region and translocated tRNALEU, derived features found in all alethinophidian snakes studied to date. The new sequence data were aligned with mt genome data for 21 other species of snakes and used in phylogenetic analyses. Phylogenetic results agreed with many other studies in recovering several robust clades, including Colubroidea, Caenophidia, and Cylindrophiidae+Uropeltidae. Nodes within Henophidia that have been difficult to resolve robustly in previous analyses remained uncompellingly resolved here. Comparisons of relative rates of evolution of rRNA vs. protein-coding genes were conducted by estimating branch lengths across the tree. Our expanded sampling revealed dramatic acceleration along the branch leading to Typhlopidae, particularly long rRNA terminal branches within Scolecophidia, and that most of the dramatic acceleration in protein-coding gene rate along Serpentes and Alethinophidia branches occurred before Anilius diverged from other alethinophidians. Conclusions Mitochondrial gene sequence data alone may not be able to robustly resolve basal divergences among alethinophidian snakes. Taxon sampling plays an important role in identifying mitogenomic evolutionary events within snakes, and in testing hypotheses explaining their origin. Dramatic rate shifts in mitogenomic evolution occur within Scolecophidia as well as Alethinophidia, thus falsifying the hypothesis that these shifts in snakes are associated exclusively with evolution of a non-burrowing lifestyle, macrostomatan feeding ecology and/or duplication of the control region, both restricted to alethinophidians among living snakes. PMID:20055998

Tau mRNA 3'UTR-to-CDS ratio is increased in Alzheimer disease.

PubMed

García-Escudero, Vega; Gargini, Ricardo; Martín-Maestro, Patricia; García, Esther; García-Escudero, Ramón; Avila, Jesús

2017-08-10

Neurons frequently show an imbalance in expression of the 3' untranslated region (3'UTR) relative to the coding DNA sequence (CDS) region of mature messenger RNAs (mRNA). The ratio varies among different cells or parts of the brain. The Map2 protein levels per cell depend on the 3'UTR-to-CDS ratio rather than the total mRNA amount, which suggests powerful regulation of protein expression by 3'UTR sequences. Here we found that MAPT (the microtubule-associated protein tau gene) 3'UTR levels are particularly high with respect to other genes; indeed, the 3'UTR-to-CDS ratio of MAPT is balanced in healthy brain in mouse and human. The tau protein accumulates in Alzheimer diseased brain. We nonetheless observed that the levels of RNA encoding MAPT/tau were diminished in these patients' brains. To explain this apparently contradictory result, we studied MAPT mRNA stoichiometry in coding and non-coding regions, and found that the 3'UTR-to-CDS ratio was higher in the hippocampus of Alzheimer disease patients, with higher tau protein but lower total mRNA levels. Our data indicate that changes in the 3'UTR-to-CDS ratio have a regulatory role in the disease. Future research should thus consider not only mRNA levels, but also the ratios between coding and non-coding regions. Copyright © 2017 Elsevier B.V. All rights reserved.

The Comprehensive AOCMF Classification: Skull Base and Cranial Vault Fractures – Level 2 and 3 Tutorial

PubMed Central

Ieva, Antonio Di; Audigé, Laurent; Kellman, Robert M.; Shumrick, Kevin A.; Ringl, Helmut; Prein, Joachim; Matula, Christian

2014-01-01

The AOCMF Classification Group developed a hierarchical three-level craniomaxillofacial classification system with increasing level of complexity and details. The highest level 1 system distinguish four major anatomical units, including the mandible (code 91), midface (code 92), skull base (code 93), and cranial vault (code 94). This tutorial presents the level 2 and more detailed level 3 systems for the skull base and cranial vault units. The level 2 system describes fracture location outlining the topographic boundaries of the anatomic regions, considering in particular the endocranial and exocranial skull base surfaces. The endocranial skull base is divided into nine regions; a central skull base adjoining a left and right side are divided into the anterior, middle, and posterior skull base. The exocranial skull base surface and cranial vault are divided in regions defined by the names of the bones involved: frontal, parietal, temporal, sphenoid, and occipital bones. The level 3 system allows assessing fracture morphology described by the presence of fracture fragmentation, displacement, and bone loss. A documentation of associated intracranial diagnostic features is proposed. This tutorial is organized in a sequence of sections dealing with the description of the classification system with illustrations of the topographical skull base and cranial vault regions along with rules for fracture location and coding, a series of case examples with clinical imaging and a general discussion on the design of this classification. PMID:25489394

Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate

PubMed Central

Juul, Malene; Bertl, Johanna; Guo, Qianyun; Nielsen, Morten Muhlig; Świtnicki, Michał; Hornshøj, Henrik; Madsen, Tobias; Hobolth, Asger; Pedersen, Jakob Skou

2017-01-01

Non-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here, we develop a statistically founded non-coding driver-detection method, ncdDetect, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using ncdDetect, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n = 505), which top-ranked known drivers and identified new candidates. For individual candidates, presence of non-coding mutations associates with altered expression or decreased patient survival across an independent pan-cancer sample set (n = 5454). This includes an antigen-presenting gene (CD1A), where 5’UTR mutations correlate significantly with decreased survival in melanoma. Additionally, mutations in a base-excision-repair gene (SMUG1) correlate with a C-to-T mutational-signature. Overall, we find that a rich model of mutational heterogeneity facilitates non-coding driver identification and integrative analysis points to candidates of potential clinical relevance. DOI: http://dx.doi.org/10.7554/eLife.21778.001 PMID:28362259

Attention enhances multi-voxel representation of novel objects in frontal, parietal and visual cortices.

PubMed

Woolgar, Alexandra; Williams, Mark A; Rich, Anina N

2015-04-01

Selective attention is fundamental for human activity, but the details of its neural implementation remain elusive. One influential theory, the adaptive coding hypothesis (Duncan, 2001, An adaptive coding model of neural function in prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single neurons in certain frontal and parietal regions dynamically adjust their responses to selectively encode relevant information. This selective representation may in turn support selective processing in more specialized brain regions such as the visual cortices. Here, we use multi-voxel decoding of functional magnetic resonance images to demonstrate selective representation of attended--and not distractor--objects in frontal, parietal, and visual cortices. In addition, we highlight a critical role for task demands in determining which brain regions exhibit selective coding. Strikingly, representation of attended objects in frontoparietal cortex was highest under conditions of high perceptual demand, when stimuli were hard to perceive and coding in early visual cortex was weak. Coding in early visual cortex varied as a function of attention and perceptual demand, while coding in higher visual areas was sensitive to the allocation of attention but robust to changes in perceptual difficulty. Consistent with high-profile reports, peripherally presented objects could also be decoded from activity at the occipital pole, a region which corresponds to the fovea. Our results emphasize the flexibility of frontoparietal and visual systems. They support the hypothesis that attention enhances the multi-voxel representation of information in the brain, and suggest that the engagement of this attentional mechanism depends critically on current task demands. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.

PubMed

Nudel, R; Simpson, N H; Baird, G; O'Hare, A; Conti-Ramsden, G; Bolton, P F; Hennessy, E R; Ring, S M; Davey Smith, G; Francks, C; Paracchini, S; Monaco, A P; Fisher, S E; Newbury, D F

2014-04-01

Specific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 (P = 3.74 × 10(-8)) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10(-7)). A subsequent targeted association of six single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Maternal Disrupted Communication During Face-to-Face Interaction at 4 months: Relation to Maternal and Infant Cortisol Among at-Risk Families.

PubMed

Crockett, Erin E; Holmes, Bjarne M; Granger, Douglas A; Lyons-Ruth, Karlen

2013-11-01

The study evaluated the association between maternal disrupted communication and the reactivity and regulation of the psychobiology of the stress response in infancy. Mothers and infants were recruited via the National Health Service from the 20% most economically impoverished data zones in a suburban region of Scotland. Mothers ( N = 63; M age = 25.9) and their 4-month-old infants (35 boys, 28 girls) were videotaped interacting for 8 min, including a still-face procedure as a stress inducer and a 5-min coded recovery period. Saliva samples were collected from the dyads prior to, during, and after the still-face procedure and later assayed for cortisol. Level of disruption in maternal communication with the infant was coded from the 5-min videotaped interaction during the recovery period which followed the still-face procedure. Severely disrupted maternal communication was associated with lower levels of maternal cortisol and a greater divergence between mothers' and infants' cortisol levels. Results point to low maternal cortisol as a possible mechanism contributing to the mother's difficulty in sensitively attuning to her infant's cues, which in turn has implications for the infant's reactivity to and recovery from a mild stressor in early infancy.

Brazil’s Market for Trading Forest Certificates

PubMed Central

Soares-Filho, Britaldo; Rajão, Raoni; Merry, Frank; Rodrigues, Hermann; Davis, Juliana; Lima, Letícia; Macedo, Marcia; Coe, Michael; Carneiro, Arnaldo; Santiago, Leonardo

2016-01-01

Brazil faces an enormous challenge to implement its revised Forest Code. Despite big losses for the environment, the law introduces new mechanisms to facilitate compliance and foster payment for ecosystem services (PES). The most promising of these is a market for trading forest certificates (CRAs) that allows landowners to offset their restoration obligations by paying for maintaining native vegetation elsewhere. We analyzed the economic potential for the emerging CRA market in Brazil and its implications for PES programs. Results indicate a potential market for trading 4.2 Mha of CRAs with a gross value of US$ 9.2±2.4 billion, with main regional markets forming in the states of Mato Grosso and São Paulo. This would be the largest market for trading forests in the world. Overall, the potential supply of CRAs in Brazilian states exceeds demand, creating an opportunity for additional PES programs to use the CRA market. This expanded market could provide not only monetary incentives to conserve native vegetation, but also environmental co-benefits by fostering PES programs focused on biodiversity, water conservation, and climate regulation. Effective implementation of the Forest Code will be vital to the success of this market and this hurdle brings uncertainty into the market. Long-term commitment, both within Brazil and abroad, will be essential to overcome the many challenges ahead. PMID:27050309

Brazil's Market for Trading Forest Certificates.

PubMed

Soares-Filho, Britaldo; Rajão, Raoni; Merry, Frank; Rodrigues, Hermann; Davis, Juliana; Lima, Letícia; Macedo, Marcia; Coe, Michael; Carneiro, Arnaldo; Santiago, Leonardo

2016-01-01

Brazil faces an enormous challenge to implement its revised Forest Code. Despite big losses for the environment, the law introduces new mechanisms to facilitate compliance and foster payment for ecosystem services (PES). The most promising of these is a market for trading forest certificates (CRAs) that allows landowners to offset their restoration obligations by paying for maintaining native vegetation elsewhere. We analyzed the economic potential for the emerging CRA market in Brazil and its implications for PES programs. Results indicate a potential market for trading 4.2 Mha of CRAs with a gross value of US$ 9.2±2.4 billion, with main regional markets forming in the states of Mato Grosso and São Paulo. This would be the largest market for trading forests in the world. Overall, the potential supply of CRAs in Brazilian states exceeds demand, creating an opportunity for additional PES programs to use the CRA market. This expanded market could provide not only monetary incentives to conserve native vegetation, but also environmental co-benefits by fostering PES programs focused on biodiversity, water conservation, and climate regulation. Effective implementation of the Forest Code will be vital to the success of this market and this hurdle brings uncertainty into the market. Long-term commitment, both within Brazil and abroad, will be essential to overcome the many challenges ahead.

Cloning and expression of colonization factor antigen I (CFA/I) epitopes of enterotoxigenic Escherichia coli (ETEC) in Salmonella flagellin.

PubMed

Luna, M G; Martins, M M; Newton, S M; Costa, S O; Almeida, D F; Ferreira, L C

1997-01-01

Oligonucleotides coding for linear epitopes of the fimbrial colonization factor antigen I (CFA/I) of enterotoxigenic Escherichia coli (ETEC) were cloned and expressed in a deleted form of the Salmonella muenchen flagellin fliC (H1-d) gene. Four synthetic oligonucleotide pairs coding for regions corresponding to amino acids 1 to 15 (region I), amino acids 11 to 25 (region II), amino acids 32 to 45 (region III) and amino acids 88 to 102 (region IV) were synthesized and cloned in the Salmonella flagellin-coding gene. All four hybrid flagellins were exported to the bacterial surface where they produced flagella, but only three constructs were fully motile. Sera recovered from mice immunized with intraperitoneal injections of purified flagella containing region II (FlaII) or region IV (FlaIV) showed high titres against dissociated solid-phase-bound CFA/I subunits. Hybrid flagellins containing region I (FlaI) or region III (FlaIII) elicited a weak immune response as measured in enzyme-linked immunosorbent assay (ELISA) with dissociated CFA/I subunits. None of the sera prepared with purified hybrid flagella were able to agglutinate or inhibit haemagglutination promoted by CFA/I-positive strains. Moreover, inhibition ELISA tests indicated that antisera directed against region I, II, III or IV cloned in flagellin were not able to recognize surface-exposed regions on the intact CFA/I fimbriae.

Cracking the code: the accuracy of coding shoulder procedures and the repercussions.

PubMed

Clement, N D; Murray, I R; Nie, Y X; McBirnie, J M

2013-05-01

Coding of patients' diagnosis and surgical procedures is subject to error levels of up to 40% with consequences on distribution of resources and financial recompense. Our aim was to explore and address reasons behind coding errors of shoulder diagnosis and surgical procedures and to evaluate a potential solution. A retrospective review of 100 patients who had undergone surgery was carried out. Coding errors were identified and the reasons explored. A coding proforma was designed to address these errors and was prospectively evaluated for 100 patients. The financial implications were also considered. Retrospective analysis revealed the correct primary diagnosis was assigned in 54 patients (54%) had an entirely correct diagnosis, and only 7 (7%) patients had a correct procedure code assigned. Coders identified indistinct clinical notes and poor clarity of procedure codes as reasons for errors. The proforma was significantly more likely to assign the correct diagnosis (odds ratio 18.2, p < 0.0001) and the correct procedure code (odds ratio 310.0, p < 0.0001). Using the proforma resulted in a £28,562 increase in revenue for the 100 patients evaluated relative to the income generated from the coding department. High error levels for coding are due to misinterpretation of notes and ambiguity of procedure codes. This can be addressed by allowing surgeons to assign the diagnosis and procedure using a simplified list that is passed directly to coding.

Regional TEC model under quiet geomagnetic conditions and low-to-moderate solar activity based on CODE GIMs

NASA Astrophysics Data System (ADS)

Feng, Jiandi; Jiang, Weiping; Wang, Zhengtao; Zhao, Zhenzhen; Nie, Linjuan

2017-08-01

Global empirical total electron content (TEC) models based on TEC maps effectively describe the average behavior of the ionosphere. However, the accuracy of these global models for a certain region may not be ideal. Due to the number and distribution of the International GNSS Service (IGS) stations, the accuracy of TEC maps is geographically different. The modeling database derived from the global TEC maps with different accuracy is likely one of the main reasons that limits the accuracy of the new models. Moreover, many anomalies in the ionosphere are geographic or geomagnetic dependent, and as such the accuracy of global models can deteriorate if these anomalies are not fully incorporated into the modeling approach. For regional models built in small areas, these influences on modeling are immensely weakened. Thus, the regional TEC models may better reflect the temporal and spatial variations of TEC. In our previous work (Feng et al., 2016), a regional TEC model TECM-NEC is proposed for northeast China. However, this model is only directed against the typical region of Mid-latitude Summer Nighttime Anomaly (MSNA) occurrence, which is meaningless in other regions without MSNA. Following the technique of TECM-NEC model, this study proposes another regional empirical TEC model for other regions in mid-latitudes. Taking a small area BeiJing-TianJin-Tangshan (JJT) region (37.5°-42.5° N, 115°-120° E) in China as an example, a regional empirical TEC model (TECM-JJT) is proposed using the TEC grid data from January 1, 1999 to June 30, 2015 provided by the Center for Orbit Determination in Europe (CODE) under quiet geomagnetic conditions. The TECM-JJT model fits the input CODE TEC data with a bias of 0.11TECU and a root mean square error of 3.26TECU. Result shows that the regional model TECM-JJT is consistent with CODE TEC data and GPS-TEC data.

CRITICA: coding region identification tool invoking comparative analysis

NASA Technical Reports Server (NTRS)

Badger, J. H.; Olsen, G. J.; Woese, C. R. (Principal Investigator)

1999-01-01

Gene recognition is essential to understanding existing and future DNA sequence data. CRITICA (Coding Region Identification Tool Invoking Comparative Analysis) is a suite of programs for identifying likely protein-coding sequences in DNA by combining comparative analysis of DNA sequences with more common noncomparative methods. In the comparative component of the analysis, regions of DNA are aligned with related sequences from the DNA databases; if the translation of the aligned sequences has greater amino acid identity than expected for the observed percentage nucleotide identity, this is interpreted as evidence for coding. CRITICA also incorporates noncomparative information derived from the relative frequencies of hexanucleotides in coding frames versus other contexts (i.e., dicodon bias). The dicodon usage information is derived by iterative analysis of the data, such that CRITICA is not dependent on the existence or accuracy of coding sequence annotations in the databases. This independence makes the method particularly well suited for the analysis of novel genomes. CRITICA was tested by analyzing the available Salmonella typhimurium DNA sequences. Its predictions were compared with the DNA sequence annotations and with the predictions of GenMark. CRITICA proved to be more accurate than GenMark, and moreover, many of its predictions that would seem to be errors instead reflect problems in the sequence databases. The source code of CRITICA is freely available by anonymous FTP (rdp.life.uiuc.edu in/pub/critica) and on the World Wide Web (http:/(/)rdpwww.life.uiuc.edu).

Structure and expression of canary myc family genes.

PubMed Central

Collum, R G; Clayton, D F; Alt, F W

1991-01-01

We found that the canary N-myc gene is highly related to mammalian N-myc genes in both the protein-coding region and the long 3' untranslated region. Examined coding regions of the canary c-myc gene were also highly related to their mammalian counterparts, but in contrast to N-myc, the canary and mammalian c-myc genes were quite divergent in their 3' untranslated regions. We readily detected N-myc and c-myc expression in the adult canary brain and found N-myc expression both at sites of proliferating neuronal precursors and in mature neurons. Images PMID:1996121

DNA methylation of miRNA coding sequences putatively associated with childhood obesity.

PubMed

Mansego, M L; Garcia-Lacarte, M; Milagro, F I; Marti, A; Martinez, J A

2017-02-01

Epigenetic mechanisms may be involved in obesity onset and its consequences. The aim of the present study was to evaluate whether DNA methylation status in microRNA (miRNA) coding regions is associated with childhood obesity. DNA isolated from white blood cells of 24 children (identification sample: 12 obese and 12 non-obese) from the Grupo Navarro de Obesidad Infantil study was hybridized in a 450 K methylation microarray. Several CpGs whose DNA methylation levels were statistically different between obese and non-obese were validated by MassArray® in 95 children (validation sample) from the same study. Microarray analysis identified 16 differentially methylated CpGs between both groups (6 hypermethylated and 10 hypomethylated). DNA methylation levels in miR-1203, miR-412 and miR-216A coding regions significantly correlated with body mass index standard deviation score (BMI-SDS) and explained up to 40% of the variation of BMI-SDS. The network analysis identified 19 well-defined obesity-relevant biological pathways from the KEGG database. MassArray® validation identified three regions located in or near miR-1203, miR-412 and miR-216A coding regions differentially methylated between obese and non-obese children. The current work identified three CpG sites located in coding regions of three miRNAs (miR-1203, miR-412 and miR-216A) that were differentially methylated between obese and non-obese children, suggesting a role of miRNA epigenetic regulation in childhood obesity. © 2016 World Obesity Federation.

The analysis of the complete mitochondrial genome of Lecanicillium muscarium (synonym Verticillium lecanii) suggests a minimum common gene organization in mtDNAs of Sordariomycetes: phylogenetic implications.

PubMed

Kouvelis, Vassili N; Ghikas, Dimitri V; Typas, Milton A

2004-10-01

The mitochondrial genome (mtDNA) of the entomopathogenic fungus Lecanicillium muscarium (synonym Verticillium lecanii) with a total size of 24,499-bp has been analyzed. So far, it is the smallest known mitochondrial genome among Pezizomycotina, with an extremely compact gene organization and only one group-I intron in its large ribosomal RNA (rnl) gene. It contains the 14 typical genes coding for proteins related to oxidative phosphorylation, the two rRNA genes, one intronic ORF coding for a possible ribosomal protein (rps), and a set of 25 tRNA genes which recognize codons for all amino acids, except alanine and cysteine. All genes are transcribed from the same DNA strand. Gene order comparison with all available complete fungal mtDNAs-representatives of all four Phyla are included-revealed some characteristic common features like uninterrupted gene pairs, overlapping genes, and extremely variable intergenic regions, that can all be exploited for the study of fungal mitochondrial genomes. Moreover, a minimum common mtDNA gene order could be detected, in two units, for all known Sordariomycetes namely nad1-nad4-atp8-atp6 and rns-cox3-rnl, which can be extended in Hypocreales, to nad4L-nad5-cob-cox1-nad1-nad4-atp8-atp6 and rns-cox3-rnl nad2-nad3, respectively. Phylogenetic analysis of all fungal mtDNA essential protein-coding genes as one unit, clearly demonstrated the superiority of small genome (mtDNA) over single gene comparisons.

Balancing the Direct and Indirect Approaches: Implications for Ending the Violence in Southern Thailand

DTIC Science & Technology

2009-12-01

DIRECT AND INDIRECT APPROACHES: IMPLICATIONS FOR ENDING THE VIOLENCE IN SOUTHERN THAILAND by Chaiyo Rodthong December 2009 Thesis Advisor... Thailand 6. AUTHOR(S) Chaiyo Rodthong 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) The instability in the Southern Border Provinces of Thailand resurged on

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

Mebarki, F.; Forest, M.G.; Josso, N.

The androgen insensivity syndrome (AIS) is a recessive X-linked disorder resulting from a deficient function of the androgen receptor (AR). The human AR gene has 3 functional domains: N-terminal encoded by exon 1, DNA-binding domain encoded by exons 2 and 3, and androgen-binding domain encoded by exons 4 to 8. In order to characterize the molecular defects of the AR gene in AIS, the entire coding regions and the intronic bording sequences of the AR gene were amplified by PCR before automatic direct sequencing in 45 patients. Twenty seven different point mutations were found in 32 unrelated AIS patients: 18more » with a complete form (CAIS), 14 with a partial form (PAIS); 18 of these mutations are novel mutations, not published to date. Only 3 mutations were repeatedly found: R804H in 3 families; M780I in 3 families and R774C in 2 families. For 26 patients out of the 32 found to have a mutation, maternal DNA was collected and sequenced: 6 de novo mutations were detected (i.e. 23% of the cases). Finally, no mutation was detected in 13 patients (29%): 7 with CAIS and 6 familial severe PAIS. The latter all presented with perineal hypospadias, micropenis, 4 out of 6 being raised as girl. Diagnosis of AIS in these 13 families in whom no mutation was detected is supported by the following criteria: clinical data, familial history (2 or 3 index cases in the same family), familial segregation of the polymorphic CAG repeat of the AR gene. Mutations in intronic regions or the promoter of the AR gene could not explain all cases of AIS without mutations in the AR coding regions, because AR binding (performed in 9 out of 13) was normal in 6, suggesting the synthesis of an AR protein. This situation led us to speculate that another X-linked factor associated with the AR could be implicated in some cases of AIS.« less

Intron-exon organization of the active human protein S gene PS. alpha. and its pseudogene PS. beta. : Duplication and silencing during primate evolution

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

Ploos van Amstel, H.; Reitsma, P.H.; van der Logt, C.P.

The human protein S locus on chromosome 3 consists of two protein S genes, PS{alpha} and PS{beta}. Here the authors report the cloning and characterization of both genes. Fifteen exons of the PS{alpha} gene were identified that together code for protein S mRNA as derived from the reported protein S cDNAs. Analysis by primer extension of liver protein S mRNA, however, reveals the presence of two mRNA forms that differ in the length of their 5{prime}-noncoding region. Both transcripts contain a 5{prime}-noncoding region longer than found in the protein S cDNAs. The two products may arise from alternative splicing ofmore » an additional intron in this region or from the usage of two start sites for transcription. The intron-exon organization of the PS{alpha} gene fully supports the hypothesis that the protein S gene is the product of an evolutional assembling process in which gene modules coding for structural/functional protein units also found in other coagulation proteins have been put upstream of the ancestral gene of a steroid hormone binding protein. The PS{beta} gene is identified as a pseudogene. It contains a large variety of detrimental aberrations, viz., the absence of exon I, a splice site mutation, three stop codons, and a frame shift mutation. Overall the two genes PS{alpha} and PS{beta} show between their exonic sequences 96.5% homology. Southern analysis of primate DNA showed that the duplication of the ancestral protein S gene has occurred after the branching of the orangutan from the African apes. A nonsense mutation that is present in the pseudogene of man also could be identified in one of the two protein S genes of both chimpanzee and gorilla. This implicates that silencing of one of the two protein S genes must have taken place before the divergence of the three African apes.« less

Hemispheric processing asymmetries: implications for memory.

PubMed

Funnell, M G; Corballis, P M; Gazzaniga, M S

2001-01-01

Recent research has demonstrated that memory for words elicits left hemisphere activation, faces right hemisphere activation, and nameable objects bilateral activation. This pattern of results was attributed to dual coding of information, with the left hemisphere employing a verbal code and the right a nonverbal code. Nameable objects can be encoded either verbally or nonverbally and this accounts for their bilateral activation. We investigated this hypothesis in a callosotomy patient. Consistent with dual coding, the left hemisphere was superior to the right in memory for words, whereas the right was superior for faces. Contrary to prediction, performance on nameable pictures was not equivalent in the two hemispheres, but rather resulted in a right hemisphere superiority. In addition, memory for pictures was significantly better than for either words or faces. These findings suggest that the dual code hypothesis is an oversimplification of the processing capabilities of the two hemispheres.

