Sample records for internal guide sequence

  1. Brief Guide to Genomics: DNA, Genes and Genomes

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  2. Epigenomics

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  3. Cloning

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  4. Chromosomes

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  5. Transcriptome

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  6. "The devil's in the detail": Release of an expanded, enhanced and dynamically revised forensic STR Sequence Guide.

    PubMed

    Phillips, C; Gettings, K Butler; King, J L; Ballard, D; Bodner, M; Borsuk, L; Parson, W

    2018-05-01

    The STR sequence template file published in 2016 as part of the considerations from the DNA Commission of the International Society for Forensic Genetics on minimal STR sequence nomenclature requirements, has been comprehensively revised and audited using the latest GRCh38 genome assembly. The list of forensic STRs characterized was expanded by including supplementary autosomal, X- and Y-chromosome microsatellites in less common use for routine DNA profiling, but some likely to be adopted in future massively parallel sequencing (MPS) STR panels. We outline several aspects of sequence alignment and annotation that required care and attention to detail when comparing sequences to GRCh37 and GRCh38 assemblies, as well as the necessary matching of MPS-based allele descriptions to previously established repeat region structures described in initial sequencing studies of the less well known forensic STRs. The revised sequence guide is now available in a dynamically updated FTP format from the STRidER website with a date-stamped change log to allow users to explore their own MPS data with the most up-to-date forensic STR sequence information compiled in a simple guide. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Genetic Mapping

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  8. Biological Pathways

    MedlinePlus

    ... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

  9. Moving Stimuli Facilitate Synchronization But Not Temporal Perception

    PubMed Central

    Silva, Susana; Castro, São Luís

    2016-01-01

    Recent studies have shown that a moving visual stimulus (e.g., a bouncing ball) facilitates synchronization compared to a static stimulus (e.g., a flashing light), and that it can even be as effective as an auditory beep. We asked a group of participants to perform different tasks with four stimulus types: beeps, siren-like sounds, visual flashes (static) and bouncing balls. First, participants performed synchronization with isochronous sequences (stimulus-guided synchronization), followed by a continuation phase in which the stimulus was internally generated (imagery-guided synchronization). Then they performed a perception task, in which they judged whether the final part of a temporal sequence was compatible with the previous beat structure (stimulus-guided perception). Similar to synchronization, an imagery-guided variant was added, in which sequences contained a gap in between (imagery-guided perception). Balls outperformed flashes and matched beeps (powerful ball effect) in stimulus-guided synchronization but not in perception (stimulus- or imagery-guided). In imagery-guided synchronization, performance accuracy decreased for beeps and balls, but not for flashes and sirens. Our findings suggest that the advantages of moving visual stimuli over static ones are grounded in action rather than perception, and they support the hypothesis that the sensorimotor coupling mechanisms for auditory (beeps) and moving visual stimuli (bouncing balls) overlap. PMID:27909419

  10. Moving Stimuli Facilitate Synchronization But Not Temporal Perception.

    PubMed

    Silva, Susana; Castro, São Luís

    2016-01-01

    Recent studies have shown that a moving visual stimulus (e.g., a bouncing ball) facilitates synchronization compared to a static stimulus (e.g., a flashing light), and that it can even be as effective as an auditory beep. We asked a group of participants to perform different tasks with four stimulus types: beeps, siren-like sounds, visual flashes (static) and bouncing balls. First, participants performed synchronization with isochronous sequences (stimulus-guided synchronization), followed by a continuation phase in which the stimulus was internally generated (imagery-guided synchronization). Then they performed a perception task, in which they judged whether the final part of a temporal sequence was compatible with the previous beat structure (stimulus-guided perception). Similar to synchronization, an imagery-guided variant was added, in which sequences contained a gap in between (imagery-guided perception). Balls outperformed flashes and matched beeps (powerful ball effect) in stimulus-guided synchronization but not in perception (stimulus- or imagery-guided). In imagery-guided synchronization, performance accuracy decreased for beeps and balls, but not for flashes and sirens. Our findings suggest that the advantages of moving visual stimuli over static ones are grounded in action rather than perception, and they support the hypothesis that the sensorimotor coupling mechanisms for auditory (beeps) and moving visual stimuli (bouncing balls) overlap.

  11. Base pairing between the 3' exon and an internal guide sequence increases 3' splice site specificity in the Tetrahymena self-splicing rRNA intron.

    PubMed Central

    Suh, E R; Waring, R B

    1990-01-01

    It has been proposed that recognition of the 3' splice site in many group I introns involves base pairing between the start of the 3' exon and a region of the intron known as the internal guide sequence (R. W. Davies, R. B. Waring, J. Ray, T. A. Brown, and C. Scazzocchio, Nature [London] 300:719-724, 1982). We have examined this hypothesis, using the self-splicing rRNA intron from Tetrahymena thermophila. Mutations in the 3' exon that weaken this proposed pairing increased use of a downstream cryptic 3' splice site. Compensatory mutations in the guide sequence that restore this pairing resulted in even stronger selection of the normal 3' splice site. These changes in 3' splice site usage were more pronounced in the background of a mutation (414A) which resulted in an adenine instead of a guanine being the last base of the intron. These results show that the proposed pairing (P10) plays an important role in ensuring that cryptic 3' splice sites are selected against. Surprisingly, the 414A mutation alone did not result in activation of the cryptic 3' splice site. Images PMID:2342465

  12. Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

    PubMed

    Joseph, Thomas T; Osman, Roman

    2012-01-01

    In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of a large number of internal allosteric pathways.

  13. Convergent Transmission of RNAi Guide-Target Mismatch Information across Argonaute Internal Allosteric Network

    PubMed Central

    Joseph, Thomas T.; Osman, Roman

    2012-01-01

    In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand “seed region” have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of a large number of internal allosteric pathways. PMID:23028290

  14. Guide and position of the International Society of Nutrigenetics/Nutrigenomics on personalised nutrition: Part 1 - fields of precision nutrition

    USDA-ARS?s Scientific Manuscript database

    Diversity in the genetic profile between individuals and specific ethnic groups affects nutrient requirements, metabolism and response to nutritional and dietary interventions. Indeed, individuals respond differently to lifestyle interventions (diet, physical activity, smoking, etc.). The sequencing...

  15. International Interlaboratory Digital PCR Study Demonstrating High Reproducibility for the Measurement of a Rare Sequence Variant.

    PubMed

    Whale, Alexandra S; Devonshire, Alison S; Karlin-Neumann, George; Regan, Jack; Javier, Leanne; Cowen, Simon; Fernandez-Gonzalez, Ana; Jones, Gerwyn M; Redshaw, Nicholas; Beck, Julia; Berger, Andreas W; Combaret, Valérie; Dahl Kjersgaard, Nina; Davis, Lisa; Fina, Frederic; Forshew, Tim; Fredslund Andersen, Rikke; Galbiati, Silvia; González Hernández, Álvaro; Haynes, Charles A; Janku, Filip; Lacave, Roger; Lee, Justin; Mistry, Vilas; Pender, Alexandra; Pradines, Anne; Proudhon, Charlotte; Saal, Lao H; Stieglitz, Elliot; Ulrich, Bryan; Foy, Carole A; Parkes, Helen; Tzonev, Svilen; Huggett, Jim F

    2017-02-07

    This study tested the claim that digital PCR (dPCR) can offer highly reproducible quantitative measurements in disparate laboratories. Twenty-one laboratories measured four blinded samples containing different quantities of a KRAS fragment encoding G12D, an important genetic marker for guiding therapy of certain cancers. This marker is challenging to quantify reproducibly using quantitative PCR (qPCR) or next generation sequencing (NGS) due to the presence of competing wild type sequences and the need for calibration. Using dPCR, 18 laboratories were able to quantify the G12D marker within 12% of each other in all samples. Three laboratories appeared to measure consistently outlying results; however, proper application of a follow-up analysis recommendation rectified their data. Our findings show that dPCR has demonstrable reproducibility across a large number of laboratories without calibration. This could enable the reproducible application of molecular stratification to guide therapy and, potentially, for molecular diagnostics.

  16. Simultaneous orthogonal plane imaging.

    PubMed

    Mickevicius, Nikolai J; Paulson, Eric S

    2017-11-01

    Intrafraction motion can result in a smearing of planned external beam radiation therapy dose distributions, resulting in an uncertainty in dose actually deposited in tissue. The purpose of this paper is to present a pulse sequence that is capable of imaging a moving target at a high frame rate in two orthogonal planes simultaneously for MR-guided radiotherapy. By balancing the zero gradient moment on all axes, slices in two orthogonal planes may be spatially encoded simultaneously. The orthogonal slice groups may be acquired with equal or nonequal echo times. A Cartesian spoiled gradient echo simultaneous orthogonal plane imaging (SOPI) sequence was tested in phantom and in vivo. Multiplexed SOPI acquisitions were performed in which two parallel slices were imaged along two orthogonal axes simultaneously. An autocalibrating phase-constrained 2D-SENSE-GRAPPA (generalized autocalibrating partially parallel acquisition) algorithm was implemented to reconstruct the multiplexed data. SOPI images without intraslice motion artifacts were reconstructed at a maximum frame rate of 8.16 Hz. The 2D-SENSE-GRAPPA reconstruction separated the parallel slices aliased along each orthogonal axis. The high spatiotemporal resolution provided by SOPI has the potential to be beneficial for intrafraction motion management during MR-guided radiation therapy or other MRI-guided interventions. Magn Reson Med 78:1700-1710, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  17. Planning activity for internally generated reward goals in monkey amygdala neurons

    PubMed Central

    Schultz, Wolfram

    2015-01-01

    The best rewards are often distant and can only be achieved by planning and decision-making over several steps. We designed a multi-step choice task in which monkeys followed internal plans to save rewards towards self-defined goals. During this self-controlled behavior, amygdala neurons showed future-oriented activity that reflected the animal’s plan to obtain specific rewards several trials ahead. This prospective activity encoded crucial components of the animal’s plan, including value and length of the planned choice sequence. It began on initial trials when a plan would be formed, reappeared step-by-step until reward receipt, and readily updated with a new sequence. It predicted performance, including errors, and typically disappeared during instructed behavior. Such prospective activity could underlie the formation and pursuit of internal plans characteristic for goal-directed behavior. The existence of neuronal planning activity in the amygdala suggests an important role for this structure in guiding behavior towards internally generated, distant goals. PMID:25622146

  18. Reading Strategy Guides to Assist Middle School Educators of Students with Dyslexia

    NASA Astrophysics Data System (ADS)

    Nichols-Yehling, M.; Strohl, C.

    2014-07-01

    According to the 2010 International Dyslexia Association publication, “Knowledge and Practice Standards for Teachers of Reading,” effective instruction is the key to addressing students' reading difficulties associated with dyslexia, a language-based disorder of learning to read and write. “Informed and effective classroom instruction. . . can prevent or at least effectively address and limit the severity of reading and writing problems.” The Interstellar Boundary Explorer (IBEX) mission Education and Public Outreach program recently funded the development of six strategy guides for teachers of middle school students with reading difficulties, especially dyslexia. These guides utilize space science-themed reading materials developed by the Great Exploration in Math and Science (GEMS), including the IBEX-funded GEMS Space Science Sequence (Grades 6-8). The aforementioned reading strategy guides are now available on the IBEX mission website.

  19. Simple chained guide trees give high-quality protein multiple sequence alignments

    PubMed Central

    Boyce, Kieran; Sievers, Fabian; Higgins, Desmond G.

    2014-01-01

    Guide trees are used to decide the order of sequence alignment in the progressive multiple sequence alignment heuristic. These guide trees are often the limiting factor in making large alignments, and considerable effort has been expended over the years in making these quickly or accurately. In this article we show that, at least for protein families with large numbers of sequences that can be benchmarked with known structures, simple chained guide trees give the most accurate alignments. These also happen to be the fastest and simplest guide trees to construct, computationally. Such guide trees have a striking effect on the accuracy of alignments produced by some of the most widely used alignment packages. There is a marked increase in accuracy and a marked decrease in computational time, once the number of sequences goes much above a few hundred. This is true, even if the order of sequences in the guide tree is random. PMID:25002495

  20. A population study of the minicircles in Trypanosoma cruzi: predicting guide RNAs in the absence of empirical RNA editing.

    PubMed

    Thomas, Sean; Martinez, L L Isadora Trejo; Westenberger, Scott J; Sturm, Nancy R

    2007-05-24

    The structurally complex network of minicircles and maxicircles comprising the mitochondrial DNA of kinetoplastids mirrors the complexity of the RNA editing process that is required for faithful expression of encrypted maxicircle genes. Although a few of the guide RNAs that direct this editing process have been discovered on maxicircles, guide RNAs are mostly found on the minicircles. The nuclear and maxicircle genomes have been sequenced and assembled for Trypanosoma cruzi, the causative agent of Chagas disease, however the complement of 1.4-kb minicircles, carrying four guide RNA genes per molecule in this parasite, has been less thoroughly characterised. Fifty-four CL Brener and 53 Esmeraldo strain minicircle sequence reads were extracted from T. cruzi whole genome shotgun sequencing data. With these sequences and all published T. cruzi minicircle sequences, 108 unique guide RNAs from all known T. cruzi minicircle sequences and two guide RNAs from the CL Brener maxicircle were predicted using a local alignment algorithm and mapped onto predicted or experimentally determined sequences of edited maxicircle open reading frames. For half of the sequences no statistically significant guide RNA could be assigned. Likely positions of these unidentified gRNAs in T. cruzi minicircle sequences are estimated using a simple Hidden Markov Model. With the local alignment predictions as a standard, the HMM had an ~85% chance of correctly identifying at least 20 nucleotides of guide RNA from a given minicircle sequence. Inter-minicircle recombination was documented. Variable regions contain species-specific areas of distinct nucleotide preference. Two maxicircle guide RNA genes were found. The identification of new minicircle sequences and the further characterization of all published minicircles are presented, including the first observation of recombination between minicircles. Extrapolation suggests a level of 4% recombinants in the population, supporting a relatively high recombination rate that may serve to minimize the persistence of gRNA pseudogenes. Characteristic nucleotide preferences observed within variable regions provide potential clues regarding the transcription and maturation of T. cruzi guide RNAs. Based on these preferences, a method of predicting T. cruzi guide RNAs using only primary minicircle sequence data was created.

  1. Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor

    PubMed Central

    Wan, Min; Zhang, Wenhua; Tian, Yangli; Xu, Chanjuan; Xu, Tao; Liu, Jianfeng; Zhang, Rongying

    2015-01-01

    Endocytosis and postendocytic sorting of G-protein-coupled receptors (GPCRs) is important for the regulation of both their cell surface density and signaling profile. Unlike the mechanisms of clathrin-dependent endocytosis (CDE), the mechanisms underlying the control of GPCR signaling by clathrin-independent endocytosis (CIE) remain largely unknown. Among the muscarinic acetylcholine receptors (mAChRs), the M4 mAChR undergoes CDE and recycling, whereas the M2 mAChR is internalized through CIE and targeted to lysosomes. Here we investigated the endocytosis and postendocytic trafficking of M2 mAChR based on a comparative analysis of the third cytoplasmic domain in M2 and M4 mAChRs. For the first time, we identified that the sequence 374KKKPPPS380 servers as a sorting signal for the clathrin-independent internalization of M2 mAChR. Switching 374KKKPPPS380 to the i3 loop of the M4 mAChR shifted the receptor into lysosomes through the CIE pathway; and therefore away from CDE and recycling. We also found another previously unidentified sequence that guides CDE of the M2 mAChR, 361VARKIVKMTKQPA373, which is normally masked in the presence of the downstream sequence 374KKKPPPS380. Taken together, our data indicate that endocytosis and postendocytic sorting of GPCRs that undergo CIE could be sequence-dependent. PMID:26094760

  2. Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Li, Mengfei; Yuan, Zhefan; Wu, Dan; Chen, Jia-da; Feng, Jie

    2016-10-01

    A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K10), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K10, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.

  3. Utilization of Ancillary Studies in the Cytologic Diagnosis of Respiratory Lesions

    PubMed Central

    Layfield, Lester J.; Roy-Chowdhuri, Sinchita; Baloch, Zubair; Ehya, Hormoz; Geisinger, Kim; Hsiao, Susan J.; Lin, Oscar; Lindeman, Neal I.; Roh, Michael; Schmitt, Fernando; Sidiropoulos, Nikoletta; VanderLaan, Paul A.

    2017-01-01

    The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT-guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS-FNA), as well as recommendations for classification and criteria, ancillary testing and post-cytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next-generation sequencing are discussed. PMID:27561242

  4. Geologic field-trip guide to Long Valley Caldera, California

    USGS Publications Warehouse

    Hildreth, Wes; Fierstein, Judy

    2017-07-26

    This guide to the geology of Long Valley Caldera is presented in four parts: (1) An overview of the volcanic geology; (2) a chronological summary of the principal geologic events; (3) a road log with directions and descriptions for 38 field-trip stops; and (4) a summary of the geophysical unrest since 1978 and discussion of its causes. The sequence of stops is arranged as a four-day excursion for the quadrennial General Assembly of the International Association of Volcanology and Chemistry of the Earth’s Interior (IAVCEI), centered in Portland, Oregon, in August 2017. Most stops, however, are written freestanding, with directions that allow each one to be visited independently, in any order selected.

  5. Career Academy Course Sequences.

    ERIC Educational Resources Information Center

    Markham, Thom; Lenz, Robert

    This career academy course sequence guide is designed to give teachers a quick overview of the course sequences of well-known career academy and career pathway programs from across the country. The guide presents a variety of sample course sequences for the following academy themes: (1) arts and communication; (2) business and finance; (3)…

  6. TP53, PIK3CA, FBXW7 and KRAS Mutations in Esophageal Cancer Identified by Targeted Sequencing.

    PubMed

    Zheng, Huili; Wang, Yan; Tang, Chuanning; Jones, Lindsey; Ye, Hua; Zhang, Guangchun; Cao, Weihai; Li, Jingwen; Liu, Lifeng; Liu, Zhencong; Zhang, Chao; Lou, Feng; Liu, Zhiyuan; Li, Yangyang; Shi, Zhenfen; Zhang, Jingbo; Zhang, Dandan; Sun, Hong; Dong, Haichao; Dong, Zhishou; Guo, Baishuai; Yan, H E; Lu, Qingyu; Huang, Xue; Chen, Si-Yi

    2016-01-01

    Esophageal cancer (EC) is a common malignancy with significant morbidity and mortality. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in EC that may serve as biomarkers might help predict patient outcome and guide treatment. Traditionally, personalized cancer DNA sequencing was impractical and expensive. Recent technological advancements have made targeted DNA sequencing more cost- and time-effective with reliable results. This technology may be useful for clinicians to direct patient treatment. The Ion PGM and AmpliSeq Cancer Panel was used to identify mutations at 737 hotspot loci of 45 cancer-related genes in 64 EC samples from Chinese patients. Frequent mutations were found in TP53 and less frequent mutations in PIK3CA, FBXW7 and KRAS. These results demonstrate that targeted sequencing can reliably identify mutations in individual tumors that make this technology a possibility for clinical use. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  7. Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Version 3.0 User Guide

    EPA Science Inventory

    User Guide to describe the complete functionality of the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Version 3.0 online tool. The US Environmental Protection Agency Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS; https://seqa...

  8. Health Occupations: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 3-year program in health occupations. The guide consists of a course description; general course…

  9. VOE Computer Programming: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 3-year program in computer programming. The guide consists of a course description; general course…

  10. Urban Horticulture: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 4-year program in urban horticulture. The guide consists of a course description; general course…

  11. VOE Accounting: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 2-year program in accounting. The guide consists of a course description; general course objectives;…

  12. Agriculture: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 3-year program in agriculture. The guide consists of a course description; general course objectives;…

  13. Focal point determination in magnetic resonance-guided focused ultrasound using tracking coils.

    PubMed

    Svedin, Bryant T; Beck, Michael J; Hadley, J Rock; Merrill, Robb; de Bever, Joshua T; Bolster, Bradley D; Payne, Allison; Parker, Dennis L

    2017-06-01

    To develop a method for rapid prediction of the geometric focus location in MR coordinates of a focused ultrasound (US) transducer with arbitrary position and orientation without sonicating. Three small tracker coil circuits were designed, constructed, attached to the transducer housing of a breast-specific MR-guided focused US (MRgFUS) system with 5 degrees of freedom, and connected to receiver channel inputs of an MRI scanner. A one-dimensional sequence applied in three orthogonal directions determined the position of each tracker, which was then corrected for gradient nonlinearity. In a calibration step, low-level heating located the US focus in one transducer position orientation where the tracker positions were also known. Subsequent US focus locations were determined from the isometric transformation of the trackers. The accuracy of this method was verified by comparing the tracking coil predictions to thermal center of mass calculated using MR thermometry data acquired at 16 different transducer positions for MRgFUS sonications in a homogeneous gelatin phantom. The tracker coil predicted focus was an average distance of 2.1 ± 1.1 mm from the thermal center of mass. The one-dimensional locator sequence and prediction calculations took less than 1 s to perform. This technique accurately predicts the geometric focus for a transducer with arbitrary position and orientation without sonicating. Magn Reson Med 77:2424-2430, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  14. External Guide Sequences Targeting the aac(6′)-Ib mRNA Induce Inhibition of Amikacin Resistance▿

    PubMed Central

    Bistué, Alfonso J. C. Soler; Ha, Hongphuc; Sarno, Renee; Don, Michelle; Zorreguieta, Angeles; Tolmasky, Marcelo E.

    2007-01-01

    The dissemination of AAC(6′)-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6′)-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native aac(6′)-Ib mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into Escherichia coli harboring aac(6′)-Ib, and the transformant strains were tested to determine their resistance to amikacin. The two external guide sequences that showed the strongest binding efficiency to the mRNA in vitro, EGSC3 and EGSA2, interfered with expression of the resistance phenotype at different degrees. Growth curve experiments showed that E. coli cells harboring a plasmid coding for EGSC3, the external guide sequence with the highest mRNA binding affinity in vitro, did not grow for at least 300 min in the presence of 15 μg of amikacin/ml. EGSA2, which had a lower mRNA-binding affinity in vitro than EGSC3, inhibited the expression of amikacin resistance at a lesser level; growth of E. coli harboring a plasmid coding for EGSA2, in the presence of 15 μg of amikacin/ml was undetectable for 200 min but reached an optical density at 600 nm of 0.5 after 5 h of incubation. Our results indicate that the use of external guide sequences could be a viable strategy to preserve the efficacy of amikacin. PMID:17387154

  15. Iteratively Refined Guide Trees Help Improving Alignment and Phylogenetic Inference in the Mushroom Family Bolbitiaceae

    PubMed Central

    Tóth, Annamária; Hausknecht, Anton; Krisai-Greilhuber, Irmgard; Papp, Tamás; Vágvölgyi, Csaba; Nagy, László G.