The effect of a redundant color code on an overlearned identification task

NASA Technical Reports Server (NTRS)

Obrien, Kevin

1992-01-01

The possibility of finding redundancy gains with overlearned tasks was examined using a paradigm varying familiarity with the stimulus set. Redundant coding in a multidimensional stimulus was demonstrated to result in increased identification accuracy and decreased latency of identification when compared to stimuli varying on only one dimension. The advantages attributable to redundant coding are referred to as redundancy gain and were found for a variety of stimulus dimension combinations, including the use of hue or color as one of the dimensions. Factors that have affected redundancy gain include the discriminability of the levels of one stimulus dimension and the level of stimulus-to-response association. The results demonstrated that response time is in part a function of familiarity, but no effect of redundant color coding was demonstrated. Implications of research on coding in identification tasks for display design are discussed.

Use of quick response coding to create interactive patient and provider resources.

PubMed

Bellot, Jennifer; Shaffer, Kathryn; Wang, Mary

2015-04-01

Since their creation more than 20 years ago, the proliferation of Quick Response (QR) codes has expanded tremendously. Little was found in the literature to support the innovative use of QR coding in the classroom or in health care provision. Thus, the authors created a doctoral-level practicum experience using QR coding to create interactive, individualized patient or provider resource guides. Short, descriptive surveys were used before and after implementation of the practicum experience to determine students' comfort level using QR technology, their knowledge base, ease of use, and overall satisfaction with the practicum. Students reported high levels of satisfaction with this exercise, and all agreed that use of QR coding could have important implications in the clinical environment. This practicum experience was a creative, practical, and valuable example of integrating emerging technology into individualized patient care. Copyright 2015, SLACK Incorporated.

Verification of low-Mach number combustion codes using the method of manufactured solutions

NASA Astrophysics Data System (ADS)

Shunn, Lee; Ham, Frank; Knupp, Patrick; Moin, Parviz

2007-11-01

Many computational combustion models rely on tabulated constitutive relations to close the system of equations. As these reactive state-equations are typically multi-dimensional and highly non-linear, their implications on the convergence and accuracy of simulation codes are not well understood. In this presentation, the effects of tabulated state-relationships on the computational performance of low-Mach number combustion codes are explored using the method of manufactured solutions (MMS). Several MMS examples are developed and applied, progressing from simple one-dimensional configurations to problems involving higher dimensionality and solution-complexity. The manufactured solutions are implemented in two multi-physics hydrodynamics codes: CDP developed at Stanford University and FUEGO developed at Sandia National Laboratories. In addition to verifying the order-of-accuracy of the codes, the MMS problems help highlight certain robustness issues in existing variable-density flow-solvers. Strategies to overcome these issues are briefly discussed.

Natural variation in non-coding regions underlying phenotypic diversity in budding yeast

PubMed Central

Salinas, Francisco; de Boer, Carl G.; Abarca, Valentina; García, Verónica; Cuevas, Mara; Araos, Sebastian; Larrondo, Luis F.; Martínez, Claudio; Cubillos, Francisco A.

2016-01-01

Linkage mapping studies in model organisms have typically focused their efforts in polymorphisms within coding regions, ignoring those within regulatory regions that may contribute to gene expression variation. In this context, differences in transcript abundance are frequently proposed as a source of phenotypic diversity between individuals, however, until now, little molecular evidence has been provided. Here, we examined Allele Specific Expression (ASE) in six F1 hybrids from Saccharomyces cerevisiae derived from crosses between representative strains of the four main lineages described in yeast. ASE varied between crosses with levels ranging between 28% and 60%. Part of the variation in expression levels could be explained by differences in transcription factors binding to polymorphic cis-regulations and to differences in trans-activation depending on the allelic form of the TF. Analysis on highly expressed alleles on each background suggested ASN1 as a candidate transcript underlying nitrogen consumption differences between two strains. Further promoter allele swap analysis under fermentation conditions confirmed that coding and non-coding regions explained aspartic and glutamic acid consumption differences, likely due to a polymorphism affecting Uga3 binding. Together, we provide a new catalogue of variants to bridge the gap between genotype and phenotype. PMID:26898953

Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events

PubMed Central

Ashouri, Arghavan; Sayin, Volkan I.; Van den Eynden, Jimmy; Singh, Simranjit X.; Papagiannakopoulos, Thales; Larsson, Erik

2016-01-01

Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here we make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Our screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways. The associations are often highly reproducible across cancer types, and while many lncRNAs are co-expressed with their protein-coding hosts or neighbours, some are intergenic and independent. We highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. Our study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers. PMID:28959951

What the success of brain imaging implies about the neural code

PubMed Central

Guest, Olivia; Love, Bradley C

2017-01-01

The success of fMRI places constraints on the nature of the neural code. The fact that researchers can infer similarities between neural representations, despite fMRI’s limitations, implies that certain neural coding schemes are more likely than others. For fMRI to succeed given its low temporal and spatial resolution, the neural code must be smooth at the voxel and functional level such that similar stimuli engender similar internal representations. Through proof and simulation, we determine which coding schemes are plausible given both fMRI’s successes and its limitations in measuring neural activity. Deep neural network approaches, which have been forwarded as computational accounts of the ventral stream, are consistent with the success of fMRI, though functional smoothness breaks down in the later network layers. These results have implications for the nature of the neural code and ventral stream, as well as what can be successfully investigated with fMRI. DOI: http://dx.doi.org/10.7554/eLife.21397.001 PMID:28103186

A measure of short-term visual memory based on the WISC-R coding subtest.

PubMed

Collaer, M L; Evans, J R

1982-07-01

Adapted the Coding subtest of the WISC-R to provide a measure of visual memory. Three hundred and five children, aged 8 through 12, were administered the Coding test using standard directions. A few seconds after completion the key was taken away, and each was given a paper with only the digits and asked to write the appropriate matching symbol below each. This was termed "Coding Recall." To provide validity data, a subgroup of 50 Ss also was administered the Attention Span for Letters subtest from the Detroit Tests of Learning Aptitude (as a test of visual memory for sequences of letters) and a Bender Gestalt recall test (as a measure of visual memory for geometric forms). Coding Recall means and standard deviations are reported separately by sex and age level. Implications for clinicans are discussed. Reservations about clinical use of the data are given in view of the possible lack of representativeness of the sample used and the limited reliability and validity of Coding Recall.

Neural representation of objects in space: a dual coding account.

PubMed Central

Humphreys, G W

1998-01-01

I present evidence on the nature of object coding in the brain and discuss the implications of this coding for models of visual selective attention. Neuropsychological studies of task-based constraints on: (i) visual neglect; and (ii) reading and counting, reveal the existence of parallel forms of spatial representation for objects: within-object representations, where elements are coded as parts of objects, and between-object representations, where elements are coded as independent objects. Aside from these spatial codes for objects, however, the coding of visual space is limited. We are extremely poor at remembering small spatial displacements across eye movements, indicating (at best) impoverished coding of spatial position per se. Also, effects of element separation on spatial extinction can be eliminated by filling the space with an occluding object, indicating that spatial effects on visual selection are moderated by object coding. Overall, there are separate limits on visual processing reflecting: (i) the competition to code parts within objects; (ii) the small number of independent objects that can be coded in parallel; and (iii) task-based selection of whether within- or between-object codes determine behaviour. Between-object coding may be linked to the dorsal visual system while parallel coding of parts within objects takes place in the ventral system, although there may additionally be some dorsal involvement either when attention must be shifted within objects or when explicit spatial coding of parts is necessary for object identification. PMID:9770227

Financial and clinical governance implications of clinical coding accuracy in neurosurgery: a multidisciplinary audit.

PubMed

Haliasos, N; Rezajooi, K; O'neill, K S; Van Dellen, J; Hudovsky, Anita; Nouraei, Sar

2010-04-01

Clinical coding is the translation of documented clinical activities during an admission to a codified language. Healthcare Resource Groupings (HRGs) are derived from coding data and are used to calculate payment to hospitals in England, Wales and Scotland and to conduct national audit and benchmarking exercises. Coding is an error-prone process and an understanding of its accuracy within neurosurgery is critical for financial, organizational and clinical governance purposes. We undertook a multidisciplinary audit of neurosurgical clinical coding accuracy. Neurosurgeons trained in coding assessed the accuracy of 386 patient episodes. Where clinicians felt a coding error was present, the case was discussed with an experienced clinical coder. Concordance between the initial coder-only clinical coding and the final clinician-coder multidisciplinary coding was assessed. At least one coding error occurred in 71/386 patients (18.4%). There were 36 diagnosis and 93 procedure errors and in 40 cases, the initial HRG changed (10.4%). Financially, this translated to pound111 revenue-loss per patient episode and projected to pound171,452 of annual loss to the department. 85% of all coding errors were due to accumulation of coding changes that occurred only once in the whole data set. Neurosurgical clinical coding is error-prone. This is financially disadvantageous and with the coding data being the source of comparisons within and between departments, coding inaccuracies paint a distorted picture of departmental activity and subspecialism in audit and benchmarking. Clinical engagement improves accuracy and is encouraged within a clinical governance framework.

Design of ACM system based on non-greedy punctured LDPC codes

NASA Astrophysics Data System (ADS)

Lu, Zijun; Jiang, Zihong; Zhou, Lin; He, Yucheng

2017-08-01

In this paper, an adaptive coded modulation (ACM) scheme based on rate-compatible LDPC (RC-LDPC) codes was designed. The RC-LDPC codes were constructed by a non-greedy puncturing method which showed good performance in high code rate region. Moreover, the incremental redundancy scheme of LDPC-based ACM system over AWGN channel was proposed. By this scheme, code rates vary from 2/3 to 5/6 and the complication of the ACM system is lowered. Simulations show that more and more obvious coding gain can be obtained by the proposed ACM system with higher throughput.

Requirements for migration of NSSD code systems from LTSS to NLTSS

NASA Technical Reports Server (NTRS)

Pratt, M.

1984-01-01

The purpose of this document is to address the requirements necessary for a successful conversion of the Nuclear Design (ND) application code systems to the NLTSS environment. The ND application code system community can be characterized as large-scale scientific computation carried out on supercomputers. NLTSS is a distributed operating system being developed at LLNL to replace the LTSS system currently in use. The implications of change are examined including a description of the computational environment and users in ND. The discussion then turns to requirements, first in a general way, followed by specific requirements, including a proposal for managing the transition.

What if pediatric residents could bill for their outpatient services?

PubMed

Ng, M; Lawless, S T

2001-10-01

We prospectively studied the potential of billing and coding practices of pediatric residents in outpatient clinics and extrapolated our results to assess the financial implications of billing inaccuracies. Using Medicare as a common measure of "currency," we also used the relative value unit (RVU) and ambulatory payment class methodologies as means of assessing the productivity and financial value of resident-staffed pediatric clinics. Residents were asked to submit voluntarily shadow billing forms and documentation of outpatient clinic visits. Documentation of work was assessed by a blinded reviewer, and current procedure terminology evaluation and management codes were assigned. Comparisons between resident codes and calculated codes were made. Financial implications of physician productivity were calculated in terms of dollar amounts and RVUs. Resource intensity was measured using the ambulatory payment class methodology. A total of 344 charts were reviewed. Coding agreement for health maintenance visits was 86%, whereas agreement for acute care visits was 38%. Eighty-three percent of coding disagreement in the latter group was resulting from undercoding by residents. Errors accounted for a 4.79% difference in potential reimbursement for all visit types and a 19.10% difference for acute care visits. No significant differences in shadow billing discrepancies were found between different levels of training. Residents were predicted to generate $67 230, $87 593, and $96 072 in Medicare revenue in the outpatient clinic setting during each successive year of training. On average, residents generated 1.17 +/- 0.01 and 0.81 +/- 0.02 work RVUs for each health maintenance visit and office visit, respectively. Annual productivity from outpatient clinic settings was estimated at 548, 735, and 893 work RVUs in the postgraduate levels 1, 2, and 3, respectively. When pediatric residents are not trained adequately in proper coding practices, the potential for billing discrepancies is high and potential reimbursement differences may be substantial. Discussion of financial issues should be considered in curriculum development.

A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior.

PubMed

Lear, Bridget C; Merrill, C Elaine; Lin, Jui-Ming; Schroeder, Analyne; Zhang, Luoying; Allada, Ravi

2005-10-20

The neuropeptide Pigment-Dispersing Factor (PDF) plays a critical role in mediating circadian control of behavior in Drosophila. Here we identify mutants (groom-of-PDF; gop) that display phase-advanced evening activity and poor free-running rhythmicity, phenocopying pdf mutants. In gop mutants, a spontaneous retrotransposon disrupts a coding exon of a G protein-coupled receptor, CG13758. Disruption of the receptor is accompanied by phase-advanced oscillations of the core clock protein PERIOD. Moreover, effects on circadian timing induced by perturbation of PDF neurons require gop. Yet PDF oscillations themselves remain robust in gop mutants, suggesting that GOP acts downstream of PDF. gop is expressed most strongly in the dorsal brain in regions that lie in proximity to PDF-containing nerve terminals. Taken together, these studies implicate GOP as a PDF receptor in Drosophila.

Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.

PubMed

Vincent, John B; Kolozsvari, Debbie; Roberts, Wendy S; Bolton, Patrick F; Gurling, Hugh M D; Scherer, Stephen W

2004-08-15

Autism, a childhood neuropsychiatric disorder with a strong genetic component, is currently the focus of considerable attention within the field of human genetics as well many other medical-related disciplines. A recent study has implicated two X-chromosomal neuroligin genes, NLGN3 and NLGN4, as having an etiological role in autism, having identified a frameshift mutation in one gene and a substitution mutation in the other, segregating in multiplex autism spectrum families (Jamain et al. [2003: Nat Genet 34:27-29]). The function of neuroligin as a trigger for synapse formation would suggest that such mutations would likely result in some form of pathological manifestation. Our own study, screening a larger sample of 196 autism probands, failed to identify any mutations that would affect the coding regions of these genes. Our findings suggest that mutations in these two genes are infrequent in autism. Copyright 2004 Wiley-Liss, Inc.

The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease.

PubMed

Campion, D; Martin, C; Heilig, R; Charbonnier, F; Moreau, V; Flaman, J M; Petit, J L; Hannequin, D; Brice, A; Frebourg, T

1995-03-20

The major component of the vascular and plaque amyloid deposits in Alzheimer disease is the amyloid beta peptide (A beta). A second intrinsic component of amyloid, the NAC (non-A beta component of amyloid) peptide, has recently been identified, and its precursor protein was named NACP. A computer homology search allowed us to establish that the human NACP gene was homologous to the rat synuclein gene. We mapped the NACP/synuclein gene to chromosome 4 and cloned three alternatively spliced transcripts in lymphocytes derived from a normal subject. We analyzed by RT-PCR and direct sequencing the entire coding region of the NACP/synuclein gene in a group of patients with familial early onset Alzheimer disease. No mutation was found in 26 unrelated patients. Further studies are required to investigate the implication of the NACP/synuclein gene in Alzheimer disease.

The NACP/synuclein gene: Chromosomal assignment and screening for alterations in Alzheimer disease

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

Campion, D.; Martin, C.; Charbonnier, F.

1995-03-20

The major component of the vascular and plaque amyloid deposits in Alzheimer disease is the amyloid {beta} peptide (A{beta}). A second intrinsic component of amyloid, the NAC (non-A{beta} component of amyloid) peptide, has recently been identified, and its precursor protein was named NACP. A computer homology search allowed us to establish that the human NACP gene was homologous to the rat synuclein gene. We mapped the NACP/synuclein gene to chromosome 4 and cloned three alternatively spliced transcripts in lymphocytes derived from a normal subject. We analyzed by RT-PCR and direct sequencing the entire coding region of the NACP/synuclein gene inmore » a group of patients with familial early onset Alzheimer disease. No mutation was found in 26 unrelated patients. Further studies are required to investigate the implication of the NACP/synuclein gene in Alzheimer disease. 21 refs., 3 tabs.« less

Numerical and analytical bounds on threshold error rates for hypergraph-product codes

NASA Astrophysics Data System (ADS)

Kovalev, Alexey A.; Prabhakar, Sanjay; Dumer, Ilya; Pryadko, Leonid P.

2018-06-01

We study analytically and numerically decoding properties of finite-rate hypergraph-product quantum low density parity-check codes obtained from random (3,4)-regular Gallager codes, with a simple model of independent X and Z errors. Several nontrivial lower and upper bounds for the decodable region are constructed analytically by analyzing the properties of the homological difference, equal minus the logarithm of the maximum-likelihood decoding probability for a given syndrome. Numerical results include an upper bound for the decodable region from specific heat calculations in associated Ising models and a minimum-weight decoding threshold of approximately 7 % .

The complete mitochondrial genome of a spiraling whitefly, Aleurodicus dispersus Russell (Hemiptera: Aleyrodidae).

PubMed

Ming-Xing, Lu; Zhi-Teng, Chen; Wei-Wei, Yu; Yu-Zhou, Du

2017-03-01

We report the complete mitochondrial genome (mitogenome) of a spiraling whitefly, Aleurodicus dispersus (Hemiptera: Aleyrodidae). The 16 170 bp long genome consists of 13 protein-coding genes, 20 transfer RNAs, 2 ribosomal RNAs, and a control region. The A. dispersus mitogenome also includes a cytb-like non-coding region and shows several variations relative to the typical insect mitogenome. A phylogenetic tree has been constructed using the 13 protein-coding genes of 12 related species from Hemiptera. Our results would contribute to further study of phylogeny in Aleyrodidae and Hemiptera.

Design with high strength steel: A case of failure and its implications

NASA Astrophysics Data System (ADS)

Rahka, Klaus

1992-10-01

A recent proof test failure of a high strength steel pressure vessel is scrutinized. Apparent deficiencies in the procedures to account for elasto-plastic local strain are indicated for the applicable routine (code) strength calculations. Tentative guidance is given for the use of material tensile fracture strain and its strain state (plane strain) correction in fracture margin estimation. A hypothesis that the calculated local strain is comparable with a gauge length weighted tensile ductility for fracture to initiate at a notch root is given. A discussion about the actual implications of the failure case and the suggested remedy in the light of the ASME Boiler and Pressure Vessel Code section 3 and 8 is presented. Further needs for research and development are delineated. Possible yield and ductility related design limits and their use as material quality indices are discussed.

Gene Expression and Polymorphism of Myostatin Gene and its Association with Growth Traits in Chicken.

PubMed

Dushyanth, K; Bhattacharya, T K; Shukla, R; Chatterjee, R N; Sitaramamma, T; Paswan, C; Guru Vishnu, P

2016-10-01

Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage.

Complete mitochondrial genome of the whiter-spotted flower chafer, Protaetia brevitarsis (Coleoptera: Scarabaeidae).

PubMed

Kim, Min Jee; Im, Hyun Hwak; Lee, Kwang Youll; Han, Yeon Soo; Kim, Iksoo

2014-06-01

Abstract The complete nucleotide sequences of the mitochondrial genome from the whiter-spotted flower chafer, Protaetia brevitarsis (Coleoptera: Scarabaeidae), was determined. The 20,319-bp long circular genome is the longest among completely sequenced Coleoptera. As is typical in animals, the P. brevitarsis genome consisted of two ribosomal RNAs, 22 transfer RNAs, 13 protein-coding genes and one A + T-rich region. Although the size of the coding genes was typical, the non-coding A + T-rich region was 5654 bp, which is the longest in insects. The extraordinary length of this region was composed of 28,117-bp tandem repeats and 782-bp tandem repeats. These repeat sequences were encompassed by three non-repeat sequences constituting 1804 bp.

Mu-Like Prophage in Serogroup B Neisseria meningitidis Coding for Surface-Exposed Antigens

PubMed Central

Masignani, Vega; Giuliani, Marzia Monica; Tettelin, Hervé; Comanducci, Maurizio; Rappuoli, Rino; Scarlato, Vincenzo

2001-01-01

Sequence analysis of the genome of Neisseria meningititdis serogroup B revealed the presence of an ∼35-kb region inserted within a putative gene coding for an ABC-type transporter. The region contains 46 open reading frames, 29 of which are colinear and homologous to the genes of Escherichia coli Mu phage. Two prophages with similar organizations were also found in serogroup A meningococcus, and one was found in Haemophilus influenzae. Early and late phage functions are well preserved in this family of Mu-like prophages. Several regions of atypical nucleotide content were identified. These likely represent genes acquired by horizontal transfer. Three of the acquired genes are shown to code for surface-associated antigens, and the encoded proteins are able to induce bactericidal antibodies. PMID:11254622

42 CFR 137.328 - Must a construction project proposal incorporate provisions of Federal construction guidelines...

Code of Federal Regulations, 2014 CFR

2014-10-01

..., the Self-Governance Tribe and the Secretary must agree upon and specify appropriate building codes and...-Governance Tribe in the preparation of its construction project proposal. If Tribal construction codes and standards (including national, regional, State, or Tribal building codes or construction industry standards...

42 CFR 137.328 - Must a construction project proposal incorporate provisions of Federal construction guidelines...

Code of Federal Regulations, 2012 CFR

2012-10-01

..., the Self-Governance Tribe and the Secretary must agree upon and specify appropriate building codes and...-Governance Tribe in the preparation of its construction project proposal. If Tribal construction codes and standards (including national, regional, State, or Tribal building codes or construction industry standards...

42 CFR 137.328 - Must a construction project proposal incorporate provisions of Federal construction guidelines...

Code of Federal Regulations, 2013 CFR

2013-10-01

..., the Self-Governance Tribe and the Secretary must agree upon and specify appropriate building codes and...-Governance Tribe in the preparation of its construction project proposal. If Tribal construction codes and standards (including national, regional, State, or Tribal building codes or construction industry standards...

42 CFR 137.328 - Must a construction project proposal incorporate provisions of Federal construction guidelines...

Code of Federal Regulations, 2011 CFR

2011-10-01

..., the Self-Governance Tribe and the Secretary must agree upon and specify appropriate building codes and...-Governance Tribe in the preparation of its construction project proposal. If Tribal construction codes and standards (including national, regional, State, or Tribal building codes or construction industry standards...

42 CFR 137.328 - Must a construction project proposal incorporate provisions of Federal construction guidelines...

Code of Federal Regulations, 2010 CFR

2010-10-01

..., the Self-Governance Tribe and the Secretary must agree upon and specify appropriate building codes and...-Governance Tribe in the preparation of its construction project proposal. If Tribal construction codes and standards (including national, regional, State, or Tribal building codes or construction industry standards...

Arbitrariness is not enough: towards a functional approach to the genetic code.

PubMed

Lacková, Ľudmila; Matlach, Vladimír; Faltýnek, Dan

2017-12-01

Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

Amodal processing in human prefrontal cortex.

PubMed

Tamber-Rosenau, Benjamin J; Dux, Paul E; Tombu, Michael N; Asplund, Christopher L; Marois, René

2013-07-10

Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex.

Peptide code-on-a-microplate for protease activity analysis via MALDI-TOF mass spectrometric quantitation.

PubMed

Hu, Junjie; Liu, Fei; Ju, Huangxian

2015-04-21

A peptide-encoded microplate was proposed for MALDI-TOF mass spectrometric (MS) analysis of protease activity. The peptide codes were designed to contain a coding region and the substrate of protease for enzymatic cleavage, respectively, and an internal standard method was proposed for the MS quantitation of the cleavage products of these peptide codes. Upon the cleavage reaction in the presence of target proteases, the coding regions were released from the microplate, which were directly quantitated by using corresponding peptides with one-amino acid difference as the internal standards. The coding region could be used as the unique "Protease ID" for the identification of corresponding protease, and the amount of the cleavage product was used for protease activity analysis. Using trypsin and chymotrypsin as the model proteases to verify the multiplex protease assay, the designed "Trypsin ID" and "Chymotrypsin ID" occurred at m/z 761.6 and 711.6. The logarithm value of the intensity ratio of "Protease ID" to internal standard was proportional to trypsin and chymotrypsin concentration in a range from 5.0 to 500 and 10 to 500 nM, respectively. The detection limits for trypsin and chymotrypsin were 2.3 and 5.2 nM, respectively. The peptide-encoded microplate showed good selectivity. This proposed method provided a powerful tool for convenient identification and activity analysis of multiplex proteases.

New PAH gene promoter KLF1 and 3'-region C/EBPalpha motifs influence transcription in vitro.

PubMed

Klaassen, Kristel; Stankovic, Biljana; Kotur, Nikola; Djordjevic, Maja; Zukic, Branka; Nikcevic, Gordana; Ugrin, Milena; Spasovski, Vesna; Srzentic, Sanja; Pavlovic, Sonja; Stojiljkovic, Maja

2017-02-01

Phenylketonuria (PKU) is a metabolic disease caused by mutations in the phenylalanine hydroxylase (PAH) gene. Although the PAH genotype remains the main determinant of PKU phenotype severity, genotype-phenotype inconsistencies have been reported. In this study, we focused on unanalysed sequences in non-coding PAH gene regions to assess their possible influence on the PKU phenotype. We transiently transfected HepG2 cells with various chloramphenicol acetyl transferase (CAT) reporter constructs which included PAH gene non-coding regions. Selected non-coding regions were indicated by in silico prediction to contain transcription factor binding sites. Furthermore, electrophoretic mobility shift assay (EMSA) and supershift assays were performed to identify which transcriptional factors were engaged in the interaction. We found novel KLF1 motif in the PAH promoter, which decreases CAT activity by 50 % in comparison to basal transcription in vitro. The cytosine at the c.-170 promoter position creates an additional binding site for the protein complex involving KLF1 transcription factor. Moreover, we assessed for the first time the role of a multivariant variable number tandem repeat (VNTR) region located in the 3'-region of the PAH gene. We found that the VNTR3, VNTR7 and VNTR8 constructs had approximately 60 % of CAT activity. The regulation is mediated by the C/EBPalpha transcription factor, present in protein complex binding to VNTR3. Our study highlighted two novel promoter KLF1 and 3'-region C/EBPalpha motifs in the PAH gene which decrease transcription in vitro and, thus, could be considered as PAH expression modifiers. New transcription motifs in non-coding regions will contribute to better understanding of the PKU phenotype complexity and may become important for the optimisation of PKU treatment.

The Prerogative of "Corrective Recasts" as a Sign of Hegemony in the Use of Language: Further Thoughts on Eric Hauser's (2005) "Coding 'Corrective Recasts': The Maintenance of Meaning and More Fundamental Problems"

ERIC Educational Resources Information Center

Rajagopalan, Kanavillil

2006-01-01

The objective of this response article is to think through some of what I see as the far-reaching implications of a recent paper by Eric Hauser (2005) entitled "Coding 'corrective recasts': the maintenance of meaning and more fundamental problems". Hauser makes a compelling, empirically-backed case for his contention that, contrary to widespread…

Decision-making in schizophrenia: A predictive-coding perspective.

PubMed

Sterzer, Philipp; Voss, Martin; Schlagenhauf, Florian; Heinz, Andreas

2018-05-31

Dysfunctional decision-making has been implicated in the positive and negative symptoms of schizophrenia. Decision-making can be conceptualized within the framework of hierarchical predictive coding as the result of a Bayesian inference process that uses prior beliefs to infer states of the world. According to this idea, prior beliefs encoded at higher levels in the brain are fed back as predictive signals to lower levels. Whenever these predictions are violated by the incoming sensory data, a prediction error is generated and fed forward to update beliefs encoded at higher levels. Well-documented impairments in cognitive decision-making support the view that these neural inference mechanisms are altered in schizophrenia. There is also extensive evidence relating the symptoms of schizophrenia to aberrant signaling of prediction errors, especially in the domain of reward and value-based decision-making. Moreover, the idea of altered predictive coding is supported by evidence for impaired low-level sensory mechanisms and motor processes. We review behavioral and neural findings from these research areas and provide an integrated view suggesting that schizophrenia may be related to a pervasive alteration in predictive coding at multiple hierarchical levels, including cognitive and value-based decision-making processes as well as sensory and motor systems. We relate these findings to decision-making processes and propose that varying degrees of impairment in the implicated brain areas contribute to the variety of psychotic experiences. Copyright © 2018 Elsevier Inc. All rights reserved.

An Enterprising Approach to Regional Growth: Implications for Policy and the Role of VET--Support Document

ERIC Educational Resources Information Center

Garlick, Steve; Taylor, Michael; Plummer, Paul

2007-01-01

"An Enterprising Approach to Regional Growth: Implications for Policy and the Role of Vocational Education and Training" explores patterns of regional economic growth in Australia over the period 1984 to 2002 with the aim of identifying the drivers of variation in regional growth; the research also aimed to identify regional…

Genomic Sequence around Butterfly Wing Development Genes: Annotation and Comparative Analysis

PubMed Central

Conceição, Inês C.; Long, Anthony D.; Gruber, Jonathan D.; Beldade, Patrícia

2011-01-01

Background Analysis of genomic sequence allows characterization of genome content and organization, and access beyond gene-coding regions for identification of functional elements. BAC libraries, where relatively large genomic regions are made readily available, are especially useful for species without a fully sequenced genome and can increase genomic coverage of phylogenetic and biological diversity. For example, no butterfly genome is yet available despite the unique genetic and biological properties of this group, such as diversified wing color patterns. The evolution and development of these patterns is being studied in a few target species, including Bicyclus anynana, where a whole-genome BAC library allows targeted access to large genomic regions. Methodology/Principal Findings We characterize ∼1.3 Mb of genomic sequence around 11 selected genes expressed in B. anynana developing wings. Extensive manual curation of in silico predictions, also making use of a large dataset of expressed genes for this species, identified repetitive elements and protein coding sequence, and highlighted an expansion of Alcohol dehydrogenase genes. Comparative analysis with orthologous regions of the lepidopteran reference genome allowed assessment of conservation of fine-scale synteny (with detection of new inversions and translocations) and of DNA sequence (with detection of high levels of conservation of non-coding regions around some, but not all, developmental genes). Conclusions The general properties and organization of the available B. anynana genomic sequence are similar to the lepidopteran reference, despite the more than 140 MY divergence. Our results lay the groundwork for further studies of new interesting findings in relation to both coding and non-coding sequence: 1) the Alcohol dehydrogenase expansion with higher similarity between the five tandemly-repeated B. anynana paralogs than with the corresponding B. mori orthologs, and 2) the high conservation of non-coding sequence around the genes wingless and Ecdysone receptor, both involved in multiple developmental processes including wing pattern formation. PMID:21909358

A Two-Locus Global DNA Barcode for Land Plants: The Coding rbcL Gene Complements the Non-Coding trnH-psbA Spacer Region

PubMed Central

Kress, W. John; Erickson, David L.

2007-01-01

Background A useful DNA barcode requires sufficient sequence variation to distinguish between species and ease of application across a broad range of taxa. Discovery of a DNA barcode for land plants has been limited by intrinsically lower rates of sequence evolution in plant genomes than that observed in animals. This low rate has complicated the trade-off in finding a locus that is universal and readily sequenced and has sufficiently high sequence divergence at the species-level. Methodology/Principal Findings Here, a global plant DNA barcode system is evaluated by comparing universal application and degree of sequence divergence for nine putative barcode loci, including coding and non-coding regions, singly and in pairs across a phylogenetically diverse set of 48 genera (two species per genus). No single locus could discriminate among species in a pair in more than 79% of genera, whereas discrimination increased to nearly 88% when the non-coding trnH-psbA spacer was paired with one of three coding loci, including rbcL. In silico trials were conducted in which DNA sequences from GenBank were used to further evaluate the discriminatory power of a subset of these loci. These trials supported the earlier observation that trnH-psbA coupled with rbcL can correctly identify and discriminate among related species. Conclusions/Significance A combination of the non-coding trnH-psbA spacer region and a portion of the coding rbcL gene is recommended as a two-locus global land plant barcode that provides the necessary universality and species discrimination. PMID:17551588

Differentiation of Populus species using chloroplast single nucleotide polymorphism (SNP) markers--essential for comprehensible and reliable poplar breeding.

PubMed

Schroeder, H; Hoeltken, A M; Fladung, M

2012-03-01

Within the genus Populus several species belonging to different sections are cross-compatible. Hence, high numbers of interspecies hybrids occur naturally and, additionally, have been artificially produced in huge breeding programmes during the last 100 years. Therefore, determination of a single poplar species, used for the production of 'multi-species hybrids' is often difficult, and represents a great challenge for the use of molecular markers in species identification. Within this study, over 20 chloroplast regions, both intergenic spacers and coding regions, have been tested for their ability to differentiate different poplar species using 23 already published barcoding primer combinations and 17 newly designed primer combinations. About half of the published barcoding primers yielded amplification products, whereas the new primers designed on the basis of the total sequenced cpDNA genome of Populus trichocarpa Torr. & Gray yielded much higher amplification success. Intergenic spacers were found to be more variable than coding regions within the genus Populus. The highest discrimination power of Populus species was found in the combination of two intergenic spacers (trnG-psbK, psbK-psbl) and the coding region rpoC. In barcoding projects, the coding regions matK and rbcL are often recommended, but within the genus Populus they only show moderate variability and are not efficient in species discrimination. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

The θ-γ neural code.

PubMed

Lisman, John E; Jensen, Ole

2013-03-20

Theta and gamma frequency oscillations occur in the same brain regions and interact with each other, a process called cross-frequency coupling. Here, we review evidence for the following hypothesis: that the dual oscillations form a code for representing multiple items in an ordered way. This form of coding has been most clearly demonstrated in the hippocampus, where different spatial information is represented in different gamma subcycles of a theta cycle. Other experiments have tested the functional importance of oscillations and their coupling. These involve correlation of oscillatory properties with memory states, correlation with memory performance, and effects of disrupting oscillations on memory. Recent work suggests that this coding scheme coordinates communication between brain regions and is involved in sensory as well as memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

Internal ballistics model update for ASRM dome

NASA Technical Reports Server (NTRS)

Bowden, Mark H.; Jenkins, Billy Z.

1991-01-01

A previous report (no. 5-32279, contract NAS8-36955, DO 51) describes the measures taken to adapt the NASA Complex Burning Region Model and code so that is was applicable to the Advanced Solid Rocket Motor as envisioned at that time. The code so modified was called the CBRM-A. CBRM-A could calculate the port volume and burning area for the star, transition, and cylindrically perforated regions of the motor. Described here is a subsequent effort to add computation of port volume and burning area for the Advanced Solid Rocket Motor head dome. Sample output, input, and overview of the models are included. The software was configured in two forms - a stand alone head dome code and a code integrating the head dome solution with the CBRM-A.

In silico screening of the chicken genome for overlaps between genomic regions: microRNA genes, coding and non-coding transcriptional units, QTL, and genetic variations.

PubMed

Zorc, Minja; Kunej, Tanja

2016-05-01

MicroRNAs (miRNAs) are a class of non-coding RNAs involved in posttranscriptional regulation of target genes. Regulation requires complementarity between target mRNA and the mature miRNA seed region, responsible for their recognition and binding. It has been estimated that each miRNA targets approximately 200 genes, and genetic variability of miRNA genes has been reported to affect phenotypic variability and disease susceptibility in humans, livestock species, and model organisms. Polymorphisms in miRNA genes could therefore represent biomarkers for phenotypic traits in livestock animals. In our previous study, we collected polymorphisms within miRNA genes in chicken. In the present study, we identified miRNA-related genomic overlaps to prioritize genomic regions of interest for further functional studies and biomarker discovery. Overlapping genomic regions in chicken were analyzed using the following bioinformatics tools and databases: miRNA SNiPer, Ensembl, miRBase, NCBI Blast, and QTLdb. Out of 740 known pre-miRNA genes, 263 (35.5 %) contain polymorphisms; among them, 35 contain more than three polymorphisms The most polymorphic miRNA genes in chicken are gga-miR-6662, containing 23 single nucleotide polymorphisms (SNPs) within the pre-miRNA region, including five consecutive SNPs, and gga-miR-6688, containing ten polymorphisms including three consecutive polymorphisms. Several miRNA-related genomic hotspots have been revealed in chicken genome; polymorphic miRNA genes are located within protein-coding and/or non-coding transcription units and quantitative trait loci (QTL) associated with production traits. The present study includes the first description of an exonic miRNA in a chicken genome, an overlap between the miRNA gene and the exon of the protein-coding gene (gga-miR-6578/HADHB), and the first report of a missense polymorphism located within a mature miRNA seed region. Identified miRNA-related genomic hotspots in chicken can serve researchers as a starting point for further functional studies and association studies with poultry production and health traits and the basis for systematic screening of exonic miRNAs and missense/miRNA seed polymorphisms in other genomes.

Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for highly accurate CNV and SNP/INDEL detection.

PubMed

Alvarado, David M; Yang, Ping; Druley, Todd E; Lovett, Michael; Gurnett, Christina A

2014-06-01

Despite declining sequencing costs, few methods are available for cost-effective single-nucleotide polymorphism (SNP), insertion/deletion (INDEL) and copy number variation (CNV) discovery in a single assay. Commercially available methods require a high investment to a specific region and are only cost-effective for large samples. Here, we introduce a novel, flexible approach for multiplexed targeted sequencing and CNV analysis of large genomic regions called multiplexed direct genomic selection (MDiGS). MDiGS combines biotinylated bacterial artificial chromosome (BAC) capture and multiplexed pooled capture for SNP/INDEL and CNV detection of 96 multiplexed samples on a single MiSeq run. MDiGS is advantageous over other methods for CNV detection because pooled sample capture and hybridization to large contiguous BAC baits reduces sample and probe hybridization variability inherent in other methods. We performed MDiGS capture for three chromosomal regions consisting of ∼ 550 kb of coding and non-coding sequence with DNA from 253 patients with congenital lower limb disorders. PITX1 nonsense and HOXC11 S191F missense mutations were identified that segregate in clubfoot families. Using a novel pooled-capture reference strategy, we identified recurrent chromosome chr17q23.1q23.2 duplications and small HOXC 5' cluster deletions (51 kb and 12 kb). Given the current interest in coding and non-coding variants in human disease, MDiGS fulfills a niche for comprehensive and low-cost evaluation of CNVs, coding, and non-coding variants across candidate regions of interest. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Prevalence of Chronic Hypoparathyroidism in a Mediterranean Region as Estimated by the Analysis of Anonymous Healthcare Database.

PubMed

Cianferotti, Luisella; Parri, Simone; Gronchi, Giorgio; Marcucci, Gemma; Cipriani, Cristiana; Pepe, Jessica; Raglianti, Marco; Minisola, Salvatore; Brandi, Maria Luisa

2018-03-08

Epidemiological data on prevalence and incidence of chronic hypoparathyroidism are still scarce. This study aimed to establish prevalence of chronic hypoparathyroidism and incidence of surgical hypoparathyroidism using the analysis of electronic anonymous public health care database. Data referred to a 5-year period (2009-2013, Region of Tuscany, Italy, as a sample representative of the whole Mediterranean/European population, estimated mean population: 3,750,000 inhabitants) were retrieved by the analysis of pharmaceutical distribution dataset, containing data related to drugs reimbursed by public health system, hospital discharge and procedures codes, and ICD9 exemption codes for chronic diseases. The application of a specific algorithm was applied to indirectly identify people with chronic hypoparathyroidism as assuming chronic therapy with active vitamin D metabolites (AVDM). The number of people taking AVDM for a period equal to or longer than 6 months till the end of the study period, with ICD9 exemption code for hypoparathyroidism, and with a disease-related discharge code were identified. Within this restricted group, patients with chronic kidney disease and osteoporosis were excluded. The indirect estimate of chronic hypoparathyroidism in a European Mediterranean subpopulation by means of the analysis of chronic therapy with AVDM was 27/100,000 inhabitants (female:male ratio = 2.2:1), with a mean age of 63.5 ± 16.7 years. The risk of developing hypoparathyroidism after neck surgery was 1.5%. While the epidemiological approaches based on disease code and hospital discharge code greatly underestimates the prevalence of hypoparathyroidism, the indirect estimate of this disease through the analysis of prescriptions of AVDM in a European region is in line with the results of studies performed in other regions of the world.

A Primer on Choosing the Medium for Multimedia: Videodisc vs. Videotape.

ERIC Educational Resources Information Center

Shamp, Scott A.

1993-01-01

Discusses videodisc and videotape basic needs, software development issues, user workstation issues, appropriate applications for the different audio/visual storage media, counter vs. time-code VCRs, and implications for student development. (MDH)

Negligible impact of rare autoimmune-locus coding-region variants on missing heritability.

PubMed

Hunt, Karen A; Mistry, Vanisha; Bockett, Nicholas A; Ahmad, Tariq; Ban, Maria; Barker, Jonathan N; Barrett, Jeffrey C; Blackburn, Hannah; Brand, Oliver; Burren, Oliver; Capon, Francesca; Compston, Alastair; Gough, Stephen C L; Jostins, Luke; Kong, Yong; Lee, James C; Lek, Monkol; MacArthur, Daniel G; Mansfield, John C; Mathew, Christopher G; Mein, Charles A; Mirza, Muddassar; Nutland, Sarah; Onengut-Gumuscu, Suna; Papouli, Efterpi; Parkes, Miles; Rich, Stephen S; Sawcer, Steven; Satsangi, Jack; Simmonds, Matthew J; Trembath, Richard C; Walker, Neil M; Wozniak, Eva; Todd, John A; Simpson, Michael A; Plagnol, Vincent; van Heel, David A

2013-06-13

Genome-wide association studies (GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute. To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set. This approach fails to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon-sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 UK residents of white European origin, comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility. These results do not support the rare-variant synthetic genome-wide-association hypothesis (in which unobserved rare causal variants lead to association detected at common tag variants). Many known autoimmune disease risk loci contain multiple, independently associated, common and low-frequency variants, and so genes at these loci are a priori stronger candidates for harbouring rare coding-region variants than other genes. Our data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect.

Mars Atmospheric Temperature and Dust Storm Tracking

NASA Image and Video Library

2016-06-09

This graphic overlays Martian atmospheric temperature data as curtains over an image of Mars taken during a regional dust storm. The temperature profiles extend from the surface to about 50 miles (80 kilometers) up. Temperatures are color coded, ranging from minus 243 degrees Fahrenheit (minus 153 degrees Celsius) where coded purple to minus 9 F (minus 23 C) where coded red. The temperature data and global image were both recorded on Oct. 18, 2014, by instruments on NASA's Mars Reconnaissance Orbiter: Mars Climate Sounder and Mars Color Imager. On that day a regional dust storm was active in the Acidalia Planitia region of northern Mars, at the upper center of this image. A storm from this area in typically travels south and grows into a large regional storm in the southern hemisphere during southern spring. That type of southern-spring storm and two other large regional dust storms repeat as a three-storm series most Martian years. The pattern has been identified from their effects on atmospheric temperature in a layer about 16 miles (25 kilometers) above the surface. http://photojournal.jpl.nasa.gov/catalog/PIA20747

Reliability of cause of death coding: an international comparison.

PubMed

Antini, Carmen; Rajs, Danuta; Muñoz-Quezada, María Teresa; Mondaca, Boris Andrés Lucero; Heiss, Gerardo

2015-07-01

This study evaluates the agreement of nosologic coding of cardiovascular causes of death between a Chilean coder and one in the United States, in a stratified random sample of death certificates of persons aged ≥ 60, issued in 2008 in the Valparaíso and Metropolitan regions, Chile. All causes of death were converted to ICD-10 codes in parallel by both coders. Concordance was analyzed with inter-coder agreement and Cohen's kappa coefficient by level of specification ICD-10 code for the underlying cause and the total causes of death coding. Inter-coder agreement was 76.4% for all causes of death and 80.6% for the underlying cause (agreement at the four-digit level), with differences by the level of specification of the ICD-10 code, by line of the death certificate, and by number of causes of death per certificate. Cohen's kappa coefficient was 0.76 (95%CI: 0.68-0.84) for the underlying cause and 0.75 (95%CI: 0.74-0.77) for the total causes of death. In conclusion, causes of death coding and inter-coder agreement for cardiovascular diseases in two regions of Chile are comparable to an external benchmark and with reports from other countries.

A long-term, integrated impact assessment of alternative building energy code scenarios in China

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

Yu, Sha; Eom, Jiyong; Evans, Meredydd

2014-04-01

China is the second largest building energy user in the world, ranking first and third in residential and commercial energy consumption. Beginning in the early 1980s, the Chinese government has developed a variety of building energy codes to improve building energy efficiency and reduce total energy demand. This paper studies the impact of building energy codes on energy use and CO2 emissions by using a detailed building energy model that represents four distinct climate zones each with three building types, nested in a long-term integrated assessment framework GCAM. An advanced building stock module, coupled with the building energy model, ismore » developed to reflect the characteristics of future building stock and its interaction with the development of building energy codes in China. This paper also evaluates the impacts of building codes on building energy demand in the presence of economy-wide carbon policy. We find that building energy codes would reduce Chinese building energy use by 13% - 22% depending on building code scenarios, with a similar effect preserved even under the carbon policy. The impact of building energy codes shows regional and sectoral variation due to regionally differentiated responses of heating and cooling services to shell efficiency improvement.« less

Quality of head injury coding from autopsy reports with AIS © 2005 update 2008.

PubMed

Schick, Sylvia; Humrich, Anton; Graw, Matthias

2018-02-28

ABSTACT Objective: Coding injuries from autopsy reports of traffic accident victims according to Abbreviated Injury Scale AIS © 2005 update 2008 [1] is quite time consuming. The suspicion arose, that many issues leading to discussion between coder and control reader were based on information required by the AIS that was not documented in the autopsy reports. To quantify this suspicion, we introduced an AIS-detail-indicator (AIS-DI). To each injury in the AIS Codebook one letter from A to N was assigned indicating the level of detail. Rules were formulated to receive repeatable assignments. This scheme was applied to a selection of 149 multiply injured traffic fatalities. The frequencies of "not A" codes were calculated for each body region and it was analysed, why the most detailed level A had not been coded. As a first finding, the results of the head region are presented. 747 AIS head injury codes were found in 137 traffic fatalities, and 60% of these injuries were coded with an AIS-DI of level A. There are three different explanations for codes of AIS-DI "not A": Group 1 "Missing information in autopsy report" (5%), Group 2 "Clinical data required by AIS" (20%), and Group 3 "AIS system determined" (15%). Groups 1 and 2 show consequences for the ISS in 25 cases. Other body regions might perform differently. The AIS-DI can indicate the quality of the underlying data basis and, depending on the aims of different AIS users it can be a helpful tool for quality checks.

Health sciences librarians' awareness and assessment of the Medical Library Association Code of Ethics for Health Sciences Librarianship: the results of a membership survey

PubMed Central

Byrd, Gary D.; Devine, Patricia J.; Corcoran, Kate E.

2014-01-01

Objective: The Medical Library Association (MLA) Board of Directors and president charged an Ethical Awareness Task Force and recommended a survey to determine MLA members' awareness of and opinions about the current Code of Ethics for Health Sciences Librarianship. Methods: The task force and MLA staff crafted a survey to determine: (1) awareness of the MLA code and its provisions, (2) use of the MLA code to resolve professional ethical issues, (3) consultation of other ethical codes or guides, (4) views regarding the relative importance of the eleven MLA code statements, (5) challenges experienced in following any MLA code provisions, and (6) ethical problems not clearly addressed by the code. Results: Over 500 members responded (similar to previous MLA surveys), and while most were aware of the code, over 30% could not remember when they had last read or thought about it, and nearly half had also referred to other codes or guidelines. The large majority thought that: (1) all code statements were equally important, (2) none were particularly difficult or challenging to follow, and (3) the code covered every ethical challenge encountered in their professional work. Implications: Comments provided by respondents who disagreed with the majority views suggest that the MLA code could usefully include a supplementary guide with practical advice on how to reason through a number of ethically challenging situations that are typically encountered by health sciences librarians. PMID:25349544

Nonlinear Equatorial Spread F: The Effect of Neutral Winds and Background Pedersen Conductivity.

DTIC Science & Technology

1981-07-29

course of our simulation. This is tantamount to neglecting compressibility (Pedersen mobility ) effects in the E region plasma. Thus, we are utilizing...Neier - Code 4141 Or. C. Szszczowlcz - Code 4187 Utah State Universityr. j. Goodn - code 4180 4th N. and 8th Streets Science Aplications . Inc. Loan

Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function.

PubMed

Pauli, Andreina; Prata, Diana P; Mechelli, Andrea; Picchioni, Marco; Fu, Cynthia H Y; Chaddock, Christopher A; Kane, Fergus; Kalidindi, Sridevi; McDonald, Colm; Kravariti, Eugenia; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Ehlert, Natascha; Georgiades, Anna; Murray, Robin; Collier, David A; McGuire, Philip

2013-09-01

The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

The overexpression of RXam1, a cassava gene coding for an RLK, confers disease resistance to Xanthomonas axonopodis pv. manihotis.

PubMed

Díaz Tatis, Paula A; Herrera Corzo, Mariana; Ochoa Cabezas, Juan C; Medina Cipagauta, Adriana; Prías, Mónica A; Verdier, Valerie; Chavarriaga Aguirre, Paul; López Carrascal, Camilo E

2018-04-01

The overexpression of RXam1 leads to a reduction in bacterial growth of XamCIO136, suggesting that RXam1 might be implicated in strain-specific resistance. Cassava bacterial blight (CBB) caused by Xanthomonas axonopodis pv. manihotis (Xam) is a prevalent disease in all regions, where cassava is cultivated. CBB is a foliar and vascular disease usually controlled through host resistance. Previous studies have found QTLs explaining resistance to several Xam strains. Interestingly, one QTL called XM5 that explained 13% of resistance to XamCIO136 was associated with a similar fragment of the rice Xa21-resistance gene called PCR250. In this study, we aimed to further identify and characterize this fragment and its role in resistance to CBB. Screening and hybridization of a BAC library using the molecular marker PCR250 as a probe led to the identification of a receptor-like kinase similar to Xa21 and were called RXam1 (Resistance to Xam 1). Here, we report the functional characterization of susceptible cassava plants overexpressing RXam1. Our results indicated that the overexpression of RXam1 leads to a reduction in bacterial growth of XamCIO136. This suggests that RXAM1 might be implicated in strain-specific resistance to XamCIO136.

The chloroplast tRNALys(UUU) gene from mustard (Sinapis alba) contains a class II intron potentially coding for a maturase-related polypeptide.

PubMed

Neuhaus, H; Link, G

1987-01-01

The trnK gene endocing the tRNALys(UUU) has been located on mustard (Sinapis alba) chloroplast DNA, 263 bp upstream of the psbA gene on the same strand. The nucleotide sequence of the trnK gene and its flanking regions as well as the putative transcription start and termination sites are shown. The 5' end of the transcript lies 121 bp upstream of the 5' tRNA coding region and is preceded by procaryotic-type "-10" and "-35" sequence elements, while the 3' end maps 2.77 kb downstream to a DNA region with possible stemloop secondary structure. The anticodon loop of the tRNALys is interrupted by a 2,574 bp intron containing a long open reading frame, which codes for 524 amino acids. Based on conserved stem and loop structures, this intron has characteristic features of a class II intron. A region near the carboxyl terminus of the derived polypeptide appears structurally related to maturases.