    2013-01-01

    Reconciling traditional classifications, morphology, and the phylogenetic relationships of brown-spored agaric mushrooms has proven difficult in many groups, due to extensive convergence in morphological features. Here, we address the monophyly of the Bolbitiaceae, a family with over 700 described species and examine the higher-level relationships within the family using a newly constructed multilocus dataset (ITS, nrLSU rDNA and EF1-alpha). We tested whether the fast-evolving Internal Transcribed Spacer (ITS) sequences can be accurately aligned across the family, by comparing the outcome of two iterative alignment refining approaches (an automated and a manual) and various indel-treatment strategies. We used PRANK to align sequences in both cases. Our results suggest that – although PRANK successfully evades overmatching of gapped sites, referred previously to as alignment overmatching – it infers an unrealistically high number of indel events with natively generated guide-trees. This 'alignment undermatching' could be avoided by using more rigorous (e.g. ML) guide trees. The trees inferred in this study support the monophyly of the core Bolbitiaceae, with the exclusion of Panaeolus, Agrocybe, and some of the genera formerly placed in the family. Bolbitius and Conocybe were found monophyletic, however, Pholiotina and Galerella require redefinition. The phylogeny revealed that stipe coverage type is a poor predictor of phylogenetic relationships, indicating the need for a revision of the intrageneric relationships within Conocybe. PMID:23418526

  16. Marketing and Distributive Education: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 2-year program in marketing and distributive education. The guide consists of a course description;…

  17. Industrial Cooperative Education Co-op: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This guide, which was written as an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System, outlines the suggested scope and sequence of a 2-year cooperative program in industrial education. The guide consists of a course description;…

  18. DNA Multiple Sequence Alignment Guided by Protein Domains: The MSA-PAD 2.0 Method.

    PubMed

    Balech, Bachir; Monaco, Alfonso; Perniola, Michele; Santamaria, Monica; Donvito, Giacinto; Vicario, Saverio; Maggi, Giorgio; Pesole, Graziano

    2018-01-01

    Multiple sequence alignment (MSA) is a fundamental component in many DNA sequence analyses including metagenomics studies and phylogeny inference. When guided by protein profiles, DNA multiple alignments assume a higher precision and robustness. Here we present details of the use of the upgraded version of MSA-PAD (2.0), which is a DNA multiple sequence alignment framework able to align DNA sequences coding for single/multiple protein domains guided by PFAM or user-defined annotations. MSA-PAD has two alignment strategies, called "Gene" and "Genome," accounting for coding domains order and genomic rearrangements, respectively. Novel options were added to the present version, where the MSA can be guided by protein profiles provided by the user. This allows MSA-PAD 2.0 to run faster and to add custom protein profiles sometimes not present in PFAM database according to the user's interest. MSA-PAD 2.0 is currently freely available as a Web application at https://recasgateway.cloud.ba.infn.it/ .

  19. Assembling in Sequence: A Saleable Work Skill. Occupation Simulation Packet. Grades 3rd-4th.

    ERIC Educational Resources Information Center

    Hueston, Jean

    This teacher's guide for grades 3 and 4 contains simulated work experiences for students using the isolated skill concept - assembling in sequence. Teacher instructions include objectives, evaluation, and sequence of activities. The guide contains pre-tests and post-tests with instructions and answer keys. Three pre-skill activities are suggested,…

  20. Mice and Men Environmental Balance, Parts Three and Four of an Integrated Science Sequence, Teacher's Guide, 1970 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This teacher's guide contains parts three and four of the four-part first year Portland Project, a three-year secondary integrated science curriculum sequence. Part three of the guide deals with topics such as the cell, reproduction, embryology, genetics, genetic diseases, genetics and change, populations, effects of density on populations,…

  1. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites

    PubMed Central

    Naito, Yuki; Hino, Kimihiro; Bono, Hidemasa; Ui-Tei, Kumiko

    2015-01-01

    Summary: CRISPRdirect is a simple and functional web server for selecting rational CRISPR/Cas targets from an input sequence. The CRISPR/Cas system is a promising technique for genome engineering which allows target-specific cleavage of genomic DNA guided by Cas9 nuclease in complex with a guide RNA (gRNA), that complementarily binds to a ∼20 nt targeted sequence. The target sequence requirements are twofold. First, the 5′-NGG protospacer adjacent motif (PAM) sequence must be located adjacent to the target sequence. Second, the target sequence should be specific within the entire genome in order to avoid off-target editing. CRISPRdirect enables users to easily select rational target sequences with minimized off-target sites by performing exhaustive searches against genomic sequences. The server currently incorporates the genomic sequences of human, mouse, rat, marmoset, pig, chicken, frog, zebrafish, Ciona, fruit fly, silkworm, Caenorhabditis elegans, Arabidopsis, rice, Sorghum and budding yeast. Availability: Freely available at http://crispr.dbcls.jp/. Contact: y-naito@dbcls.rois.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25414360

  2. A bacterial Argonaute with noncanonical guide RNA specificity

    PubMed Central

    Kaya, Emine; Doxzen, Kevin W.; Knoll, Kilian R.; Wilson, Ross C.; Strutt, Steven C.; Kranzusch, Philip J.; Doudna, Jennifer A.

    2016-01-01

    Eukaryotic Argonaute proteins induce gene silencing by small RNA-guided recognition and cleavage of mRNA targets. Although structural similarities between human and prokaryotic Argonautes are consistent with shared mechanistic properties, sequence and structure-based alignments suggested that Argonautes encoded within CRISPR-cas [clustered regularly interspaced short palindromic repeats (CRISPR)-associated] bacterial immunity operons have divergent activities. We show here that the CRISPR-associated Marinitoga piezophila Argonaute (MpAgo) protein cleaves single-stranded target sequences using 5′-hydroxylated guide RNAs rather than the 5′-phosphorylated guides used by all known Argonautes. The 2.0-Å resolution crystal structure of an MpAgo–RNA complex reveals a guide strand binding site comprising residues that block 5′ phosphate interactions. Using structure-based sequence alignment, we were able to identify other putative MpAgo-like proteins, all of which are encoded within CRISPR-cas loci. Taken together, our data suggest the evolution of an Argonaute subclass with noncanonical specificity for a 5′-hydroxylated guide. PMID:27035975

  3. Guide-substrate base-pairing requirement for box H/ACA RNA-guided RNA pseudouridylation.

    PubMed

    De Zoysa, Meemanage D; Wu, Guowei; Katz, Raviv; Yu, Yi-Tao

    2018-06-05

    Box H/ACA RNAs are a group of small RNAs found in abundance in eukaryotes (as well as in archaea). Although their sequences differ, eukaryotic box H/ACA RNAs all share the same unique hairpin-hinge-hairpin-tail structure. Almost all of them function as guides that primarily direct pseudouridylation of rRNAs and spliceosomal snRNAs at specific sites. Although box H/ACA RNA-guided pseudouridylation has been extensively studied, the detailed rules governing this reaction, especially those concerning the guide RNA-substrate RNA base-pairing interactions that determine the specificity and efficiency of pseudouridylation, are still not exactly clear. This is particularly relevant given that the lengths of the guide sequences involved in base-pairing vary from one box H/ACA RNA to another. Here, we carry out a detailed investigation into guide-substrate base-pairing interactions, and identify the minimum number of base-pairs (8), required for RNA-guided pseudouridylation. In addition, we find that the pseudouridylation pocket, present in each hairpin of box H/ACA RNA, exhibits flexibility in fitting slightly different substrate sequences. Our results are consistent across three independent pseudouridylation pockets tested, suggesting that our findings are generally applicable to box H/ACA RNA-guided RNA pseudouridylation. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  4. Rapid construction of a whole-genome transposon insertion collection for Shewanella oneidensis by Knockout Sudoku.

    PubMed

    Baym, Michael; Shaket, Lev; Anzai, Isao A; Adesina, Oluwakemi; Barstow, Buz

    2016-11-10

    Whole-genome knockout collections are invaluable for connecting gene sequence to function, yet traditionally, their construction has required an extraordinary technical effort. Here we report a method for the construction and purification of a curated whole-genome collection of single-gene transposon disruption mutants termed Knockout Sudoku. Using simple combinatorial pooling, a highly oversampled collection of mutants is condensed into a next-generation sequencing library in a single day, a 30- to 100-fold improvement over prior methods. The identities of the mutants in the collection are then solved by a probabilistic algorithm that uses internal self-consistency within the sequencing data set, followed by rapid algorithmically guided condensation to a minimal representative set of mutants, validation, and curation. Starting from a progenitor collection of 39,918 mutants, we compile a quality-controlled knockout collection of the electroactive microbe Shewanella oneidensis MR-1 containing representatives for 3,667 genes that is functionally validated by high-throughput kinetic measurements of quinone reduction.

  5. A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

    NASA Astrophysics Data System (ADS)

    Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.

    2017-05-01

    MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

  6. Health Grades K-6. Skills-Based Scope and Sequence Guide. Target Skills and Sample Assessment Methods.

    ERIC Educational Resources Information Center

    Williamson, Anne; Beegle, Jenny; Gilbert, Lisa; Safaii, SeAnne; Eck, Paul; Remaley, Renea; Hasselquist, Claudia; Hatch, Kathy C.; Thompson, Kay

    This guide is organized around a suggested list of health skills that all students should know and be able to do at each grade level from kindergarten through grade 6. The guide will help provide parents, teachers, and students with knowledge of what is being taught in a logical scope and sequence by grade level. It is designed to help build a…

  7. Sequencing Stories in Spanish and English.

    ERIC Educational Resources Information Center

    Steckbeck, Pamela Meza

    The guide was designed for speech pathologists, bilingual teachers, and specialists in English as a second language who work with Spanish-speaking children. The guide contains twenty illustrated stories that facilitate the learning of auditory sequencing, auditory and visual memory, receptive and expressive vocabulary, and expressive language…

  8. A guide to federal-aid programs, projects, and other uses of highway funds

    DOT National Transportation Integrated Search

    2000-07-01

    This Guide, Volume 2 - Websites, is part of the International Guide to Highway Transportation Information, a multi-volume set of Guides that provide highway transportation information resources for domestic and international professionals. In this Vo...

  9. Best Practices for Environmental Site Management: A Practical Guide for Applying Environmental Sequence Stratigraphy to Improve Conceptual Site Models

    EPA Science Inventory

    Presented here is a practical guide on the application of the geologic principles of sequence stratigraphy and facies models to the characterization of stratigraphic heterogeneity at hazardous waste sites. This technology is applicable to sites underlain by clastic aquifers (int...

  10. Getting to Know You...All about You: Preschool Orientation Manual.

    ERIC Educational Resources Information Center

    San Ysidro School District, CA.

    Designed to guide teachers through a 20-day sequence of preschool orientation activities, the manual presents a numbered sequence of topics with related objectives and explanations, preparation and planning needs, and specific activities for children. Section I is entitled "All Around Us" and focuses on guiding preschool children and…

  11. Two low coverage bird genomes and a comparison of reference-guided versus de novo genome assemblies.

    PubMed

    Card, Daren C; Schield, Drew R; Reyes-Velasco, Jacobo; Fujita, Matthew K; Andrew, Audra L; Oyler-McCance, Sara J; Fike, Jennifer A; Tomback, Diana F; Ruggiero, Robert P; Castoe, Todd A

    2014-01-01

    As a greater number and diversity of high-quality vertebrate reference genomes become available, it is increasingly feasible to use these references to guide new draft assemblies for related species. Reference-guided assembly approaches may substantially increase the contiguity and completeness of a new genome using only low levels of genome coverage that might otherwise be insufficient for de novo genome assembly. We used low-coverage (∼3.5-5.5x) Illumina paired-end sequencing to assemble draft genomes of two bird species (the Gunnison Sage-Grouse, Centrocercus minimus, and the Clark's Nutcracker, Nucifraga columbiana). We used these data to estimate de novo genome assemblies and reference-guided assemblies, and compared the information content and completeness of these assemblies by comparing CEGMA gene set representation, repeat element content, simple sequence repeat content, and GC isochore structure among assemblies. Our results demonstrate that even lower-coverage genome sequencing projects are capable of producing informative and useful genomic resources, particularly through the use of reference-guided assemblies.

  12. Two low coverage bird genomes and a comparison of reference-guided versus de novo genome assemblies

    USGS Publications Warehouse

    Card, Daren C.; Schield, Drew R.; Reyes-Velasco, Jacobo; Fujita, Matthre K.; Andrew, Audra L.; Oyler-McCance, Sara J.; Fike, Jennifer A.; Tomback, Diana F.; Ruggiero, Robert P.; Castoe, Todd A.

    2014-01-01

    As a greater number and diversity of high-quality vertebrate reference genomes become available, it is increasingly feasible to use these references to guide new draft assemblies for related species. Reference-guided assembly approaches may substantially increase the contiguity and completeness of a new genome using only low levels of genome coverage that might otherwise be insufficient for de novo genome assembly. We used low-coverage (~3.5–5.5x) Illumina paired-end sequencing to assemble draft genomes of two bird species (the Gunnison Sage-Grouse, Centrocercus minimus, and the Clark's Nutcracker, Nucifraga columbiana). We used these data to estimate de novo genome assemblies and reference-guided assemblies, and compared the information content and completeness of these assemblies by comparing CEGMA gene set representation, repeat element content, simple sequence repeat content, and GC isochore structure among assemblies. Our results demonstrate that even lower-coverage genome sequencing projects are capable of producing informative and useful genomic resources, particularly through the use of reference-guided assemblies.

  13. Structure and specificity of the RNA-guided endonuclease Cas9 during DNA interrogation, target binding and cleavage

    PubMed Central

    Josephs, Eric A.; Kocak, D. Dewran; Fitzgibbon, Christopher J.; McMenemy, Joshua; Gersbach, Charles A.; Marszalek, Piotr E.

    2015-01-01

    CRISPR-associated endonuclease Cas9 cuts DNA at variable target sites designated by a Cas9-bound RNA molecule. Cas9's ability to be directed by single ‘guide RNA’ molecules to target nearly any sequence has been recently exploited for a number of emerging biological and medical applications. Therefore, understanding the nature of Cas9's off-target activity is of paramount importance for its practical use. Using atomic force microscopy (AFM), we directly resolve individual Cas9 and nuclease-inactive dCas9 proteins as they bind along engineered DNA substrates. High-resolution imaging allows us to determine their relative propensities to bind with different guide RNA variants to targeted or off-target sequences. Mapping the structural properties of Cas9 and dCas9 to their respective binding sites reveals a progressive conformational transformation at DNA sites with increasing sequence similarity to its target. With kinetic Monte Carlo (KMC) simulations, these results provide evidence of a ‘conformational gating’ mechanism driven by the interactions between the guide RNA and the 14th–17th nucleotide region of the targeted DNA, the stabilities of which we find correlate significantly with reported off-target cleavage rates. KMC simulations also reveal potential methodologies to engineer guide RNA sequences with improved specificity by considering the invasion of guide RNAs into targeted DNA duplex. PMID:26384421

  14. COMOC 2: Two-dimensional aerodynamics sequence, computer program user's guide

    NASA Technical Reports Server (NTRS)

    Manhardt, P. D.; Orzechowski, J. A.; Baker, A. J.

    1977-01-01

    The COMOC finite element fluid mechanics computer program system is applicable to diverse problem classes. The two dimensional aerodynamics sequence was established for solution of the potential and/or viscous and turbulent flowfields associated with subsonic flight of elementary two dimensional isolated airfoils. The sequence is constituted of three specific flowfield options in COMOC for two dimensional flows. These include the potential flow option, the boundary layer option, and the parabolic Navier-Stokes option. By sequencing through these options, it is possible to computationally construct a weak-interaction model of the aerodynamic flowfield. This report is the user's guide to operation of COMOC for the aerodynamics sequence.

  15. International Student Guide to U.S. Community Colleges, 2008-2009

    ERIC Educational Resources Information Center

    American Association of Community Colleges (NJ1), 2008

    2008-01-01

    The "International Student Guide to U.S. Community Colleges" is the only publication of its kind that targets prospective international students. Published annually, the Guide is designed to inform, advise, assist, and influence postsecondary students in other countries who plan to pursue education options in the United States. The Guide…

  16. GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas nucleases.

    PubMed

    Zhu, Lihua Julie; Lawrence, Michael; Gupta, Ankit; Pagès, Hervé; Kucukural, Alper; Garber, Manuel; Wolfe, Scot A

    2017-05-15

    Genome editing technologies developed around the CRISPR-Cas9 nuclease system have facilitated the investigation of a broad range of biological questions. These nucleases also hold tremendous promise for treating a variety of genetic disorders. In the context of their therapeutic application, it is important to identify the spectrum of genomic sequences that are cleaved by a candidate nuclease when programmed with a particular guide RNA, as well as the cleavage efficiency of these sites. Powerful new experimental approaches, such as GUIDE-seq, facilitate the sensitive, unbiased genome-wide detection of nuclease cleavage sites within the genome. Flexible bioinformatics analysis tools for processing GUIDE-seq data are needed. Here, we describe an open source, open development software suite, GUIDEseq, for GUIDE-seq data analysis and annotation as a Bioconductor package in R. The GUIDEseq package provides a flexible platform with more than 60 adjustable parameters for the analysis of datasets associated with custom nuclease applications. These parameters allow data analysis to be tailored to different nuclease platforms with different length and complexity in their guide and PAM recognition sequences or their DNA cleavage position. They also enable users to customize sequence aggregation criteria, and vary peak calling thresholds that can influence the number of potential off-target sites recovered. GUIDEseq also annotates potential off-target sites that overlap with genes based on genome annotation information, as these may be the most important off-target sites for further characterization. In addition, GUIDEseq enables the comparison and visualization of off-target site overlap between different datasets for a rapid comparison of different nuclease configurations or experimental conditions. For each identified off-target, the GUIDEseq package outputs mapped GUIDE-Seq read count as well as cleavage score from a user specified off-target cleavage score prediction algorithm permitting the identification of genomic sequences with unexpected cleavage activity. The GUIDEseq package enables analysis of GUIDE-data from various nuclease platforms for any species with a defined genomic sequence. This software package has been used successfully to analyze several GUIDE-seq datasets. The software, source code and documentation are freely available at http://www.bioconductor.org/packages/release/bioc/html/GUIDEseq.html .

  17. BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes.

    PubMed

    Staňková, Helena; Hastie, Alex R; Chan, Saki; Vrána, Jan; Tulpová, Zuzana; Kubaláková, Marie; Visendi, Paul; Hayashi, Satomi; Luo, Mingcheng; Batley, Jacqueline; Edwards, David; Doležel, Jaroslav; Šimková, Hana

    2016-07-01

    The assembly of a reference genome sequence of bread wheat is challenging due to its specific features such as the genome size of 17 Gbp, polyploid nature and prevalence of repetitive sequences. BAC-by-BAC sequencing based on chromosomal physical maps, adopted by the International Wheat Genome Sequencing Consortium as the key strategy, reduces problems caused by the genome complexity and polyploidy, but the repeat content still hampers the sequence assembly. Availability of a high-resolution genomic map to guide sequence scaffolding and validate physical map and sequence assemblies would be highly beneficial to obtaining an accurate and complete genome sequence. Here, we chose the short arm of chromosome 7D (7DS) as a model to demonstrate for the first time that it is possible to couple chromosome flow sorting with genome mapping in nanochannel arrays and create a de novo genome map of a wheat chromosome. We constructed a high-resolution chromosome map composed of 371 contigs with an N50 of 1.3 Mb. Long DNA molecules achieved by our approach facilitated chromosome-scale analysis of repetitive sequences and revealed a ~800-kb array of tandem repeats intractable to current DNA sequencing technologies. Anchoring 7DS sequence assemblies obtained by clone-by-clone sequencing to the 7DS genome map provided a valuable tool to improve the BAC-contig physical map and validate sequence assembly on a chromosome-arm scale. Our results indicate that creating genome maps for the whole wheat genome in a chromosome-by-chromosome manner is feasible and that they will be an affordable tool to support the production of improved pseudomolecules. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Teaching/Learning Guide: Level I.

    ERIC Educational Resources Information Center

    Carbon - Lehigh Intermediate Unit, Schnecksville, PA.

    The manual presents sequences of skills designed for use as guides to teaching/learning objectives and as a basis for evaluating and recording special education students' progress. It is explained that the goal of the first level of objectives (sequenced in this document) is to enable the student to function at a motor/psychomotor state of…

  19. Self-guided management of exome and whole-genome sequencing results: changing the results return model.

    PubMed

    Yu, Joon-Ho; Jamal, Seema M; Tabor, Holly K; Bamshad, Michael J

    2013-09-01

    Researchers and clinicians face the practical and ethical challenge of if and how to offer for return the wide and varied scope of results available from individual exome sequencing and whole-genome sequencing. We argue that rather than viewing individual exome sequencing and whole-genome sequencing as a test for which results need to be "returned," that the technology should instead be framed as a dynamic resource of information from which results should be "managed" over the lifetime of an individual. We further suggest that individual exome sequencing and whole-genome sequencing results management is optimized using a self-guided approach that enables individuals to self-select among results offered for return in a convenient, confidential, personalized context that is responsive to their value system. This approach respects autonomy, allows individuals to maximize potential benefits of genomic information (beneficence) and minimize potential harms (nonmaleficence), and also preserves their right to an open future to the extent they desire or think is appropriate. We describe key challenges and advantages of such a self-guided management system and offer guidance on implementation using an information systems approach.

  20. Electrical Programming of Soft Matter: Using Temporally Varying Electrical Inputs To Spatially Control Self Assembly.

    PubMed

    Yan, Kun; Liu, Yi; Zhang, Jitao; Correa, Santiago O; Shang, Wu; Tsai, Cheng-Chieh; Bentley, William E; Shen, Jana; Scarcelli, Giuliano; Raub, Christopher B; Shi, Xiao-Wen; Payne, Gregory F

    2018-02-12

    The growing importance of hydrogels in translational medicine has stimulated the development of top-down fabrication methods, yet often these methods lack the capabilities to generate the complex matrix architectures observed in biology. Here we show that temporally varying electrical signals can cue a self-assembling polysaccharide to controllably form a hydrogel with complex internal patterns. Evidence from theory and experiment indicate that internal structure emerges through a subtle interplay between the electrical current that triggers self-assembly and the electrical potential (or electric field) that recruits and appears to orient the polysaccharide chains at the growing gel front. These studies demonstrate that short sequences (minutes) of low-power (∼1 V) electrical inputs can provide the program to guide self-assembly that yields hydrogels with stable, complex, and spatially varying structure and properties.

  1. Fast imaging employing steady-state acquisition (FIESTA) MRI to investigate cerebrospinal fluid (CSF) within dural reflections of posterior fossa cranial nerves

    PubMed Central

    Scoffings, Daniel; Ajithkumar, Thankamma; Williams, Michael V; Jefferies, Sarah J

    2016-01-01

    Objective: There is no consensus approach to covering skull base meningeal reflections—and cerebrospinal fluid (CSF) therein—of the posterior fossa cranial nerves (CNs VII–XII) when planning radiotherapy (RT) for medulloblastoma and ependymoma. We sought to determine whether MRI and specifically fast imaging employing steady-state acquisition (FIESTA) sequences can answer this anatomical question and guide RT planning. Methods: 96 posterior fossa FIESTA sequences were reviewed. Following exclusions, measurements were made on the following scans for each foramen respectively (left, right); internal acoustic meatus (IAM) (86, 84), jugular foramen (JF) (83, 85) and hypoglossal canal (HC) (42, 45). A protocol describes measurement procedure. Two observers measured distances for five cases and agreement was assessed. One observer measured all the remaining cases. Results: IAM and JF measurement interobserver variability was compared. Mean measurement difference between observers was −0.275 mm (standard deviation 0.557). IAM and JF measurements were normally distributed. Mean IAM distance was 12.2 mm [95% confidence interval (CI) 8.8–15.6]; JF was 7.3 mm (95% CI 4.0–10.6). The HC was difficult to visualize on many images and data followed a bimodal distribution. Conclusion: Dural reflections of posterior fossa CNs are well demonstrated by FIESTA MRI. Measuring CSF extension into these structures is feasible and robust; mean CSF extension into IAM and JF was measured. We plan further work to assess coverage of these structures with photon and proton RT plans. Advances in knowledge: We have described CSF extension beyond the internal table of the skull into the IAM, JF and HC. Oncologists planning RT for patients with medulloblastoma and ependymoma may use these data to guide contouring. PMID:27636022

  2. Fast imaging employing steady-state acquisition (FIESTA) MRI to investigate cerebrospinal fluid (CSF) within dural reflections of posterior fossa cranial nerves.