TREM2 is associated with increased risk for Alzheimer's disease in African Americans.

PubMed

Jin, Sheng Chih; Carrasquillo, Minerva M; Benitez, Bruno A; Skorupa, Tara; Carrell, David; Patel, Dwani; Lincoln, Sarah; Krishnan, Siddharth; Kachadoorian, Michaela; Reitz, Christiane; Mayeux, Richard; Wingo, Thomas S; Lah, James J; Levey, Allan I; Murrell, Jill; Hendrie, Hugh; Foroud, Tatiana; Graff-Radford, Neill R; Goate, Alison M; Cruchaga, Carlos; Ertekin-Taner, Nilüfer

2015-04-10

TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin. This study evaluated the role of TREM2 in LOAD risk in African-American (AA) subjects. We performed exonic sequencing and validation in two independent cohorts of >800 subjects. We selected six coding variants (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, and p.L211P) for case-control analyses in a total of 906 LOAD cases vs. 2,487 controls. We identified significant LOAD risk association with p.L211P (p=0.01, OR=1.27, 95%CI=1.05-1.54) and suggestive association with p.W191X (p=0.08, OR=1.35, 95%CI=0.97-1.87). Conditional analysis suggests that p.L211P, which is in linkage disequilibrium with p.W191X, may be the stronger variant of the two, but does not rule out independent contribution of the latter. TREM2 p.L211P resides within the cytoplasmic domain and p.W191X is a stop-gain mutation within the shorter TREM-2V transcript. The coding variants within the extracellular domain of TREM2 previously shown to confer LOAD risk in Caucasians were extremely rare in our AA cohort and did not associate with LOAD risk. Our findings suggest that TREM2 coding variants also confer LOAD risk in AA, but implicate variants within different regions of the gene than those identified for Caucasian subjects. These results underscore the importance of investigating different ethnic populations for disease risk variant discovery, which may uncover allelic heterogeneity with potentially diverse mechanisms of action.

Major trauma: the unseen financial burden to trauma centres, a descriptive multicentre analysis.

PubMed

Curtis, Kate; Lam, Mary; Mitchell, Rebecca; Dickson, Cara; McDonnell, Karon

2014-02-01

This research examines the existing funding model for in-hospital trauma patient episodes in New South Wales (NSW), Australia and identifies factors that cause above-average treatment costs. Accurate information on the treatment costs of injury is needed to guide health-funding strategy and prevent inadvertent underfunding of specialist trauma centres, which treat a high trauma casemix. Admitted trauma patient data provided by 12 trauma centres were linked with financial data for 2008-09. Actual costs incurred by each hospital were compared with state-wide Australian Refined Diagnostic Related Groups (AR-DRG) average costs. Patient episodes where actual cost was higher than AR-DRG cost allocation were examined. There were 16693 patients at a total cost of AU$178.7million. The total costs incurred by trauma centres were $14.7million above the NSW peer-group average cost estimates. There were 10 AR-DRG where the total cost variance was greater than $500000. The AR-DRG with the largest proportion of patients were the upper limb injury categories, many of whom had multiple body regions injured and/or a traumatic brain injury (P<0.001). AR-DRG classifications do not adequately describe the trauma patient episode and are not commensurate with the expense of trauma treatment. A revision of AR-DRG used for trauma is needed. WHAT IS KNOWN ABOUT THIS TOPIC? Severely injured trauma patients often have multiple injuries, in more than one body region and the determination of appropriate AR-DRG can be difficult. Pilot research suggests that the AR-DRG do not accurately represent the care that is required for these patients. WHAT DOES THIS PAPER ADD? This is the first multicentre analysis of treatment costs and coding variance for major trauma in Australia. This research identifies the limitations of the current AR-DRGS and those that are particularly problematic. The value of linking trauma registry and financial data within each trauma centre is demonstrated. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Further work should be conducted between trauma services, clinical coding and finance departments to improve the accuracy of clinical coding, review funding models and ensure that AR-DRG allocation is commensurate with the expense of trauma treatment.

Simple tool for the rapid, automated quantification of glacier advance/retreat observations using multiple methods

NASA Astrophysics Data System (ADS)

Lea, J.

2017-12-01

The quantification of glacier change is a key variable within glacier monitoring, with the method used potentially being crucial to ensuring that data can be appropriately compared with environmental data. The topic and timescales of study (e.g. land/marine terminating environments; sub-annual/decadal/centennial/millennial timescales) often mean that different methods are more suitable for different problems. However, depending on the GIS/coding expertise of the user, some methods can potentially be time consuming to undertake, making large-scale studies problematic. In addition, examples exist where different users have nominally applied the same methods in different studies, though with minor methodological inconsistencies in their approach. In turn, this will have implications for data homogeneity where regional/global datasets may be constructed. Here, I present a simple toolbox scripted in a Matlab® environment that requires only glacier margin and glacier centreline data to quantify glacier length, glacier change between observations, rate of change, in addition to other metrics. The toolbox includes the option to apply the established centreline or curvilinear box methods, or a new method: the variable box method - designed for tidewater margins where box width is defined as the total width of the individual terminus observation. The toolbox is extremely flexible, and has the option to be applied as either Matlab® functions within user scripts, or via a graphical user interface (GUI) for those unfamiliar with a coding environment. In both instances, there is potential to apply the methods quickly to large datasets (100s-1000s of glaciers, with potentially similar numbers of observations each), thus ensuring large scale methodological consistency (and therefore data homogeneity) and allowing regional/global scale analyses to be achievable for those with limited GIS/coding experience. The toolbox has been evaluated against idealised scenarios demonstrating its accuracy, while feedback from undergraduate students who have trialled the toolbox is that it is intuitive and simple to use. When released, the toolbox will be free and open source allowing users to potentially modify, improve and expand upon the current version.

Genetic Diversity and Natural Selection in 42 kDa Region of Plasmodium vivax Merozoite Surface Protein-1 from China-Myanmar Endemic Border.

PubMed

Zhou, Xia; Tambo, Ernest; Su, Jing; Fang, Qiang; Ruan, Wei; Chen, Jun-Hu; Yin, Ming-Bo; Zhou, Xiao-Nong

2017-10-01

Plasmodium vivax merozoite surface protein-1 (PvMSP1) gene codes for a major malaria vaccine candidate antigen. However, its polymorphic nature represents an obstacle to the design of a protective vaccine. In this study, we analyzed the genetic polymorphism and natural selection of the C-terminal 42 kDa fragment within PvMSP1 gene (Pv MSP142) from 77 P. vivax isolates, collected from imported cases of China-Myanmar border (CMB) areas in Yunnan province and the inland cases from Anhui, Yunnan, and Zhejiang province in China during 2009-2012. Totally, 41 haplotypes were identified and 30 of them were new haplotypes. The differences between the rates of non-synonymous and synonymous mutations suggest that PvMSP142 has evolved under natural selection, and a high selective pressure preferentially acted on regions identified of PvMSP133. Our results also demonstrated that PvMSP142 of P. vivax isolates collected on China-Myanmar border areas display higher genetic polymorphisms than those collected from inland of China. Such results have significant implications for understanding the dynamic of the P. vivax population and may be useful information towards China malaria elimination campaign strategies.

Broad Halpha Wing Formation in the Planetary Nebula IC 4997.

PubMed

Lee; Hyung

2000-02-10

The young and compact planetary nebula IC 4997 is known to exhibit very broad wings with a width exceeding 5000 km s-1 around Halpha. We propose that the broad wings are formed through Rayleigh-Raman scattering that involves atomic hydrogen, by which Lybeta photons with a velocity width of a few 102 km s-1 are converted to optical photons and fill the Halpha broad wing region. The conversion efficiency reaches 0.6 near the line center, where the scattering optical depth is much larger than 1, and rapidly decreases in the far wings. Assuming that close to the central star there exists an unresolved inner compact core of high density, nH approximately 109-1010 cm-3, we use the photoionization code "CLOUDY" to show that sufficient Lybeta photons for scattering are produced. Using a top-hat-incident profile for the Lybeta flux and a scattering region with a H i column density NHi=2x1020 cm-2 and a substantial covering factor, we perform a profile-fitting analysis in order to obtain a satisfactory fit to the observed flux. We briefly discuss the astrophysical implications of the Rayleigh-Raman processes in planetary nebulae and other emission objects.

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

PubMed Central

2014-01-01

Background Although genetic variation is believed to contribute to an individual’s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder. Results Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Conclusions Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease. PMID:24694013

Lack of mutations in the leptin receptor gene in severely obese children.

PubMed

Dias, Natasha Favoretto; Fernandes, Ariana Ester; Melo, Maria Edna de; Reinhardt, Heidi Lui; Cercato, Cintia; Villares, Sandra Mara Ferreira; Halpern, Alfredo; Mancini, Marcio C

2012-04-01

To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients.

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes.

PubMed

Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A

2015-10-01

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. © The Author 2014. Published by Oxford University Press.

The expanding roles of microRNAs in kidney pathophysiology.

PubMed

Metzinger-Le Meuth, Valérie; Fourdinier, Ophélie; Charnaux, Nathalie; Massy, Ziad A; Metzinger, Laurent

2018-05-25

MicroRNAs (miRNAs) are short single-stranded RNAs that control gene expression through base pairing with regions within the 3'-untranslated region of target mRNAs. These small non-coding RNAs are now increasingly known to be involved in kidney physiopathology. In this review we will describe how miRNAs were in recent years implicated in cellular and animal models of kidney disease but also in chronic kidney disease, haemodialysed and grafted patients, acute kidney injury patients and so on. At the moment miRNAs are considered as potential biomarkers in nephrology, but larger cohorts as well as the standardization of methods of measurement will be needed to confirm their usefulness. It will further be of the utmost importance to select specific tissues and biofluids to make miRNAs appropriate in day-to-day clinical practice. In addition, up- or down-regulating miRNAs that were described as deregulated in kidney diseases may represent innovative therapeutic methods to cure these disorders. We will enumerate in this review the most recent methods that can be used to deliver miRNAs in a specific and suitable way in kidney and other organs damaged by kidney failure, such as the cardiovascular system.

Social responsibility of nursing: a global perspective.

PubMed

Tyer-Viola, Lynda; Nicholas, Patrice K; Corless, Inge B; Barry, Donna M; Hoyt, Pamela; Fitzpatrick, Joyce J; Davis, Sheila M

2009-05-01

This study addresses social responsibility in the discipline of nursing and implications for global health. The concept of social responsibility is explicated and its relevance for nursing is examined, grounded in the American Nurses Association Code of Ethics and the International Council of Nurses Code of Ethics. Social justice, human rights, nurse migration, and approaches to nursing education are discussed within the framework of nursing's social responsibility. Strategies for addressing nursing workforce issues and education within a framework of social responsibility are explored.

International labour migration in the Asian-Pacific region: patterns, policies and economic implications.

PubMed

Athukorala, P

1993-11-01

"This paper reviews the literature on international labour migration from and within the Asian-Pacific region. It deals with patterns and characteristics of migration flows, government policies towards labour migration, and economic implications of labour migration for both labour-exporting and importing countries in the region. The indications are that, despite gradual slowing down of labour flows to the western industrial countries and the Middle East, labour migration will continue to be a major economic influence on surplus-labour countries in the region. As an integral part of the growth dynamism in the region, labour migration has now begun to take on a regional dimension, with immense implications for the process of industrial restructuring in high growth economies and the changing pattern of economic interdependence among countries." excerpt

The adaptive significance of adult neurogenesis: an integrative approach

PubMed Central

Konefal, Sarah; Elliot, Mick; Crespi, Bernard

2013-01-01

Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts. PMID:23882188

Categorical encoding of color in the brain

PubMed Central

Bird, Chris M.; Berens, Samuel C.; Horner, Aidan J.; Franklin, Anna

2014-01-01

The areas of the brain that encode color categorically have not yet been reliably identified. Here, we used functional MRI adaptation to identify neuronal populations that represent color categories irrespective of metric differences in color. Two colors were successively presented within a block of trials. The two colors were either from the same or different categories (e.g., “blue 1 and blue 2” or “blue 1 and green 1”), and the size of the hue difference was varied. Participants performed a target detection task unrelated to the difference in color. In the middle frontal gyrus of both hemispheres and to a lesser extent, the cerebellum, blood-oxygen level-dependent response was greater for colors from different categories relative to colors from the same category. Importantly, activation in these regions was not modulated by the size of the hue difference, suggesting that neurons in these regions represent color categorically, regardless of metric color difference. Representational similarity analyses, which investigated the similarity of the pattern of activity across local groups of voxels, identified other regions of the brain (including the visual cortex), which responded to metric but not categorical color differences. Therefore, categorical and metric hue differences appear to be coded in qualitatively different ways and in different brain regions. These findings have implications for the long-standing debate on the origin and nature of color categories, and also further our understanding of how color is processed by the brain. PMID:24591602

The PARTRAC code: Status and recent developments

NASA Astrophysics Data System (ADS)

Friedland, Werner; Kundrat, Pavel

Biophysical modeling is of particular value for predictions of radiation effects due to manned space missions. PARTRAC is an established tool for Monte Carlo-based simulations of radiation track structures, damage induction in cellular DNA and its repair [1]. Dedicated modules describe interactions of ionizing particles with the traversed medium, the production and reactions of reactive species, and score DNA damage determined by overlapping track structures with multi-scale chromatin models. The DNA repair module describes the repair of DNA double-strand breaks (DSB) via the non-homologous end-joining pathway; the code explicitly simulates the spatial mobility of individual DNA ends in parallel with their processing by major repair enzymes [2]. To simulate the yields and kinetics of radiation-induced chromosome aberrations, the repair module has been extended by tracking the information on the chromosome origin of ligated fragments as well as the presence of centromeres [3]. PARTRAC calculations have been benchmarked against experimental data on various biological endpoints induced by photon and ion irradiation. The calculated DNA fragment distributions after photon and ion irradiation reproduce corresponding experimental data and their dose- and LET-dependence. However, in particular for high-LET radiation many short DNA fragments are predicted below the detection limits of the measurements, so that the experiments significantly underestimate DSB yields by high-LET radiation [4]. The DNA repair module correctly describes the LET-dependent repair kinetics after (60) Co gamma-rays and different N-ion radiation qualities [2]. First calculations on the induction of chromosome aberrations have overestimated the absolute yields of dicentrics, but correctly reproduced their relative dose-dependence and the difference between gamma- and alpha particle irradiation [3]. Recent developments of the PARTRAC code include a model of hetero- vs euchromatin structures to enable accounting for variations in DNA damage yields, complexity and repair between these regions. Second, the applicability of the code to low-energy ions has been extended to full stopping by using a modified Barkas scaling of proton cross sections for ions heavier than helium. Third, ongoing studies aim at hitherto unprecedented benchmarking of the code against experiments with sub-muµm focused bunches of low-LET ions mimicking single high-LET ion tracks [5] which separate effects of damage clustering on a sub-mum scale from DNA damage complexity on a nanometer scale. Fourth, motivated by implications for the involvement of mitochondria in intercellular signaling and radiation-induced bystander effects, ongoing work extends the range of PARTRAC DNA models to radiation effects on mitochondrial DNA. The contribution will discuss the PARTRAC modules, benchmarks to experimental data, recent and ongoing developments of the code, with special attention to its implications and potential applications in radiation protection and space research. Acknowledgement. This work was partially funded by the EU (Contract FP7-249689 ‘DoReMi’). References 1. Friedland et al., Mutat. Res. 711, 28 (2011) 2. Friedland et al., Int. J. Radiat. Biol. 88, 129 (2012) 3. Friedland et al., Mutat. Res. 756, 213 (2013) 4. Alloni et al., Radiat. Res. 179, 690 (2013) 5. Schmid et al., Phys. Med. Biol. 57, 5889 (2012)

Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation

PubMed Central

Pujar, Shashikant; O’Leary, Nuala A; Farrell, Catherine M; Mudge, Jonathan M; Wallin, Craig; Diekhans, Mark; Barnes, If; Bennett, Ruth; Berry, Andrew E; Cox, Eric; Davidson, Claire; Goldfarb, Tamara; Gonzalez, Jose M; Hunt, Toby; Jackson, John; Joardar, Vinita; Kay, Mike P; Kodali, Vamsi K; McAndrews, Monica; McGarvey, Kelly M; Murphy, Michael; Rajput, Bhanu; Rangwala, Sanjida H; Riddick, Lillian D; Seal, Ruth L; Webb, David; Zhu, Sophia; Aken, Bronwen L; Bult, Carol J; Frankish, Adam; Pruitt, Kim D

2018-01-01

Abstract The Consensus Coding Sequence (CCDS) project provides a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assembly in genome annotations produced independently by NCBI and the Ensembl group at EMBL-EBI. This dataset is the product of an international collaboration that includes NCBI, Ensembl, HUGO Gene Nomenclature Committee, Mouse Genome Informatics and University of California, Santa Cruz. Identically annotated coding regions, which are generated using an automated pipeline and pass multiple quality assurance checks, are assigned a stable and tracked identifier (CCDS ID). Additionally, coordinated manual review by expert curators from the CCDS collaboration helps in maintaining the integrity and high quality of the dataset. The CCDS data are available through an interactive web page (https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi) and an FTP site (ftp://ftp.ncbi.nlm.nih.gov/pub/CCDS/). In this paper, we outline the ongoing work, growth and stability of the CCDS dataset and provide updates on new collaboration members and new features added to the CCDS user interface. We also present expert curation scenarios, with specific examples highlighting the importance of an accurate reference genome assembly and the crucial role played by input from the research community. PMID:29126148

Mutations in nsP1 and PE2 are critical determinants of Ross River virus-induced musculoskeletal inflammatory disease in a mouse model

PubMed Central

Jupille, Henri J.; Oko, Lauren; Stoermer, Kristina A.; Heise, Mark T.; Mahalingam, Suresh; Gunn, Bronwyn M.; Morrison, Thomas E.

2010-01-01

The viral determinants of Alphavirus-induced rheumatic disease have not been elucidated. We identified an RRV strain (DC5692) which, in contrast to the T48 strain, does not induce musculoskeletal inflammation in a mouse model of RRV disease. Substitution of the RRV T48 strain nonstructural protein 1 (nsP1) coding sequence with that from strain DC5692 generated a virus that was attenuated in vivo despite similar viral loads in tissues. In contrast, substitution of the T48 PE2 coding region with the PE2 coding region from DC5692 resulted in attenuation in vivo and reduced viral loads in tissues. In gain of virulence experiments, substitution of the DC5692 strain nsP1 and PE2 coding regions with those from the T48 strain was sufficient to restore full virulence to the DC5692 strain. These findings indicate that determinants in both nsP1 and PE2 have critical and distinct roles in the pathogenesis of RRV-induced musculoskeletal inflammatory disease in mice. PMID:21131014

Surgical Approach and Anesthetic Modality for Carpal Tunnel Release: A Nationwide Database Study With Health Care Cost Implications.

PubMed

Foster, Brock D; Sivasundaram, Lakshmanan; Heckmann, Nathanael; Cohen, Jeremiah R; Pannell, William C; Wang, Jeffrey C; Ghiassi, Alidad

2017-03-01

Background: Carpal tunnel release (CTR) is commonly performed for carpal tunnel syndrome once conservative treatment has failed. Operative technique and anesthetic modality vary by surgeon preference and patient factors. However, CTR practices and anesthetic trends have, to date, not been described on a nationwide scale in the United States. Methods: The PearlDiver Patient Records Database was used to search Current Procedural Terminology codes for elective CTR from 2007 to 2011. Anesthetic modality (eg, general and regional anesthesia vs local anesthesia) and surgical approach (eg, endoscopic vs open) were recorded for this patient population. Cost analysis, patient demographics, regional variation, and annual changes in CTR surgery were evaluated. Results: We identified 86 687 patients who underwent carpal tunnel surgery during this 5-year time period. In this patient sample, 80.5% of CTR procedures were performed using general or regional anesthesia, compared with 19.5% of procedures performed using local anesthesia; 83.9% of all CTR were performed in an open fashion, and 16.1% were performed using an endoscopic technique. Endoscopic surgery was on average $794 more expensive than open surgery, and general or regional anesthesia was $654 more costly than local anesthesia. Conclusions: In the United States, open CTR under local anesthesia is the most cost-effective way to perform a CTR. However, only a small fraction of elective CTR procedures are performed with this technique, representing a potential area for significant health care cost savings. In addition, regional and age variations exist in procedure and anesthetic type utilized.

Using multi-level Bayesian lesion-symptom mapping to probe the body-part-specificity of gesture imitation skills.

PubMed

Achilles, Elisabeth I S; Weiss, Peter H; Fink, Gereon R; Binder, Ellen; Price, Cathy J; Hope, Thomas M H

2017-11-01

Past attempts to identify the neural substrates of hand and finger imitation skills in the left hemisphere of the brain have yielded inconsistent results. Here, we analyse those associations in a large sample of 257 left hemisphere stroke patients. By introducing novel Bayesian methods, we characterise lesion symptom associations at three levels: the voxel-level, the single-region level (using anatomically defined regions), and the region-pair level. The results are inconsistent across those three levels and we argue that each level of analysis makes assumptions which constrain the results it can produce. Regardless of the inconsistencies across levels, and contrary to past studies which implicated differential neural substrates for hand and finger imitation, we find no consistent voxels or regions, where damage affects one imitation skill and not the other, at any of the three analysis levels. Our novel Bayesian approach indicates that any apparent differences appear to be driven by an increased sensitivity of hand imitation skills to lesions that also impair finger imitation. In our analyses, the results of the highest level of analysis (region-pairs) emphasise a role of the primary somatosensory and motor cortices, and the occipital lobe in imitation. We argue that this emphasis supports an account of both imitation tasks based on direct sensor-motor connections, which throws doubt on past accounts which imply the need for an intermediate (e.g. body-part-coding) system of representation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Assessment of genetic mutations in the XRCC2 coding region by high resolution melting curve analysis and the risk of differentiated thyroid carcinoma in Iran

PubMed Central

Fayaz, Shima; Fard-Esfahani, Pezhman; Fard-Esfahani, Armaghan; Mostafavi, Ehsan; Meshkani, Reza; Mirmiranpour, Hossein; Khaghani, Shahnaz

2012-01-01

Homologous recombination (HR) is the major pathway for repairing double strand breaks (DSBs) in eukaryotes and XRCC2 is an essential component of the HR repair machinery. To evaluate the potential role of mutations in gene repair by HR in individuals susceptible to differentiated thyroid carcinoma (DTC) we used high resolution melting (HRM) analysis, a recently introduced method for detecting mutations, to examine the entire XRCC2 coding region in an Iranian population. HRM analysis was used to screen for mutations in three XRCC2 coding regions in 50 patients and 50 controls. There was no variation in the HRM curves obtained from the analysis of exons 1 and 2 in the case and control groups. In exon 3, an Arg188His polymorphism (rs3218536) was detected as a new melting curve group (OR: 1.46; 95%CI: 0.432–4.969; p = 0.38) compared with the normal melting curve. We also found a new Ser150Arg polymorphism in exon 3 of the control group. These findings suggest that genetic variations in the XRCC2 coding region have no potential effects on susceptibility to DTC. However, further studies with larger populations are required to confirm this conclusion. PMID:22481871

Parametric modulation of reward sequences during a reversal task in ACC and VMPFC but not amygdala and striatum.

PubMed

Becker, Michael P I; Nitsch, Alexander M; Hewig, Johannes; Miltner, Wolfgang H R; Straube, Thomas

2016-12-01

Several regions of the frontal cortex interact with striatal and amygdala regions to mediate the evaluation of reward-related information and subsequent adjustment of response choices. Recent theories discuss the particular relevance of dorsal anterior cingulate cortex (dACC) for switching behavior; consecutively, ventromedial prefrontal cortex (VMPFC) is involved in mediating exploitative behaviors by tracking reward values unfolding after the behavioral switch. Amygdala, on the other hand, has been implied in coding the valence of stimulus-outcome associations and the ventral striatum (VS) has consistently been shown to code a reward prediction error (RPE). Here, we used fMRI data acquired in humans during a reversal task to parametrically model different sequences of positive feedback in order to unravel differential contributions of these brain regions to the tracking and exploitation of rewards. Parameters from an Optimal Bayesian Learner accurately predicted the divergent involvement of dACC and VMPFC during feedback processing: dACC signaled the first, but not later, presentations of positive feedback, while VMPFC coded trial-by-trial accumulations in reward value. Our results confirm that dACC carries a prominent confirmatory signal during processing of first positive feedback. Amygdala coded positive feedbacks more uniformly, while striatal regions were associated with RPE. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of the insula in intuitive expert bug detection in computer code: an fMRI study.

PubMed

Castelhano, Joao; Duarte, Isabel C; Ferreira, Carlos; Duraes, Joao; Madeira, Henrique; Castelo-Branco, Miguel

2018-05-09

Software programming is a complex and relatively recent human activity, involving the integration of mathematical, recursive thinking and language processing. The neural correlates of this recent human activity are still poorly understood. Error monitoring during this type of task, requiring the integration of language, logical symbol manipulation and other mathematical skills, is particularly challenging. We therefore aimed to investigate the neural correlates of decision-making during source code understanding and mental manipulation in professional participants with high expertise. The present fMRI study directly addressed error monitoring during source code comprehension, expert bug detection and decision-making. We used C code, which triggers the same sort of processing irrespective of the native language of the programmer. We discovered a distinct role for the insula in bug monitoring and detection and a novel connectivity pattern that goes beyond the expected activation pattern evoked by source code understanding in semantic language and mathematical processing regions. Importantly, insula activity levels were critically related to the quality of error detection, involving intuition, as signalled by reported initial bug suspicion, prior to final decision and bug detection. Activity in this salience network (SN) region evoked by bug suspicion was predictive of bug detection precision, suggesting that it encodes the quality of the behavioral evidence. Connectivity analysis provided evidence for top-down circuit "reutilization" stemming from anterior cingulate cortex (BA32), a core region in the SN that evolved for complex error monitoring such as required for this type of recent human activity. Cingulate (BA32) and anterolateral (BA10) frontal regions causally modulated decision processes in the insula, which in turn was related to activity of math processing regions in early parietal cortex. In other words, earlier brain regions used during evolution for other functions seem to be reutilized in a top-down manner for a new complex function, in an analogous manner as described for other cultural creations such as reading and literacy.

Representations of Pitch and Timbre Variation in Human Auditory Cortex

PubMed Central

2017-01-01

Pitch and timbre are two primary dimensions of auditory perception, but how they are represented in the human brain remains a matter of contention. Some animal studies of auditory cortical processing have suggested modular processing, with different brain regions preferentially coding for pitch or timbre, whereas other studies have suggested a distributed code for different attributes across the same population of neurons. This study tested whether variations in pitch and timbre elicit activity in distinct regions of the human temporal lobes. Listeners were presented with sequences of sounds that varied in either fundamental frequency (eliciting changes in pitch) or spectral centroid (eliciting changes in brightness, an important attribute of timbre), with the degree of pitch or timbre variation in each sequence parametrically manipulated. The BOLD responses from auditory cortex increased with increasing sequence variance along each perceptual dimension. The spatial extent, region, and laterality of the cortical regions most responsive to variations in pitch or timbre at the univariate level of analysis were largely overlapping. However, patterns of activation in response to pitch or timbre variations were discriminable in most subjects at an individual level using multivoxel pattern analysis, suggesting a distributed coding of the two dimensions bilaterally in human auditory cortex. SIGNIFICANCE STATEMENT Pitch and timbre are two crucial aspects of auditory perception. Pitch governs our perception of musical melodies and harmonies, and conveys both prosodic and (in tone languages) lexical information in speech. Brightness—an aspect of timbre or sound quality—allows us to distinguish different musical instruments and speech sounds. Frequency-mapping studies have revealed tonotopic organization in primary auditory cortex, but the use of pure tones or noise bands has precluded the possibility of dissociating pitch from brightness. Our results suggest a distributed code, with no clear anatomical distinctions between auditory cortical regions responsive to changes in either pitch or timbre, but also reveal a population code that can differentiate between changes in either dimension within the same cortical regions. PMID:28025255

A novel class sensitive hashing technique for large-scale content-based remote sensing image retrieval

NASA Astrophysics Data System (ADS)

Reato, Thomas; Demir, Begüm; Bruzzone, Lorenzo

2017-10-01

This paper presents a novel class sensitive hashing technique in the framework of large-scale content-based remote sensing (RS) image retrieval. The proposed technique aims at representing each image with multi-hash codes, each of which corresponds to a primitive (i.e., land cover class) present in the image. To this end, the proposed method consists of a three-steps algorithm. The first step is devoted to characterize each image by primitive class descriptors. These descriptors are obtained through a supervised approach, which initially extracts the image regions and their descriptors that are then associated with primitives present in the images. This step requires a set of annotated training regions to define primitive classes. A correspondence between the regions of an image and the primitive classes is built based on the probability of each primitive class to be present at each region. All the regions belonging to the specific primitive class with a probability higher than a given threshold are highly representative of that class. Thus, the average value of the descriptors of these regions is used to characterize that primitive. In the second step, the descriptors of primitive classes are transformed into multi-hash codes to represent each image. This is achieved by adapting the kernel-based supervised locality sensitive hashing method to multi-code hashing problems. The first two steps of the proposed technique, unlike the standard hashing methods, allow one to represent each image by a set of primitive class sensitive descriptors and their hash codes. Then, in the last step, the images in the archive that are very similar to a query image are retrieved based on a multi-hash-code-matching scheme. Experimental results obtained on an archive of aerial images confirm the effectiveness of the proposed technique in terms of retrieval accuracy when compared to the standard hashing methods.

Synchrony and motor mimicking in chimpanzee observational learning

PubMed Central

Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

2014-01-01

Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function. PMID:24923651

Genetics and culture: the geneticization thesis.

PubMed

ten Have, H A

2001-01-01

The concept of 'geneticization' has been introduced in the scholarly literature to describe the various interlocking and imperceptible mechanisms of interaction between medicine, genetics, society and culture. It is argued that Western culture currently is deeply involved in a process of geneticization. This process implies a redefinition of individuals in terms of DNA codes, a new language to describe and interpret human life and behavior in a genomic vocabulary of codes, blueprints, traits, dispositions, genetic mapping, and a gentechnological approach to disease, health and the body. This article analyses the thesis of 'geneticization'. Explaining the implications of the thesis, and discussing the critical refutations, it is argued that 'geneticization' primarily is a heuristic tool that can help to re-focus the moral debate on the implications of new genetic knowledge towards interpersonal relations, the power of medicine, the cultural context and social constraints, rather than emphasizing issues as personal autonomy and individual rights.

Synchrony and motor mimicking in chimpanzee observational learning.

PubMed

Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

2014-06-13

Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function.

Validation of Hydrodynamic Load Models Using CFD for the OC4-DeepCwind Semisubmersible: Preprint

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

Benitz, M. A.; Schmidt, D. P.; Lackner, M. A.

Computational fluid dynamics (CFD) simulations were carried out on the OC4-DeepCwind semi-submersible to obtain a better understanding of how to set hydrodynamic coefficients for the structure when using an engineering tool such as FAST to model the system. The focus here was on the drag behavior and the effects of the free-surface, free-ends and multi-member arrangement of the semi-submersible structure. These effects are investigated through code-to-code comparisons and flow visualizations. The implications on mean load predictions from engineering tools are addressed. The work presented here suggests that selection of drag coefficients should take into consideration a variety of geometric factors.more » Furthermore, CFD simulations demonstrate large time-varying loads due to vortex shedding, which FAST's hydrodynamic module, HydroDyn, does not model. The implications of these oscillatory loads on the fatigue life needs to be addressed.« less

Moral codes of mothering and the introduction of welfare-to-work in Ontario.

PubMed

Gazso, Amber

2012-02-01

In this paper, I trace how the reform of social assistance in Ontario, especially the post-1990s enforcement of lone mothers' employability via welfare-to-work programs, parallels shifts in dominant moral codes of mothering, from "mother-carer" to "mother-worker." Additionally, I use this case as an entry point to consider the implications of public and policy allegiance to these moral codes for all mothers. The central argument I make is that the introduction of welfare-to-work programs in Ontario did not occur in a neoliberal state-sanctioned vacuum but also involved the circulation of ideas about moral mothering outside of policy into policy.

Transcoding method from H.264/AVC to high efficiency video coding based on similarity of intraprediction, interprediction, and motion vector

NASA Astrophysics Data System (ADS)

Liu, Mei-Feng; Zhong, Guo-Yun; He, Xiao-Hai; Qing, Lin-Bo

2016-09-01

Currently, most video resources on line are encoded in the H.264/AVC format. More fluent video transmission can be obtained if these resources are encoded in the newest international video coding standard: high efficiency video coding (HEVC). In order to improve the video transmission and storage on line, a transcoding method from H.264/AVC to HEVC is proposed. In this transcoding algorithm, the coding information of intraprediction, interprediction, and motion vector (MV) in H.264/AVC video stream are used to accelerate the coding in HEVC. It is found through experiments that the region of interprediction in HEVC overlaps that in H.264/AVC. Therefore, the intraprediction for the region in HEVC, which is interpredicted in H.264/AVC, can be skipped to reduce coding complexity. Several macroblocks in H.264/AVC are combined into one PU in HEVC when the MV difference between two of the macroblocks in H.264/AVC is lower than a threshold. This method selects only one coding unit depth and one prediction unit (PU) mode to reduce the coding complexity. An MV interpolation method of combined PU in HEVC is proposed according to the areas and distances between the center of one macroblock in H.264/AVC and that of the PU in HEVC. The predicted MV accelerates the motion estimation for HEVC coding. The simulation results show that our proposed algorithm achieves significant coding time reduction with a little loss in bitrates distortion rate, compared to the existing transcoding algorithms and normal HEVC coding.

NESSY: NLTE spectral synthesis code for solar and stellar atmospheres

NASA Astrophysics Data System (ADS)

Tagirov, R. V.; Shapiro, A. I.; Schmutz, W.

2017-07-01

Context. Physics-based models of solar and stellar magnetically-driven variability are based on the calculation of synthetic spectra for various surface magnetic features as well as quiet regions, which are a function of their position on the solar or stellar disc. Such calculations are performed with radiative transfer codes tailored for modeling broad spectral intervals. Aims: We aim to present the NLTE Spectral SYnthesis code (NESSY), which can be used for modeling of the entire (UV-visible-IR and radio) spectra of solar and stellar magnetic features and quiet regions. Methods: NESSY is a further development of the COde for Solar Irradiance (COSI), in which we have implemented an accelerated Λ-iteration (ALI) scheme for co-moving frame (CMF) line radiation transfer based on a new estimate of the local approximate Λ-operator. Results: We show that the new version of the code performs substantially faster than the previous one and yields a reliable calculation of the entire solar spectrum. This calculation is in a good agreement with the available observations.

RPS8—a New Informative DNA Marker for Phylogeny of Babesia and Theileria Parasites in China

PubMed Central

Tian, Zhan-Cheng; Liu, Guang-Yuan; Yin, Hong; Luo, Jian-Xun; Guan, Gui-Quan; Luo, Jin; Xie, Jun-Ren; Shen, Hui; Tian, Mei-Yuan; Zheng, Jin-feng; Yuan, Xiao-song; Wang, Fang-fang

2013-01-01

Piroplasmosis is a serious debilitating and sometimes fatal disease. Phylogenetic relationships within piroplasmida are complex and remain unclear. We compared the intron–exon structure and DNA sequences of the RPS8 gene from Babesia and Theileria spp. isolates in China. Similar to 18S rDNA, the 40S ribosomal protein S8 gene, RPS8, including both coding and non-coding regions is a useful and novel genetic marker for defining species boundaries and for inferring phylogenies because it tends to have little intra-specific variation but considerable inter-specific difference. However, more samples are needed to verify the usefulness of the RPS8 (coding and non-coding regions) gene as a marker for the phylogenetic position and detection of most Babesia and Theileria species, particularly for some closely related species. PMID:24244571

Molecular analysis of two genes between let-653 and let-56 in the unc-22(IV) region of Caenorhabditis elegans.

PubMed

Marra, M A; Prasad, S S; Baillie, D L

1993-01-01

A previous study of genomic organization described the identification of nine potential coding regions in 150 kb of genomic DNA from the unc-22(IV) region of Caenorhabditis elegans. In this study, we focus on the genomic organization of a small interval of 0.1 map unit bordered on the right by unc-22 and on the left by the left-hand breakpoints of the deficiencies sDf9, sDf19 and sDf65. This small interval at present contains a single mutagenically defined locus, the essential gene let-56. The cosmid C11F2 has previously been used to rescue let-56. Therefore, at least some of C11F2 must reside in the interval. In this paper, we report the characterization of two coding elements that reside on C11F2. Analysis of nucleotide sequence data obtained from cDNAs and cosmid subclones revealed that one of the coding elements closely resembles aromatic amino acid decarboxylases from several species. The other of these coding elements was found to closely resemble a human growth factor activatable Na+/H+ antiporter. Paris of oligonucleotide primers, predicted from both coding elements, have been used in PCR experiments to position these coding elements between the left breakpoint of sDf19 and the left breakpoint of sDf65, between the essential genes let-653 and let-56.

Utility of linking primary care electronic medical records with Canadian census data to study the determinants of chronic disease: an example based on socioeconomic status and obesity.

PubMed

Biro, Suzanne; Williamson, Tyler; Leggett, Jannet Ann; Barber, David; Morkem, Rachael; Moore, Kieran; Belanger, Paul; Mosley, Brian; Janssen, Ian

2016-03-11

Electronic medical records (EMRs) used in primary care contain a breadth of data that can be used in public health research. Patient data from EMRs could be linked with other data sources, such as a postal code linkage with Census data, to obtain additional information on environmental determinants of health. While promising, successful linkages between primary care EMRs with geographic measures is limited due to ethics review board concerns. This study tested the feasibility of extracting full postal code from primary care EMRs and linking this with area-level measures of the environment to demonstrate how such a linkage could be used to examine the determinants of disease. The association between obesity and area-level deprivation was used as an example to illustrate inequalities of obesity in adults. The analysis included EMRs of 7153 patients aged 20 years and older who visited a single, primary care site in 2011. Extracted patient information included demographics (date of birth, sex, postal code) and weight status (height, weight). Information extraction and management procedures were designed to mitigate the risk of individual re-identification when extracting full postal code from source EMRs. Based on patients' postal codes, area-based deprivation indexes were created using the smallest area unit used in Canadian censuses. Descriptive statistics and socioeconomic disparity summary measures of linked census and adult patients were calculated. The data extraction of full postal code met technological requirements for rendering health information extracted from local EMRs into anonymized data. The prevalence of obesity was 31.6 %. There was variation of obesity between deprivation quintiles; adults in the most deprived areas were 35 % more likely to be obese compared with adults in the least deprived areas (Chi-Square = 20.24(1), p < 0.0001). Maps depicting spatial representation of regional deprivation and obesity were created to highlight high risk areas. An area based socio-economic measure was linked with EMR-derived objective measures of height and weight to show a positive association between area-level deprivation and obesity. The linked dataset demonstrates a promising model for assessing health disparities and ecological factors associated with the development of chronic diseases with far reaching implications for informing public health and primary health care interventions and services.

The organization of the posterior parietal cortex devoted to upper limb actions: An fMRI study

PubMed Central

Ferri, Stefania; Rizzolatti, Giacomo

2015-01-01

Abstract The present fMRI study examined whether upper‐limb action classes differing in their motor goal are encoded by different PPC sectors. Action observation was used as a proxy for action execution. Subjects viewed actors performing object‐related (e.g., grasping), skin‐displacing (e.g., rubbing the skin), and interpersonal upper limb actions (e.g., pushing someone). Observation of the three action classes activated a three‐level network including occipito‐temporal, parietal, and premotor cortex. The parietal region common to observing all three action classes was located dorsally to the left intraparietal sulcus (DIPSM/DIPSA border). Regions specific for observing an action class were obtained by combining the interaction between observing action classes and stimulus types with exclusive masking for observing the other classes, while for regions considered preferentially active for a class the interaction was exclusively masked with the regions common to all observed actions. Left putative human anterior intraparietal was specific for observing manipulative actions, and left parietal operculum including putative human SII region, specific for observing skin‐displacing actions. Control experiments demonstrated that this latter activation depended on seeing the skin being moved and not simply on seeing touch. Psychophysiological interactions showed that the two specific parietal regions had similar connectivities. Finally, observing interpersonal actions preferentially activated a dorsal sector of left DIPSA, possibly the homologue of ventral intraparietal coding the impingement of the target person's body into the peripersonal space of the actor. These results support the importance of segregation according to the action class as principle of posterior parietal cortex organization for action observation and by implication for action execution. Hum Brain Mapp 36:3845–3866, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26129732

Molecular and Genetic Characterization of the Drosophila Melanogaster 87e Actin Gene Region

PubMed Central

Manseau, L. J.; Ganetzky, B.; Craig, E. A.

1988-01-01

A combined molecular and genetic analysis of the 87E actin gene (Act87E) in Drosophila melanogaster was undertaken. A clone of Act87E was isolated and characterized. The Act87E transcription unit is 1.57 kb and includes a 556-base intervening sequence in the 5' leader of the gene. The protein-coding region is contiguous and encodes a protein that is >93% identical to the other Drosophila actins. By in situ hybridization with a series of deficiencies that break in 87E, Act87E was localized to a region encompassing one to three faint, polytene chromosome bands. The region between the deficiency endpoints that flank the actin gene was isolated and measures approximately 24-30 kb. The closest proximal deficiency endpoint lies 8-10 kb 5' to the actin gene; the closest distal deficiency endpoint lies 16-20 kb 3' to the actin gene. A single, recessive lethal complementation group lies between the deficiency endpoints that flank the actin gene. An EMS mutagenesis screen produced four additional members of this recessive lethal complementation group. Molecular analysis of the members of this complementation group indicated that two of the newly induced mutations have deletions of approximately 1 kb in a transcribed region 4-5 kb 3' (distal) to the actin gene. This result suggests that the recessive lethal complementation group represents a gene separate from and distal to the actin gene. The mutagenesis screen failed to identify additional recessive lethal complementation groups in the actin gene-containing region. The implications of the failure to identify recessive lethal mutations in the actin gene are discussed in reference to studies of other conserved multigene families and other muscle protein mutations. PMID:2840338

Disentangling representations of shape and action components in the tool network.

PubMed

Wang, Xiaoying; Zhuang, Tonghe; Shen, Jiasi; Bi, Yanchao

2018-05-30

Shape and how they should be used are two key components of our knowledge about tools. Viewing tools preferentially activated a frontoparietal and occipitotemporal network, with dorsal regions implicated in computation of tool-related actions and ventral areas in shape representation. As shape and manners of manipulation are highly correlated for daily tools, whether they are independently represented in different regions remains inconclusive. In the current study, we collected fMRI data when participants viewed blocks of pictures of four daily tools (i.e., paintbrush, corkscrew, screwdriver, razor) where shape and action (manner of manipulation for functional use) were orthogonally manipulated, to tease apart these two dimensions. Behavioral similarity judgments tapping on object shape and finer aspects of actions (i.e., manners of motion, magnitude of arm movement, configuration of hand) were also collected to further disentangle the representation of object shape and different action components. Information analysis and representational similarity analysis were conducted on regional neural activation patterns of the tool-preferring network. In both analyses, the bilateral lateral occipitotemporal cortex showed robust shape representations but could not effectively distinguish between tool-use actions. The frontal and precentral regions represented kinematic action components, whereas the left parietal region (in information analyses) exhibited coding of both shape and tool-use action. By teasing apart shape and action components, we found both dissociation and association of them within the tool network. Taken together, our study disentangles representations for object shape from finer tool-use action components in the tool network, revealing the potential dissociable roles different tool-preferring regions play in tool processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Paradigm Shift in the Implementation of Ethics Codes in Construction Organizations in Hong Kong: Towards an Ethical Behaviour.

PubMed

Ho, Christabel Man-Fong; Oladinrin, Olugbenga Timo

2018-01-30

Due to the economic globalization which is characterized with business scandals, scholars and practitioners are increasingly engaged with the implementation of codes of ethics as a regulatory mechanism for stimulating ethical behaviours within an organization. The aim of this study is to examine various organizational practices regarding the effective implementation of codes of ethics within construction contracting companies. Views on ethics management in construction organizations together with the recommendations for improvement were gleaned through 19 semi-structured interviews, involving construction practitioners from various construction companies in Hong Kong. The findings suggested some practices for effective implementation of codes of ethics in order to diffuse ethical behaviours in an organizational setting which include; introduction of effective reward schemes, arrangement of ethics training for employees, and leadership responsiveness to reported wrongdoings. Since most of the construction companies in Hong Kong have codes of ethics, emphasis is made on the practical implementation of codes within the organizations. Hence, implications were drawn from the recommended measures to guide construction companies and policy makers.

Design implications for task-specific search utilities for retrieval and re-engineering of code

NASA Astrophysics Data System (ADS)

Iqbal, Rahat; Grzywaczewski, Adam; Halloran, John; Doctor, Faiyaz; Iqbal, Kashif

2017-05-01

The importance of information retrieval systems is unquestionable in the modern society and both individuals as well as enterprises recognise the benefits of being able to find information effectively. Current code-focused information retrieval systems such as Google Code Search, Codeplex or Koders produce results based on specific keywords. However, these systems do not take into account developers' context such as development language, technology framework, goal of the project, project complexity and developer's domain expertise. They also impose additional cognitive burden on users in switching between different interfaces and clicking through to find the relevant code. Hence, they are not used by software developers. In this paper, we discuss how software engineers interact with information and general-purpose information retrieval systems (e.g. Google, Yahoo!) and investigate to what extent domain-specific search and recommendation utilities can be developed in order to support their work-related activities. In order to investigate this, we conducted a user study and found that software engineers followed many identifiable and repeatable work tasks and behaviours. These behaviours can be used to develop implicit relevance feedback-based systems based on the observed retention actions. Moreover, we discuss the implications for the development of task-specific search and collaborative recommendation utilities embedded with the Google standard search engine and Microsoft IntelliSense for retrieval and re-engineering of code. Based on implicit relevance feedback, we have implemented a prototype of the proposed collaborative recommendation system, which was evaluated in a controlled environment simulating the real-world situation of professional software engineers. The evaluation has achieved promising initial results on the precision and recall performance of the system.

Polarization simulations of stellar wind bow-shock nebulae - I. The case of electron scattering

NASA Astrophysics Data System (ADS)

Shrestha, Manisha; Neilson, Hilding R.; Hoffman, Jennifer L.; Ignace, Richard

2018-06-01

Bow shocks and related density enhancements produced by the winds of massive stars moving through the interstellar medium provide important information regarding the motions of the stars, the properties of their stellar winds, and the characteristics of the local medium. Since bow-shock nebulae are aspherical structures, light scattering within them produces a net polarization signal even if the region is spatially unresolved. Scattering opacity arising from free electrons and dust leads to a distribution of polarized intensity across the bow-shock structure. That polarization encodes information about the shape, composition, opacity, density, and ionization state of the material within the structure. In this paper, we use the Monte Carlo radiative transfer code SLIP to investigate the polarization created when photons scatter in a bow-shock-shaped region of enhanced density surrounding a stellar source. We present results for electron scattering, and investigate the polarization behaviour as a function of optical depth, temperature, and source of photons for two different cases: pure scattering and scattering with absorption. In both regimes, we consider resolved and unresolved cases. We discuss the implications of these results as well as their possible use along with observational data to constrain the properties of observed bow-shock systems. In different situations and under certain assumptions, our simulations can constrain viewing angle, optical depth and temperature of the scattering region, and the relative luminosities of the star and shock.

Implications of Water Use and Hydroclimatic Anomalies on the Freshwater Sustainability across the US Sunbelt

NASA Astrophysics Data System (ADS)

Arumugam, S.; Sabo, J. L.; Ruhí, A.; Sinha, T.; Kominoski, J. S.; Hagler, M.; Kunkel, K.; Berglund, E.; Larson, K.; Mahinthakumar, K.

2014-12-01

A synthesis on freshwater sustainability is investigated across the US Sunbelt. Spatio-temporal variability of potential drivers - hydroclimate and water use - influencing the freshwater sustainability are examined both individually as well as collectively by considering the eco-region and 4-digit Hydrologic Unit Code (HUC-4)as the spatial reference for the analysis. A detailed analysis on national water use also indicates a north-south gradient with Frostbelt being more efficient in water use as opposed to the Sunbelt. This basically stems from the understanding of regional cross-differences in public supply consumption per capita which is significantly low in high-income urban counties. National analyses on agricultural water use efficiency (i.e., per-acreage application) also shows sprinkler irrigation and micro-irrigation being the primary drivers of differences in agricultural consumption. Given the well-known hydroclimatic west (arid)-east (humid) gradient across the Sunbelt, the study also evaluates the role of flow anomalies - represented by the changes in magnitude, frequency and timing of extremes (high flows and low flows) and by the changes in seasonality - in influencing native fish diversity patterns, as a proxy for freshwater biodiversity, in virgin basins and in basins influenced by significant storage and pumping. Cross-regional differences in water consumption during and after droughts are also presented in the context of adaptations and policy relevance.

THE CODE OF THE STREET AND INMATE VIOLENCE: INVESTIGATING THE SALIENCE OF IMPORTED BELIEF SYSTEMS*

PubMed Central

MEARS, DANIEL P.; STEWART, ERIC A.; SIENNICK, SONJA E.; SIMONS, RONALD L.

2013-01-01

Scholars have long argued that inmate behaviors stem in part from cultural belief systems that they “import” with them into incarcerative settings. Even so, few empirical assessments have tested this argument directly. Drawing on theoretical accounts of one such set of beliefs—the code of the street—and on importation theory, we hypothesize that individuals who adhere more strongly to the street code will be more likely, once incarcerated, to engage in violent behavior and that this effect will be amplified by such incarceration experiences as disciplinary sanctions and gang involvement, as well as the lack of educational programming, religious programming, and family support. We test these hypotheses using unique data that include measures of the street code belief system and incarceration experiences. The results support the argument that the code of the street belief system affects inmate violence and that the effect is more pronounced among inmates who lack family support, experience disciplinary sanctions, and are gang involved. Implications of these findings are discussed. PMID:24068837

Indexing sensory plasticity: Evidence for distinct Predictive Coding and Hebbian learning mechanisms in the cerebral cortex.