    PubMed

    Noble, David J; Scoffings, Daniel; Ajithkumar, Thankamma; Williams, Michael V; Jefferies, Sarah J

    2016-11-01

    There is no consensus approach to covering skull base meningeal reflections-and cerebrospinal fluid (CSF) therein-of the posterior fossa cranial nerves (CNs VII-XII) when planning radiotherapy (RT) for medulloblastoma and ependymoma. We sought to determine whether MRI and specifically fast imaging employing steady-state acquisition (FIESTA) sequences can answer this anatomical question and guide RT planning. 96 posterior fossa FIESTA sequences were reviewed. Following exclusions, measurements were made on the following scans for each foramen respectively (left, right); internal acoustic meatus (IAM) (86, 84), jugular foramen (JF) (83, 85) and hypoglossal canal (HC) (42, 45). A protocol describes measurement procedure. Two observers measured distances for five cases and agreement was assessed. One observer measured all the remaining cases. IAM and JF measurement interobserver variability was compared. Mean measurement difference between observers was -0.275 mm (standard deviation 0.557). IAM and JF measurements were normally distributed. Mean IAM distance was 12.2 mm [95% confidence interval (CI) 8.8-15.6]; JF was 7.3 mm (95% CI 4.0-10.6). The HC was difficult to visualize on many images and data followed a bimodal distribution. Dural reflections of posterior fossa CNs are well demonstrated by FIESTA MRI. Measuring CSF extension into these structures is feasible and robust; mean CSF extension into IAM and JF was measured. We plan further work to assess coverage of these structures with photon and proton RT plans. Advances in knowledge: We have described CSF extension beyond the internal table of the skull into the IAM, JF and HC. Oncologists planning RT for patients with medulloblastoma and ependymoma may use these data to guide contouring.

  3. A common neural circuit mechanism for internally guided and externally reinforced forms of motor learning.

    PubMed

    Hisey, Erin; Kearney, Matthew Gene; Mooney, Richard

    2018-04-01

    The complex skills underlying verbal and musical expression can be learned without external punishment or reward, indicating their learning is internally guided. The neural mechanisms that mediate internally guided learning are poorly understood, but a circuit comprising dopamine-releasing neurons in the midbrain ventral tegmental area (VTA) and their targets in the basal ganglia are important to externally reinforced learning. Juvenile zebra finches copy a tutor song in a process that is internally guided and, in adulthood, can learn to modify the fundamental frequency (pitch) of a target syllable in response to external reinforcement with white noise. Here we combined intersectional genetic ablation of VTA neurons, reversible blockade of dopamine receptors in the basal ganglia, and singing-triggered optogenetic stimulation of VTA terminals to establish that a common VTA-basal ganglia circuit enables internally guided song copying and externally reinforced syllable pitch learning.

  4. [Application of the International Guide for the Diagnosis and Treatment of Asthma using first-contact physicians, before and after an educational strategy].

    PubMed

    Segura Méndez, Nora Hilda; Herrera, Sonia; Hernández Martínez, Eduardo; Torres Salazar, Augusto; Espinola Reyna, Gerardo; del Rivero Hernández, Leonel

    2003-01-01

    The objective of the International Guide on Diagnosis and Treatment of Asthma is to reduce prevalence, mortality and morbidity of asthma. To demonstrate that implementation of educational workshop increases the knowledge of first contact physicians on the International Guide for Diagnosis and Treatment of Asthma. Fifty-nine first contact physicians participated. A validated questionnaire was applied before and after the workshop on the International Guide on Diagnosis and Treatment of Asthma. The Student's t test of the program SPSS was used for a statistical analysis. The grades obtained were 36% of correct answers before the workshop and 59% of correct answers after the workshop with a significant p < 0.05 specially in the general area of knowledge. As an educational technique this workshop improves the level of knowledge on the International Guide on Diagnosis and Treatment of Asthma of first contact physicians.

  5. Guiding principles for peptide nanotechnology through directed discovery.

    PubMed

    Lampel, A; Ulijn, R V; Tuttle, T

    2018-05-21

    Life's diverse molecular functions are largely based on only a small number of highly conserved building blocks - the twenty canonical amino acids. These building blocks are chemically simple, but when they are organized in three-dimensional structures of tremendous complexity, new properties emerge. This review explores recent efforts in the directed discovery of functional nanoscale systems and materials based on these same amino acids, but that are not guided by copying or editing biological systems. The review summarises insights obtained using three complementary approaches of searching the sequence space to explore sequence-structure relationships for assembly, reactivity and complexation, namely: (i) strategic editing of short peptide sequences; (ii) computational approaches to predicting and comparing assembly behaviours; (iii) dynamic peptide libraries that explore the free energy landscape. These approaches give rise to guiding principles on controlling order/disorder, complexation and reactivity by peptide sequence design.

  6. Reference-guided de novo assembly approach improves genome reconstruction for related species.

    PubMed

    Lischer, Heidi E L; Shimizu, Kentaro K

    2017-11-10

    The development of next-generation sequencing has made it possible to sequence whole genomes at a relatively low cost. However, de novo genome assemblies remain challenging due to short read length, missing data, repetitive regions, polymorphisms and sequencing errors. As more and more genomes are sequenced, reference-guided assembly approaches can be used to assist the assembly process. However, previous methods mostly focused on the assembly of other genotypes within the same species. We adapted and extended a reference-guided de novo assembly approach, which enables the usage of a related reference sequence to guide the genome assembly. In order to compare and evaluate de novo and our reference-guided de novo assembly approaches, we used a simulated data set of a repetitive and heterozygotic plant genome. The extended reference-guided de novo assembly approach almost always outperforms the corresponding de novo assembly program even when a reference of a different species is used. Similar improvements can be observed in high and low coverage situations. In addition, we show that a single evaluation metric, like the widely used N50 length, is not enough to properly rate assemblies as it not always points to the best assembly evaluated with other criteria. Therefore, we used the summed z-scores of 36 different statistics to evaluate the assemblies. The combination of reference mapping and de novo assembly provides a powerful tool to improve genome reconstruction by integrating information of a related genome. Our extension of the reference-guided de novo assembly approach enables the application of this strategy not only within but also between related species. Finally, the evaluation of genome assemblies is often not straight forward, as the truth is not known. Thus one should always use a combination of evaluation metrics, which not only try to assess the continuity but also the accuracy of an assembly.

  7. Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation

    PubMed Central

    Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

    2017-01-01

    The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA–DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA–DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs. PMID:28484024

  8. Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation.

    PubMed

    Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

    2017-05-23

    The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA-DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA-DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs.

  9. Distinction between Externally vs. Internally Guided Decision-Making: Operational Differences, Meta-Analytical Comparisons and Their Theoretical Implications

    PubMed Central

    Nakao, Takashi; Ohira, Hideki; Northoff, Georg

    2012-01-01

    Most experimental studies of decision-making have specifically examined situations in which a single less-predictable correct answer exists (externally guided decision-making under uncertainty). Along with such externally guided decision-making, there are instances of decision-making in which no correct answer based on external circumstances is available for the subject (internally guided decision-making). Such decisions are usually made in the context of moral decision-making as well as in preference judgment, where the answer depends on the subject’s own, i.e., internal, preferences rather than on external, i.e., circumstantial, criteria. The neuronal and psychological mechanisms that allow guidance of decisions based on more internally oriented criteria in the absence of external ones remain unclear. This study was undertaken to compare decision-making of these two kinds empirically and theoretically. First, we reviewed studies of decision-making to clarify experimental–operational differences between externally guided and internally guided decision-making. Second, using multi-level kernel density analysis, a whole-brain-based quantitative meta-analysis of neuroimaging studies was performed. Our meta-analysis revealed that the neural network used predominantly for internally guided decision-making differs from that for externally guided decision-making under uncertainty. This result suggests that studying only externally guided decision-making under uncertainty is insufficient to account for decision-making processes in the brain. Finally, based on the review and results of the meta-analysis, we discuss the differences and relations between decision-making of these two types in terms of their operational, neuronal, and theoretical characteristics. PMID:22403525

  10. State of Iowa Scope and Sequence for Vocational Home Economics.

    ERIC Educational Resources Information Center

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

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

  11. Two Low Coverage Bird Genomes and a Comparison of Reference-Guided versus De Novo Genome Assemblies

    PubMed Central

    Card, Daren C.; Schield, Drew R.; Reyes-Velasco, Jacobo; Fujita, Matthew K.; Andrew, Audra L.; Oyler-McCance, Sara J.; Fike, Jennifer A.; Tomback, Diana F.; Ruggiero, Robert P.; Castoe, Todd A.

    2014-01-01

    As a greater number and diversity of high-quality vertebrate reference genomes become available, it is increasingly feasible to use these references to guide new draft assemblies for related species. Reference-guided assembly approaches may substantially increase the contiguity and completeness of a new genome using only low levels of genome coverage that might otherwise be insufficient for de novo genome assembly. We used low-coverage (∼3.5–5.5x) Illumina paired-end sequencing to assemble draft genomes of two bird species (the Gunnison Sage-Grouse, Centrocercus minimus, and the Clark's Nutcracker, Nucifraga columbiana). We used these data to estimate de novo genome assemblies and reference-guided assemblies, and compared the information content and completeness of these assemblies by comparing CEGMA gene set representation, repeat element content, simple sequence repeat content, and GC isochore structure among assemblies. Our results demonstrate that even lower-coverage genome sequencing projects are capable of producing informative and useful genomic resources, particularly through the use of reference-guided assemblies. PMID:25192061

  12. Populations, Teacher's Guide.

    ERIC Educational Resources Information Center

    Conard, David; Lawson, Chester A.

    This Teacher's Guide is designed for use with the Science Curriculum Improvement Study's (SCIS) unit Population. Populations is the third of a six-unit sequence of SCIS's Life Science Program for grades K-6. The Populations guide consists of activity outlines along with suggestions for guiding children's observation and manipulations of living…

  13. Connecting the Human Variome Project to nutrigenomics.

    PubMed

    Kaput, Jim; Evelo, Chris T; Perozzi, Giuditta; van Ommen, Ben; Cotton, Richard

    2010-12-01

    Nutrigenomics is the science of analyzing and understanding gene-nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that ~90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene-nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts.

  14. Connecting the Human Variome Project to nutrigenomics

    PubMed Central

    Evelo, Chris T.; Perozzi, Giuditta; van Ommen, Ben; Cotton, Richard

    2010-01-01

    Nutrigenomics is the science of analyzing and understanding gene–nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that ~90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene–nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts. PMID:28300226

  15. Unique nucleotide sequence-guided assembly of repetitive DNA parts for synthetic biology applications

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

    Torella, JP; Lienert, F; Boehm, CR

    2014-08-07

    Recombination-based DNA construction methods, such as Gibson assembly, have made it possible to easily and simultaneously assemble multiple DNA parts, and they hold promise for the development and optimization of metabolic pathways and functional genetic circuits. Over time, however, these pathways and circuits have become more complex, and the increasing need for standardization and insulation of genetic parts has resulted in sequence redundancies-for example, repeated terminator and insulator sequences-that complicate recombination-based assembly. We and others have recently developed DNA assembly methods, which we refer to collectively as unique nucleotide sequence (UNS)-guided assembly, in which individual DNA parts are flanked withmore » UNSs to facilitate the ordered, recombination-based assembly of repetitive sequences. Here we present a detailed protocol for UNS-guided assembly that enables researchers to convert multiple DNA parts into sequenced, correctly assembled constructs, or into high-quality combinatorial libraries in only 2-3 d. If the DNA parts must be generated from scratch, an additional 2-5 d are necessary. This protocol requires no specialized equipment and can easily be implemented by a student with experience in basic cloning techniques.« less

  16. Unique nucleotide sequence (UNS)-guided assembly of repetitive DNA parts for synthetic biology applications

    PubMed Central

    Torella, Joseph P.; Lienert, Florian; Boehm, Christian R.; Chen, Jan-Hung; Way, Jeffrey C.; Silver, Pamela A.

    2016-01-01

    Recombination-based DNA construction methods, such as Gibson assembly, have made it possible to easily and simultaneously assemble multiple DNA parts and hold promise for the development and optimization of metabolic pathways and functional genetic circuits. Over time, however, these pathways and circuits have become more complex, and the increasing need for standardization and insulation of genetic parts has resulted in sequence redundancies — for example repeated terminator and insulator sequences — that complicate recombination-based assembly. We and others have recently developed DNA assembly methods that we refer to collectively as unique nucleotide sequence (UNS)-guided assembly, in which individual DNA parts are flanked with UNSs to facilitate the ordered, recombination-based assembly of repetitive sequences. Here we present a detailed protocol for UNS-guided assembly that enables researchers to convert multiple DNA parts into sequenced, correctly-assembled constructs, or into high-quality combinatorial libraries in only 2–3 days. If the DNA parts must be generated from scratch, an additional 2–5 days are necessary. This protocol requires no specialized equipment and can easily be implemented by a student with experience in basic cloning techniques. PMID:25101822

  17. The role of replay and theta sequences in mediating hippocampal-prefrontal interactions for memory and cognition.

    PubMed

    Zielinski, Mark C; Tang, Wenbo; Jadhav, Shantanu P

    2017-12-18

    Sequential activity is seen in the hippocampus during multiple network patterns, prominently as replay activity during both awake and sleep sharp-wave ripples (SWRs), and as theta sequences during active exploration. Although various mnemonic and cognitive functions have been ascribed to these hippocampal sequences, evidence for these proposed functions remains primarily phenomenological. Here, we briefly review current knowledge about replay events and theta sequences in spatial memory tasks. We reason that in order to gain a mechanistic and causal understanding of how these patterns influence memory and cognitive processing, it is important to consider how these sequences influence activity in other regions, and in particular, the prefrontal cortex, which is crucial for memory-guided behavior. For spatial memory tasks, we posit that hippocampal-prefrontal interactions mediated by replay and theta sequences play complementary and overlapping roles at different stages in learning, supporting memory encoding and retrieval, deliberative decision making, planning, and guiding future actions. This framework offers testable predictions for future physiology and closed-loop feedback inactivation experiments for specifically targeting hippocampal sequences as well as coordinated prefrontal activity in different network states, with the potential to reveal their causal roles in memory-guided behavior. © 2017 Wiley Periodicals, Inc.

  18. Calibration of visually guided reaching is driven by error-corrective learning and internal dynamics.

    PubMed

    Cheng, Sen; Sabes, Philip N

    2007-04-01

    The sensorimotor calibration of visually guided reaching changes on a trial-to-trial basis in response to random shifts in the visual feedback of the hand. We show that a simple linear dynamical system is sufficient to model the dynamics of this adaptive process. In this model, an internal variable represents the current state of sensorimotor calibration. Changes in this state are driven by error feedback signals, which consist of the visually perceived reach error, the artificial shift in visual feedback, or both. Subjects correct for > or =20% of the error observed on each movement, despite being unaware of the visual shift. The state of adaptation is also driven by internal dynamics, consisting of a decay back to a baseline state and a "state noise" process. State noise includes any source of variability that directly affects the state of adaptation, such as variability in sensory feedback processing, the computations that drive learning, or the maintenance of the state. This noise is accumulated in the state across trials, creating temporal correlations in the sequence of reach errors. These correlations allow us to distinguish state noise from sensorimotor performance noise, which arises independently on each trial from random fluctuations in the sensorimotor pathway. We show that these two noise sources contribute comparably to the overall magnitude of movement variability. Finally, the dynamics of adaptation measured with random feedback shifts generalizes to the case of constant feedback shifts, allowing for a direct comparison of our results with more traditional blocked-exposure experiments.

  19. To Guide or Not to Guide: Issues in the Sequencing of Pedagogical Structure in Computational Model-Based Learning

    ERIC Educational Resources Information Center

    Jacobson, Michael J.; Kim, Beaumie; Pathak, Suneeta; Zhang, BaoHui

    2015-01-01

    This research explores issues related to the sequencing of structure that is provided as pedagogical guidance. A study was conducted that involved grade 10 students in Singapore as they learned concepts about electricity using four NetLogo Investigations of Electricity agent-based models. It was found that the low-to-high structure learning…

  20. Heat, Energy, and Order, Part Two of an Integrated Science Sequence, Teacher's Guide, 1970 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This teacher's guide contains part two of the four-part first year Portland Project, a three-year secondary integrated science curriculum sequence. This part involves the student with unifying principles essential for deeper understanding of the concept of energy. Confidence in the atomic nature of matter is built by relating heat in terms of…

  1. Students' Guided Reinvention of Definition of Limit of a Sequence with Interactive Technology

    ERIC Educational Resources Information Center

    Flores, Alfinio; Park, Jungeun

    2016-01-01

    In a course emphasizing interactive technology, 19 students, including 18 mathematics education majors, mostly in their first year, reinvented the definition of limit of a sequence while working in small cooperative groups. The class spent four sessions of 75 minutes each on a cyclical process of guided reinvention of the definition of limit of a…

  2. Waves and Particles, The Orbital Atom, Parts One and Two of an Integrated Science Sequence, Teacher's Guide, 1973 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This teacher's guide includes parts one and two of the four-part third year Portland Project, a three-year integrated secondary science curriculum sequence. The Harvard Project Physics textbook is used for reading assignments for part one. Assignments relate to waves, light, electricity, magnetic fields, Faraday and the electrical age,…

  3. Improving CRISPR-Cas specificity with chemical modifications in single-guide RNAs.

    PubMed

    Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Bruhn, Laurakay; Dellinger, Douglas J

    2018-01-25

    CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence ('guide sequence') and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2'-O-methyl-3'-phosphonoacetate, or 'MP') incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. MR-guided interstitial laser thermotherapy of colorectal liver metastases: efficiency, safety and patient survival.

    PubMed

    Pech, M; Wieners, G; Freund, T; Dudeck, O; Fischbach, F; Ricke, J; Seemann, M D

    2007-04-26

    Evaluation of MR-guided interstitial laser thermotherapy (ILT) of colorectal liver metastases under consideration of efficacy, safety and patient survival. Sixty-six inoperable patients with a total of 117 colorectal liver metastases were treated with MR-guided laser therapy in 96 sessions. 40.9% of patients presented metastases from rectum carcinoma, 30.3% from sigmoid carcinoma and 28.8% from colon carcinoma. Inclusion criteria were < or =5 metastases < or =5 cm in greatest diameter and no extrahepatic tumor spread. Internally water-cooled 9F power-laser-applicators were placed under CT-fluoroscopy. For MR-guided ILT, a 1064 nm Nd-YAG-lasers with a beam divider with multi applicator technique was used. The energy applied was 10 watt per centimeter diffusor length, with the diffusor length ranging from 20 to 40 mm. The mean duration of the energy application was 23 minutes (range: 15 - 37 minutes). The endpoint of the laser ablation was defined as the absence of hyperintense tumor tissue in the continuously monitored T2-w fat saturated gradient-echo sequences. Follow-up included contrast-enhanced MRI using T1- and T2-weighted spin-echo and gradient-echo sequences every three months after treatment. Survival times were calculated using the Kaplan-Meier method. The median follow-up was 8.7 months (mean 11.8; standard deviation 9.9; range 1 to 36). The overall median progression free survival was 6.1 months (range, 0.3 to 27+ months). Median survival was 23 months (95% CI, 17-29 months). The rate of major complications was 2.1% (n = 2) and peri-procedural mortality (30 days) was 3% (n = 2). After 3, 6, 9, and 12 months, local tumor control was 98.3%, 91.4%, 76.1%, and 69.4%, respectively. In no patient metastatic deposits along the catheter access route were found. In patients with colorectal liver metastases, interstitial laser thermotherapy is an effective and safe therapeutic option and therefore suitable not only in palliative situations.

  5. Recommendations to guide revision of the Guides to the Evaluation of Permanent Impairment. American Medical Association.

    PubMed

    Spieler, E A; Barth, P S; Burton, J F; Himmelstein, J; Rudolph, L

    2000-01-26

    The American Medical Association's Guides to the Evaluation of Permanent Impairment, Fourth Edition, is the most commonly used tool in the United States for rating permanent impairments for disability systems. The Guides, currently undergoing revision, has been the focus of considerable controversy. Criticisms have focused on 2 areas: internal deficiencies, including the lack of a comprehensive, valid, reliable, unbiased, and evidence-based system for rating impairments; and the way in which workers' compensation systems use the ratings, resulting in inappropriate compensation. We focus on the internal deficiencies and recommend that the Guides remains a tool for evaluation of permanent impairment, not disability. To maintain wide acceptance of the Guides, its authors need to improve the validity, internal consistency, and comprehensiveness of the ratings; document reliability and reproducibility of the results; and make the Guides easily comprehensible and accessible to physicians.

  6. Industrial Arts Curriculum Guide for Industrial Ceramics.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford. Div. of Vocational and Adult Education.

    This curriculum guide for industrial ceramics courses is part of a series of curriculum guides for use in the industrial arts curriculum in Connecticut. The guide provides information on the scope and sequence of the industrial arts curriculum, specific guidelines for industrial arts, and program goals and objectives. The content of the industrial…

  7. Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers

    PubMed Central

    Hirshfield, Kim M.; Tolkunov, Denis; Zhong, Hua; Ali, Siraj M.; Stein, Mark N.; Murphy, Susan; Vig, Hetal; Vazquez, Alexei; Glod, John; Moss, Rebecca A.; Belyi, Vladimir; Chan, Chang S.; Chen, Suzie; Goodell, Lauri; Foran, David; Yelensky, Roman; Palma, Norma A.; Sun, James X.; Miller, Vincent A.; Stephens, Philip J.; Ross, Jeffrey S.; Kaufman, Howard; Poplin, Elizabeth; Mehnert, Janice; Tan, Antoinette R.; Bertino, Joseph R.; Aisner, Joseph; DiPaola, Robert S.

    2016-01-01

    Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents. PMID:27566247

  8. Foot-Matics. Teacher's Guide.

    ERIC Educational Resources Information Center

    Frame, Laurence

    This teacher's guide contains the following sections: Teacher Objectives; Student Objectives; Teacher Aide Suggestions; Objectives Overview; Scope and Sequence (K-8); Teacher's Guide; NFL Public Relations Director; NFL Team Addresses and Art (Helmet) Pages; Football Field Dimensions; Age Problems; Statistics from a Newspaper; Standings; Weight…

  9. Lessons learnt from developing a Health Impact Assessment guide in Iran.

    PubMed

    Fakhri, Ali; Harris, Patrick; Maleki, Mohammadreza

    2016-12-01

    For others wishing to develop Health Impact Assessment (HIA) guides (manuals) and to adjust them to conditions in their countries, we draw lessons from developing an HIA guide in Iran. We derive the lessons from our research comparing HIA guides found in the international literature and our experiences in adapting international experience to an HIA model for Iran that incorporates Iranian experts' opinions.

  10. in silico Whole Genome Sequencer & Analyzer (iWGS): A Computational Pipeline to Guide the Design and Analysis of de novo Genome Sequencing Studies

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

    Zhou, Xiaofan; Peris, David; Kominek, Jacek

    The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding its potential for understanding the biology and evolution of the full spectrum of biodiversity. The increasing diversity of sequencing technologies, assays, and de novo assembly algorithms have augmented the complexity of de novo genome sequencing projects in nonmodel organisms. To reduce the costs and challenges in de novo genome sequencing projects and streamline their experimentalmore » design and analysis, we developed iWGS (in silico Whole Genome Sequencer and Analyzer), an automated pipeline for guiding the choice of appropriate sequencing strategy and assembly protocols. iWGS seamlessly integrates the four key steps of a de novo genome sequencing project: data generation (through simulation), data quality control, de novo assembly, and assembly evaluation and validation. The last three steps can also be applied to the analysis of real data. iWGS is designed to enable the user to have great flexibility in testing the range of experimental designs available for genome sequencing projects, and supports all major sequencing technologies and popular assembly tools. Three case studies illustrate how iWGS can guide the design of de novo genome sequencing projects, and evaluate the performance of a wide variety of user-specified sequencing strategies and assembly protocols on genomes of differing architectures. iWGS, along with a detailed documentation, is freely available at https://github.com/zhouxiaofan1983/iWGS.« less

  11. in silico Whole Genome Sequencer & Analyzer (iWGS): A Computational Pipeline to Guide the Design and Analysis of de novo Genome Sequencing Studies

    DOE PAGES

    Zhou, Xiaofan; Peris, David; Kominek, Jacek; ...