PubMed

Spriggs, M J; Sumner, R L; McMillan, R L; Moran, R J; Kirk, I J; Muthukumaraswamy, S D

2018-04-30

The Roving Mismatch Negativity (MMN), and Visual LTP paradigms are widely used as independent measures of sensory plasticity. However, the paradigms are built upon fundamentally different (and seemingly opposing) models of perceptual learning; namely, Predictive Coding (MMN) and Hebbian plasticity (LTP). The aim of the current study was to compare the generative mechanisms of the MMN and visual LTP, therefore assessing whether Predictive Coding and Hebbian mechanisms co-occur in the brain. Forty participants were presented with both paradigms during EEG recording. Consistent with Predictive Coding and Hebbian predictions, Dynamic Causal Modelling revealed that the generation of the MMN modulates forward and backward connections in the underlying network, while visual LTP only modulates forward connections. These results suggest that both Predictive Coding and Hebbian mechanisms are utilized by the brain under different task demands. This therefore indicates that both tasks provide unique insight into plasticity mechanisms, which has important implications for future studies of aberrant plasticity in clinical populations. Copyright © 2018 Elsevier Inc. All rights reserved.

Coupled anisotropic and isotropic tomography of the upper mantle beneath northern Fennoscandia - Application of a novel code AniTomo

NASA Astrophysics Data System (ADS)

Munzarova, Helena; Plomerova, Jaroslava; Kissling, Edi; Vecsey, Ludek; Babuska, Vladislav

2017-04-01

Seismological investigations of the continental mantle lithosphere, particularly its anisotropic structure, advance our understanding of plate tectonics and formation of continents. Orientation of the anisotropic fabrics reflects stress fields during the lithosphere origin and its later deformations. To contribute to studies of the large-scale upper-mantle anisotropy, we have developed code AniTomo for regional anisotropic tomography. AniTomo allows a simultaneous inversion of relative travel time residuals of teleseismic P waves for 3D distribution of isotropic-velocity perturbations and anisotropy in the upper mantle. Weak hexagonal anisotropy with symmetry axis oriented generally in 3D is assumed. The code was successfully tested on a large series of synthetic datasets and synthetic structures. In this contribution we present results of the first application of novel code AniTomo to real data, i.e., relative travel-time residuals of teleseismic P waves recorded during passive seismic experiment LAPNET in the northern Fennoscandia between 2007 and 2009. The region of Fennoscandia is a suitable choice for the first application of the new code. This Precambrian region is tectonically stable and has a thick anisotropic mantle lithosphere (Plomerova and Babuska, Lithos 2010) without significant thermal heterogeneities. In the resulting anisotropic model of the upper mantle beneath the northern Fennoscandia, the strongest anisotropy and the largest velocity perturbations concentrate in the mantle lithosphere. We delimit regions of laterally and vertically consistent anisotropy in the mantle-lithospheric part of the model. In general, the identified anisotropic regions correspond to domains detected by joint interpretation of lateral variations of the P- and SKS-wave anisotropic parameters (Plomerova et al., Solid Earth 2011). Particularly, the mantle lithosphere in the western part of the volume studied exhibits a distinct and uniform fabric that is sharply separated from the surrounding regions. The eastern boundary of this region gradually shifts westward with increasing depth in the tomographic model. We connect the retrieved domain-like anisotropic structure of the mantle lithosphere in the northern Fennoscandia with preserved fossil fabrics of the Archean micro-plates, accreted during the Precambrian orogenic processes.

Video traffic characteristics of modern encoding standards: H.264/AVC with SVC and MVC extensions and H.265/HEVC.

PubMed

Seeling, Patrick; Reisslein, Martin

2014-01-01

Video encoding for multimedia services over communication networks has significantly advanced in recent years with the development of the highly efficient and flexible H.264/AVC video coding standard and its SVC extension. The emerging H.265/HEVC video coding standard as well as 3D video coding further advance video coding for multimedia communications. This paper first gives an overview of these new video coding standards and then examines their implications for multimedia communications by studying the traffic characteristics of long videos encoded with the new coding standards. We review video coding advances from MPEG-2 and MPEG-4 Part 2 to H.264/AVC and its SVC and MVC extensions as well as H.265/HEVC. For single-layer (nonscalable) video, we compare H.265/HEVC and H.264/AVC in terms of video traffic and statistical multiplexing characteristics. Our study is the first to examine the H.265/HEVC traffic variability for long videos. We also illustrate the video traffic characteristics and statistical multiplexing of scalable video encoded with the SVC extension of H.264/AVC as well as 3D video encoded with the MVC extension of H.264/AVC.

Video Traffic Characteristics of Modern Encoding Standards: H.264/AVC with SVC and MVC Extensions and H.265/HEVC

PubMed Central

2014-01-01

Video encoding for multimedia services over communication networks has significantly advanced in recent years with the development of the highly efficient and flexible H.264/AVC video coding standard and its SVC extension. The emerging H.265/HEVC video coding standard as well as 3D video coding further advance video coding for multimedia communications. This paper first gives an overview of these new video coding standards and then examines their implications for multimedia communications by studying the traffic characteristics of long videos encoded with the new coding standards. We review video coding advances from MPEG-2 and MPEG-4 Part 2 to H.264/AVC and its SVC and MVC extensions as well as H.265/HEVC. For single-layer (nonscalable) video, we compare H.265/HEVC and H.264/AVC in terms of video traffic and statistical multiplexing characteristics. Our study is the first to examine the H.265/HEVC traffic variability for long videos. We also illustrate the video traffic characteristics and statistical multiplexing of scalable video encoded with the SVC extension of H.264/AVC as well as 3D video encoded with the MVC extension of H.264/AVC. PMID:24701145

Compression of digital images over local area networks. Appendix 1: Item 3. M.S. Thesis

NASA Technical Reports Server (NTRS)

Gorjala, Bhargavi

1991-01-01

Differential Pulse Code Modulation (DPCM) has been used with speech for many years. It has not been as successful for images because of poor edge performance. The only corruption in DPC is quantizer error but this corruption becomes quite large in the region of an edge because of the abrupt changes in the statistics of the signal. We introduce two improved DPCM schemes; Edge correcting DPCM and Edge Preservation Differential Coding. These two coding schemes will detect the edges and take action to correct them. In an Edge Correcting scheme, the quantizer error for an edge is encoded using a recursive quantizer with entropy coding and sent to the receiver as side information. In an Edge Preserving scheme, when the quantizer input falls in the overload region, the quantizer error is encoded and sent to the receiver repeatedly until the quantizer input falls in the inner levels. Therefore these coding schemes increase the bit rate in the region of an edge and require variable rate channels. We implement these two variable rate coding schemes on a token wing network. Timed token protocol supports two classes of messages; asynchronous and synchronous. The synchronous class provides a pre-allocated bandwidth and guaranteed response time. The remaining bandwidth is dynamically allocated to the asynchronous class. The Edge Correcting DPCM is simulated by considering the edge information under the asynchronous class. For the simulation of the Edge Preserving scheme, the amount of information sent each time is fixed, but the length of the packet or the bit rate for that packet is chosen depending on the availability capacity. The performance of the network, and the performance of the image coding algorithms, is studied.

Transonic aerodynamics of dense gases. M.S. Thesis - Virginia Polytechnic Inst. and State Univ., Apr. 1990

NASA Technical Reports Server (NTRS)

Morren, Sybil Huang

1991-01-01

Transonic flow of dense gases for two-dimensional, steady-state, flow over a NACA 0012 airfoil was predicted analytically. The computer code used to model the dense gas behavior was a modified version of Jameson's FL052 airfoil code. The modifications to the code enabled modeling the dense gas behavior near the saturated vapor curve and critical pressure region where the fundamental derivative, Gamma, is negative. This negative Gamma region is of interest because the nonclassical gas behavior such as formation and propagation of expansion shocks, and the disintegration of inadmissible compression shocks may exist. The results indicated that dense gases with undisturbed thermodynamic states in the negative Gamma region show a significant reduction in the extent of the transonic regime as compared to that predicted by the perfect gas theory. The results support existing theories and predictions of the nonclassical, dense gas behavior from previous investigations.

Region-Based Prediction for Image Compression in the Cloud.

PubMed

Begaint, Jean; Thoreau, Dominique; Guillotel, Philippe; Guillemot, Christine

2018-04-01

Thanks to the increasing number of images stored in the cloud, external image similarities can be leveraged to efficiently compress images by exploiting inter-images correlations. In this paper, we propose a novel image prediction scheme for cloud storage. Unlike current state-of-the-art methods, we use a semi-local approach to exploit inter-image correlation. The reference image is first segmented into multiple planar regions determined from matched local features and super-pixels. The geometric and photometric disparities between the matched regions of the reference image and the current image are then compensated. Finally, multiple references are generated from the estimated compensation models and organized in a pseudo-sequence to differentially encode the input image using classical video coding tools. Experimental results demonstrate that the proposed approach yields significant rate-distortion performance improvements compared with the current image inter-coding solutions such as high efficiency video coding.

Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs.

PubMed

Ricaño-Ponce, Isis; Zhernakova, Daria V; Deelen, Patrick; Luo, Oscar; Li, Xingwang; Isaacs, Aaron; Karjalainen, Juha; Di Tommaso, Jennifer; Borek, Zuzanna Agnieszka; Zorro, Maria M; Gutierrez-Achury, Javier; Uitterlinden, Andre G; Hofman, Albert; van Meurs, Joyce; Netea, Mihai G; Jonkers, Iris H; Withoff, Sebo; van Duijn, Cornelia M; Li, Yang; Ruan, Yijun; Franke, Lude; Wijmenga, Cisca; Kumar, Vinod

2016-04-01

Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Screening for rare variants in the PNPLA3 gene in obese liver biopsy patients.

PubMed

Zegers, Doreen; Verrijken, An; Francque, Sven; de Freitas, Fenna; Beckers, Sigri; Aerts, Evi; Ruppert, Martin; Hubens, Guy; Michielsen, Peter; Van Hul, Wim; Van Gaal, Luc F

2016-12-01

Previous research has clearly implicated the PNPLA3 gene in the etiology of nonalcoholic fatty liver disease as a polymorphism in the gene was found to be robustly associated to the disease. However, data on the involvement of rare PNPLA3 variants in the development of nonalcoholic fatty liver disease (NAFLD) is currently limited. Therefore, we performed an extensive mutation analysis study on a cohort of obese liver biopsy patients to determine PNPLA3 variation and its correlation with fatty liver disease. We screened the entire coding region of the PNPLA3 gene in DNA samples of 393 obese liver biopsy patients with varying degrees of fatty liver disease. Mutation analysis was performed by high-resolution melting curve analysis in combination with direct sequencing. We identified several common polymorphisms as well as one rare synonymous variant (c.867G>A rs139896256), one rare intronic variant (c.979+13C>T) and 3 nonsynonymous coding variants (p.A76T, p.A104V and p.T200M) in the PNPLA3 gene. In silico analysis indicated that the p.A104V variant will probably have no functional effect, whereas for the p.A76T and p.T200M variant a possible pathogenic effect is suggested. Overall, we showed that novel variants in PNPLA3 are very rare in our liver biopsy cohort, thereby indicating that their impact on the etiology of NAFLD is probably limited. Nevertheless, for the three rare coding variants that were identified in patients with advanced liver disease, further functional characterization will be essential to verify their potential disease causality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The importance of immune gene variability (MHC) in evolutionary ecology and conservation

PubMed Central

Sommer, Simone

2005-01-01

Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies. PMID:16242022

CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC

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

Congrains, Ada; Kamide, Kei; Katsuya, Tomohiro

Highlights: Black-Right-Pointing-Pointer ANRIL maps in the strongest susceptibility locus for cardiovascular disease. Black-Right-Pointing-Pointer Silencing of ANRIL leads to altered expression of tissue remodeling-related genes. Black-Right-Pointing-Pointer The effects of ANRIL on gene expression are splicing variant specific. Black-Right-Pointing-Pointer ANRIL affects progression of cardiovascular disease by regulating proliferation and apoptosis pathways. -- Abstract: ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of thismore » non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies.« less

Determination of coronal magnetic fields from vector magnetograms

NASA Technical Reports Server (NTRS)

Mikic, Zoran

1992-01-01

The determination of coronal magnetic fields from vector magnetograms, including the development and application of algorithms to determine force-free coronal fields above selected observations of active regions is studied. Two additional active regions were selected and analyzed. The restriction of periodicity in the 3-D code which is used to determine the coronal field was removed giving the new code variable mesh spacing and is thus able to provide a more realistic description of coronal fields. The NOAA active region AR5747 of 20 Oct. 1989 was studied. A brief account of progress during the research performed is reported.

The adaptive evolution of the mammalian mitochondrial genome

PubMed Central

da Fonseca, Rute R; Johnson, Warren E; O'Brien, Stephen J; Ramos, Maria João; Antunes, Agostinho

2008-01-01

Background The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures. Results Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to low energy diet or large body size, such as in elephant, dugong, sloth, and pangolin, and adaptation to unusual oxygen requirements, for example diving in cetaceans, flying in bats, and living at high altitudes in alpacas). Signatures of adaptive variation in the NADH dehydrogenase complex were restricted to the loop regions of the transmembrane units which likely function as protons pumps. Evidence of adaptive variation in the cytochrome c oxidase complex was observed mostly at the interface between the mitochondrial and nuclear-encoded subunits, perhaps evidence of co-evolution. The ATP8 subunit, which has an important role in the assembly of F0, exhibited the highest signal of adaptive variation. ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas. Conclusion Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation. We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation. PMID:18318906

Phonological coding during reading.

PubMed

Leinenger, Mallorie

2014-11-01

The exact role that phonological coding (the recoding of written, orthographic information into a sound based code) plays during silent reading has been extensively studied for more than a century. Despite the large body of research surrounding the topic, varying theories as to the time course and function of this recoding still exist. The present review synthesizes this body of research, addressing the topics of time course and function in tandem. The varying theories surrounding the function of phonological coding (e.g., that phonological codes aid lexical access, that phonological codes aid comprehension and bolster short-term memory, or that phonological codes are largely epiphenomenal in skilled readers) are first outlined, and the time courses that each maps onto (e.g., that phonological codes come online early [prelexical] or that phonological codes come online late [postlexical]) are discussed. Next the research relevant to each of these proposed functions is reviewed, discussing the varying methodologies that have been used to investigate phonological coding (e.g., response time methods, reading while eye-tracking or recording EEG and MEG, concurrent articulation) and highlighting the advantages and limitations of each with respect to the study of phonological coding. In response to the view that phonological coding is largely epiphenomenal in skilled readers, research on the use of phonological codes in prelingually, profoundly deaf readers is reviewed. Finally, implications for current models of word identification (activation-verification model, Van Orden, 1987; dual-route model, e.g., M. Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001; parallel distributed processing model, Seidenberg & McClelland, 1989) are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Phonological coding during reading

PubMed Central

Leinenger, Mallorie

2014-01-01

The exact role that phonological coding (the recoding of written, orthographic information into a sound based code) plays during silent reading has been extensively studied for more than a century. Despite the large body of research surrounding the topic, varying theories as to the time course and function of this recoding still exist. The present review synthesizes this body of research, addressing the topics of time course and function in tandem. The varying theories surrounding the function of phonological coding (e.g., that phonological codes aid lexical access, that phonological codes aid comprehension and bolster short-term memory, or that phonological codes are largely epiphenomenal in skilled readers) are first outlined, and the time courses that each maps onto (e.g., that phonological codes come online early (pre-lexical) or that phonological codes come online late (post-lexical)) are discussed. Next the research relevant to each of these proposed functions is reviewed, discussing the varying methodologies that have been used to investigate phonological coding (e.g., response time methods, reading while eyetracking or recording EEG and MEG, concurrent articulation) and highlighting the advantages and limitations of each with respect to the study of phonological coding. In response to the view that phonological coding is largely epiphenomenal in skilled readers, research on the use of phonological codes in prelingually, profoundly deaf readers is reviewed. Finally, implications for current models of word identification (activation-verification model (Van Order, 1987), dual-route model (e.g., Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001), parallel distributed processing model (Seidenberg & McClelland, 1989)) are discussed. PMID:25150679

Efficient depth intraprediction method for H.264/AVC-based three-dimensional video coding

NASA Astrophysics Data System (ADS)

Oh, Kwan-Jung; Oh, Byung Tae

2015-04-01

We present an intracoding method that is applicable to depth map coding in multiview plus depth systems. Our approach combines skip prediction and plane segmentation-based prediction. The proposed depth intraskip prediction uses the estimated direction at both the encoder and decoder, and does not need to encode residual data. Our plane segmentation-based intraprediction divides the current block into biregions, and applies a different prediction scheme for each segmented region. This method avoids incorrect estimations across different regions, resulting in higher prediction accuracy. Simulation results demonstrate that the proposed scheme is superior to H.264/advanced video coding intraprediction and has the ability to improve the subjective rendering quality.

Water Supply Deficiency and Implications for Rural Development in the Niger-Delta Region of Nigeria

ERIC Educational Resources Information Center

Nkwocha, E. E.

2009-01-01

There is a growing concern about the marginalization of the Niger Delta region of Nigeria in terms of infrastructural and social services provision. This study examined the water supply deficiency and its general implications for rural development within the region. Data and other study characteristics were extracted from 501 subjects drawn from…

Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

PubMed

Miyamoto, T; Koh, E; Tsujimura, A; Miyagawa, Y; Saijo, Y; Namiki, M; Sengoku, K

2014-04-01

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre-replication complex assembly in G1 and chromatin organization in post-G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single-nucleotide polymorphisms (SNP1-SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P < 0.05). These results suggest the critical role of LRWD1 in human spermatogenesis. © 2013 Blackwell Verlag GmbH.

Disruption of Neurexin 1 Associated with Autism Spectrum Disorder

PubMed Central

Kim, Hyung-Goo; Kishikawa, Shotaro; Higgins, Anne W.; Seong, Ihn-Sik; Donovan, Diana J.; Shen, Yiping; Lally, Eric; Weiss, Lauren A.; Najm, Juliane; Kutsche, Kerstin; Descartes, Maria; Holt, Lynn; Braddock, Stephen; Troxell, Robin; Kaplan, Lee; Volkmar, Fred; Klin, Ami; Tsatsanis, Katherine; Harris, David J.; Noens, Ilse; Pauls, David L.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Quade, Bradley J.; Gusella, James F.

2008-01-01

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ∼750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD. PMID:18179900

Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina.

PubMed

Simon, Perikles; Schott, Klaus; Williams, Robert W; Schaeffel, Frank

2004-12-01

Synaptic plasticity is modulated by differential regulation of transcription factors such as EGR1 which binds to DNA via a zinc finger binding domain. Inactivation of EGR1 has implicated this gene as a key regulator of memory formation and learning. However, it remains puzzling how synaptic input can lead to an up-regulation of the EGR-1 protein within only a few minutes. Here, we show by immunohistochemical staining that the EGR-1 protein is localized in synapses throughout the mouse retina. We demonstrate for the first time that two variants of Egr-1 mRNA are produced in the retina by alternative polyadenylation, with the longer version having an additional 293 base pairs at the end of the 3'UTR. Remarkably, the use of the alternative polyadenylation site is controlled by light. The additional 3'UTR sequence of the longer variant displays an even higher level of phylogenetic conservation than the coding region of this highly conserved gene. Additionally, it harbours a cytoplasmic polyadenylation element which is known to respond to NMDA receptor activation. The longer version of the Egr-1 mRNA could therefore rapidly respond to excitatory stimuli such as light or glutamate release whereas the short variant, which is predominantly expressed and contains the full coding sequence, lacks the regulatory elements for cytoplasmic polyadenylation in its 3'UTR.

Interpretation of the 12 May 2012 ground level enhancement event

NASA Astrophysics Data System (ADS)

Wu, C. C.; Dryer, Ph D., M.; Liou, K.; Wu, S. T.

2015-12-01

The 12 May 2012 solar event is associated with a moderate flare (M5.1) and, surprisingly, a ground level enhancement (GLE) event. It is the first GLE of the solar cycle 24 (or since December 2006). Because GLEs are considered as the highest energy tail in the solar energetic particle (SEP) spectrum, it is generally believed that GLEs must be generated at very strong shocks. Here, we conduct a simulation study of a number of major (> M5.0) flare events that occurred in the current solar cycle up to 2013, using the H3DMHD simulation code. The H3DMHD (Wu et al. 2007, JGR) combines the kinematic solar wind model (HAF) for regions near the solar surface (2.5-18 Rs) and a three-dimensional magnetohydrodynamics model (Han et al. 1988), which takes output from HAF at 18 Rs and propagates outward up to 1.7 AU. The H3DMHD code has been fully tested and is suitable for simulating not only the quiet solar wind, but also disturbances propagating in the solar wind. Our preliminary study result suggests that the 12 May 2012 was magnetically well connected, whereas others were not. We will present the detailed result, including the shock structure and intensity driven by the 12 May 2012 CME event, and discuss the result implication.

Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis).

PubMed

Fisher, S E; van Bakel, I; Lloyd, S E; Pearce, S H; Thakker, R V; Craig, I W

1995-10-10

Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, and eventual renal failure. We have previously used positional cloning to identify the 3' part of a novel kidney-specific gene (initially termed hClC-K2, but now referred to as CLCN5), which is deleted in patients from one pedigree segregating Dent disease. Mutations that disrupt this gene have been identified in other patients with this disorder. Here we describe the isolation and characterization of the complete open reading frame of the human CLCN5 gene, which is predicted to encode a protein of 746 amino acids, with significant homology to all known members of the ClC family of voltage-gated chloride channels. CLCN5 belongs to a distinct branch of this family, which also includes the recently identified genes CLCN3 and CLCN4. We have shown that the coding region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and have determined the sequence of each exon-intron boundary. The elucidation of the coding sequence and exon-intron organization of CLCN5 will both expedite the evaluation of structure/function relationships of these ion channels and facilitate the screening of other patients with renal tubular dysfunction for mutations at this locus.

Analytical and numerical study of the transverse Kelvin-Helmholtz instability in tokamak edge plasmas

DOE PAGES

Myra, James R.; D'Ippolito, Daniel A.; Russell, David A.; ...

2016-04-11

Sheared flows perpendicular to the magnetic field can be driven by the Reynolds stress or ion pressure gradient effects and can potentially influence the stability and turbulent saturation level of edge plasma modes. On the other hand, such flows are subject to the transverse Kelvin- Helmholtz (KH) instability. Here, the linear theory of KH instabilities is first addressed with an analytic model in the asymptotic limit of long wavelengths compared with the flow scale length. The analytic model treats sheared ExB flows, ion diamagnetism (including gyro-viscous terms), density gradients and parallel currents in a slab geometry, enabling a unified summarymore » that encompasses and extends previous results. In particular, while ion diamagnetism, density gradients and parallel currents each individually reduce KH growth rates, the combined effect of density and ion pressure gradients is more complicated and partially counteracting. Secondly, the important role of realistic toroidal geometry is explored numerically using an invariant scaling analysis together with the 2DX eigenvalue code to examine KH modes in both closed and open field line regions. For a typical spherical torus magnetic geometry, it is found that KH modes are more unstable at and just outside the separatrix as a result of the distribution of magnetic shear. Lastly implications for reduced edge turbulence modeling codes are discussed.« less

Olfactory coding: giant inhibitory neuron governs sparse odor codes.

PubMed

Gupta, Nitin; Stopfer, Mark

2011-07-12

Electrophysiological investigations in locusts have revealed that the sparseness of odor representations, in the brain region expected to mediate olfactory learning, is shaped by a unique inhibitory neuron. Copyright © 2011 Elsevier Ltd. All rights reserved.

The complete chloroplast genome of Cinnamomum camphora and its comparison with related Lauraceae species.

PubMed

Chen, Caihui; Zheng, Yongjie; Liu, Sian; Zhong, Yongda; Wu, Yanfang; Li, Jiang; Xu, Li-An; Xu, Meng

2017-01-01

Cinnamomum camphora , a member of the Lauraceae family, is a valuable aromatic and timber tree that is indigenous to the south of China and Japan. All parts of Cinnamomum camphora have secretory cells containing different volatile chemical compounds that are utilized as herbal medicines and essential oils. Here, we reported the complete sequencing of the chloroplast genome of Cinnamomum camphora using illumina technology. The chloroplast genome of Cinnamomum camphora is 152,570 bp in length and characterized by a relatively conserved quadripartite structure containing a large single copy region of 93,705 bp, a small single copy region of 19,093 bp and two inverted repeat (IR) regions of 19,886 bp. Overall, the genome contained 123 coding regions, of which 15 were repeated in the IR regions. An analysis of chloroplast sequence divergence revealed that the small single copy region was highly variable among the different genera in the Lauraceae family. A total of 40 repeat structures and 83 simple sequence repeats were detected in both the coding and non-coding regions. A phylogenetic analysis indicated that Calycanthus is most closely related to Lauraceae , both being members of Laurales , which forms a sister group to Magnoliids . The complete sequence of the chloroplast of Cinnamomum camphora will aid in in-depth taxonomical studies of the Lauraceae family in the future. The genetic sequence information will also have valuable applications for chloroplast genetic engineering.

The Development of Bimodal Bilingualism: Implications for Linguistic Theory.

PubMed

Lillo-Martin, Diane; de Quadros, Ronice Müller; Pichler, Deborah Chen

2016-01-01

A wide range of linguistic phenomena contribute to our understanding of the architecture of the human linguistic system. In this paper we present a proposal dubbed Language Synthesis to capture bilingual phenomena including code-switching and 'transfer' as automatic consequences of the addition of a second language, using basic concepts of Minimalism and Distributed Morphology. Bimodal bilinguals, who use a sign language and a spoken language, provide a new type of evidence regarding possible bilingual phenomena, namely code-blending, the simultaneous production of (aspects of) a message in both speech and sign. We argue that code-blending also follows naturally once a second articulatory interface is added to the model. Several different types of code-blending are discussed in connection to the predictions of the Synthesis model. Our primary data come from children developing as bimodal bilinguals, but our proposal is intended to capture a wide range of bilingual effects across any language pair.