    2016-09-16

    The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding its potential for understanding the biology and evolution of the full spectrum of biodiversity. The increasing diversity of sequencing technologies, assays, and de novo assembly algorithms have augmented the complexity of de novo genome sequencing projects in nonmodel organisms. To reduce the costs and challenges in de novo genome sequencing projects and streamline their experimentalmore » design and analysis, we developed iWGS (in silico Whole Genome Sequencer and Analyzer), an automated pipeline for guiding the choice of appropriate sequencing strategy and assembly protocols. iWGS seamlessly integrates the four key steps of a de novo genome sequencing project: data generation (through simulation), data quality control, de novo assembly, and assembly evaluation and validation. The last three steps can also be applied to the analysis of real data. iWGS is designed to enable the user to have great flexibility in testing the range of experimental designs available for genome sequencing projects, and supports all major sequencing technologies and popular assembly tools. Three case studies illustrate how iWGS can guide the design of de novo genome sequencing projects, and evaluate the performance of a wide variety of user-specified sequencing strategies and assembly protocols on genomes of differing architectures. iWGS, along with a detailed documentation, is freely available at https://github.com/zhouxiaofan1983/iWGS.« less

  12. Motion and Energy Chemical Reactions, Parts One and Two of an Integrated Science Sequence, Teacher's Guide, 1973 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This teacher's guide is for the second year of the Portland Project, a three-year integrated secondary science curriculum sequence. The first of two parts in this volume, "Motion and Energy," begins with the study of motion, going from the quantitative description to a consideration of what causes motion and a discussion of Newton's…

  13. Discovering [superscript 13]C NMR, [superscript 1]H NMR, and IR Spectroscopy in the General Chemistry Laboratory through a Sequence of Guided-Inquiry Exercises

    ERIC Educational Resources Information Center

    Iler, H. Darrell; Justice, David; Brauer, Shari; Landis, Amanda

    2012-01-01

    This sequence of three guided-inquiry labs is designed for a second-semester general chemistry course and challenges students to discover basic theoretical principles associated with [superscript 13]C NMR, [superscript 1]H NMR, and IR spectroscopy. Students learn to identify and explain basic concepts of magnetic resonance and vibrational…

  14. Chemistry of Living Matter, Energy Capture & Growth, Parts Three & Four of an Integrated Science Sequence, Teacher's Guide, 1973 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This teacher's guide includes parts three and four of the four-part third year Portland Project, a three-year integrated secondary science curriculum sequence. The underlying intention of the third year is to study energy and its importance to life. Energy-related concepts considered in year one and two, and the concepts related to atomic…

  15. TIMSS 2011 User Guide for the International Database. Supplement 2: National Adaptations of International Background Questionnaires

    ERIC Educational Resources Information Center

    Foy, Pierre, Ed.; Arora, Alka, Ed.; Stanco, Gabrielle M., Ed.

    2013-01-01

    This supplement describes national adaptations made to the international version of the TIMSS 2011 background questionnaires. This information provides users with a guide to evaluate the availability of internationally comparable data for use in secondary analyses involving the TIMSS 2011 background variables. Background questionnaire adaptations…

  16. Reference-guided assembly of four diverse Arabidopsis thaliana genomes

    PubMed Central

    Schneeberger, Korbinian; Ossowski, Stephan; Ott, Felix; Klein, Juliane D.; Wang, Xi; Lanz, Christa; Smith, Lisa M.; Cao, Jun; Fitz, Joffrey; Warthmann, Norman; Henz, Stefan R.; Huson, Daniel H.; Weigel, Detlef

    2011-01-01

    We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg erecta (Ler-1), C24, Bur-0, and Kro-0 strains, which have been sequenced as part of the 1,001 Genomes Project for this species. Using alignments against the reference sequence, we first reduced the complexity of the de novo assembly and later integrated reads without similarity to the reference sequence. As an example, half of the noncentromeric C24 genome was covered by scaffolds that are longer than 260 kb, with a maximum of 2.2 Mb. Moreover, over 96% of the reference genome was covered by the reference-guided assembly, compared with only 87% with a complete de novo assembly. Comparisons with 2 Mb of dideoxy sequence reveal that the per-base error rate of the reference-guided assemblies was below 1 in 10,000. Our assemblies provide a detailed, genomewide picture of large-scale differences between A. thaliana individuals, most of which are difficult to access with alignment-consensus methods only. We demonstrate their practical relevance in studying the expression differences of polymorphic genes and show how the analysis of sRNA sequencing data can lead to erroneous conclusions if aligned against the reference genome alone. Genome assemblies, raw reads, and further information are accessible through http://1001genomes.org/projects/assemblies.html. PMID:21646520

  17. Memory-guided selective attention: Single experiences with conflict have long-lasting effects on cognitive control.

    PubMed

    Brosowsky, Nicholaus P; Crump, Matthew J C

    2018-05-17

    Adjustments in cognitive control, as measured by congruency sequence effects, are thought to be influenced by both external stimuli and internal goals. However, this dichotomy has often overshadowed the potential contribution of past experience stored in memory. Here, we examine the role of long-term episodic memory in guiding selective attention. Our aim was to demonstrate new evidence that selective attention can be modulated by long-term retrieval of stimulus-specific attentional control settings. All the experiments used a modified flanker task involving multiple unique stimuli. Critically, each stimulus was only presented twice during the experiment: first as a prime, and second as a probe. Experiments 1 and 2 varied the number of intervening trials between prime and probe and manipulated the amount of conflict using a secondary task. Experiment 3 ensured that specific colors assigned to prime stimuli were not repeated when presented as probes. Across both Experiments 1 and 2, we consistently found smaller congruency effects on probe trials when its associated prime trial was incongruent compared with congruent, demonstrating long-term congruency sequence effects. However, Experiment 3 showed no evidence for long-term effects. These findings suggest long-term preservation of selective attention processing at the episodic level, and implicate a role for memory in updating cognitive control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  18. Review and International Recommendation of Methods for Typing Neisseria gonorrhoeae Isolates and Their Implications for Improved Knowledge of Gonococcal Epidemiology, Treatment, and Biology

    PubMed Central

    Unemo, Magnus; Dillon, Jo-Anne R.

    2011-01-01

    Summary: Gonorrhea, which may become untreatable due to multiple resistance to available antibiotics, remains a public health problem worldwide. Precise methods for typing Neisseria gonorrhoeae, together with epidemiological information, are crucial for an enhanced understanding regarding issues involving epidemiology, test of cure and contact tracing, identifying core groups and risk behaviors, and recommending effective antimicrobial treatment, control, and preventive measures. This review evaluates methods for typing N. gonorrhoeae isolates and recommends various methods for different situations. Phenotypic typing methods, as well as some now-outdated DNA-based methods, have limited usefulness in differentiating between strains of N. gonorrhoeae. Genotypic methods based on DNA sequencing are preferred, and the selection of the appropriate genotypic method should be guided by its performance characteristics and whether short-term epidemiology (microepidemiology) or long-term and/or global epidemiology (macroepidemiology) matters are being investigated. Currently, for microepidemiological questions, the best methods for fast, objective, portable, highly discriminatory, reproducible, typeable, and high-throughput characterization are N. gonorrhoeae multiantigen sequence typing (NG-MAST) or full- or extended-length porB gene sequencing. However, pulsed-field gel electrophoresis (PFGE) and Opa typing can be valuable in specific situations, i.e., extreme microepidemiology, despite their limitations. For macroepidemiological studies and phylogenetic studies, DNA sequencing of chromosomal housekeeping genes, such as multilocus sequence typing (MLST), provides a more nuanced understanding. PMID:21734242

  19. Procedural Guide for International Gauging Stations on Boundary Waters Between Canada and the United States of America

    USGS Publications Warehouse

    Huberman, S.; Slater, James; Condes, A.

    1985-01-01

    INTRODUCTION Since 1909, the United States of America (U.S.A.) and Canada have employed a system of monitoring stream-flow and water levels for shared waters based upon professionalism, trust and goodwill. This document has been prepared in considerable detail for use by managers and field officers at all levels of government in Canada and the United States. Its purpose is to serve as a guide in attaining uniform procedures in the designation and operation of International Gauging Stations. For special situations where these procedures do not apply, specific mention is made in appropriate sections of the guide. This guide supersedes that of November 4, 1969, and the guide entitled 'The Procedural Guide for Operation of International Gauging Stations, St. Mary- Milk Rivers,' dated March 12, 1979.

  20. Drafting Lab Management Guide.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This manual was developed to guide drafting instructors and vocational supervisors in sequencing laboratory instruction and controlling the flow of work for a 2-year machine trades training program. The first part of the guide provides information on program management (program description, safety concerns, academic issues, implementation…

  1. Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a).

    PubMed

    Singh, Digvijay; Mallon, John; Poddar, Anustup; Wang, Yanbo; Tippana, Ramreddy; Yang, Olivia; Bailey, Scott; Ha, Taekjip

    2018-05-22

    CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.

  2. Evaluation of the Abbott RealTime HCV genotype II plus RUO (PLUS) assay with reference to core and NS5B sequencing.

    PubMed

    Mallory, Melanie A; Lucic, Danijela; Ebbert, Mark T W; Cloherty, Gavin A; Toolsie, Dan; Hillyard, David R

    2017-05-01

    HCV genotyping remains a critical tool for guiding initiation of therapy and selecting the most appropriate treatment regimen. Current commercial genotyping assays may have difficulty identifying 1a, 1b and genotype 6. To evaluate the concordance for identifying 1a, 1b, and genotype 6 between two methods: the PLUS assay and core/NS5B sequencing. This study included 236 plasma and serum samples previously genotyped by core/NS5B sequencing. Of these, 25 samples were also previously tested by the Abbott RealTime HCV GT II Research Use Only (RUO) assay and yielded ambiguous results. The remaining 211 samples were routine genotype 1 (n=169) and genotype 6 (n=42). Genotypes obtained from sequence data were determined using a laboratory-developed HCV sequence analysis tool and the NCBI non-redundant database. Agreement between the PLUS assay and core/NS5B sequencing for genotype 1 samples was 95.8% (162/169), with 96% (127/132) and 95% (35/37) agreement for 1a and 1b samples respectively. PLUS results agreed with core/NS5B sequencing for 83% (35/42) of unselected genotype 6 samples, with the remaining seven "not detected" by the PLUS assay. Among the 25 samples with ambiguous GT II results, 15 were concordant by PLUS and core/NS5B sequencing, nine were not detected by PLUS, and one sample had an internal control failure. The PLUS assay is an automated method that identifies 1a, 1b and genotype 6 with good agreement with gold-standard core/NS5B sequencing and can aid in the resolution of certain genotype samples with ambiguous GT II results. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Machine Trades Lab Management Guide.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This manual was developed to guide machine trades instructors and vocational supervisors in sequencing laboratory instruction and controlling the flow of work for a 2-year machine trades training program. The first part of the guide provides information on program management (program description, safety concerns, academic issues, implementation…

  4. Application of the MAFFT sequence alignment program to large data—reexamination of the usefulness of chained guide trees

    PubMed Central

    Yamada, Kazunori D.; Tomii, Kentaro; Katoh, Kazutaka

    2016-01-01

    Motivation: Large multiple sequence alignments (MSAs), consisting of thousands of sequences, are becoming more and more common, due to advances in sequencing technologies. The MAFFT MSA program has several options for building large MSAs, but their performances have not been sufficiently assessed yet, because realistic benchmarking of large MSAs has been difficult. Recently, such assessments have been made possible through the HomFam and ContTest benchmark protein datasets. Along with the development of these datasets, an interesting theory was proposed: chained guide trees increase the accuracy of MSAs of structurally conserved regions. This theory challenges the basis of progressive alignment methods and needs to be examined by being compared with other known methods including computationally intensive ones. Results: We used HomFam, ContTest and OXFam (an extended version of OXBench) to evaluate several methods enabled in MAFFT: (1) a progressive method with approximate guide trees, (2) a progressive method with chained guide trees, (3) a combination of an iterative refinement method and a progressive method and (4) a less approximate progressive method that uses a rigorous guide tree and consistency score. Other programs, Clustal Omega and UPP, available for large MSAs, were also included into the comparison. The effect of method 2 (chained guide trees) was positive in ContTest but negative in HomFam and OXFam. Methods 3 and 4 increased the benchmark scores more consistently than method 2 for the three datasets, suggesting that they are safer to use. Availability and Implementation: http://mafft.cbrc.jp/alignment/software/ Contact: katoh@ifrec.osaka-u.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27378296

  5. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

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

    Torella, JP; Boehm, CR; Lienert, F

    2013-12-28

    In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminatormore » parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.« less

  6. GUIDE-Seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases

    PubMed Central

    Nguyen, Nhu T.; Liebers, Matthew; Topkar, Ved V.; Thapar, Vishal; Wyvekens, Nicolas; Khayter, Cyd; Iafrate, A. John; Le, Long P.; Aryee, Martin J.; Joung, J. Keith

    2014-01-01

    CRISPR RNA-guided nucleases (RGNs) are widely used genome-editing reagents, but methods to delineate their genome-wide off-target cleavage activities have been lacking. Here we describe an approach for global detection of DNA double-stranded breaks (DSBs) introduced by RGNs and potentially other nucleases. This method, called Genome-wide Unbiased Identification of DSBs Enabled by Sequencing (GUIDE-Seq), relies on capture of double-stranded oligodeoxynucleotides into breaks Application of GUIDE-Seq to thirteen RGNs in two human cell lines revealed wide variability in RGN off-target activities and unappreciated characteristics of off-target sequences. The majority of identified sites were not detected by existing computational methods or ChIP-Seq. GUIDE-Seq also identified RGN-independent genomic breakpoint ‘hotspots’. Finally, GUIDE-Seq revealed that truncated guide RNAs exhibit substantially reduced RGN-induced off-target DSBs. Our experiments define the most rigorous framework for genome-wide identification of RGN off-target effects to date and provide a method for evaluating the safety of these nucleases prior to clinical use. PMID:25513782

  7. Synchronized excitability in a network enables generation of internal neuronal sequences

    PubMed Central

    Wang, Yingxue; Roth, Zachary; Pastalkova, Eva

    2016-01-01

    Hippocampal place field sequences are supported by sensory cues and network internal mechanisms. In contrast, sharp-wave (SPW) sequences, theta sequences, and episode field sequences are internally generated. The relationship of these sequences to memory is unclear. SPW sequences have been shown to support learning and have been assumed to also support episodic memory. Conversely, we demonstrate these SPW sequences were present in trained rats even after episodic memory was impaired and after other internal sequences – episode field and theta sequences – were eliminated. SPW sequences did not support memory despite continuing to ‘replay’ all task-related sequences – place- field and episode field sequences. Sequence replay occurred selectively during synchronous increases of population excitability -- SPWs. Similarly, theta sequences depended on the presence of repeated synchronized waves of excitability – theta oscillations. Thus, we suggest that either intermittent or rhythmic synchronized changes of excitability trigger sequential firing of neurons, which in turn supports learning and/or memory. DOI: http://dx.doi.org/10.7554/eLife.20697.001 PMID:27677848

  8. Student-Created Definitions of Sequence Convergence: A Case Study

    ERIC Educational Resources Information Center

    Fisher, Brian

    2016-01-01

    This paper describes the development of an instructional sequence designed to allow students to reinvent the definition of sequence convergence in an introductory proof course. The sequence follows a heuristic of guided reinvention that encourages students to independently create their own mathematical definitions. This case study reports on how…

  9. Following Up: Huygens Data, Questions Will Guide Cassini on Its Future Titan Passes

    NASA Technical Reports Server (NTRS)

    Morring, Frank, Jr.; Taverna, Michael A.

    2005-01-01

    Planetary scientists plan to use the instruments on NASA's Cassini Saturn orbiter in future flybys of Titan to answer questions raised by Europe's Huygens probe. In particular, they hope to discover whether the dark, flat areas on the moon's surface are liquid or quasi-liquid methane seas. As the scientists plotted their next moves, European Space Agency (ESA) officials continued their investigation into how a critical command in the Huygens descent sequence was omitted costing the imaging team half of its data and rendering another Huygens instrument useless. There were suggestions that U.S. export-control rules may have hampered the sort of close international cooperation that might have caught the error.

  10. Handbook of the International Phonetic Association: A Guide to the Use of the International Phonetic Alphabet.

    ERIC Educational Resources Information Center

    International Phonetic Association.

    This guide contains concise information on the International Phonetic Alphabet, a universally agreed system of notation in use for over a century, for the sounds of languages, and guidance on how to use it. The handbook replaces the previous edition, "Principles of the International Phonetic Association," which has not been revised since 1949.…

  11. TEDS-M 2008 User Guide for the International Database. Supplement 2: National Adaptations of the TEDS-M Questionnaires

    ERIC Educational Resources Information Center

    Brese, Falk, Ed.

    2012-01-01

    This supplement contains all adaptations made by countries to the international version of the TEDS-M questionnaires under careful supervision of and approval by the TEDS-M International Study Center at Michigan State University. This information provides users of the TEDS-M International Database with a guide to evaluate the availability of…

  12. Automated real-time needle-guide tracking for fast 3-T MR-guided transrectal prostate biopsy: a feasibility study.

    PubMed

    Zamecnik, Patrik; Schouten, Martijn G; Krafft, Axel J; Maier, Florian; Schlemmer, Heinz-Peter; Barentsz, Jelle O; Bock, Michael; Fütterer, Jurgen J

    2014-12-01

    To assess the feasibility of automatic needle-guide tracking by using a real-time phase-only cross correlation ( POCC phase-only cross correlation ) algorithm-based sequence for transrectal 3-T in-bore magnetic resonance (MR)-guided prostate biopsies. This study was approved by the ethics review board, and written informed consent was obtained from all patients. Eleven patients with a prostate-specific antigen level of at least 4 ng/mL (4 μg/L) and at least one transrectal ultrasonography-guided biopsy session with negative findings were enrolled. Regions suspicious for cancer were identified on 3-T multiparametric MR images. During a subsequent MR-guided biopsy, the regions suspicious for cancer were reidentified and targeted by using the POCC phase-only cross correlation -based tracking sequence. Besides testing a general technical feasibility of the biopsy procedure by using the POCC phase-only cross correlation -based tracking sequence, the procedure times were measured, and a pathologic analysis of the biopsy cores was performed. Thirty-eight core samples were obtained from 25 regions suspicious for cancer. It was technically feasible to perform the POCC phase-only cross correlation -based biopsies in all regions suspicious for cancer in each patient, with adequate biopsy samples obtained with each biopsy attempt. The median size of the region suspicious for cancer was 8 mm (range, 4-13 mm). In each region suspicious for cancer (median number per patient, two; range, 1-4), a median of one core sample per region was obtained (range, 1-3). The median time for guidance per target was 1.5 minutes (range, 0.7-5 minutes). Nineteen of 38 core biopsy samples contained cancer. This study shows that it is feasible to perform transrectal 3-T MR-guided biopsies by using a POCC phase-only cross correlation algorithm-based real-time tracking sequence. © RSNA, 2014.

  13. snoSeeker: an advanced computational package for screening of guide and orphan snoRNA genes in the human genome.

    PubMed

    Yang, Jian-Hua; Zhang, Xiao-Chen; Huang, Zhan-Peng; Zhou, Hui; Huang, Mian-Bo; Zhang, Shu; Chen, Yue-Qin; Qu, Liang-Hu

    2006-01-01

    Small nucleolar RNAs (snoRNAs) represent an abundant group of non-coding RNAs in eukaryotes. They can be divided into guide and orphan snoRNAs according to the presence or absence of antisense sequence to rRNAs or snRNAs. Current snoRNA-searching programs, which are essentially based on sequence complementarity to rRNAs or snRNAs, exist only for the screening of guide snoRNAs. In this study, we have developed an advanced computational package, snoSeeker, which includes CDseeker and ACAseeker programs, for the highly efficient and specific screening of both guide and orphan snoRNA genes in mammalian genomes. By using these programs, we have systematically scanned four human-mammal whole-genome alignment (WGA) sequences and identified 54 novel candidates including 26 orphan candidates as well as 266 known snoRNA genes. Eighteen novel snoRNAs were further experimentally confirmed with four snoRNAs exhibiting a tissue-specific or restricted expression pattern. The results of this study provide the most comprehensive listing of two families of snoRNA genes in the human genome till date.

  14. User's Guide to Biome Information from the United States International Biological Program (IBP). First Edition.

    ERIC Educational Resources Information Center

    Hinckley, A. Dexter; Haug, Peter T.

    This publication is a guide to the biome research conducted under the International Biological Program. The guide lists biome researchers by interest and by biome as well as a central list. A site list, map, information sources section reporting abstracts, bibliographies, journals, books, evaluations, and data books are also included. Three…

  15. Guide to International Academic Standards for Athletics Eligibility for Students Entering Fall 2007

    ERIC Educational Resources Information Center

    Mills, Lisa; Nguyen, Binh; Auten, Lisa

    2007-01-01

    The "NCAA Guide to International Academic Standards for Athletics Eligibility" provides specific criteria to be used as a guide in reviewing the initial eligibility (graduation, core curriculum, grade-point average and ACT/SAT test scores) of students who have completed any portion of their secondary education in a non-United States…

  16. [Methodological quality of an article on the treatment of gastric cancer adopted as protocol by some Chilean hospitals].

    PubMed

    Manterola, Carlos; Torres, Rodrigo; Burgos, Luis; Vial, Manuel; Pineda, Viviana

    2006-07-01

    Surgery is a curative treatment for gastric cancer (GC). As relapse is frequent, adjuvant therapies such as postoperative chemo radiotherapy have been tried. In Chile, some hospitals adopted Macdonald's study as a protocol for the treatment of GC. To determine methodological quality and internal and external validity of the Macdonald study. Three instruments were applied that assess methodological quality. A critical appraisal was done and the internal and external validity of the methodological quality was analyzed with two scales: MINCIR (Methodology and Research in Surgery), valid for therapy studies and CONSORT (Consolidated Standards of Reporting Trials), valid for randomized controlled trials (RCT). Guides and scales were applied by 5 researchers with training in clinical epidemiology. The reader's guide verified that the Macdonald study was not directed to answer a clearly defined question. There was random assignment, but the method used is not described and the patients were not considered until the end of the study (36% of the group with surgery plus chemo radiotherapy did not complete treatment). MINCIR scale confirmed a multicentric RCT, not blinded, with an unclear randomized sequence, erroneous sample size estimation, vague objectives and no exclusion criteria. CONSORT system proved the lack of working hypothesis and specific objectives as well as an absence of exclusion criteria and identification of the primary variable, an imprecise estimation of sample size, ambiguities in the randomization process, no blinding, an absence of statistical adjustment and the omission of a subgroup analysis. The instruments applied demonstrated methodological shortcomings that compromise the internal and external validity of the.

  17. From Fibonacci Numbers To Geometric Sequences and the Binet Formula by Way of the Golden Ratio!

    ERIC Educational Resources Information Center

    DiDomenico, Angelo S.

    1997-01-01

    Provides activities that deal with Fibonacci-like sequences and guide students' thinking as they explore mathematical induction. Investigation leads to a discovery of an interesting relation that involves all Fibonacci-like sequences. (DDR)

  18. The gene coding for small ribosomal subunit RNA in the basidiomycete Ustilago maydis contains a group I intron.

    PubMed Central

    De Wachter, R; Neefs, J M; Goris, A; Van de Peer, Y

    1992-01-01

    The nucleotide sequence of the gene coding for small ribosomal subunit RNA in the basidiomycete Ustilago maydis was determined. It revealed the presence of a group I intron with a length of 411 nucleotides. This is the third occurrence of such an intron discovered in a small subunit rRNA gene encoded by a eukaryotic nuclear genome. The other two occurrences are in Pneumocystis carinii, a fungus of uncertain taxonomic status, and Ankistrodesmus stipitatus, a green alga. The nucleotides of the conserved core structure of 101 group I intron sequences present in different genes and genome types were aligned and their evolutionary relatedness was examined. This revealed a cluster including all group I introns hitherto found in eukaryotic nuclear genes coding for small and large subunit rRNAs. A secondary structure model was designed for the area of the Ustilago maydis small ribosomal subunit RNA precursor where the intron is situated. It shows that the internal guide sequence pairing with the intron boundaries fits between two helices of the small subunit rRNA, and that minimal rearrangement of base pairs suffices to achieve the definitive secondary structure of the 18S rRNA upon splicing. PMID:1561081

  19. Social Studies Program Guide, K-3: Primary Grades.

    ERIC Educational Resources Information Center

    Spokane School District 81, WA.

    This curriculum guide is the first of four guides which identify the scope, sequence, goals, and resources for the social studies program of the Spokane public schools. Suggested are social studies materials, resources, and activities for kindergarten and primary grade levels. Emphasizing social studies knowledge and skill development, the guide…

  20. Industrial Arts Curriculum Guide for Automated Machining in Metals Technology.

    ERIC Educational Resources Information Center

    1985

    This curriculum guide is designed to be used for creating programs in automated machining education in Connecticut. The first sections of the guide are introductory, explaining the importance of computer-numerically controlled machines, describing the industrial arts scope and sequence for kindergarten through adult levels, describing the…

  1. Latin Curriculum Guide.

    ERIC Educational Resources Information Center

    Lee, Agnes; Stevens, Patrick

    This guide delineates the scope and sequence of Latin instruction in levels 1-3 in terms of behavioral objectives. Following a review of the Bloomington, Minnesota, school philosophy and a discussion of the design of foreign language behavioral objectives on which the guide is based, the manual discusses expected terminal behavior in the level 1…

  2. Estimating the Growth of Internal Evidence Guiding Perceptual Decisions

    ERIC Educational Resources Information Center

    Ludwig, Casimir J. H.; Davies, J. Rhys

    2011-01-01

    Perceptual decision-making is thought to involve a gradual accrual of noisy evidence. Temporal integration of the evidence reduces the relative contribution of dynamic internal noise to the decision variable, thereby boosting its signal-to-noise ratio. We aimed to estimate the internal evidence guiding perceptual decisions over time, using a novel…

  3. How To Adopt Internationally: A Guide for Agency-Directed and Independent Adoptions. 2000-2002 Edition.

    ERIC Educational Resources Information Center

    Nelson-Erichsen, Jean; Erichsen, Heino R.

    Many potential adoptive parents seeking international adoption find the process to be extremely complex. This guide details the international adoption process, including organizing a home study and fulfilling state requirements as well as selecting a country from which to adopt, working through emigration and immigration agencies, and traveling…

  4. International Economic Diplomacy: A Guide to the Global Economy: The Issues, Institutions, and Influences.

    ERIC Educational Resources Information Center

    United Nations Association of the United States of America, New York, NY.

    This guide is designed to help teachers to prepare students for the rapidly arriving new world order through study of market economics and the global economy. The central section of the guide presents 10 case studies that describe a range of international economic concepts: (1) Debt and Oil; (2) Trade and Protection; (3) Foreign Exchange; (4)…

  5. The future of U.S./International life sciences cooperation for Space Shuttle and beyond - A guide for the young professional

    NASA Technical Reports Server (NTRS)

    Garshnek, V.; Davies, P.; Ballard, R.

    1992-01-01

    Current international capabilities in the space life sciences/technology areas are reviewed focusing on the cooperative potential of the international community as applied to advanced Shuttle/Spacelab flights. The review of the international experience base and mutual cooperative benefits of the United States and international partners presented in the paper provides a guide to the young professional in planning for a space life sciences career.

  6. Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes

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

    Carte, Jason; Wang, Ruiying; Li, Hong

    An RNA-based gene silencing pathway that protects bacteria and archaea from viruses and other genome invaders is hypothesized to arise from guide RNAs encoded by CRISPR loci and proteins encoded by the cas genes. CRISPR loci contain multiple short invader-derived sequences separated by short repeats. The presence of virus-specific sequences within CRISPR loci of prokaryotic genomes confers resistance against corresponding viruses. The CRISPR loci are transcribed as long RNAs that must be processed to smaller guide RNAs. Here we identified Pyrococcus furiosus Cas6 as a novel endoribonuclease that cleaves CRISPR RNAs within the repeat sequences to release individual invader targetingmore » RNAs. Cas6 interacts with a specific sequence motif in the 5{prime} region of the CRISPR repeat element and cleaves at a defined site within the 3{prime} region of the repeat. The 1.8 angstrom crystal structure of the enzyme reveals two ferredoxin-like folds that are also found in other RNA-binding proteins. The predicted active site of the enzyme is similar to that of tRNA splicing endonucleases, and concordantly, Cas6 activity is metal-independent. cas6 is one of the most widely distributed CRISPR-associated genes. Our findings indicate that Cas6 functions in the generation of CRISPR-derived guide RNAs in numerous bacteria and archaea.« less

  7. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1987-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:3575113

  8. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1990-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:2333227

  9. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1988-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:3368330

  10. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1989-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:2654889

  11. American History Curriculum Guide: Secondary Social Studies. Bulletin 1599. Revised.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Education, Baton Rouge. Div. of Academic Programs.

    Developed to enhance the quality of secondary school U.S. history instruction, this curriculum guide provides implementation suggestions and includes the Louisiana social studies: (1) program rationale; (2) curriculum goals; and (3) program scope and sequence. The guide is divided into sections that feature the following themes: (1) toward a new…

  12. World Geography Curriculum Guide: Secondary Social Studies. Bulletin 1727.

    ERIC Educational Resources Information Center

    Nicolosi, Louis J.; And Others

    This world geography curriculum guide is designed to help teachers improve the quality of secondary level geography instruction. The guide contains Louisiana's social studies curriculum goals and information about the scope and sequence of the state's social studies program. Part 1 discusses the major geographical concepts of: (1) map and globe…

  13. The Holocaust and Genocide: A Search for Conscience. A Curriculum Guide.

    ERIC Educational Resources Information Center

    Flaim, Richard F., Ed.; Reynolds, Edwin W., Jr., Ed.

    Designed to facilitate teacher development of a secondary unit on the Holocaust and genocide, this multidisciplinary curriculum guide provides a wide variety of classroom-tested objectives, learning activities, and materials. The guide is organized into six units which may be taught in sequence or used in part as supplementary materials: the…

  14. Vocational Carpentry Curriculum Guide.

    ERIC Educational Resources Information Center

    Virginia Polytechnic Inst. and State Univ., Blacksburg. Dept. of Education.

    The carpentry curriculum guide was developed as a basic guide to be used by instructors in formulating their own courses of study. The material is designed for use in vocational carpentry classes at grade levels 10, 11, and 12. Planned as a two-year sequence, it incorporates 1080 class hours of instruction and emphasizes light or residential type…

  15. Partial DNA-guided Cas9 enables genome editing with reduced off-target activity

    PubMed Central

    Yin, Hao; Song, Chun-Qing; Suresh, Sneha; Kwan, Suet-Yan; Wu, Qiongqiong; Walsh, Stephen; Ding, Junmei; Bogorad, Roman L; Zhu, Lihua Julie; Wolfe, Scot A; Koteliansky, Victor; Xue, Wen; Langer, Robert; Anderson, Daniel G

    2018-01-01

    CRISPR–Cas9 is a versatile RNA-guided genome editing tool. Here we demonstrate that partial replacement of RNA nucleotides with DNA nucleotides in CRISPR RNA (crRNA) enables efficient gene editing in human cells. This strategy of partial DNA replacement retains on-target activity when used with both crRNA and sgRNA, as well as with multiple guide sequences. Partial DNA replacement also works for crRNA of Cpf1, another CRISPR system. We find that partial DNA replacement in the guide sequence significantly reduces off-target genome editing through focused analysis of off-target cleavage, measurement of mismatch tolerance and genome-wide profiling of off-target sites. Using the structure of the Cas9–sgRNA complex as a guide, the majority of the 3′ end of crRNA can be replaced with DNA nucleotide, and the 5 - and 3′-DNA-replaced crRNA enables efficient genome editing. Cas9 guided by a DNA–RNA chimera may provide a generalized strategy to reduce both the cost and the off-target genome editing in human cells. PMID:29377001

  16. DNA targeting specificity of RNA-guided Cas9 nucleases.

    PubMed

    Hsu, Patrick D; Scott, David A; Weinstein, Joshua A; Ran, F Ann; Konermann, Silvana; Agarwala, Vineeta; Li, Yinqing; Fine, Eli J; Wu, Xuebing; Shalem, Ophir; Cradick, Thomas J; Marraffini, Luciano A; Bao, Gang; Zhang, Feng

    2013-09-01

    The Streptococcus pyogenes Cas9 (SpCas9) nuclease can be efficiently targeted to genomic loci by means of single-guide RNAs (sgRNAs) to enable genome editing. Here, we characterize SpCas9 targeting specificity in human cells to inform the selection of target sites and avoid off-target effects. Our study evaluates >700 guide RNA variants and SpCas9-induced indel mutation levels at >100 predicted genomic off-target loci in 293T and 293FT cells. We find that SpCas9 tolerates mismatches between guide RNA and target DNA at different positions in a sequence-dependent manner, sensitive to the number, position and distribution of mismatches. We also show that SpCas9-mediated cleavage is unaffected by DNA methylation and that the dosage of SpCas9 and sgRNA can be titrated to minimize off-target modification. To facilitate mammalian genome engineering applications, we provide a web-based software tool to guide the selection and validation of target sequences as well as off-target analyses.

  17. International Exchange for Educators and Librarians in Higher Education. Resource Guide.

    ERIC Educational Resources Information Center

    Clarke, Christine

    This guide will help librarians and educators in U.S. colleges and universities to develop an overview of the topic of international exchange, target those U.S. and international government organizations that have relevant information on exchange programs, and use the information tools as a gateway to more detailed research. It is assumed that the…

  18. Cosmetology: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for a cosmetology vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed by teachers, parents, and the…

  19. Aircraft Mechanics: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for an aircraft mechanics vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed by teachers, parents, and…

  20. Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research

    PubMed Central

    Wangler, Michael F.; Yamamoto, Shinya; Chao, Hsiao-Tuan; Posey, Jennifer E.; Westerfield, Monte; Postlethwait, John; Hieter, Philip; Boycott, Kym M.; Campeau, Philippe M.; Bellen, Hugo J.

    2017-01-01

    Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functions. Here, we review the current state of research into undiagnosed diseases, highlighting large efforts in North America and internationally, including the Undiagnosed Diseases Network (UDN) (Supplemental Material, File S1) and UDN International (UDNI), the Centers for Mendelian Genomics (CMG), and the Canadian Rare Diseases Models and Mechanisms Network (RDMM). We discuss how merging human genetics with model organism research guides experimental studies to solve these medical mysteries, gain new insights into disease pathogenesis, and uncover new therapeutic strategies. PMID:28874452

  1. Genomics-Guided Precise Anti-Epileptic Drug Development.

    PubMed

    Delanty, Norman; Cavallleri, Gianpiero

    2017-07-01

    Traditional antiepileptic drug development approaches have yielded many important clinically valuable anti-epileptic drugs. However, the screening of promising compounds has been naturally agnostic to epilepsy etiology in individual human patients. Now, genomic medicine is changing the way we view human disease. International collaborations are unraveling the many molecular genetic causes of the epilepsies, including the early onset epileptic encephalopathies, and some of the familial focal epilepsies. Further advances in precision diagnostics will be facilitated by ongoing large collaborations and the wider availability of whole exome and whole genome sequencing in clinical practice. Securing a precise molecular diagnosis in some individual patients will pave the way for the advent of precision therapeutics of new and re-purposed compounds in the treatment of the epilepsies. This new approach is already beginning, e.g., with the use of everolimus in patients with tuberous sclerosis complex (and perhaps other mTORopathies), the use of quinidine in some children with KCNT1 mutations, and the use of the ketogenic diet in individuals with GLUT-1 deficiency. This article explores the promise of genomics guided drug development as an approach to complement the more traditional model.

  2. K-12 Energy Education Program: A Conceptual Guide To K-12 Energy Education in Wisconsin.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Stevens Point. Energy Center of Wisconsin.

    In addition to presenting concepts that can help students understand and make decisions about energy issues, this guide provides guidance for teachers to incorporate energy education into their curricula. The guide is divided into two major sections: (1) the Energy Education Conceptual Framework and (2) the Suggested Scope and Sequence. The…

  3. Biology--Chemistry--Physics, Students' Guide, A Three-Year Sequence, Parts I and II.

    ERIC Educational Resources Information Center

    Scott, Arthur; And Others

    Parts I and II of the students' guide to the three-year integrated biology, chemistry, and physics course being prepared by the Portland Project Committee are contained in this guide. A committee reviewed and selected material developed by the national course improvement groups--Physical Science Study Committee, Chemical Bond Approach, Chemical…

  4. Textile Science Leader's Guide. 4-H Textile Science.

    ERIC Educational Resources Information Center

    Scholl, Jan

    This instructor's guide provides an overview of 4-H student project modules in the textile sciences area. The guide includes short notes explaining how to use the project modules, a flowchart chart showing how the project areas are sequenced, a synopsis of the design and content of the modules, and some program planning tips. For each of the…

  5. Spanish Oral Language Guide: Kindergarten Level. Espanol como Segundo Idioma. Teacher's Guide: Level I.

    ERIC Educational Resources Information Center

    Corbell, Gloria; And Others

    This teacher's guide to Spanish language at the kindergarten level includes a recommended subject presentation sequence for the Spanish curriculum, a sample schedule, a grouping of students using three stations, and a classroom layout. The grouping would be effective when at least one-third of the children are Spanish-speaking or bilingual. The…

  6. A Guide to Business Course Competencies. The Business Program in Virginia.

    ERIC Educational Resources Information Center

    Henrico County Public Schools, Glen Allen, VA. Virginia Vocational Curriculum and Resource Center.

    This curriculum guide was developed as a model for schools in Virginia to prepare local programs of studies in business education. The Business Program contains 21 courses plus a 4-year sequence of courses for office specialist and a local option for students with disabilities. This guide contains an overview of the Business Program, information…

  7. Advanced Marketing 8130. Planning for Entrepreneurship. Teacher's Resource Guide.

    ERIC Educational Resources Information Center

    Virginia State Dept. of Education, Richmond.

    This teacher's guide is designed for use in a one-semester course to provide marketing and distributive education students with the skills necessary to open a marketing business. Included in the guide are a task list, a suggested teaching sequence, and a series of nine instructional units. The following topics are addressed in the individual…

  8. LATIN FOR SECONDARY SCHOOLS (A GUIDE TO MINIMUM ESSENTIALS).

    ERIC Educational Resources Information Center

    LEAMON, M. PHILLIP; AND OTHERS

    A SET OF MINIMUM ESSENTIALS FOR EACH LEVEL OF A 4-YEAR SEQUENCE OF LATIN IN SECONDARY SCHOOLS IS PRESENTED IN THIS CURRICULUM GUIDE. FOLLOWING STATEMENTS OF THE OBJECTIVES OF LATIN STUDY--READING THE LATIN OF THE GREAT ROMAN AUTHORS, ATTAINING A LINGUISTIC PROFICIENCY, AND ACQUIRING A WIDER HISTORICAL AND CULTURAL AWARENESS--THE GUIDE OUTLINES FOR…

  9. Auto Mechanics: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for an auto mechanics vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed by teachers, parents, and the…

  10. Diesel Mechanics: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for a diesel mechanics vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed by teachers, parents, and the…

  11. Air Conditioning, Heating, and Refrigeration: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for an air conditioning, heating, and refrigeration vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed…

  12. Commercial Art: Scope and Sequence.

    ERIC Educational Resources Information Center

    Nashville - Davidson County Metropolitan Public Schools, TN.

    This scope and sequence guide, developed for a commercial art vocational education program, represents an initial step in the development of a systemwide articulated curriculum sequence for all vocational programs within the Metropolitan Nashville Public School System. It was developed as a result of needs expressed by teachers, parents, and the…

  13. From Arithmetic Sequences to Linear Equations

    ERIC Educational Resources Information Center

    Matsuura, Ryota; Harless, Patrick

    2012-01-01

    The first part of the article focuses on deriving the essential properties of arithmetic sequences by appealing to students' sense making and reasoning. The second part describes how to guide students to translate their knowledge of arithmetic sequences into an understanding of linear equations. Ryota Matsuura originally wrote these lessons for…

  14. RNA-programmed genome editing in human cells

    PubMed Central

    Jinek, Martin; East, Alexandra; Cheng, Aaron; Lin, Steven; Ma, Enbo; Doudna, Jennifer

    2013-01-01

    Type II CRISPR immune systems in bacteria use a dual RNA-guided DNA endonuclease, Cas9, to cleave foreign DNA at specific sites. We show here that Cas9 assembles with hybrid guide RNAs in human cells and can induce the formation of double-strand DNA breaks (DSBs) at a site complementary to the guide RNA sequence in genomic DNA. This cleavage activity requires both Cas9 and the complementary binding of the guide RNA. Experiments using extracts from transfected cells show that RNA expression and/or assembly into Cas9 is the limiting factor for Cas9-mediated DNA cleavage. In addition, we find that extension of the RNA sequence at the 3′ end enhances DNA targeting activity in vivo. These results show that RNA-programmed genome editing is a facile strategy for introducing site-specific genetic changes in human cells. DOI: http://dx.doi.org/10.7554/eLife.00471.001 PMID:23386978

  15. Handbook for the Supervision of the Intern in School Administration...A Performance Based Guide for the Intern and His Advisors

    ERIC Educational Resources Information Center

    Hensarling, Paul R.; Erlandson, David A.

    This handbook is a comprehensive guide to the supervision of the intern for all positions with school administrative responsibilities: principal, superintendent, and middle administrator. It consists of eight sections, the first five of which are introductory, explaining the concept of the internship as a performance-based evaluative technique and…

  16. Know Your Rights on Campus: A Guide on Racial Profiling, and Hate Crime for International Students in the United States.

    ERIC Educational Resources Information Center

    Harvard Civil Rights Project, Cambridge, MA.

    This guide to the rights of international students explains racial profiling and hate crimes. Since the terrorist attacks of September 11, 2001, many immigrants and international students have experienced heightened scrutiny and outright discrimination. Racial profiling refers to the reliance by law enforcement officers on a person's ethnicity,…

  17. Common Criteria Evaluation and Validation Scheme for Information Technology Security: Guidance to Validators of IT Security Evaluations

    DTIC Science & Technology

    2002-02-01

    NVLAP procedures are compatible with, among others, the most recent official publications of ISO / IEC 17025 (formally ISO / IEC Guide 25), ISO Guides 2, 30... IEC Guide 17025 and the relevant requirements of ISO 9002-1994. NVLAP Handbook 150-20 contains information that is specific to Common Criteria...Evaluation Technical Report EAP Evaluation Acceptance Package IEC International Electrotechnical Commission ISO International

  18. An undergraduate laboratory class using CRISPR/Cas9 technology to mutate drosophila genes.

    PubMed

    Adame, Vanesa; Chapapas, Holly; Cisneros, Marilyn; Deaton, Carol; Deichmann, Sophia; Gadek, Chauncey; Lovato, TyAnna L; Chechenova, Maria B; Guerin, Paul; Cripps, Richard M

    2016-05-06

    CRISPR/Cas9 genome editing technology is used in the manipulation of genome sequences and gene expression. Because of the ease and rapidity with which genes can be mutated using CRISPR/Cas9, we sought to determine if a single-semester undergraduate class could be successfully taught, wherein students isolate mutants for specific genes using CRISPR/Cas9. Six students were each assigned a single Drosophila gene, for which no mutants currently exist. Each student designed and created plasmids to encode single guide RNAs that target their selected gene; injected the plasmids into Cas9-expressing embryos, in order to delete the selected gene; carried out a three-generation cross to test for germline transmission of a mutated allele and generate a stable stock of the mutant; and characterized the mutant alleles by PCR and sequencing. Three genes out of six were successfully mutated. Pre- and post- survey evaluations of the students in the class revealed that student attitudes towards their research competencies increased, although the changes were not statistically significant. We conclude that it is feasible to develop a laboratory genome editing class, to provide effective laboratory training to undergraduate students, and to generate mutant lines for use by the broader scientific community. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:263-275, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

  19. International Space Programs. Aerospace Education III.

    ERIC Educational Resources Information Center

    Air Univ., Maxwell AFB, AL. Junior Reserve Office Training Corps.

    This curriculum guide is prepared for the Aerospace Education III series publication entitled "International Space Programs." The guide is organized according to specific chapters in the textbook. It provides guidelines for teachers in terms of objectives, behavioral objectives, suggested outlines, orientation, suggested key points,…

  20. Educable Mentally Handicapped: Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton.

    The curriculum guide outlines objectives, strategies, and materials for developing academic, daily living, and vocational skills in educable mentally retarded students. An introductory section explains that the curriculum incorporates a community focus, parental involvement, developmental sequencing, and prescriptive teaching. Guidelines to…

  1. EMH Curriculum Guide.

    ERIC Educational Resources Information Center

    Gwinnett County Schools, GA.

    The guide consists of behaviorally stated, developmentally sequenced curriculum objectives for mentally retarded students from preprimary through high school levels. Five major sections present detailed skill objectives in the following areas: (1) basic academic skills (motor development, perceptual development, language development, reading,…

  2. Civil Engineering Technology Program Guide.

    ERIC Educational Resources Information Center

    Georgia Univ., Athens. Dept. of Vocational Education.

    This program guide presents civil engineering technology curriculum for technical institutes in Georgia. The general information section contains the following: purpose and objectives; program description, including admissions, typical job titles, and accreditation and certification; and curriculum model, including standard curriculum sequence and…

  3. A Randomized Parallel Study for Simulated Internal Jugular Vein Cannulation Using Simple Needle Guide Device

    ClinicalTrials.gov

    2017-08-14

    Doctors Attending a Central Line Insertion Training Courses for New Residents of a University Hospital From March 2017 to June 2017; Physicians Who Had Less Than 10 Ultrasound Guided Internal Jugular Vein Cannulation Participate in This Study

  4. Mice and Men Environmental Balance, Parts Three and Four of an Integrated Science Sequence, Student Guide, 1970 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This student guide is divided into two sections: "Mice and Men" and "Environmental Balance," and constitutes parts three and four of the first year of the Portland Project, a three-year, integrated high school science curriculum. Part One of the guide deals with topics such as cell, reproduction, embryology, genetics, genetic…

  5. Building a Linked Learning Pathway: A Guide for Transforming High Schools for College and Career Success

    ERIC Educational Resources Information Center

    Atterbury, Rob

    2014-01-01

    This guide provides an overview of a more robust online guide and toolkit available through ConnectEd Studios. It supplies a glimpse of the sequence of steps involved in creating a new Linked Learning pathway. This publication can help coaches, district leadership, and pathway teams gain an understanding of the overall process of designing and…

  6. Optimized guide RNA structure for genome editing via Cas9

    PubMed Central

    Xu, Jianyong; Lian, Wei; Jia, Yuning; Li, Lingyun; Huang, Zhong

    2017-01-01

    The genome editing tool Cas9-gRNA (guide RNA) has been successfully applied in different cell types and organisms with high efficiency. However, more efforts need to be made to enhance both efficiency and specificity. In the current study, we optimized the guide RNA structure of Streptococcus pyogenes CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas (CRISPR-associated) system to improve its genome editing efficiency. Comparing with the original functional structure of guide RNA, which is composed of crRNA and tracrRNA, the widely used chimeric gRNA has shorter crRNA and tracrRNA sequence. The deleted RNA sequence could form extra loop structure, which might enhance the stability of the guide RNA structure and subsequently the genome editing efficiency. Thus the genome editing efficiency of different forms of guide RNA was tested. And we found that the chimeric structure of gRNA with original full length of crRNA and tracrRNA showed higher genome editing efficiency than the conventional chimeric structure or other types of gRNA we tested. Therefore our data here uncovered the new type of gRNA structure with higher genome editing efficiency. PMID:29212218

  7. Evaluating and redesigning teaching learning sequences at the introductory physics level

    NASA Astrophysics Data System (ADS)

    Guisasola, Jenaro; Zuza, Kristina; Ametller, Jaume; Gutierrez-Berraondo, José

    2017-12-01

    In this paper we put forward a proposal for the design and evaluation of teaching and learning sequences in upper secondary school and university. We will connect our proposal with relevant contributions on the design of teaching sequences, ground it on the design-based research methodology, and discuss how teaching and learning sequences designed according to our proposal relate to learning progressions. An iterative methodology for evaluating and redesigning the teaching and learning sequence (TLS) is presented. The proposed assessment strategy focuses on three aspects: (a) evaluation of the activities of the TLS, (b) evaluation of learning achieved by students in relation to the intended objectives, and (c) a document for gathering the difficulties found when implementing the TLS to serve as a guide to teachers. Discussion of this guide with external teachers provides feedback used for the TLS redesign. The context of our implementation and evaluation is an innovative calculus-based physics course for first-year engineering and science degree students at the University of the Basque Country.