The Development of Bimodal Bilingualism: Implications for Linguistic Theory

PubMed Central

Lillo-Martin, Diane; de Quadros, Ronice Müller; Pichler, Deborah Chen

2017-01-01

A wide range of linguistic phenomena contribute to our understanding of the architecture of the human linguistic system. In this paper we present a proposal dubbed Language Synthesis to capture bilingual phenomena including code-switching and ‘transfer’ as automatic consequences of the addition of a second language, using basic concepts of Minimalism and Distributed Morphology. Bimodal bilinguals, who use a sign language and a spoken language, provide a new type of evidence regarding possible bilingual phenomena, namely code-blending, the simultaneous production of (aspects of) a message in both speech and sign. We argue that code-blending also follows naturally once a second articulatory interface is added to the model. Several different types of code-blending are discussed in connection to the predictions of the Synthesis model. Our primary data come from children developing as bimodal bilinguals, but our proposal is intended to capture a wide range of bilingual effects across any language pair. PMID:28603576

Modification of LAMPF's magnet-mapping code for offsets of center coordinates

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

Hurd, J.W.; Gomulka, S.; Merrill, F.

1991-01-01

One of the magnet measurements performed at LAMPF is the determination of the cylindrical harmonics of a quadrupole magnet using a rotating coil. The data are analyzed with the code HARMAL to derive the amplitudes of the harmonics. Initially, the origin of the polar coordinate system is the axis of the rotating coil. A new coordinate system is found by a simple translation of the old system such that the dipole moment in the new system is zero. The origin of this translated system is referred to as the magnetic center. Given this translation, the code calculates the coefficients ofmore » the cylindrical harmonics in the new system. The code has been modified to use an analytical calculation to determine these new coefficients. The method of calculation is described and some implications of this formulation are presented. 8 refs., 2 figs.« less

Users manual for the NASA Lewis three-dimensional ice accretion code (LEWICE 3D)

NASA Technical Reports Server (NTRS)

Bidwell, Colin S.; Potapczuk, Mark G.

1993-01-01

A description of the methodology, the algorithms, and the input and output data along with an example case for the NASA Lewis 3D ice accretion code (LEWICE3D) has been produced. The manual has been designed to help the user understand the capabilities, the methodologies, and the use of the code. The LEWICE3D code is a conglomeration of several codes for the purpose of calculating ice shapes on three-dimensional external surfaces. A three-dimensional external flow panel code is incorporated which has the capability of calculating flow about arbitrary 3D lifting and nonlifting bodies with external flow. A fourth order Runge-Kutta integration scheme is used to calculate arbitrary streamlines. An Adams type predictor-corrector trajectory integration scheme has been included to calculate arbitrary trajectories. Schemes for calculating tangent trajectories, collection efficiencies, and concentration factors for arbitrary regions of interest for single droplets or droplet distributions have been incorporated. A LEWICE 2D based heat transfer algorithm can be used to calculate ice accretions along surface streamlines. A geometry modification scheme is incorporated which calculates the new geometry based on the ice accretions generated at each section of interest. The three-dimensional ice accretion calculation is based on the LEWICE 2D calculation. Both codes calculate the flow, pressure distribution, and collection efficiency distribution along surface streamlines. For both codes the heat transfer calculation is divided into two regions, one above the stagnation point and one below the stagnation point, and solved for each region assuming a flat plate with pressure distribution. Water is assumed to follow the surface streamlines, hence starting at the stagnation zone any water that is not frozen out at a control volume is assumed to run back into the next control volume. After the amount of frozen water at each control volume has been calculated the geometry is modified by adding the ice at each control volume in the surface normal direction.

The influence of viral coding sequences on pestivirus IRES activity reveals further parallels with translation initiation in prokaryotes.

PubMed Central

Fletcher, Simon P; Ali, Iraj K; Kaminski, Ann; Digard, Paul; Jackson, Richard J

2002-01-01

Classical swine fever virus (CSFV) is a member of the pestivirus family, which shares many features in common with hepatitis C virus (HCV). It is shown here that CSFV has an exceptionally efficient cis-acting internal ribosome entry segment (IRES), which, like that of HCV, is strongly influenced by the sequences immediately downstream of the initiation codon, and is optimal with viral coding sequences in this position. Constructs that retained 17 or more codons of viral coding sequence exhibited full IRES activity, but with only 12 codons, activity was approximately 66% of maximum in vitro (though close to maximum in transfected BHK cells), whereas with just 3 codons or fewer, the activity was only approximately 15% of maximum. The minimal coding region elements required for high activity were exchanged between HCV and CSFV. Although maximum activity was observed in each case with the homologous combination of coding region and 5' UTR, the heterologous combinations were sufficiently active to rule out a highly specific functional interplay between the 5' UTR and coding sequences. On the other hand, inversion of the coding sequences resulted in low IRES activity, particularly with the HCV coding sequences. RNA structure probing showed that the efficiency of internal initiation of these chimeric constructs correlated most closely with the degree of single-strandedness of the region around and immediately downstream of the initiation codon. The low activity IRESs could not be rescued by addition of supplementary eIF4A (the initiation factor with ATP-dependent RNA helicase activity). The extreme sensitivity to secondary structure around the initiation codon is likely to be due to the fact that the eIF4F complex (which has eIF4A as one of its subunits) is not required for and does not participate in initiation on these IRESs. PMID:12515388

Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation.

PubMed

Pujar, Shashikant; O'Leary, Nuala A; Farrell, Catherine M; Loveland, Jane E; Mudge, Jonathan M; Wallin, Craig; Girón, Carlos G; Diekhans, Mark; Barnes, If; Bennett, Ruth; Berry, Andrew E; Cox, Eric; Davidson, Claire; Goldfarb, Tamara; Gonzalez, Jose M; Hunt, Toby; Jackson, John; Joardar, Vinita; Kay, Mike P; Kodali, Vamsi K; Martin, Fergal J; McAndrews, Monica; McGarvey, Kelly M; Murphy, Michael; Rajput, Bhanu; Rangwala, Sanjida H; Riddick, Lillian D; Seal, Ruth L; Suner, Marie-Marthe; Webb, David; Zhu, Sophia; Aken, Bronwen L; Bruford, Elspeth A; Bult, Carol J; Frankish, Adam; Murphy, Terence; Pruitt, Kim D

2018-01-04

The Consensus Coding Sequence (CCDS) project provides a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assembly in genome annotations produced independently by NCBI and the Ensembl group at EMBL-EBI. This dataset is the product of an international collaboration that includes NCBI, Ensembl, HUGO Gene Nomenclature Committee, Mouse Genome Informatics and University of California, Santa Cruz. Identically annotated coding regions, which are generated using an automated pipeline and pass multiple quality assurance checks, are assigned a stable and tracked identifier (CCDS ID). Additionally, coordinated manual review by expert curators from the CCDS collaboration helps in maintaining the integrity and high quality of the dataset. The CCDS data are available through an interactive web page (https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi) and an FTP site (ftp://ftp.ncbi.nlm.nih.gov/pub/CCDS/). In this paper, we outline the ongoing work, growth and stability of the CCDS dataset and provide updates on new collaboration members and new features added to the CCDS user interface. We also present expert curation scenarios, with specific examples highlighting the importance of an accurate reference genome assembly and the crucial role played by input from the research community. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

Chimeric mitochondrial minichromosomes of the human body louse, Pediculus humanus: evidence for homologous and non-homologous recombination.

PubMed

Shao, Renfu; Barker, Stephen C

2011-02-15

The mitochondrial (mt) genome of the human body louse, Pediculus humanus, consists of 18 minichromosomes. Each minichromosome is 3 to 4 kb long and has 1 to 3 genes. There is unequivocal evidence for recombination between different mt minichromosomes in P. humanus. It is not known, however, how these minichromosomes recombine. Here, we report the discovery of eight chimeric mt minichromosomes in P. humanus. We classify these chimeric mt minichromosomes into two groups: Group I and Group II. Group I chimeric minichromosomes contain parts of two different protein-coding genes that are from different minichromosomes. The two parts of protein-coding genes in each Group I chimeric minichromosome are joined at a microhomologous nucleotide sequence; microhomologous nucleotide sequences are hallmarks of non-homologous recombination. Group II chimeric minichromosomes contain all of the genes and the non-coding regions of two different minichromosomes. The conserved sequence blocks in the non-coding regions of Group II chimeric minichromosomes resemble the "recombination repeats" in the non-coding regions of the mt genomes of higher plants. These repeats are essential to homologous recombination in higher plants. Our analyses of the nucleotide sequences of chimeric mt minichromosomes indicate both homologous and non-homologous recombination between minichromosomes in the mitochondria of the human body louse. Copyright © 2010 Elsevier B.V. All rights reserved.

GeneMachine: gene prediction and sequence annotation.

PubMed

Makalowska, I; Ryan, J F; Baxevanis, A D

2001-09-01

A number of free-standing programs have been developed in order to help researchers find potential coding regions and deduce gene structure for long stretches of what is essentially 'anonymous DNA'. As these programs apply inherently different criteria to the question of what is and is not a coding region, multiple algorithms should be used in the course of positional cloning and positional candidate projects to assure that all potential coding regions within a previously-identified critical region are identified. We have developed a gene identification tool called GeneMachine which allows users to query multiple exon and gene prediction programs in an automated fashion. BLAST searches are also performed in order to see whether a previously-characterized coding region corresponds to a region in the query sequence. A suite of Perl programs and modules are used to run MZEF, GENSCAN, GRAIL 2, FGENES, RepeatMasker, Sputnik, and BLAST. The results of these runs are then parsed and written into ASN.1 format. Output files can be opened using NCBI Sequin, in essence using Sequin as both a workbench and as a graphical viewer. The main feature of GeneMachine is that the process is fully automated; the user is only required to launch GeneMachine and then open the resulting file with Sequin. Annotations can then be made to these results prior to submission to GenBank, thereby increasing the intrinsic value of these data. GeneMachine is freely-available for download at http://genome.nhgri.nih.gov/genemachine. A public Web interface to the GeneMachine server for academic and not-for-profit users is available at http://genemachine.nhgri.nih.gov. The Web supplement to this paper may be found at http://genome.nhgri.nih.gov/genemachine/supplement/.

An Implementation of Privacy Protection for a Surveillance Camera Using ROI Coding of JPEG2000 with Face Detection

NASA Astrophysics Data System (ADS)

Muneyasu, Mitsuji; Odani, Shuhei; Kitaura, Yoshihiro; Namba, Hitoshi

On the use of a surveillance camera, there is a case where privacy protection should be considered. This paper proposes a new privacy protection method by automatically degrading the face region in surveillance images. The proposed method consists of ROI coding of JPEG2000 and a face detection method based on template matching. The experimental result shows that the face region can be detected and hidden correctly.

The 1985 Army Experience Survey: Tabular Descriptions of First-Term Separatees. Volume 2

DTIC Science & Technology

1986-01-01

through survey receipt control and sample management systems . Data were also keyed, edited, coded, and weighted. The coding schemes developed to...270-271 048 R136 REGION OF RESIDENCE WHEN YOU JOINED ARMY ...... .................. ... 272-273 049 E137 # TERMS OF ACTIVE ENLISTMENT...STATISTIC VALUE D.F. PROB. CHISQUARE APPROX. 7.830 5 0.1658 e. U 272 R136 -- REGION OF RIESIDENCE WHEN YOU JOINED ARMY RECODED - WHAT STATE WERE YOU LIVING

The 1985 Army Experience Survey: Tabular Descriptions of Mid-Career Separatees. Volume 2

DTIC Science & Technology

1986-01-01

Survey data were processed through survey receipt control and sample management systems . Data were also keyed, edited, coded, and weighted. The coding...270-271 048 R136 REGION OF RESIDENCE WHEN YOU JOINED ARMY ................. . 272-273 049 E137 # TERMS OF ACTIVE ENLISTMENT...STATISTIC VALUE D.F. PROB. CHISQUARE APPROX. 4.449 5 0.4868 I 272 R136 -- REGION OF RESIDENCE WHEN YOU JOINED ARMY RECODED - WHAT STATE WERE YOU LIVING IN

The complete mitochondrial genome of the Giant Manta ray, Manta birostris.

PubMed

Hinojosa-Alvarez, Silvia; Díaz-Jaimes, Pindaro; Marcet-Houben, Marina; Gabaldón, Toni

2015-01-01

The complete mitochondrial genome of the giant manta ray (Manta birostris), consists of 18,075 bp with rich A + T and low G content. Gene organization and length is similar to other species of ray. It comprises of 13 protein-coding genes, 2 rRNAs genes, 23 tRNAs genes and 1 non-coding sequence, and the control region. We identified an AT tandem repeat region, similar to that reported in Mobula japanica.

Can mutational GC-pressure create new linear B-cell epitopes in herpes simplex virus type 1 glycoprotein B?

PubMed

Khrustalev, Vladislav Victorovich

2009-01-01

We showed that GC-content of nucleotide sequences coding for linear B-cell epitopes of herpes simplex virus type 1 (HSV1) glycoprotein B (gB) is higher than GC-content of sequences coding for epitope-free regions of this glycoprotein (G + C = 73 and 64%, respectively). Linear B-cell epitopes have been predicted in HSV1 gB by BepiPred algorithm ( www.cbs.dtu.dk/services/BepiPred ). Proline is an acrophilic amino acid residue (it is usually situated on the surface of protein globules, and so included in linear B-cell epitopes). Indeed, the level of proline is much higher in predicted epitopes of gB than in epitope-free regions (17.8% versus 1.8%). This amino acid is coded by GC-rich codons (CCX) that can be produced due to nucleotide substitutions caused by mutational GC-pressure. GC-pressure will also lead to disappearance of acrophobic phenylalanine, isoleucine, methionine and tyrosine coded by GC-poor codons. Results of our "in-silico directed mutagenesis" showed that single nonsynonymous substitutions in AT to GC direction in two long epitope-free regions of gB will cause formation of new linear epitopes or elongation of previously existing epitopes flanking these regions in 25% of 539 possible cases. The calculations of GC-content and amino acid content have been performed by CodonChanges algorithm ( www.barkovsky.hotmail.ru ).

Development of an Efficient Entire-Capsid-Coding-Region Amplification Method for Direct Detection of Poliovirus from Stool Extracts

PubMed Central

Kilpatrick, David R.; Nakamura, Tomofumi; Burns, Cara C.; Bukbuk, David; Oderinde, Soji B.; Oberste, M. Steven; Kew, Olen M.; Pallansch, Mark A.; Shimizu, Hiroyuki

2014-01-01

Laboratory diagnosis has played a critical role in the Global Polio Eradication Initiative since 1988, by isolating and identifying poliovirus (PV) from stool specimens by using cell culture as a highly sensitive system to detect PV. In the present study, we aimed to develop a molecular method to detect PV directly from stool extracts, with a high efficiency comparable to that of cell culture. We developed a method to efficiently amplify the entire capsid coding region of human enteroviruses (EVs) including PV. cDNAs of the entire capsid coding region (3.9 kb) were obtained from as few as 50 copies of PV genomes. PV was detected from the cDNAs with an improved PV-specific real-time reverse transcription-PCR system and nucleotide sequence analysis of the VP1 coding region. For assay validation, we analyzed 84 stool extracts that were positive for PV in cell culture and detected PV genomes from 100% of the extracts (84/84 samples) with this method in combination with a PV-specific extraction method. PV could be detected in 2/4 stool extract samples that were negative for PV in cell culture. In PV-positive samples, EV species C viruses were also detected with high frequency (27% [23/86 samples]). This method would be useful for direct detection of PV from stool extracts without using cell culture. PMID:25339406

Evidence of translation efficiency adaptation of the coding regions of the bacteriophage lambda.

PubMed

Goz, Eli; Mioduser, Oriah; Diament, Alon; Tuller, Tamir

2017-08-01

Deciphering the way gene expression regulatory aspects are encoded in viral genomes is a challenging mission with ramifications related to all biomedical disciplines. Here, we aimed to understand how the evolution shapes the bacteriophage lambda genes by performing a high resolution analysis of ribosomal profiling data and gene expression related synonymous/silent information encoded in bacteriophage coding regions.We demonstrated evidence of selection for distinct compositions of synonymous codons in early and late viral genes related to the adaptation of translation efficiency to different bacteriophage developmental stages. Specifically, we showed that evolution of viral coding regions is driven, among others, by selection for codons with higher decoding rates; during the initial/progressive stages of infection the decoding rates in early/late genes were found to be superior to those in late/early genes, respectively. Moreover, we argued that selection for translation efficiency could be partially explained by adaptation to Escherichia coli tRNA pool and the fact that it can change during the bacteriophage life cycle.An analysis of additional aspects related to the expression of viral genes, such as mRNA folding and more complex/longer regulatory signals in the coding regions, is also reported. The reported conclusions are likely to be relevant also to additional viruses. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Assessment of PWR Steam Generator modelling in RELAP5/MOD2. International Agreement Report

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

Putney, J.M.; Preece, R.J.

1993-06-01

An assessment of Steam Generator (SG) modelling in the PWR thermal-hydraulic code RELAP5/MOD2 is presented. The assessment is based on a review of code assessment calculations performed in the UK and elsewhere, detailed calculations against a series of commissioning tests carried out on the Wolf Creek PWR and analytical investigations of the phenomena involved in normal and abnormal SG operation. A number of modelling deficiencies are identified and their implications for PWR safety analysis are discussed -- including methods for compensating for the deficiencies through changes to the input deck. Consideration is also given as to whether the deficiencies willmore » still be present in the successor code RELAP5/MOD3.« less

Coding ethical behaviour: the challenges of biological weapons.

PubMed

Rappert, Brian

2003-10-01

Since 11 September 2001 and the anthrax attacks that followed in the US, public and policy concerns about the security threats posed by biological weapons have increased significantly. With this has come an expansion of those activities in civil society deemed as potential sites for applying security controls. This paper examines the assumptions and implications of national and international efforts in one such area: how a balance or integration can take place between security and openness in civilian biomedical research through devising professional codes of conduct for scientists. Future attempts to establish such codes must find a way of reconciling or at least addressing dilemmatic and tension-ridden issues about the appropriateness of research; a topic that raises fundamental questions about the position of science within society.

Variation in clinical coding lists in UK general practice: a barrier to consistent data entry?

PubMed

Tai, Tracy Waize; Anandarajah, Sobanna; Dhoul, Neil; de Lusignan, Simon

2007-01-01

Routinely collected general practice computer data are used for quality improvement; poor data quality including inconsistent coding can reduce their usefulness. To document the diversity of data entry systems currently in use in UK general practice and highlight possible implications for data quality. General practice volunteers provided screen shots of the clinical coding screen they would use to code a diagnosis or problem title in the clinical consultation. The six clinical conditions examined were: depression, cystitis, type 2 diabetes mellitus, sore throat, tired all the time, and myocardial infarction. We looked at the picking lists generated for these problem titles in EMIS, IPS, GPASS and iSOFT general practice clinical computer systems, using the Triset browser as a gold standard for comparison. A mean of 19.3 codes is offered in the picking list after entering a diagnosis or problem title. EMIS produced the longest picking lists and GPASS the shortest, with a mean number of choices of 35.2 and 12.7, respectively. Approximately three-quarters (73.5%) of codes are diagnoses, one-eighth (12.5%) symptom codes, and the remainder come from a range of Read chapters. There was no readily detectable consistent order in which codes were displayed. Velocity coding, whereby commonly-used codes are placed higher in the picking list, results in variation between practices even where they have the same brand of computer system. Current systems for clinical coding promote diversity rather than consistency of clinical coding. As the UK moves towards an integrated health IT system consistency of coding will become more important. A standardised, limited list of codes for primary care might help address this need.

STATEQ: a nonlinear least-squares code for obtaining Martin thermodynamic representations of fluids in the gaseous and dense gaseous regions

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

Milora, S. L.

1976-02-01

The use of the code NLIN (IBM Share Program No. 1428) to obtain empirical thermodynamic pressure-volume-temperature (P-V-T) relationships for substances in the gaseous and dense gaseous states is described. When sufficient experimental data exist, the code STATEQ will provide least-squares estimates for the 21 parameters of the Martin model. Another code, APPROX, is described which also obtains parameter estimates for the model by making use of the approximate generalized behavior of fluids. Use of the codes is illustrated in obtaining thermodynamic representations for isobutane. (auth)

Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci

PubMed Central

Brorsson, Caroline A.; Pociot, Flemming

2014-01-01

Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. PMID:25144376

Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity

PubMed Central

Shabalina, Svetlana A.; Spiridonov, Nikolay A.; Kashina, Anna

2013-01-01

Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions. PMID:23293005

Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

PubMed Central

Calin, George; Ranzani, Guglielmina N; Amadori, Dino; Herlea, Vlad; Matei, Irina; Barbanti-Brodano, Giuseppe; Negrini, Massimo

2001-01-01

Background Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). Methods We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. Results BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGFβ1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. Conclusions BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors. PMID:11532193

The gene coding for the B cell surface protein CD19 is localized on human chromosome 16p11.

PubMed

Stapleton, P; Kozmik, Z; Weith, A; Busslinger, M

1995-02-01

The CD19 gene codes for one of the earliest markers of the human B cell lineage and is a target for the B lymphoid-specific transcription factor BSAP (Pax-5). The transmembrane protein CD19 has been implicated in controlling proliferation of mature B lymphocytes by modulating signal transduction through the antigen receptor. In this study, we have employed Southern blot and fluorescence in situ hybridization analyses to localize the CD19 gene to human chromosome 16p11.

Stable chromosome condensation revealed by chromosome conformation capture

PubMed Central

Eagen, Kyle P.; Hartl, Tom A.; Kornberg, Roger D.

2015-01-01

SUMMARY Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to ten-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. PMID:26544940

A new method for species identification via protein-coding and non-coding DNA barcodes by combining machine learning with bioinformatic methods.

PubMed

Zhang, Ai-bing; Feng, Jie; Ward, Robert D; Wan, Ping; Gao, Qiang; Wu, Jun; Zhao, Wei-zhong

2012-01-01

Species identification via DNA barcodes is contributing greatly to current bioinventory efforts. The initial, and widely accepted, proposal was to use the protein-coding cytochrome c oxidase subunit I (COI) region as the standard barcode for animals, but recently non-coding internal transcribed spacer (ITS) genes have been proposed as candidate barcodes for both animals and plants. However, achieving a robust alignment for non-coding regions can be problematic. Here we propose two new methods (DV-RBF and FJ-RBF) to address this issue for species assignment by both coding and non-coding sequences that take advantage of the power of machine learning and bioinformatics. We demonstrate the value of the new methods with four empirical datasets, two representing typical protein-coding COI barcode datasets (neotropical bats and marine fish) and two representing non-coding ITS barcodes (rust fungi and brown algae). Using two random sub-sampling approaches, we demonstrate that the new methods significantly outperformed existing Neighbor-joining (NJ) and Maximum likelihood (ML) methods for both coding and non-coding barcodes when there was complete species coverage in the reference dataset. The new methods also out-performed NJ and ML methods for non-coding sequences in circumstances of potentially incomplete species coverage, although then the NJ and ML methods performed slightly better than the new methods for protein-coding barcodes. A 100% success rate of species identification was achieved with the two new methods for 4,122 bat queries and 5,134 fish queries using COI barcodes, with 95% confidence intervals (CI) of 99.75-100%. The new methods also obtained a 96.29% success rate (95%CI: 91.62-98.40%) for 484 rust fungi queries and a 98.50% success rate (95%CI: 96.60-99.37%) for 1094 brown algae queries, both using ITS barcodes.

A combinatorial model for dentate gyrus sparse coding

DOE PAGES

Severa, William; Parekh, Ojas; James, Conrad D.; ...

2016-12-29

The dentate gyrus forms a critical link between the entorhinal cortex and CA3 by providing a sparse version of the signal. Concurrent with this increase in sparsity, a widely accepted theory suggests the dentate gyrus performs pattern separation—similar inputs yield decorrelated outputs. Although an active region of study and theory, few logically rigorous arguments detail the dentate gyrus’s (DG) coding. We suggest a theoretically tractable, combinatorial model for this action. The model provides formal methods for a highly redundant, arbitrarily sparse, and decorrelated output signal.To explore the value of this model framework, we assess how suitable it is for twomore » notable aspects of DG coding: how it can handle the highly structured grid cell representation in the input entorhinal cortex region and the presence of adult neurogenesis, which has been proposed to produce a heterogeneous code in the DG. We find tailoring the model to grid cell input yields expansion parameters consistent with the literature. In addition, the heterogeneous coding reflects activity gradation observed experimentally. Lastly, we connect this approach with more conventional binary threshold neural circuit models via a formal embedding.« less

Data compression using adaptive transform coding. Appendix 1: Item 1. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Rost, Martin Christopher

1988-01-01

Adaptive low-rate source coders are described in this dissertation. These coders adapt by adjusting the complexity of the coder to match the local coding difficulty of the image. This is accomplished by using a threshold driven maximum distortion criterion to select the specific coder used. The different coders are built using variable blocksized transform techniques, and the threshold criterion selects small transform blocks to code the more difficult regions and larger blocks to code the less complex regions. A theoretical framework is constructed from which the study of these coders can be explored. An algorithm for selecting the optimal bit allocation for the quantization of transform coefficients is developed. The bit allocation algorithm is more fully developed, and can be used to achieve more accurate bit assignments than the algorithms currently used in the literature. Some upper and lower bounds for the bit-allocation distortion-rate function are developed. An obtainable distortion-rate function is developed for a particular scalar quantizer mixing method that can be used to code transform coefficients at any rate.