  8. International Cognition and Cancer Task Force Recommendations for Neuroimaging Methods in the Study of Cognitive Impairment in Non-CNS Cancer Patients.

    PubMed

    Deprez, Sabine; Kesler, Shelli R; Saykin, Andrew J; Silverman, Daniel H S; de Ruiter, Michiel B; McDonald, Brenna C

    2018-03-01

    Cancer- and treatment-related cognitive changes have been a focus of increasing research since the early 1980s, with meta-analyses demonstrating poorer performance in cancer patients in cognitive domains including executive functions, processing speed, and memory. To facilitate collaborative efforts, in 2011 the International Cognition and Cancer Task Force (ICCTF) published consensus recommendations for core neuropsychological tests for studies of cancer populations. Over the past decade, studies have used neuroimaging techniques, including structural and functional magnetic resonance imaging (fMRI) and positron emission tomography, to examine the underlying brain basis for cancer- and treatment-related cognitive declines. As yet, however, there have been no consensus recommendations to guide researchers new to this field or to promote the ability to combine data sets. We first discuss important methodological issues with regard to neuroimaging study design, scanner considerations, and sequence selection, focusing on concerns relevant to cancer populations. We propose a minimum recommended set of sequences, including a high-resolution T1-weighted volume and a resting state fMRI scan. Additional advanced imaging sequences are discussed for consideration when feasible, including task-based fMRI and diffusion tensor imaging. Important image data processing and analytic considerations are also reviewed. These recommendations are offered to facilitate increased use of neuroimaging in studies of cancer- and treatment-related cognitive dysfunction. They are not intended to discourage investigator-initiated efforts to develop cutting-edge techniques, which will be helpful in advancing the state of the knowledge. Use of common imaging protocols will facilitate multicenter and data-pooling initiatives, which are needed to address critical mechanistic research questions.

  9. Computer-Assisted Virtual Planning for Surgical Guide Manufacturing and Internal Distractor Adaptation in the Management of Midface Hypoplasia in Cleft Patients.

    PubMed

    Scolozzi, Paolo; Herzog, Georges

    2017-07-01

    We are reporting the treatment of severe maxillary hypoplasia in two patients with unilateral cleft lip and palate by using a specific approach combining the Le Fort I distraction osteogenesis technique coupled with computer-aided design/computer-aided manufacturing customized surgical guides and internal distractors based on virtual computational planning. This technology allows for the transfer of the virtual planned reconstruction to the operating room by using custom patient-specific implants, surgical splints, surgical cutting guides, and surgical guides to plate or distractor adaptation.

  10. Single-Molecule Counting of Point Mutations by Transient DNA Binding

    NASA Astrophysics Data System (ADS)

    Su, Xin; Li, Lidan; Wang, Shanshan; Hao, Dandan; Wang, Lei; Yu, Changyuan

    2017-03-01

    High-confidence detection of point mutations is important for disease diagnosis and clinical practice. Hybridization probes are extensively used, but are hindered by their poor single-nucleotide selectivity. Shortening the length of DNA hybridization probes weakens the stability of the probe-target duplex, leading to transient binding between complementary sequences. The kinetics of probe-target binding events are highly dependent on the number of complementary base pairs. Here, we present a single-molecule assay for point mutation detection based on transient DNA binding and use of total internal reflection fluorescence microscopy. Statistical analysis of single-molecule kinetics enabled us to effectively discriminate between wild type DNA sequences and single-nucleotide variants at the single-molecule level. A higher single-nucleotide discrimination is achieved than in our previous work by optimizing the assay conditions, which is guided by statistical modeling of kinetics with a gamma distribution. The KRAS c.34 A mutation can be clearly differentiated from the wild type sequence (KRAS c.34 G) at a relative abundance as low as 0.01% mutant to WT. To demonstrate the feasibility of this method for analysis of clinically relevant biological samples, we used this technology to detect mutations in single-stranded DNA generated from asymmetric RT-PCR of mRNA from two cancer cell lines.

  11. Ecosystems, Teacher's Guide.

    ERIC Educational Resources Information Center

    California Univ., Berkeley. Science Curriculum Improvement Study.

    The Science Curriculum Improvement Study has developed this teacher's guide to "Ecosystems," the sixth part of a six unit life science curriculum sequence. The six basic units, emphasizing organism-environment interactions, are organisms, life cycles, populations, environments, communities, and ecosystems. They make use of scientific and…

  12. Populations, Teacher's Guide.

    ERIC Educational Resources Information Center

    California Univ., Berkeley. Science Curriculum Improvement Study.

    The Science Curriculum Improvement Study has developed this teacher's guide to "Populations," the third part of a six-unit life science curriculum sequence. The six basic units, emphasizing organism-environment interactions, are organisms, life cycles, populations, environments, communities, and ecosystems; and they make use of…

  13. Communities, Teacher's Guide.

    ERIC Educational Resources Information Center

    California Univ., Berkeley. Science Curriculum Improvement Study.

    The Science Curriculum Improvement Study has developed this teacher's guide to "Communities," the fifth part of a six unit life science curriculum sequence. The six basic units, emphasizing organism-environment interactions, are organisms, life cycles, populations, environments, communities, and ecosystems, and make use of scientific and…

  14. COLLABORATIVE GUIDE: A REEF MANAGER'S GUIDE TO ...

    EPA Pesticide Factsheets

    Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental organizations, and academic institutions. Referred to as A Reef Manager's Guide to Coral Bleaching, the guide will provide coral reef managers with the latest scientific information on the causes of coral bleaching and new management strategies for responding to this significant threat to coral reef ecosystems. Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental organizations, and academic institutions. Dr. Jordan West, of the National Center for Environmental Assessment, was a major contributor to the guide. Referred to as

  15. Microform Market Place 1974/1975. An International Directory of Micropublishing.

    ERIC Educational Resources Information Center

    Veaner, Allen B., Ed.; Meckler, Alan M., Ed.

    The information for this international buyer's guide for the microform purchaser was gathered from questionnaires to the publishers themselves. The guide is divided into eight sections: directory of micropublishers, mergers and acquisitions, bibliography of first sources for the microform library, microform jobbers, organizations, a geographical…

  16. 78 FR 52777 - Implementation of the Revised International Guiding Principles for Biomedical Research Involving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Implementation of the... Institutes of Health (NIH) is providing guidance to Public Health Service (PHS) awardee institutions on implementation of the revised International Guiding Principles for Biomedical Research Involving Animals...

  17. Molecular biology at the cutting edge: A review on CRISPR/CAS9 gene editing for undergraduates.

    PubMed

    Thurtle-Schmidt, Deborah M; Lo, Te-Wen

    2018-03-01

    Disrupting a gene to determine its effect on an organism's phenotype is an indispensable tool in molecular biology. Such techniques are critical for understanding how a gene product contributes to the development and cellular identity of organisms. The explosion of genomic sequencing technologies combined with recent advances in genome-editing techniques has elevated the possibilities of genetic manipulations in numerous organisms in which these experiments were previously not readily accessible or possible. Introducing the next generation of molecular biologists to these emerging techniques is key in the modern biology classroom. This comprehensive review introduces undergraduates to CRISPR/Cas9 editing and its uses in genetic studies. The goals of this review are to explain how CRISPR functions as a prokaryotic immune system, describe how researchers generate mutations with CRISPR/Cas9, highlight how Cas9 has been adapted for new functions, and discuss ethical considerations of genome editing. Additionally, anticipatory guides and questions for discussion are posed throughout the review to encourage active exploration of these topics in the classroom. Finally, the supplement includes a study guide and practical suggestions to incorporate CRISPR/Cas9 experiments into lab courses at the undergraduate level. © 2018 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 46(2):195-205, 2018. © 2018 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

  18. [How to make your own custom cutting guides for both mandibular and fibular stair step osteotomies?

    PubMed

    Rem, K; Bosc, R; De Kermadec, H; Hersant, B; Meningaud, J-P

    2017-12-01

    Using tailored cutting guides for osteocutaneous free fibula flap in complex mandibular reconstruction after cancer resection surgery constitutes a substantial improvement. Autonomously conceiving and manufacturing the cutting guides within a plastic surgery department with computer-aided design (CAD) and three-dimensional (3D) printing allows planning more complex osteotomies, such as stair-step osteotomies, in order to achieve more stable internal fixations. For the past three years, we have been producing by ourselves patient-tailored cutting guides using CAD and 3D printing. Osteotomies were virtually planned, making the cutting lines more complex in order to optimize the internal fixation stability. We also printed reconstructed mandible templates and shaped the reconstruction plates on them. We recorded data including manufacturing techniques and surgical outcomes. Eleven consecutive patients were operated on for an oral cavity cancer. For each patient, we planned the fibular and mandibular stair-step osteotomies and we produced tailored cutting guides. In all patients, we achieved to get immediately stable internal fixations and in 10 patients, a complete bone consolidation after 6 months. Autonomously manufacturing surgical cutting guides for mandibular reconstruction by free fibula flap is a significant improvement, regarding ergonomics and precision. Planning stair-step osteotomies to perform complementary internal fixation increases contact surface and congruence between the bone segments, thus improving the reconstructed mandible stability. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. MiDAS: the field guide to the microbes of activated sludge.

    PubMed

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes--knowledge that will be an invaluable resource for the optimal design and operation of these systems. © The Author(s) 2015. Published by Oxford University Press.

  20. MiDAS: the field guide to the microbes of activated sludge

    PubMed Central

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes—knowledge that will be an invaluable resource for the optimal design and operation of these systems. Database URL: http://www.midasfieldguide.org PMID:26120139

  1. The genomic underpinnings of eukaryotic virus taxonomy: creating a sequence-based framework for family-level virus classification.

    PubMed

    Aiewsakun, Pakorn; Simmonds, Peter

    2018-02-20

    The International Committee on Taxonomy of Viruses (ICTV) classifies viruses into families, genera and species and provides a regulated system for their nomenclature that is universally used in virus descriptions. Virus taxonomic assignments have traditionally been based upon virus phenotypic properties such as host range, virion morphology and replication mechanisms, particularly at family level. However, gene sequence comparisons provide a clearer guide to their evolutionary relationships and provide the only information that may guide the incorporation of viruses detected in environmental (metagenomic) studies that lack any phenotypic data. The current study sought to determine whether the existing virus taxonomy could be reproduced by examination of genetic relationships through the extraction of protein-coding gene signatures and genome organisational features. We found large-scale consistency between genetic relationships and taxonomic assignments for viruses of all genome configurations and genome sizes. The analysis pipeline that we have called 'Genome Relationships Applied to Virus Taxonomy' (GRAViTy) was highly effective at reproducing the current assignments of viruses at family level as well as inter-family groupings into orders. Its ability to correctly differentiate assigned viruses from unassigned viruses, and classify them into the correct taxonomic group, was evaluated by threefold cross-validation technique. This predicted family membership of eukaryotic viruses with close to 100% accuracy and specificity potentially enabling the algorithm to predict assignments for the vast corpus of metagenomic sequences consistently with ICTV taxonomy rules. In an evaluation run of GRAViTy, over one half (460/921) of (near)-complete genome sequences from several large published metagenomic eukaryotic virus datasets were assigned to 127 novel family-level groupings. If corroborated by other analysis methods, these would potentially more than double the number of eukaryotic virus families in the ICTV taxonomy. A rapid and objective means to explore metagenomic viral diversity and make informed recommendations for their assignments at each taxonomic layer is essential. GRAViTy provides one means to make rule-based assignments at family and order levels in a manner that preserves the integrity and underlying organisational principles of the current ICTV taxonomy framework. Such methods are increasingly required as the vast virosphere is explored.

  2. Echoes of China.

    ERIC Educational Resources Information Center

    Chang, Pei-lan Li; Chao, Johanna T.; Chao, Yenshew Lynn; Chin, Ai-li S.; Hsieh, Charlotte Sheau-mann; Sun, Paul P.; Swartz, Leslie M.; Wang, Theresa; Wu, Fa Y.

    This curriculum guide is developed to accompany 7 Chinese Cultural Heritage kits for use in intermediate and middle school classrooms. The units in this guide may be used with or without the accompanying kits. When appropriate, units include: objectives, introductory information, suggested presentation sequence, activity instruction, evaluation…

  3. Aviation Maintenance Technology. General. Curriculum Implementation Guide.

    ERIC Educational Resources Information Center

    Moore, John, Jr.; And Others

    This curriculum implementation guide is a scope and sequence for the general section of a course in aviation maintenance technology. The course materials were prepared through a cooperative effort of airframe and powerplant mechanics, general aviation industry representatives, Federal Aviation Administration representatives, and vocational…

  4. Roundabouts : an informational guide

    DOT National Transportation Integrated Search

    2000-06-01

    The guidance supplied in this document, Roundabouts: An Informational Guide, is based on established international and U.S. practices and is supplemented by recent research. The guide is comprehensive in recognition of the diverse needs of transporta...

  5. Marketing ITS infrastructure in the public interest

    DOT National Transportation Integrated Search

    2000-10-01

    This guide, Volume 4 - Bibliographic and Non-bibliographic databases, is part of the International Guide to Highway Transportation Information - a multi-volume set of guides that provides highway transportation information resources for domestic and ...

  6. A programmable Cas9-serine recombinase fusion protein that operates on DNA sequences in mammalian cells

    PubMed Central

    Chaikind, Brian; Bessen, Jeffrey L.; Thompson, David B.; Hu, Johnny H.; Liu, David R.

    2016-01-01

    We describe the development of ‘recCas9’, an RNA-programmed small serine recombinase that functions in mammalian cells. We fused a catalytically inactive dCas9 to the catalytic domain of Gin recombinase using an optimized fusion architecture. The resulting recCas9 system recombines DNA sites containing a minimal recombinase core site flanked by guide RNA-specified sequences. We show that these recombinases can operate on DNA sites in mammalian cells identical to genomic loci naturally found in the human genome in a manner that is dependent on the guide RNA sequences. DNA sequencing reveals that recCas9 catalyzes guide RNA-dependent recombination in human cells with an efficiency as high as 32% on plasmid substrates. Finally, we demonstrate that recCas9 expressed in human cells can catalyze in situ deletion between two genomic sites. Because recCas9 directly catalyzes recombination, it generates virtually no detectable indels or other stochastic DNA modification products. This work represents a step toward programmable, scarless genome editing in unmodified cells that is independent of endogenous cellular machinery or cell state. Current and future generations of recCas9 may facilitate targeted agricultural breeding, or the study and treatment of human genetic diseases. PMID:27515511

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

    PubMed Central

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

    2010-01-01

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

  8. Preoperative magnetic resonance imaging protocol for endoscopic cranial base image-guided surgery.

    PubMed

    Grindle, Christopher R; Curry, Joseph M; Kang, Melissa D; Evans, James J; Rosen, Marc R

    2011-01-01

    Despite the increasing utilization of image-guided surgery, no radiology protocols for obtaining magnetic resonance (MR) imaging of adequate quality are available in the current literature. At our institution, more than 300 endonasal cranial base procedures including pituitary, extended pituitary, and other anterior skullbase procedures have been performed in the past 3 years. To facilitate and optimize preoperative evaluation and assessment, there was a need to develop a magnetic resonance protocol. Retrospective Technical Assessment was performed. Through a collaborative effort between the otolaryngology, neurosurgery, and neuroradiology departments at our institution, a skull base MR image-guided (IGS) protocol was developed with several ends in mind. First, it was necessary to generate diagnostic images useful for the more frequently seen pathologies to improve work flow and limit the expense and inefficiency of case specific MR studies. Second, it was necessary to generate sequences useful for IGS, preferably using sequences that best highlight that lesion. Currently, at our institution, all MR images used for IGS are obtained using this protocol as part of preoperative planning. The protocol that has been developed allows for thin cut precontrast and postcontrast axial cuts that can be used to plan intraoperative image guidance. It also obtains a thin cut T2 axial series that can be compiled separately for intraoperative imaging, or may be fused with computed tomographic images for combined modality. The outlined protocol obtains image sequences effective for diagnostic and operative purposes for image-guided surgery using both T1 and T2 sequences. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Advanced MR Imaging of the Human Nucleus Accumbens--Additional Guiding Tool for Deep Brain Stimulation.

    PubMed

    Lucas-Neto, Lia; Reimão, Sofia; Oliveira, Edson; Rainha-Campos, Alexandre; Sousa, João; Nunes, Rita G; Gonçalves-Ferreira, António; Campos, Jorge G

    2015-07-01

    The human nucleus accumbens (Acc) has become a target for deep brain stimulation (DBS) in some neuropsychiatric disorders. Nonetheless, even with the most recent advances in neuroimaging it remains difficult to accurately delineate the Acc and closely related subcortical structures, by conventional MRI sequences. It is our purpose to perform a MRI study of the human Acc and to determine whether there are reliable anatomical landmarks that enable the precise location and identification of the nucleus and its core/shell division. For the Acc identification and delineation, based on anatomical landmarks, T1WI, T1IR and STIR 3T-MR images were acquired in 10 healthy volunteers. Additionally, 32-direction DTI was obtained for Acc segmentation. Seed masks for the Acc were generated with FreeSurfer and probabilistic tractography was performed using FSL. The probability of connectivity between the seed voxels and distinct brain areas was determined and subjected to k-means clustering analysis, defining 2 different regions. With conventional T1WI, the Acc borders are better defined through its surrounding anatomical structures. The DTI color-coded vector maps and IR sequences add further detail in the Acc identification and delineation. Additionally, using probabilistic tractography it is possible to segment the Acc into a core and shell division and establish its structural connectivity with different brain areas. Advanced MRI techniques allow in vivo delineation and segmentation of the human Acc and represent an additional guiding tool in the precise and safe target definition for DBS. © 2015 International Neuromodulation Society.

  10. The estimation of the measurement results with using statistical methods

    NASA Astrophysics Data System (ADS)

    Velychko, O.; Gordiyenko, T.

    2015-02-01

    The row of international standards and guides describe various statistical methods that apply for a management, control and improvement of processes with the purpose of realization of analysis of the technical measurement results. The analysis of international standards and guides on statistical methods estimation of the measurement results recommendations for those applications in laboratories is described. For realization of analysis of standards and guides the cause-and-effect Ishikawa diagrams concerting to application of statistical methods for estimation of the measurement results are constructed.

  11. Coalescent-Based Analyses of Genomic Sequence Data Provide a Robust Resolution of Phylogenetic Relationships among Major Groups of Gibbons

    PubMed Central

    Shi, Cheng-Min; Yang, Ziheng

    2018-01-01

    Abstract The phylogenetic relationships among extant gibbon species remain unresolved despite numerous efforts using morphological, behavorial, and genetic data and the sequencing of whole genomes. A major challenge in reconstructing the gibbon phylogeny is the radiative speciation process, which resulted in extremely short internal branches in the species phylogeny and extensive incomplete lineage sorting with extensive gene-tree heterogeneity across the genome. Here, we analyze two genomic-scale data sets, with ∼10,000 putative noncoding and exonic loci, respectively, to estimate the species tree for the major groups of gibbons. We used the Bayesian full-likelihood method bpp under the multispecies coalescent model, which naturally accommodates incomplete lineage sorting and uncertainties in the gene trees. For comparison, we included three heuristic coalescent-based methods (mp-est, SVDQuartets, and astral) as well as concatenation. From both data sets, we infer the phylogeny for the four extant gibbon genera to be (Hylobates, (Nomascus, (Hoolock, Symphalangus))). We used simulation guided by the real data to evaluate the accuracy of the methods used. Astral, while not as efficient as bpp, performed well in estimation of the species tree even in presence of excessive incomplete lineage sorting. Concatenation, mp-est and SVDQuartets were unreliable when the species tree contains very short internal branches. Likelihood ratio test of gene flow suggests a small amount of migration from Hylobates moloch to H. pileatus, while cross-genera migration is absent or rare. Our results highlight the utility of coalescent-based methods in addressing challenging species tree problems characterized by short internal branches and rampant gene tree-species tree discordance. PMID:29087487

  12. The International Development Research Centre: A Guide for the Canadian University Research Community = Le Centre de recherches pour le developpement international: guide a l'intention des scientifiques des universites Canadiennes.

    ERIC Educational Resources Information Center

    Tillman, George; Wasilewski, Ania, Ed.

    Written in both English and French this is a manual for the Canadian research community. It describes the International Development Research Centre (IDRC) and its operations. The main objective of the IDRC is to assist scientists in developing countries to identify and conduct research into long term practical solutions to development problems.…

  13. Science Guide for Secondary Schools.

    ERIC Educational Resources Information Center

    Georgia State Dept. of Education, Atlanta. Office of Instructional Services.

    This six-chapter guide is designed to help Georgia teachers adopt or adapt various options into the local school's science curriculum. Major areas addressed in the chapters are: (1) secondary school curriculum development (focusing on performance objectives, sequencing the curriculum, evaluation, and scientific literacy); (2) teaching methods…

  14. Extra Luminal Entrapment of Guide Wire; A Rare Complication of Central Venous Catheter Placement in Right Internal Jugular Vein.

    PubMed

    Ansari, Md Abu Masud; Kumar, Naveen; Kumar, Shailesh; Kumari, Sarita

    2016-10-01

    Central venous Catheterization (CVC) is a commonly performed procedure for venous access. It is associated with several complications. We report a rare case of extra luminal entrapment of guide wire during CVC placement in right jugular vein. We report a case of 28 years old female patient presented in our emergency with history of entrapped guide wire in right side of neck during CVC. X-ray showed coiling of guide wire in neck. CT Angiography showed guide wire coursing in between common carotid artery and internal jugular vein (IJV), closely abutting the wall of both vessels. The guide wire was coiled with end coursing behind the esophageal wall. Guide wire was removed under fluoroscopic guide manipulation under local anesthesia. We want to emphasize that even though CVC placement is common and simple procedure, serious complication can occur in hands of untrained operator. The procedure should be performed under supervision, if done by trainee. Force should never be applied to advance the guide wire if resistance is encountered.

  15. Structure of yeast Argonaute with guide RNA

    PubMed Central

    Nakanishi, Kotaro; Weinberg, David E.; Bartel, David P.; Patel, Dinshaw J.

    2012-01-01

    The RNA-induced silencing complex, comprising Argonaute and guide RNA, mediates RNA interference. Here we report the 3.2 Å crystal structure of Kluyveromyces Argonaute (KpAGO) fortuitously complexed with guide RNA originating from small-RNA duplexes autonomously loaded and processed by recombinant KpAGO. Despite their diverse sequences, guide-RNA nucleotides 1–8 are positioned similarly, with sequence-independent contacts to bases, phosphates and 2′-hydroxyl groups pre-organizing the backbone of nucleotides 2–8 in a near–A-form conformation. Compared with prokaryotic Argonautes, KpAGO has numerous surface-exposed insertion segments, with a cluster of conserved insertions repositioning the N domain to enable full propagation of guide–target pairing. Compared with Argonautes in inactive conformations, KpAGO has a hydrogen-bond network that stabilizes an expanded and repositioned loop, which inserts an invariant glutamate into the catalytic pocket. Mutation analyses and analogies to Ribonuclease H indicate that insertion of this glutamate finger completes a universally conserved catalytic tetrad, thereby activating Argonaute for RNA cleavage. PMID:22722195

  16. Phylogeny-guided (meta)genome mining approach for the targeted discovery of new microbial natural products.

    PubMed

    Kang, Hahk-Soo

    2017-02-01

    Genomics-based methods are now commonplace in natural products research. A phylogeny-guided mining approach provides a means to quickly screen a large number of microbial genomes or metagenomes in search of new biosynthetic gene clusters of interest. In this approach, biosynthetic genes serve as molecular markers, and phylogenetic trees built with known and unknown marker gene sequences are used to quickly prioritize biosynthetic gene clusters for their metabolites characterization. An increase in the use of this approach has been observed for the last couple of years along with the emergence of low cost sequencing technologies. The aim of this review is to discuss the basic concept of a phylogeny-guided mining approach, and also to provide examples in which this approach was successfully applied to discover new natural products from microbial genomes and metagenomes. I believe that the phylogeny-guided mining approach will continue to play an important role in genomics-based natural products research.

  17. Improving CRISPR–Cas specificity with chemical modifications in single-guide RNAs

    PubMed Central

    Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Dellinger, Douglas J

    2018-01-01

    Abstract CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2′-O-methyl-3′-phosphonoacetate, or ‘MP’) incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. PMID:29216382

  18. Upper internals arrangement for a pressurized water reactor

    DOEpatents

    Singleton, Norman R; Altman, David A; Yu, Ching; Rex, James A; Forsyth, David R

    2013-07-09

    In a pressurized water reactor with all of the in-core instrumentation gaining access to the core through the reactor head, each fuel assembly in which the instrumentation is introduced is aligned with an upper internals instrumentation guide-way. In the elevations above the upper internals upper support assembly, the instrumentation is protected and aligned by upper mounted instrumentation columns that are part of the instrumentation guide-way and extend from the upper support assembly towards the reactor head in hue with a corresponding head penetration. The upper mounted instrumentation columns are supported laterally at one end by an upper guide tube and at the other end by the upper support plate.

  19. Delphi Method Validation of a Procedural Performance Checklist for Insertion of an Ultrasound-Guided Internal Jugular Central Line.

    PubMed

    Hartman, Nicholas; Wittler, Mary; Askew, Kim; Manthey, David

    2016-01-01

    Placement of ultrasound-guided central lines is a critical skill for physicians in several specialties. Improving the quality of care delivered surrounding this procedure demands rigorous measurement of competency, and validated tools to assess performance are essential. Using the iterative, modified Delphi technique and experts in multiple disciplines across the United States, the study team created a 30-item checklist designed to assess competency in the placement of ultrasound-guided internal jugular central lines. Cronbach α was .94, indicating an excellent degree of internal consistency. Further validation of this checklist will require its implementation in simulated and clinical environments. © The Author(s) 2014.

  20. SEQassembly: A Practical Tools Program for Coding Sequences Splicing

    NASA Astrophysics Data System (ADS)

    Lee, Hongbin; Yang, Hang; Fu, Lei; Qin, Long; Li, Huili; He, Feng; Wang, Bo; Wu, Xiaoming

    CDS (Coding Sequences) is a portion of mRNA sequences, which are composed by a number of exon sequence segments. The construction of CDS sequence is important for profound genetic analysis such as genotyping. A program in MATLAB environment is presented, which can process batch of samples sequences into code segments under the guide of reference exon models, and splice these code segments of same sample source into CDS according to the exon order in queue file. This program is useful in transcriptional polymorphism detection and gene function study.

  1. CRISPR/Cas9 in Genome Editing and Beyond.

    PubMed

    Wang, Haifeng; La Russa, Marie; Qi, Lei S

    2016-06-02

    The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers.

  2. International Conflict and the Media: A Curriculum Guide.

    ERIC Educational Resources Information Center

    Smith, Andrew F.

    This social studies curriculum guide broadly examines the relationships between the media and the military during wartime. It is divided into three units and includes 25 activities. The first unit, "Media and Conflict," begins with an examination of the historical context of the U.S. press and media and international conflicts. The…

  3. Ten Guiding Principles for Designing Online Modules That Involve International Collaborations

    ERIC Educational Resources Information Center

    Porcaro, David; Carrier, Carol

    2014-01-01

    As ideas and personnel flow across borders, there are many opportunities for instructional designers to collaboratively design online modules with international teams. These collaborations can take many shapes, as varying levels of localization and within-team communication are employed. This paper looks at ten guiding principles that are shaping…

  4. Decision Making for Democratic Leadership in a Guided Internship

    ERIC Educational Resources Information Center

    Klinker, JoAnn Franklin; Hoover, J. Duane; Valle, Fernando; Hardin, Fred

    2014-01-01

    Experience in problem-based learning, authentic experiences, on-the-job decision making, and critical reflection on decisions made formed the conceptual framework of an internship to develop democratic leadership as a professional ethic in interns. Interns in an on-the-job guided internship examined decisions over a 13-week period as they…

  5. Waves and Particles--The Orbital Atom, Parts One & Two of an Integrated Science Sequence, Student Guide, 1971 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    The third year of the Portland Project, a three-year secondary school curriculum in integrated science, consists of four parts, the first two of which are covered in this student guide. The reading assignments for part one, "Waves and Particles," are listed in the student guide and are to be read in the Harvard Project Physics textbook.…

  6. EMR Behavioral Curriculum and Student Record.

    ERIC Educational Resources Information Center

    Hartnett, John J.

    Intended for use as a curriculum guide, a source for objectives for the individualized educational plan, and an evaluation instrument to measure handicapped students' learning, the guide lists sequences of developmental tasks. Tasks are outlined for primary, intermediate, and secondary levels in the following areas (sample subskills in…

  7. Business Computer Programming I. Curriculum Guide. Second Edition.

    ERIC Educational Resources Information Center

    Patton, Jan

    This guide provides instructors of business computer programming with a curriculum correlated directly to the office education essential elements mandated by the Texas Education Agency. Introductory materials include a scope and sequence and lists of suggested textbooks, resource books, software, audiovisuals, and magazines. Eleven units are…

  8. A systems theory approach to career development: Exploring factors that affect science as a career choice

    NASA Astrophysics Data System (ADS)

    Liskey, Brian K.

    This research project was designed to examine the factors that affect students' choice in a career. Specifically, the factors of (a) achievement, (b) interest, (c) self-efficacy, (d) perceived preparation for a career, and (e) being informed about a career will be under investigation. Of key importance to the study is how these factors can affect a student's perception about choosing a science career. A quantitative analysis of secondary data from the 2006 and 2009 Program for International Student Assessment (PISA) international assessment and attitudinal questionnaire provided data on student perceptions and aptitude in science. The sample from PISA included over 400,000 15 year-old students from 57 countries. From the 57 countries, 30 countries, comprised by Organization for Economic and Cooperative Development (OECD), were isolated for analysis. Within this group of 30, 11 were selected for comparison based on their questionnaire response to expectations for a career in science at age 30. The Institute for Educational Science's, International Data Explorer was utilized to acquire and analyze data from the 2006 and 2009 PISA international tests and questionnaires to determine significance between scaled scores and PISA indices. Variables were chosen as factors affecting student's perception on various systems outlined by the Systems Theory of Career Development (Patton & McMahon, 1997) and the Systems Theory of Career Development Framework (Patton & McMahon, 1999). Four country groups were established based on student responses to question 30a from the 2006 PISA attitudinal questionnaire, which asks what career students expected to have at age 30. The results from comparing country groups showed that countries in Group A, which showed the highest values for students expecting a career in science, also had the highest average values for achievement on the PISA science literacy assessment. Likewise, countries that had the lowest values for expecting a career in science (Group B) also had the lowest average values for achievement in science as assessed by science literacy score according to PISA. The United States (Group C) and the International Average (Group D) were both intermediate in each of the two categories. The analysis also showed an identical country group sequence from highest responses to lowest responses for the "systems" or variables of a) self-efficacy, b) preparation for a science career, and c) information about a career in science. The group sequence from high to low values was Group C, Group B, Group D, Group A. When comparing this country group sequence there appears to be a weak negative association between students in countries that expect a career in science and the values for self-efficacy, being prepared for, and informed about a career in science. The findings from this study indicate that the greatest factor affecting students' perception for expecting a career in science is high achievement in science. These results provide key insight on the Systems Theory of Career Development missing from the existing body of literature. Leaders in the fields of education and educational policy can use this information to guide practices and promote programs that will aid in higher achievement in science and engineering. This research can also be used by leaders in career counseling to advise students on appropriate career paths and prepare students for future careers in science and technology. Finally, leadership within state and federal institutions can utilize results from this study to guide future research and funding that encourages students on career pathways in the fields of Science Technology Engineering and Mathematics (STEM).

  9. Bacterial Genome Engineering and Synthetic Biology: Combating Pathogens

    DTIC Science & Technology

    2016-11-04

    engineering and SB methods such as recombineering, clustered regularly interspaced short palindromic repeats ( CRISPR ), and bacterial cell-cell...Cholera# Yersinia pseudotuberculosis# Staphylococcus aureus* Phage Engineering CRISPR /Cas9 Delivery of CRISPR genes and RNA guides for sequence...bear very close sequence alignment to the harmless strains via the use of the CRISPR /Cas9 system. The CRISPR system specifically targets a DNA sequence

  10. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization

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

    Varney, Peter J.

    2002-04-23

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development.

  11. Magnetic Resonance Imaging–Guided versus Surrogate-Based Motion Tracking in Liver Radiation Therapy: A Prospective Comparative Study

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

    Paganelli, Chiara, E-mail: chiara.paganelli@polimi.it; Seregni, Matteo; Fattori, Giovanni

    Purpose: This study applied automatic feature detection on cine–magnetic resonance imaging (MRI) liver images in order to provide a prospective comparison between MRI-guided and surrogate-based tracking methods for motion-compensated liver radiation therapy. Methods and Materials: In a population of 30 subjects (5 volunteers plus 25 patients), 2 oblique sagittal slices were acquired across the liver at high temporal resolution. An algorithm based on scale invariant feature transform (SIFT) was used to extract and track multiple features throughout the image sequence. The position of abdominal markers was also measured directly from the image series, and the internal motion of each featuremore » was quantified through multiparametric analysis. Surrogate-based tumor tracking with a state-of-the-art external/internal correlation model was simulated. The geometrical tracking error was measured, and its correlation with external motion parameters was also investigated. Finally, the potential gain in tracking accuracy relying on MRI guidance was quantified as a function of the maximum allowed tracking error. Results: An average of 45 features was extracted for each subject across the whole liver. The multi-parametric motion analysis reported relevant inter- and intrasubject variability, highlighting the value of patient-specific and spatially-distributed measurements. Surrogate-based tracking errors (relative to the motion amplitude) were were in the range 7% to 23% (1.02-3.57mm) and were significantly influenced by external motion parameters. The gain of MRI guidance compared to surrogate-based motion tracking was larger than 30% in 50% of the subjects when considering a 1.5-mm tracking error tolerance. Conclusions: Automatic feature detection applied to cine-MRI allows detailed liver motion description to be obtained. Such information was used to quantify the performance of surrogate-based tracking methods and to provide a prospective comparison with respect to MRI-guided radiation therapy, which could support the definition of patient-specific optimal treatment strategies.« less

  12. International Guide to Highway Transportation Information: Volume 2 - Websites

    DOT National Transportation Integrated Search

    2013-10-01

    "This guide addresses the selection and use of axle loading defaults for Mechanistic-Empirical Pavement Design Guide (MEPDG) applications. The defaults were developed based on weigh-in-motion (WIM) data from the Long- Term Pavement Performance (LTPP)...

  13. 76 FR 54739 - Pacific Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-02

    ... Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific Halibut in...) for the guided sport fishery in International Pacific Halibut Commission (IPHC) Regulatory Areas 2C... sport fishery for halibut. The GHLs are benchmark harvest levels for participants in the guided sport...

  14. 78 FR 18323 - Pacific Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific Halibut in...) for the guided sport fishery in International Pacific Halibut Commission (IPHC) Regulatory Areas 2C... the guided sport fishery for halibut. The GHLs are benchmark harvest levels for participants in the...

  15. How Design Guides Learning from Matrix Diagrams

    ERIC Educational Resources Information Center

    van der Meij, Jan; van Amelsvoort, Marije; Anjewierden, Anjo

    2017-01-01

    Compared to text, diagrams are superior in their ability to structure and summarize information and to show relations between concepts and ideas. Perceptual cues, like arrows, are expected to improve the retention of diagrams by guiding the learner towards important elements or showing a preferred reading sequence. In our experiment, we analyzed…

  16. Industrial Arts Curriculum Guide for Plastics.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford. Div. of Vocational Education.

    This curriculum guide provides topic outlines and objectives for 12 units of an industrial arts program in plastics at any grade level. Introductory material describes the scope and sequence of an Industrial Arts program, gives specific guidelines for Industrial Arts, and briefly discusses the nature of plastics. Unit titles include Orientation of…

  17. Dance: A Guide to Curriculum Development in the Arts.

    ERIC Educational Resources Information Center

    Iowa State Dept. of Public Instruction, Des Moines.

    The purpose of this guide is to present dance education as a discipline and to encourage student participation in a wide range of dance activities. The unit, "Rationale/Philosophy/Goals," contains an introduction to the program, a rationale, and overall goals. "Scope/Sequence/Strategies," presents a chart which lists basic…

  18. 76 FR 39243 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-53; Small Entity Compliance Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... ADMINISTRATION 48 CFR Chapter 1 [Docket FAR 2011-0077, Sequence 5] Federal Acquisition Regulation; Federal Acquisition Circular 2005-53; Small Entity Compliance Guide AGENCY: Department of Defense (DoD), General... Federal Acquisition Circular (FAC) 2005-53, which amend the Federal Acquisition Regulation (FAR). An...

  19. Forestry Occupations. A Curriculum Guide.

    ERIC Educational Resources Information Center

    Mercer, R. J., Ed.

    Developed as a part of a larger project to revise the total agricultural education curriculum in South Carolina, this curriculum guide is designed for a 2-year course in forestry occupations. A paradigm accompanies the document and illustrates a possible time frame and sequence. The units covered by the curriculum include an orientation to…

  20. Industrial Arts Curriculum Guide for Electricity/Electronics.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford. Div. of Vocational Education.

    This curriculum provides a behaviorally written guide that offers a possible list of objectives to assist in establishing or revising an electrical/electronics curriculum. Teachers may choose specific objectives to suit age group and educational level or expertise. Introductory material describes the scope and sequence of an Industrial Arts…

  1. Industrial Technology Orientation Curriculum Guide.

    ERIC Educational Resources Information Center

    Illinois State Board of Education, Springfield. Dept. of Adult, Vocational and Technical Education.

    The four courses in this guide were designed to meet the specifications for the career orientation level of Illinois' Education for Employment Curriculum Model. These orientation-level courses can be taken by high school students in any sequence: (1) communication technology; (2) energy utilization technology; (3) production technology; and (4)…

  2. Elementary Art Education Guide.

    ERIC Educational Resources Information Center

    Frederick County Public Schools, MD.

    This curriculum guide for elementary art education is divided into 21 parts. Following a preface and acknowledgements, the philosophy, framework, goals, and objectives of the art curriculum for Frederick County (Maryland) are outlined. Grade level course overviews and scope and sequence for art education in grades 1-5 are then presented. An…

  3. Reforming the core clerkship in internal medicine: the SGIM/CDIM Project. Society of General Internal Medicine/Clerkship Directors in Internal Medicine.

    PubMed

    Goroll, A H; Morrison, G; Bass, E B; Jablonover, R; Blackman, D; Platt, R; Whelan, A; Hekelman, F P

    2001-01-02

    Dramatic changes in health care have stimulated reform of undergraduate medical education. In an effort to improve the teaching of generalist competencies and encourage learning in the outpatient setting, the Society of General Internal Medicine joined with the Clerkship Directors in Internal Medicine in a federally sponsored initiative to develop a new curriculum for the internal medicine core clerkship. Using a broad-based advisory committee and working closely with key stakeholders (especially clerkship directors), the project collaborators helped forge a new national consensus on the learning agenda for the clerkship (a prioritized set of basic generalist competencies) and on the proportion of time that should be devoted to outpatient care (at least one third of the clerkship). From this consensus emerged a new curricular model that served as the basis for production of a curriculum guide and faculty resource package. The guide features the prioritized set of basic generalist competencies and specifies the requisite knowledge, skills, and attitudes/values needed to master them, as well as a list of suggested training problems. It also includes recommended training experiences, schedules, and approaches to faculty development, precepting, and student evaluation. Demand for the guide has been strong and led to production of a second edition, which includes additional materials, an electronic version, and a pocket guide for students and faculty. A follow-up survey of clerkship directors administered soon after completion of the first edition revealed widespread use of the curricular guide but also important barriers to full implementation of the new curriculum. Although this collaborative effort appears to have initiated clerkship reform, long-term success will require an enhanced educational infrastructure to support teaching in the outpatient setting.

  4. Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

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

    Dyk, Pawel; Jiang, Naomi; Sun, Baozhou

    2014-11-15

    Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodesmore » by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.« less

  5. U.S. TIMSS and PIRLS 2011 Technical Report and User's Guide. NCES 2013-046

    ERIC Educational Resources Information Center

    Kastberg, David; Roey, Stephen; Ferraro, David; Lemanski, Nita; Erberber, Ebru

    2013-01-01

    The "U.S. TIMSS and PIRLS 2011 Technical Report and User's Guide" provides an overview of the design and implementation of the Trends in International Mathematics and Science Study (TIMSS) 2011 and the Progress in International Reading Literacy Study (PIRLS) 2011 in the United States and the nine participating benchmarking states:…

  6. Guided Interaction as Intercultural Learning: Designing Internationalisation into a Mixed Delivery Teacher Education Programme

    ERIC Educational Resources Information Center

    Spiro, Jane

    2011-01-01

    In this paper the process of building an international student community is explored. Strategies discussed include guided interaction within a virtual environment between home students studying in their own culture and international students studying at a distance. The context includes both the state and private sector in South East Asia, Latin…

  7. The International Cometary Explorer (ICE)wallsheet teacher's guide

    NASA Technical Reports Server (NTRS)

    Maran, S. P. (Editor)

    1985-01-01

    On September 11, 1985, the veteran NASA spacecraft ISEE-3 which has been renamed the International Cometary Explorer (ICE) will make the first visit of a spacecraft to a comet. A teachers' guide to the NASA wallsheet on the ICE and its mission is presented. This circumstance of course results from the current interest in the return of Halley's Comet. This teacher's guide will be helpful in understanding scientists strong interest in sending the ICE spacecraft to investigate the tail of a much less famous object Comet Giacobin-Zinner.

  8. The bench scientist's guide to RNA-Seq analysis

    USDA-ARS?s Scientific Manuscript database

    RNA sequencing (RNA-Seq) is emerging as a highly accurate method to quantify transcript abundance. However, analyses of the large data sets obtained by sequencing the entire transcriptome of organisms have generally been performed by bioinformatic specialists. Here we outline a methods strategy desi...

  9. Mycobacterium tuberculosis and whole genome sequencing: a practical guide and online tools available for the clinical microbiologist.

    PubMed

    Satta, G; Atzeni, A; McHugh, T D

    2017-02-01

    Whole genome sequencing (WGS) has the potential to revolutionize the diagnosis of Mycobacterium tuberculosis infection but the lack of bioinformatic expertise among clinical microbiologists is a barrier for adoption. Software products for analysis should be simple, free of charge, able to accept data directly from the sequencer (FASTQ files) and to provide the basic functionalities all-in-one. The main aim of this narrative review is to provide a practical guide for the clinical microbiologist, with little or no practical experience of WGS analysis, with a specific focus on software products tailor-made for M. tuberculosis analysis. With sequencing performed by an external provider, it is now feasible to implement WGS analysis in the routine clinical practice of any microbiology laboratory, with the potential to detect resistance weeks before traditional phenotypic culture methods, but the clinical microbiologist should be aware of the limitations of this approach. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Identification of the bacterial etiology of culture-negative endocarditis by amplification and sequencing of a small ribosomal RNA gene.

    PubMed

    Khulordava, Irakli; Miller, Geraldine; Haas, David; Li, Haijing; McKinsey, Joel; Vanderende, Daniel; Tang, Yi-Wei

    2003-05-01

    We report two cases of culture-negative bacterial endocarditis in which the organisms were identified by amplification and sequencing of the bacterial 16S rRNA gene. These results support an important role for polymerase chain reaction followed by direct sequencing to determine the etiology of culture-negative bacterial endocarditis and to guide appropriate antimicrobial therapy.

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

    PubMed

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

    2018-04-06

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

  12. AACR precision medicine series: Highlights of the integrating clinical genomics and cancer therapy meeting.

    PubMed

    Maggi, Elaine; Montagna, Cristina

    2015-12-01

    The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice. The plenary sessions and panel discussions covered current platforms and sequencing approaches adopted for NGS assays of cancer genome at several national and international institutions, different approaches used to map and classify targetable sequence variants, and how information acquired with the sequencing of the cancer genome is used to guide treatment options. While challenges still exist from a technological perspective, it emerged that there exists considerable need for the development of tools to aid the identification of the therapy most suitable based on the mutational profile of the somatic cancer genome. The process to match patients to ongoing clinical trials is still complex. In addition, the need for centralized data repositories, preferably linked to well annotated clinical records, that aid sharing of sequencing information is central to begin understanding the contribution of variants of unknown significance to tumor etiology and response to therapy. Here we summarize the highlights of this stimulating four-day conference with a major emphasis on the open problems that the clinical genomics community is currently facing and the tools most needed for advancing this field. Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  13. Simultaneous phylogeny reconstruction and multiple sequence alignment

    PubMed Central

    Yue, Feng; Shi, Jian; Tang, Jijun

    2009-01-01

    Background A phylogeny is the evolutionary history of a group of organisms. To date, sequence data is still the most used data type for phylogenetic reconstruction. Before any sequences can be used for phylogeny reconstruction, they must be aligned, and the quality of the multiple sequence alignment has been shown to affect the quality of the inferred phylogeny. At the same time, all the current multiple sequence alignment programs use a guide tree to produce the alignment and experiments showed that good guide trees can significantly improve the multiple alignment quality. Results We devise a new algorithm to simultaneously align multiple sequences and search for the phylogenetic tree that leads to the best alignment. We also implemented the algorithm as a C program package, which can handle both DNA and protein data and can take simple cost model as well as complex substitution matrices, such as PAM250 or BLOSUM62. The performance of the new method are compared with those from other popular multiple sequence alignment tools, including the widely used programs such as ClustalW and T-Coffee. Experimental results suggest that this method has good performance in terms of both phylogeny accuracy and alignment quality. Conclusion We present an algorithm to align multiple sequences and reconstruct the phylogenies that minimize the alignment score, which is based on an efficient algorithm to solve the median problems for three sequences. Our extensive experiments suggest that this method is very promising and can produce high quality phylogenies and alignments. PMID:19208110

  14. CRISPR: From Prokaryotic Immune Systems to Plant Genome Editing Tools.

    PubMed

    Bandyopadhyay, Anindya; Mazumdar, Shamik; Yin, Xiaojia; Quick, William Paul

    2017-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) system is a prokaryotic adaptive immune system that has the ability to identify specific locations on the bacteriophage (phage) genome to create breaks in it, and internalize the phage genome fragments in its own genome as CRISPR arrays for memory-dependent resistance. Although CRISPR has been used in the dairy industry for a long time, it recently gained importance in the field of genome editing because of its ability to precisely target locations in a genome. This system has further been modified to locate and target any region of a genome of choice due to modifications in the components of the system. By changing the nucleotide sequence of the 20-nucleotide target sequence in the guide RNA, targeting any location is possible. It has found an application in the modification of plant genomes with its ability to generate mutations and insertions, thus helping to create new varieties of plants. With the ability to introduce specific sequences into the plant genome after cleavage by the CRISPR system and subsequent DNA repair through homology-directed repair (HDR), CRISPR ensures that genome editing can be successfully applied in plants, thus generating stronger and more improved traits. Also, the use of the CRISPR editing system can generate plants that are transgene-free and have mutations that are stably inherited, thus helping to circumvent current GMO regulations.