Regional vertical total electron content (VTEC) modeling together with satellite and receiver differential code biases (DCBs) using semi-parametric multivariate adaptive regression B-splines (SP-BMARS)

NASA Astrophysics Data System (ADS)

Durmaz, Murat; Karslioglu, Mahmut Onur

2015-04-01

There are various global and regional methods that have been proposed for the modeling of ionospheric vertical total electron content (VTEC). Global distribution of VTEC is usually modeled by spherical harmonic expansions, while tensor products of compactly supported univariate B-splines can be used for regional modeling. In these empirical parametric models, the coefficients of the basis functions as well as differential code biases (DCBs) of satellites and receivers can be treated as unknown parameters which can be estimated from geometry-free linear combinations of global positioning system observables. In this work we propose a new semi-parametric multivariate adaptive regression B-splines (SP-BMARS) method for the regional modeling of VTEC together with satellite and receiver DCBs, where the parametric part of the model is related to the DCBs as fixed parameters and the non-parametric part adaptively models the spatio-temporal distribution of VTEC. The latter is based on multivariate adaptive regression B-splines which is a non-parametric modeling technique making use of compactly supported B-spline basis functions that are generated from the observations automatically. This algorithm takes advantage of an adaptive scale-by-scale model building strategy that searches for best-fitting B-splines to the data at each scale. The VTEC maps generated from the proposed method are compared numerically and visually with the global ionosphere maps (GIMs) which are provided by the Center for Orbit Determination in Europe (CODE). The VTEC values from SP-BMARS and CODE GIMs are also compared with VTEC values obtained through calibration using local ionospheric model. The estimated satellite and receiver DCBs from the SP-BMARS model are compared with the CODE distributed DCBs. The results show that the SP-BMARS algorithm can be used to estimate satellite and receiver DCBs while adaptively and flexibly modeling the daily regional VTEC.

A Sabin 3-Derived Poliovirus Recombinant Contained a Sequence Homologous with Indigenous Human Enterovirus Species C in the Viral Polymerase Coding Region†

PubMed Central

Arita, Minetaro; Zhu, Shuang-Li; Yoshida, Hiromu; Yoneyama, Tetsuo; Miyamura, Tatsuo; Shimizu, Hiroyuki

2005-01-01

Outbreaks of poliomyelitis caused by circulating vaccine-derived polioviruses (cVDPVs) have been reported in areas where indigenous wild polioviruses (PVs) were eliminated by vaccination. Most of these cVDPVs contained unidentified sequences in the nonstructural protein coding region which were considered to be derived from human enterovirus species C (HEV-C) by recombination. In this study, we report isolation of a Sabin 3-derived PV recombinant (Cambodia-02) from an acute flaccid paralysis (AFP) case in Cambodia in 2002. We attempted to identify the putative recombination counterpart of Cambodia-02 by sequence analysis of nonpolio enterovirus isolates from AFP cases in Cambodia from 1999 to 2003. Based on the previously estimated evolution rates of PVs, the recombination event resulting in Cambodia-02 was estimated to have occurred within 6 months after the administration of oral PV vaccine (99.3% nucleotide identity in VP1 region). The 2BC and the 3Dpol coding regions of Cambodia-02 were grouped into the genetic cluster of indigenous coxsackie A virus type 17 (CAV17) (the highest [87.1%] nucleotide identity) and the cluster of indigenous CAV13-CAV18 (the highest [94.9%] nucleotide identity) by the phylogenic analysis of the HEV-C isolates in 2002, respectively. CAV13-CAV18 and CAV17 were the dominant HEV-C serotypes in 2002 but not in 2001 and in 2003. We found a putative recombination between CAV13-CAV18 and CAV17 in the 3CDpro coding region of a CAV17 isolate. These results suggested that a part of the 3Dpol coding region of PV3(Cambodia-02) was derived from a HEV-C strain genetically related to indigenous CAV13-CAV18 strains in 2002 in Cambodia. PMID:16188967

Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy.

PubMed

González, Carolina; Tabernero, David; Cortese, Maria Francesca; Gregori, Josep; Casillas, Rosario; Riveiro-Barciela, Mar; Godoy, Cristina; Sopena, Sara; Rando, Ariadna; Yll, Marçal; Lopez-Martinez, Rosa; Quer, Josep; Esteban, Rafael; Buti, Maria; Rodríguez-Frías, Francisco

2018-05-21

To detect hyper-conserved regions in the hepatitis B virus (HBV) X gene ( HBX ) 5' region that could be candidates for gene therapy. The study included 27 chronic hepatitis B treatment-naive patients in various clinical stages (from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeAg-negative and HBeAg-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/mL, the HBX 5' end region [nucleotide (nt) 1255-1611] was PCR-amplified and submitted to next-generation sequencing (NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences (haplotypes) obtained by NGS. Conservation at the HBx protein amino acid (aa) level was also analyzed. NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample (2487-9279, IQR 2817). In 14/27 patients (51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region (nt 1255-1286) and the other in the 5' end coding region (nt 1519-1603). This last region coded for a conserved amino acid region (aa 63-76) that partially overlaps a Kunitz-like domain. Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

Residential photovoltaic module and array requirements study, appendices

NASA Technical Reports Server (NTRS)

Nearhoof, S. L.; Oster, J. R.

1979-01-01

Regional building code variations, federal and city codes, and the national electric code are reviewed for their possible effects on the design of photovoltaic modules. Problems that photovoltaic arrays may impose on the insurability of residences are also discussed. Mounting configurations are developed for the modules, and grounding, wiring, terminal, and voltage requirements are established. Installation and materials costs are presented along with performance criteria.

Monte Carlo Modeling of the Initial Radiation Emitted by a Nuclear Device in the National Capital Region

DTIC Science & Technology

2013-07-01

also simulated in the models. Data was derived from calculations using the three-dimensional Monte Carlo radiation transport code MCNP (Monte Carlo N...32  B.  MCNP PHYSICS OPTIONS ......................................................................................... 33  C.  HAZUS...input deck’) for the MCNP , Monte Carlo N-Particle, radiation transport code. MCNP is a general-purpose code designed to simulate neutron, photon

Influence of Familial Spirituality: Implications for School Counseling Professionals

ERIC Educational Resources Information Center

Davis, Keith M.; Lambie, Glenn W.; Ieva, Kara P.

2011-01-01

This article (a) addresses the importance of familial spirituality on students' holistic development; (b) explores professional ethical codes, standards, and counseling competencies relating to students' familial spirituality; (c) introduces educational activities to assist school counselors in increasing their understanding and appreciation of…

Systematic screening for mutations in the promoter and the coding region of the 5-HT{sub 1A} gene

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

Erdmann, J.; Shimron-Abarbanell, D.; Cichon, S.

1995-10-09

In the present study we sought to identify genetic variation in the 5-HT{sub 1A} receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains amore » functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A{yields}G) in nucleotide position 82 which leads to an amino acid exchange (Ile{yields}Val) in position 28 of the receptor protein and a silent mutation (C{yields}T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT{sub 1A} gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette`s syndrome. 29 refs., 4 figs., 1 tab.« less

Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation

PubMed Central

Crescenzo-Chaigne, Bernadette; Barbezange, Cyril; Frigard, Vianney; Poulain, Damien; van der Werf, Sylvie

2014-01-01

Exchange of the non coding regions of the NP segment between type A and C influenza viruses was used to demonstrate the importance not only of the proximal panhandle, but also of the initial distal panhandle strength in type specificity. Both elements were found to be compulsory to rescue infectious virus by reverse genetics systems. Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication. PMID:25268971

Cosmology in one dimension: Vlasov dynamics.

PubMed

Manfredi, Giovanni; Rouet, Jean-Louis; Miller, Bruce; Shiozawa, Yui

2016-04-01

Numerical simulations of self-gravitating systems are generally based on N-body codes, which solve the equations of motion of a large number of interacting particles. This approach suffers from poor statistical sampling in regions of low density. In contrast, Vlasov codes, by meshing the entire phase space, can reach higher accuracy irrespective of the density. Here, we perform one-dimensional Vlasov simulations of a long-standing cosmological problem, namely, the fractal properties of an expanding Einstein-de Sitter universe in Newtonian gravity. The N-body results are confirmed for high-density regions and extended to regions of low matter density, where the N-body approach usually fails.

Methodological studies on the VVER-440 control assembly calculations

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

Hordosy, G.; Kereszturi, A.; Maraczy, C.

1995-12-31

The control assembly regions of VVER-440 reactors are represented by 2-group albedo matrices in the global calculations of the KARATE code system. Some methodological aspects of calculating albedo matrices with the COLA transport code are presented. Illustrations are given how these matrices depend on the relevant parameters describing the boron steel and steel regions of the control assemblies. The calculation of the response matrix for a node consisting of two parts filled with different materials is discussed.

Identification of Methanococcus Jannaschii Proteins in 2-D Gel Electrophoresis Patterns by Mass Spectrometry

DOE R&D Accomplishments Database

Liang, X.

1998-06-10

The genome of Methanococcus jannaschii has been sequenced completely and has been found to contain approximately 1,770 predicted protein-coding regions. When these coding regions are expressed and how their expression is regulated, however, remain open questions. In this work, mass spectrometry was combined with two-dimensional gel electrophoresis to identify which proteins the genes produce under different growth conditions, and thus investigate the regulation of genes responsible for functions characteristic of this thermophilic representative of the methanogenic Archaea.

Comparison of FDNS liquid rocket engine plume computations with SPF/2

NASA Technical Reports Server (NTRS)

Kumar, G. N.; Griffith, D. O., II; Warsi, S. A.; Seaford, C. M.

1993-01-01

Prediction of a plume's shape and structure is essential to the evaluation of base region environments. The JANNAF standard plume flowfield analysis code SPF/2 predicts plumes well, but cannot analyze base regions. Full Navier-Stokes CFD codes can calculate both zones; however, before they can be used, they must be validated. The CFD code FDNS3D (Finite Difference Navier-Stokes Solver) was used to analyze the single plume of a Space Transportation Main Engine (STME) and comparisons were made with SPF/2 computations. Both frozen and finite rate chemistry models were employed as well as two turbulence models in SPF/2. The results indicate that FDNS3D plume computations agree well with SPF/2 predictions for liquid rocket engine plumes.

Continuing medical education revisited: theoretical assumptions and practical implications: a qualitative study.

PubMed

Dionyssopoulos, Alexander; Karalis, Thanassis; Panitsides, Eugenia A

2014-12-31

Recent research has evidenced that although investment in Continuing Medical Education (CME), both in terms of participation as well as financial resources allocated to it, has been steadily increasing to catch up with accelerating advances in health information and technology, effectiveness of CME is reported to be rather limited. Poor and disproportional returns can be attributed to failure of CME courses to address and stimulate an adult audience. The present study initially drew on research findings and adult learning theories, providing the basis for comprehending adult learning, while entailing practical implications on fostering effectiveness in the design and delivery of CME. On a second level, a qualitative study was conducted with the aim to elucidate parameters accounting for effectiveness in educational interventions. Qualitative data was retrieved through 12 in-depth interviews, conducted with a random sample of participants in the 26th European Workshop of Advanced Plastic Surgery (EWAPS). The data underwent a three level qualitative analysis, following the "grounded theory" methodology, comprising 'open coding', 'axial coding' and 'selective coding'. Findings from the EWAPS study come in line with relevant literature, entailing significant implications for the necessity to apply a more effective and efficient paradigm in the design and delivery of educational interventions, advocating for implementing learner-centered schemata in CME and benefiting from a model that draws on the learning environment and social aspects of learning. What emerged as a pivotal parameter in designing educational interventions is to focus on small group educational events which could provide a supportive friendly context, enhance motivation through learner-centered approaches and allow interaction, experimentation and critical reflection. It should be outlined however that further research is required as the present study is limited in scope, having dealt with a limited sample.

Human ESP1/CRP2, a member of the LIM domain protein family: Characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3

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

Karim, Mohammad Azharul; Ohta, Kohji; Matsuda, Ichiro

1996-01-15

The LIM domain is present in a wide variety of proteins with diverse functions and exhibits characteristic arrangements of Cys and His residues with a novel zinc-binding motif. LIM domain proteins have been implicated in development, cell regulation, and cell structure. A LIM domain protein was identified by screening a human cDNA library with rat cysteine-rich intestinal protein (CRIP) as a probe, under conditions of low stringency. Comparison of the predicted amino acid sequence with several LIM domain proteins revealed 93% of the residues to be identical to rat LIM domain protein, termed ESP1 or CRP2. Thus, the protein ismore » hereafter referred to as human ESP1/CRP2. The cDNA encompasses a 1171-base region, including 26, 624, and 521 bases in the 5{prime}-noncoding region, coding region, and 3{prime}-noncoding regions, respectively, and encodes the entire ESP1/CRP2 protein has two LIM domains, and each shares 35.1% and 77 or 79% identical residues with human cysteine-rich protein (CRP) and rat CRIP, respectively. Northern blot analysis of ESP1/CRP2 in various human tissues showed distinct tissue distributions compared with CRP and CRIP, suggesting that each might serve related but specific roles in tissue organization or function. Using a panel of human-rodent somatic cell hybrids, the ESP1/CRP2 locus was assigned to chromosome 14. Fluorescence in situ hybridization, using cDNA and a genome DNA fragment of the ESP1/CRP2 as probes, confirms this assignment and relegates regional localization to band 14q32.3 47 refs., 7 figs.« less

Exceptionally High Levels of Genetic Diversity in Wheat Curl Mite (Acari: Eriophyidae) Populations from Turkey.

PubMed

Szydło, W; Hein, G; Denizhan, E; Skoracka, A

2015-08-01

Recent research on the wheat curl mite species complex has revealed extensive genetic diversity that has distinguished several genetic lineages infesting bread wheat (Triticum aestivum L.) and other cereals worldwide. Turkey is the historical region of wheat and barley (Hordeum vulgare L.) domestication and diversification. The close relationship between these grasses and the wheat curl mite provoked the question of the genetic diversity of the wheat curl mite in this region. The scope of the study was to investigate genetic differentiation within the wheat curl mite species complex on grasses in Turkey. Twenty-one wheat curl mite populations from 16 grass species from nine genera (Agropyron sp., Aegilops sp., Bromus sp., Elymus sp., Eremopyrum sp., Hordeum sp., Poa sp., Secale sp., and Triticum sp.) were sampled in eastern and southeastern Turkey for genetic analyses. Two molecular markers were amplified: the cytochrome oxidase subunit I coding region of mtDNA (COI) and the D2 region of 28S rDNA. Phylogenetic analyses revealed high genetic variation of the wheat curl mite in Turkey, primarily on Bromus and Hordeum spp., and exceptionally high diversity of populations associated with bread wheat. Three wheat-infesting wheat curl mite lineages known to occur on other continents of the world, including North and South America, Australia and Europe, were found in Turkey, and at least two new genetic lineages were discovered. These regions of Turkey exhibit rich wheat curl mite diversity on native grass species. The possible implications for further studies on the wheat curl mite are discussed. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Deletion or underexpression of the Y-chromosome genes CDY2 and HSFY is associated with maturation arrest in American men with nonobstructive azoospermia.

PubMed

Stahl, Peter J; Mielnik, Anna N; Barbieri, Christopher E; Schlegel, Peter N; Paduch, Darius A

2012-09-01

Maturation arrest (MA) refers to failure of germ cell development leading to clinical nonobstructive azoospermia. Although the azoospermic factor (AZF) region of the human Y chromosome is clearly implicated in some cases, thus far very little is known about which individual Y-chromosome genes are important for complete male germ cell development. We sought to identify single genes on the Y chromosome that may be implicated in the pathogenesis of nonobstructive azoospermia associated with MA in the American population. Genotype-phenotype analysis of 132 men with Y-chromosome microdeletions was performed. Protein-coding genes associated with MA were identified by visual analysis of a genotype-phenotype map. Genes associated with MA were selected as those genes within a segment of the Y chromosome that, when completely or partially deleted, were always associated with MA and absence of retrievable testicular sperm. Expression of each identified gene transcript was then measured with quantitative RT-PCR in testicular tissue from separate cohorts of patients with idiopathic MA and obstructive azoospermia. Ten candidate genes for association with MA were identified within an 8.4-Mb segment of the Y chromosome overlapping the AZFb region. CDY2 and HSFY were the only identified genes for which differences in expression were observed between the MA and obstructive azoospermia cohorts. Men with obstructive azoospermia had 12-fold higher relative expression of CDY2 transcript (1.33 ± 0.40 vs. 0.11 ± 0.04; P=0.0003) and 16-fold higher expression of HSFY transcript (0.78 ± 0.32 vs. 0.05 ± 0.02; P=0.0005) compared to men with MA. CDY2 and HSFY were also underexpressed in patients with Sertoli cell only syndrome. These data indicate that CDY2 and HSFY are located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with MA. These observations suggest that impairments in CDY2 or HSFY expression could be implicated in the pathogenesis of MA.

A benchmark study of scoring methods for non-coding mutations.

PubMed

Drubay, Damien; Gautheret, Daniel; Michiels, Stefan

2018-05-15

Detailed knowledge of coding sequences has led to different candidate models for pathogenic variant prioritization. Several deleteriousness scores have been proposed for the non-coding part of the genome, but no large-scale comparison has been realized to date to assess their performance. We compared the leading scoring tools (CADD, FATHMM-MKL, Funseq2 and GWAVA) and some recent competitors (DANN, SNP and SOM scores) for their ability to discriminate assumed pathogenic variants from assumed benign variants (using the ClinVar, COSMIC and 1000 genomes project databases). Using the ClinVar benchmark, CADD was the best tool for detecting the pathogenic variants that are mainly located in protein coding gene regions. Using the COSMIC benchmark, FATHMM-MKL, GWAVA and SOMliver outperformed the other tools for pathogenic variants that are typically located in lincRNAs, pseudogenes and other parts of the non-coding genome. However, all tools had low precision, which could potentially be improved by future non-coding genome feature discoveries. These results may have been influenced by the presence of potential benign variants in the COSMIC database. The development of a gold standard as consistent as ClinVar for these regions will be necessary to confirm our tool ranking. The Snakemake, C++ and R codes are freely available from https://github.com/Oncostat/BenchmarkNCVTools and supported on Linux. damien.drubay@gustaveroussy.fr or stefan.michiels@gustaveroussy.fr. Supplementary data are available at Bioinformatics online.

Video coding for 3D-HEVC based on saliency information

NASA Astrophysics Data System (ADS)

Yu, Fang; An, Ping; Yang, Chao; You, Zhixiang; Shen, Liquan

2016-11-01

As an extension of High Efficiency Video Coding ( HEVC), 3D-HEVC has been widely researched under the impetus of the new generation coding standard in recent years. Compared with H.264/AVC, its compression efficiency is doubled while keeping the same video quality. However, its higher encoding complexity and longer encoding time are not negligible. To reduce the computational complexity and guarantee the subjective quality of virtual views, this paper presents a novel video coding method for 3D-HEVC based on the saliency informat ion which is an important part of Human Visual System (HVS). First of all, the relationship between the current coding unit and its adjacent units is used to adjust the maximum depth of each largest coding unit (LCU) and determine the SKIP mode reasonably. Then, according to the saliency informat ion of each frame image, the texture and its corresponding depth map will be divided into three regions, that is, salient area, middle area and non-salient area. Afterwards, d ifferent quantization parameters will be assigned to different regions to conduct low complexity coding. Finally, the compressed video will generate new view point videos through the renderer tool. As shown in our experiments, the proposed method saves more bit rate than other approaches and achieves up to highest 38% encoding time reduction without subjective quality loss in compression or rendering.

Convergence Studies of Mass Transport in Disks with Gravitational Instabilities. II. The Radiative Cooling Case

NASA Astrophysics Data System (ADS)

Steiman-Cameron, Thomas Y.; Durisen, Richard H.; Boley, Aaron C.; Michael, Scott; McConnell, Caitlin R.

2013-05-01

We conduct a convergence study of a protoplanetary disk subject to gravitational instabilities (GIs) at a time of approximate balance between heating produced by the GIs and radiative cooling governed by realistic dust opacities. We examine cooling times, characterize GI-driven spiral waves and their resultant gravitational torques, and evaluate how accurately mass transport can be represented by an α-disk formulation. Four simulations, identical except for azimuthal resolution, are conducted with a grid-based three-dimensional hydrodynamics code. There are two regions in which behaviors differ as resolution increases. The inner region, which contains 75% of the disk mass and is optically thick, has long cooling times and is well converged in terms of various measures of structure and mass transport for the three highest resolutions. The longest cooling times coincide with radii where the Toomre Q has its minimum value. Torques are dominated in this region by two- and three-armed spirals. The effective α arising from gravitational stresses is typically a few × 10-3 and is only roughly consistent with local balance of heating and cooling when time-averaged over many dynamic times and a wide range of radii. On the other hand, the outer disk region, which is mostly optically thin, has relatively short cooling times and does not show convergence as resolution increases. Treatment of unstable disks with optical depths near unity with realistic radiative transport is a difficult numerical problem requiring further study. We discuss possible implications of our results for numerical convergence of fragmentation criteria in disk simulations.

The response of phospholipid-encapsulated microbubbles to chirp-coded excitation: Implications for high-frequency nonlinear imaging

PubMed Central

Shekhar, Himanshu; Doyley, Marvin M.

2013-01-01

The current excitation strategy for harmonic and subharmonic imaging (HI and SHI) uses short sine-bursts. However, alternate pulsing strategies may be useful for enhancing nonlinear emissions from ultrasound contrast agents. The goal of this study was to corroborate the hypothesis that chirp-coded excitation can improve the performance of high-frequency HI and SHI. A secondary goal was to understand the mechanisms that govern the response of ultrasound contrast agents to chirp-coded and sine-burst excitation schemes. Numerical simulations and acoustic measurements were conducted to evaluate the response of a commercial contrast agent (Targestar-P®) to chirp-coded and sine-burst excitation (10 MHz frequency, peak pressures 290 kPa). The results of the acoustic measurements revealed an improvement in signal-to-noise ratio by 4 to 14 dB, and a two- to threefold reduction in the subharmonic threshold with chirp-coded excitation. Simulations conducted with the Marmottant model suggest that an increase in expansion-dominated radial excursion of microbubbles was the mechanism responsible for the stronger nonlinear response. Additionally, chirp-coded excitation detected the nonlinear response for a wider range of agent concentrations than sine-bursts. Therefore, chirp-coded excitation could be a viable approach for enhancing the performance of HI and SHI. PMID:23654417

The response of phospholipid-encapsulated microbubbles to chirp-coded excitation: implications for high-frequency nonlinear imaging.

PubMed

Shekhar, Himanshu; Doyley, Marvin M

2013-05-01

The current excitation strategy for harmonic and subharmonic imaging (HI and SHI) uses short sine-bursts. However, alternate pulsing strategies may be useful for enhancing nonlinear emissions from ultrasound contrast agents. The goal of this study was to corroborate the hypothesis that chirp-coded excitation can improve the performance of high-frequency HI and SHI. A secondary goal was to understand the mechanisms that govern the response of ultrasound contrast agents to chirp-coded and sine-burst excitation schemes. Numerical simulations and acoustic measurements were conducted to evaluate the response of a commercial contrast agent (Targestar-P(®)) to chirp-coded and sine-burst excitation (10 MHz frequency, peak pressures 290 kPa). The results of the acoustic measurements revealed an improvement in signal-to-noise ratio by 4 to 14 dB, and a two- to threefold reduction in the subharmonic threshold with chirp-coded excitation. Simulations conducted with the Marmottant model suggest that an increase in expansion-dominated radial excursion of microbubbles was the mechanism responsible for the stronger nonlinear response. Additionally, chirp-coded excitation detected the nonlinear response for a wider range of agent concentrations than sine-bursts. Therefore, chirp-coded excitation could be a viable approach for enhancing the performance of HI and SHI.

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

PubMed Central

Carter, Charles W.; Wolfenden, Richard

2016-01-01

abstract The universal genetic code is a translation table by which nucleic acid sequences can be interpreted as polypeptides with a wide range of biological functions. That information is used by aminoacyl-tRNA synthetases to translate the code. Moreover, amino acid properties dictate protein folding. We recently reported that digital correlation techniques could identify patterns in tRNA identity elements that govern recognition by synthetases. Our analysis, and the functionality of truncated synthetases that cannot recognize the tRNA anticodon, support the conclusion that the tRNA acceptor stem houses an independent code for the same 20 amino acids that likely functioned earlier in the emergence of genetics. The acceptor-stem code, related to amino acid size, is distinct from a code in the anticodon that is related to amino acid polarity. Details of the acceptor-stem code suggest that it was useful in preserving key properties of stereochemically-encoded peptides that had developed the capacity to interact catalytically with RNA. The quantitative embedding of the chemical properties of amino acids into tRNA bases has implications for the origins of molecular biology. PMID:26595350

On the biological plausibility of grandmother cells: implications for neural network theories in psychology and neuroscience.

PubMed

Bowers, Jeffrey S

2009-01-01

A fundamental claim associated with parallel distributed processing (PDP) theories of cognition is that knowledge is coded in a distributed manner in mind and brain. This approach rejects the claim that knowledge is coded in a localist fashion, with words, objects, and simple concepts (e.g. "dog"), that is, coded with their own dedicated representations. One of the putative advantages of this approach is that the theories are biologically plausible. Indeed, advocates of the PDP approach often highlight the close parallels between distributed representations learned in connectionist models and neural coding in brain and often dismiss localist (grandmother cell) theories as biologically implausible. The author reviews a range a data that strongly challenge this claim and shows that localist models provide a better account of single-cell recording studies. The author also contrast local and alternative distributed coding schemes (sparse and coarse coding) and argues that common rejection of grandmother cell theories in neuroscience is due to a misunderstanding about how localist models behave. The author concludes that the localist representations embedded in theories of perception and cognition are consistent with neuroscience; biology only calls into question the distributed representations often learned in PDP models.