  15. Directing folding pathways for multi-component DNA origami nanostructures with complex topology

    NASA Astrophysics Data System (ADS)

    Marras, A. E.; Zhou, L.; Kolliopoulos, V.; Su, H.-J.; Castro, C. E.

    2016-05-01

    Molecular self-assembly has become a well-established technique to design complex nanostructures and hierarchical mesoscale assemblies. The typical approach is to design binding complementarity into nucleotide or amino acid sequences to achieve the desired final geometry. However, with an increasing interest in dynamic nanodevices, the need to design structures with motion has necessitated the development of multi-component structures. While this has been achieved through hierarchical assembly of similar structural units, here we focus on the assembly of topologically complex structures, specifically with concentric components, where post-folding assembly is not feasible. We exploit the ability to direct folding pathways to program the sequence of assembly and present a novel approach of designing the strand topology of intermediate folding states to program the topology of the final structure, in this case a DNA origami slider structure that functions much like a piston-cylinder assembly in an engine. The ability to program the sequence and control orientation and topology of multi-component DNA origami nanostructures provides a foundation for a new class of structures with internal and external moving parts and complex scaffold topology. Furthermore, this work provides critical insight to guide the design of intermediate states along a DNA origami folding pathway and to further understand the details of DNA origami self-assembly to more broadly control folding states and landscapes.

  16. Long-axis view for ultrasound-guided central venous catheter placement via the internal jugular vein.

    PubMed

    Mahan, Angel F; McEvoy, Matthew D; Gravenstein, Nikolaus

    2016-04-01

    In modern practice, real-time ultrasound guidance is commonly employed for the placement of internal jugular vein catheters. With a new tool, such as ultrasound, comes the opportunity to refine and further optimize the ultrasound view during jugular vein catheterization. We describe jugular vein access techniques and use the long-axis view as an alternative to the commonly employed short-axis cross-section view for internal jugular vein access and cannulation. The long-axis ultrasound-guided internal jugular vein approach for internal jugular vein cannulation is a useful alternative technique that can provide better needle tip and guidewire visualization than the more traditional short-axis ultrasound view.

  17. An approach for identification of unknown viruses using sequencing-by-hybridization.

    PubMed

    Katoski, Sarah E; Meyer, Hermann; Ibrahim, Sofi

    2015-09-01

    Accurate identification of biological threat agents, especially RNA viruses, in clinical or environmental samples can be challenging because the concentration of viral genomic material in a given sample is usually low, viral genomic RNA is liable to degradation, and RNA viruses are extremely diverse. A two-tiered approach was used for initial identification, then full genomic characterization of 199 RNA viruses belonging to virus families Arenaviridae, Bunyaviridae, Filoviridae, Flaviviridae, and Togaviridae. A Sequencing-by-hybridization (SBH) microarray was used to tentatively identify a viral pathogen then, the identity is confirmed by guided next-generation sequencing (NGS). After optimization and evaluation of the SBH and NGS methodologies with various virus species and strains, the approach was used to test the ability to identify viruses in blinded samples. The SBH correctly identified two Ebola viruses in the blinded samples within 24 hr, and by using guided amplicon sequencing with 454 GS FLX, the identities of the viruses in both samples were confirmed. SBH provides at relatively low-cost screening of biological samples against a panel of viral pathogens that can be custom-designed on a microarray. Once the identity of virus is deduced from the highest hybridization signal on the SBH microarray, guided (amplicon) NGS sequencing can be used not only to confirm the identity of the virus but also to provide further information about the strain or isolate, including a potential genetic manipulation. This approach can be useful in situations where natural or deliberate biological threat incidents might occur and a rapid response is required. © 2015 Wiley Periodicals, Inc.

  18. A global view of structure–function relationships in the tautomerase superfamily

    PubMed Central

    Davidson, Rebecca; Baas, Bert-Jan; Akiva, Eyal; Holliday, Gemma L.; Polacco, Benjamin J.; LeVieux, Jake A.; Pullara, Collin R.; Zhang, Yan Jessie; Whitman, Christian P.

    2018-01-01

    The tautomerase superfamily (TSF) consists of more than 11,000 nonredundant sequences present throughout the biosphere. Characterized members have attracted much attention because of the unusual and key catalytic role of an N-terminal proline. These few characterized members catalyze a diverse range of chemical reactions, but the full scale of their chemical capabilities and biological functions remains unknown. To gain new insight into TSF structure–function relationships, we performed a global analysis of similarities across the entire superfamily and computed a sequence similarity network to guide classification into distinct subgroups. Our results indicate that TSF members are found in all domains of life, with most being present in bacteria. The eukaryotic members of the cis-3-chloroacrylic acid dehalogenase subgroup are limited to fungal species, whereas the macrophage migration inhibitory factor subgroup has wide eukaryotic representation (including mammals). Unexpectedly, we found that 346 TSF sequences lack Pro-1, of which 85% are present in the malonate semialdehyde decarboxylase subgroup. The computed network also enabled the identification of similarity paths, namely sequences that link functionally diverse subgroups and exhibit transitional structural features that may help explain reaction divergence. A structure-guided comparison of these linker proteins identified conserved transitions between them, and kinetic analysis paralleled these observations. Phylogenetic reconstruction of the linker set was consistent with these findings. Our results also suggest that contemporary TSF members may have evolved from a short 4-oxalocrotonate tautomerase–like ancestor followed by gene duplication and fusion. Our new linker-guided strategy can be used to enrich the discovery of sequence/structure/function transitions in other enzyme superfamilies. PMID:29184004

  19. 76 FR 19708 - Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels in Alaska

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    .... 110325225-1224-02] RIN 0648-BA96 Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels... regulations that apply to vessels operating in the guided sport (charter) fishery for halibut in International... charter vessels in the guided sport fishery, codified at 50 CFR 300.67. Charter Halibut Limited Access...

  20. RNA-Seq Atlas of Glycine max: a guide to the soybean transcriptome

    USDA-ARS?s Scientific Manuscript database

    A first analysis of the Glycine max (L.) Merr. (soybean) transcriptome using next generation sequencing technology and RNA-Sequencing (RNA-Seq) is presented. This analysis will provide an important resource for understanding transcription and gene co-regulatory networks in soybean, the most economic...

  1. Collaborative Guide: A Reef Manager's Guide to Coral Bleaching

    EPA Science Inventory

    Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental...

  2. Draft Genome Sequences of Several Fungal Strains Selected for Exposure to Microgravity at the International Space Station

    DOE PAGES

    Singh, Nitin K.; Blachowicz, Adriana; Romsdahl, Jillian; ...

    2017-04-13

    Presented here are the whole-genome sequences of eight fungal strains that were selected for exposure to microgravity at the International Space Station. These baseline sequences will help to understand the observed production of novel bioactive compounds.

  3. Draft Genome Sequences of Several Fungal Strains Selected for Exposure to Microgravity at the International Space Station

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

    Singh, Nitin K.; Blachowicz, Adriana; Romsdahl, Jillian

    Presented here are the whole-genome sequences of eight fungal strains that were selected for exposure to microgravity at the International Space Station. These baseline sequences will help to understand the observed production of novel bioactive compounds.

  4. Single-cell genomic sequencing using Multiple Displacement Amplification.

    PubMed

    Lasken, Roger S

    2007-10-01

    Single microbial cells can now be sequenced using DNA amplified by the Multiple Displacement Amplification (MDA) reaction. The few femtograms of DNA in a bacterium are amplified into micrograms of high molecular weight DNA suitable for DNA library construction and Sanger sequencing. The MDA-generated DNA also performs well when used directly as template for pyrosequencing by the 454 Life Sciences method. While MDA from single cells loses some of the genomic sequence, this approach will greatly accelerate the pace of sequencing from uncultured microbes. The genetically linked sequences from single cells are also a powerful tool to be used in guiding genomic assembly of shotgun sequences of multiple organisms from environmental DNA extracts (metagenomic sequences).

  5. How to Build an Export Business. An International Marketing Guide for the Minority-Owned Firm.

    ERIC Educational Resources Information Center

    Joyner, Nelson T., Jr.; Lurie, Richard G.

    Designed to aid minority firms who are inexperienced in the export market, this handbook provides a step-by-step guide to the development of an export business, describing what to do, how to do it, and where to find more information on specific international marketing help. Starting with the easiest opportunities that do not require any…

  6. Internal urethrotomy combined with antegrade flexible cystoscopy for management of obliterative urethral stricture.

    PubMed

    Hosseini, Seyed Jali; Kaviani, Ali; Vazirnia, Ali Reza

    2008-01-01

    We studied the safety and efficacy of flexible cystoscopy-guided internal urethrotomy in the management of obliterative urethral strictures. Forty-three flexible cystoscopy-guided internal urethrotomies were performed between 1999 and 2005. The indication for the procedure was nearly blinded bulbar or membranous urethral strictures not longer than 1 cm that would not allow passage of guide wire. Candidates were those who refused or were unable to undergo urtheroplasty. By monitoring any impression of the urethrotome on the monitor through the flexible cystoscope, we were able to do under-vision urethrotomy. All of the patients were started clean intermittent catheterization afterwards which was tapered over the following 6 months. Follow-up continued for 24 months after the last internal urethrotomy. Seventeen patients were younger than 65 years with a history of failed posterior urethroplasty, and 26 were older than 65 with poor cardiopulmonary conditions who had bulbar urethral stricture following straddle or iatrogenic injuries. Urethral stricture stabilized in 16 patients (37.2%) with a single session of urethrotomy and in 17 (39.5%) with 2 urethrotomies. Overall, urethral stricture stabilized in 76.7% of patients with 1 or 2 internal urethrotomies within 24 months of follow-up. No severe complication was reported. Flexible cystoscopy-guided internal urethrotomy is a simple, safe, and under-vision procedure in obliterative urethral strictures shorter than 1 cm. It can be an ideal option for patients who do not accept posterior urethroplasty or are in a poor cardiopulmonary condition that precludes general anesthesia.

  7. Diversity and Periodicity: An Inorganic Chemistry Module. Teacher's Guide.

    ERIC Educational Resources Information Center

    Huheey, James; Sandoval, Amado

    This teacher's guide is designed to provide science teachers with the necessary guidance and suggestions for teaching inorganic chemistry. The material in this book can be integrated with the other modules in a sequence that helps students to see that chemistry is a unified science. Contents include: (1) "Periodicity: A Chemical Calendar"; (2)…

  8. Communities of Molecules: A Physical Chemistry Module. Teacher's Guide.

    ERIC Educational Resources Information Center

    DeVoe, Howard; Hearle, Robert

    This teacher's guide is designed to provide science teachers with the necessary guidance and suggestions for teaching physical chemistry. The material in this book can be integrated with the other modules in a sequence that helps students see that chemistry is a unified science. Contents include: (1) "Introduction of Physical Chemistry"; (2) "The…

  9. Farm Crops: Unit Manual Eleven. Curriculum Guide.

    ERIC Educational Resources Information Center

    Lewis, Ann; And Others

    This is number 11 in a series of resource manuals consisting of 11 sequenced curriculum guides developed by the Demonstration and Research Center for Early Education (DARCEE) for use in early childhood education programs. Emphasis is placed on the development of sensory, abstracting and mediating, and response skills. The projected order of the…

  10. Business Economics: Task Analyses. Competency-Based Education.

    ERIC Educational Resources Information Center

    Henrico County Public Schools, Glen Allen, VA. Virginia Vocational Curriculum Center.

    This task analyses guide is designed to be used in combination with the "Business Education Service Area Resource" in order to implement competency-based education in the Business Economics course in Virginia. The task analyses guide contains the task inventory, suggested task sequence list, and content outline for the specific course in business…

  11. Resources for Teaching HERO: Food Service Occupations in Montana.

    ERIC Educational Resources Information Center

    Parsons, Angelina O.; Harris, Pamela R.

    This resource guide is designed to help home economics teachers in Montana to develop occupational programs for food service. It provides resources that can be used with the "Food Service Occupations in Montana: Scope and Sequence in Wage-Earning Home Economics." The guide contains 13 sections. The first section explains the core…

  12. Air University Suggested Professional Reading Guide.

    ERIC Educational Resources Information Center

    Air Univ., Maxwell AFB, AL.

    One of six related documents intended for the Air Force officer, the enlisted man, or the civilian, this reading guide contains an annotated list of 26 publications that support Project Warrior and provide information about military history and the Air Force heritage. The books are listed in sequence according to a reading ease index, which…

  13. Health Education Guide: A Design for Teaching K-12.

    ERIC Educational Resources Information Center

    Barrett, Morris

    This teaching guide to health education includes instruction units for grades K-12. Section 1 discusses the need for health education and includes a scope and sequence chart for each of the instruction units. Section 2 consists of instruction units in the areas of physical development, social and emotional development, chemicals and addiction, and…

  14. Consumer Education: A Senior High Elective Course.

    ERIC Educational Resources Information Center

    Grout, Marjorie; Rozell, Anthony

    The overall objective of this elective senior course and guide is to lead the non-college-bound student toward the maturity of consumer judgement necessary in the complex economic marketplace of today. The scope and sequence section of this guide lists the eight units and includes basic objectives, and conceptual understandings for each: 1)…

  15. Using Cinematic Techniques in a Multimedia Museum Guide.

    ERIC Educational Resources Information Center

    Zancanaro, M.; Stock, O.; Alfaro, I.

    This paper introduces the idea of enhancing the audio presentation of a multimedia museum guide by using the PDA screen to travel throughout a fresco and identify the various details in it. During the presentation, a sequence of pictures is synchronized with the audio commentary, and the transitions among the pictures are planned according to…

  16. Social Studies Program Guide, 9-12: The Senior High School.

    ERIC Educational Resources Information Center

    Spokane School District 81, WA.

    This is the last of four guides which identify the scope, sequence, goals, and resources for the social studies program of the Spokane public schools. It suggests materials, resources, and activities related to social studies knowledge and skill development for grades 9 through 12. Lessons on all social science disciplines are outlined with…

  17. High School Industrial Arts. A Guide for Teachers.

    ERIC Educational Resources Information Center

    Oregon State Dept. of Education, Salem.

    This teacher's guide is designed to help high school industrial arts teachers plan activities to develop their students' awareness of technology in our culture and the variety of related careers available to them. Discussed first are the objectives, scope, and sequence of industrial arts. Next, the special characteristics and needs of adolescents,…

  18. A Planning Guide for Gifted Preschoolers.

    ERIC Educational Resources Information Center

    Malley-Crist, Justine; And Others

    Contained in the curriculum planning guide developed by the Chapel Hill Gifted-Handicapped Project are a model, a training sequence, and 17 instructional units for use with preschool gifted children. The model is explained to be based on the hierarchy of cognitive tasks developed by B. Bloom. A worksheet for teachers suggests activities to help…

  19. Western Civilization Curriculum Guide. Bulletin 1759.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Education, Baton Rouge. Div. of Academic Programs.

    Developed to stress the importance of the study of Western civilization, this Louisiana State high school curriculum guide contains social studies goals, program scopes and sequences, a list of 14 generalizations and related concepts, and a master course content outline. Ten study units teach about: (1) the ancient world; (2) the Middle Ages; (3)…

  20. Using Literature-Based Prompts To Teach Writing Competencies: Directed Reading and Writing Lessons.

    ERIC Educational Resources Information Center

    Gelsinger, Barry D.

    Intended to help teachers integrate writing instruction with the study of literature, this teaching guide offers a philosophy of writing instruction, describes a procedure for teaching reading and writing lessons, and provides a sequence of writing skills. For various literature selections, the guide defines vocabulary, provides topic discussion…

  1. World History Curriculum Guide: Secondary Social Studies. Bulletin 1758.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Education, Baton Rouge. Div. of Academic Programs.

    This state curriculum guide was developed to reaffirm the importance of world history in the Louisiana social studies curriculum. It contains statements of the Louisiana social studies goals, program scopes and sequences, a list of 14 generalizations and related concepts, and a master course content outline. Seven study units are presented that…

  2. Creativity: A Saleable Work Skill. Occupation Simulation Packet. Grades 3rd-4th.

    ERIC Educational Resources Information Center

    Dye, Dick

    This teacher's guide for grades 3 and 4 contains simulated work experiences for students using the isolated skill concept - creativity. Teacher instructions include objectives, evaluation, and sequence of activities. The guide contains pre-tests and post-tests with instructions and answer keys. Two pre-skill activities are suggested, such as…

  3. Protospacer Adjacent Motif (PAM)-Distal Sequences Engage CRISPR Cas9 DNA Target Cleavage

    PubMed Central

    Ethier, Sylvain; Schmeing, T. Martin; Dostie, Josée; Pelletier, Jerry

    2014-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)-associated enzyme Cas9 is an RNA-guided nuclease that has been widely adapted for genome editing in eukaryotic cells. However, the in vivo target specificity of Cas9 is poorly understood and most studies rely on in silico predictions to define the potential off-target editing spectrum. Using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we delineate the genome-wide binding panorama of catalytically inactive Cas9 directed by two different single guide (sg) RNAs targeting the Trp53 locus. Cas9:sgRNA complexes are able to load onto multiple sites with short seed regions adjacent to 5′NGG3′ protospacer adjacent motifs (PAM). Yet among 43 ChIP-seq sites harboring seed regions analyzed for mutational status, we find editing only at the intended on-target locus and one off-target site. In vitro analysis of target site recognition revealed that interactions between the 5′ end of the guide and PAM-distal target sequences are necessary to efficiently engage Cas9 nucleolytic activity, providing an explanation for why off-target editing is significantly lower than expected from ChIP-seq data. PMID:25275497

  4. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9.

    PubMed

    Sternberg, Samuel H; Redding, Sy; Jinek, Martin; Greene, Eric C; Doudna, Jennifer A

    2014-03-06

    The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.

  5. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9

    NASA Astrophysics Data System (ADS)

    Sternberg, Samuel H.; Redding, Sy; Jinek, Martin; Greene, Eric C.; Doudna, Jennifer A.

    2014-03-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.

  6. Draft Genome Sequences of Several Fungal Strains Selected for Exposure to Microgravity at the International Space Station

    PubMed Central

    Singh, Nitin K.; Blachowicz, Adriana; Romsdahl, Jillian; Wang, Clay; Torok, Tamas

    2017-01-01

    ABSTRACT The whole-genome sequences of eight fungal strains that were selected for exposure to microgravity at the International Space Station are presented here. These baseline sequences will help to understand the observed production of novel bioactive compounds. PMID:28408692

  7. 76 FR 34890 - Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels in Alaska

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    .... 110601314-1313-01] RIN 0648-BA99 Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels... to vessels operating in the guided sport (charter) fishery for halibut in International Pacific... charter vessels in the [[Page 34891

  8. The siRNA Non-seed Region and Its Target Sequences Are Auxiliary Determinants of Off-Target Effects.

    PubMed

    Kamola, Piotr J; Nakano, Yuko; Takahashi, Tomoko; Wilson, Paul A; Ui-Tei, Kumiko

    2015-12-01

    RNA interference (RNAi) is a powerful tool for post-transcriptional gene silencing. However, the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by a mechanism closely mirroring micro RNA (miRNA) silencing. To better understand these off-target effects, we investigated the correlation between sequence features within various subsections of siRNA guide strands, and its corresponding target sequences, with off-target activities. Our results confirm previous reports that strength of base-pairing in the siRNA seed region is the primary factor determining the efficiency of off-target silencing. However, the degree of downregulation of off-target transcripts with shared seed sequence is not necessarily similar, suggesting that there are additional auxiliary factors that influence the silencing potential. Here, we demonstrate that both the melting temperature (Tm) in a subsection of siRNA non-seed region, and the GC contents of its corresponding target sequences, are negatively correlated with the efficiency of off-target effect. Analysis of experimentally validated miRNA targets demonstrated a similar trend, indicating a putative conserved mechanistic feature of seed region-dependent targeting mechanism. These observations may prove useful as parameters for off-target prediction algorithms and improve siRNA 'specificity' design rules.

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

    USGS Publications Warehouse

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

    2016-01-01

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

  10. Are We Covering Our Own Backyards?: An Analysis of Local Research Guides Created by Academic Business Librarians

    ERIC Educational Resources Information Center

    Lyons, Charles

    2009-01-01

    This study examines local research guides created by academic business librarians to assist patrons with researching the communities (towns, cities, and regions) where their schools are located. A key finding is that only 33% of the libraries surveyed provide guides to local research, while 80% provide guides to international research. (Contains 2…

  11. On learning navigation behaviors for small mobile robots with reservoir computing architectures.

    PubMed

    Antonelo, Eric Aislan; Schrauwen, Benjamin

    2015-04-01

    This paper proposes a general reservoir computing (RC) learning framework that can be used to learn navigation behaviors for mobile robots in simple and complex unknown partially observable environments. RC provides an efficient way to train recurrent neural networks by letting the recurrent part of the network (called reservoir) be fixed while only a linear readout output layer is trained. The proposed RC framework builds upon the notion of navigation attractor or behavior that can be embedded in the high-dimensional space of the reservoir after learning. The learning of multiple behaviors is possible because the dynamic robot behavior, consisting of a sensory-motor sequence, can be linearly discriminated in the high-dimensional nonlinear space of the dynamic reservoir. Three learning approaches for navigation behaviors are shown in this paper. The first approach learns multiple behaviors based on the examples of navigation behaviors generated by a supervisor, while the second approach learns goal-directed navigation behaviors based only on rewards. The third approach learns complex goal-directed behaviors, in a supervised way, using a hierarchical architecture whose internal predictions of contextual switches guide the sequence of basic navigation behaviors toward the goal.

  12. Consistent global structures of complex RNA states through multidimensional chemical mapping

    PubMed Central

    Cheng, Clarence Yu; Chou, Fang-Chieh; Kladwang, Wipapat; Tian, Siqi; Cordero, Pablo; Das, Rhiju

    2015-01-01

    Accelerating discoveries of non-coding RNA (ncRNA) in myriad biological processes pose major challenges to structural and functional analysis. Despite progress in secondary structure modeling, high-throughput methods have generally failed to determine ncRNA tertiary structures, even at the 1-nm resolution that enables visualization of how helices and functional motifs are positioned in three dimensions. We report that integrating a new method called MOHCA-seq (Multiplexed •OH Cleavage Analysis with paired-end sequencing) with mutate-and-map secondary structure inference guides Rosetta 3D modeling to consistent 1-nm accuracy for intricately folded ncRNAs with lengths up to 188 nucleotides, including a blind RNA-puzzle challenge, the lariat-capping ribozyme. This multidimensional chemical mapping (MCM) pipeline resolves unexpected tertiary proximities for cyclic-di-GMP, glycine, and adenosylcobalamin riboswitch aptamers without their ligands and a loose structure for the recently discovered human HoxA9D internal ribosome entry site regulon. MCM offers a sequencing-based route to uncovering ncRNA 3D structure, applicable to functionally important but potentially heterogeneous states. DOI: http://dx.doi.org/10.7554/eLife.07600.001 PMID:26035425

  13. Relationship between relaxation by guided imagery and performance of working memory.

    PubMed

    Hudetz, J A; Hudetz, A G; Klayman, J

    2000-02-01

    This study tested the hypothesis that relaxation by guided imagery improves working-memory performance of healthy participants. 30 volunteers (both sexes, ages 17-56 years) were randomly assigned to one of three groups and administered the WAIS-III Letter-Number Sequencing Test before and after 10-min. treatment with guided imagery or popular music. The control group received no treatment. Groups' test scores were not different before treatment. The mean increased after relaxation by guided imagery but not after music or no treatment. This result supports the hypothesis that working-memory scores on the test are enhanced by guided imagery and implies that human information processing may be enhanced by prior relaxation.

  14. 27nt-RNAs guide histone variant deposition via 'RNA-induced DNA replication interference' and thus transmit parental genome partitioning in Stylonychia.

    PubMed

    Postberg, Jan; Jönsson, Franziska; Weil, Patrick Philipp; Bulic, Aneta; Juranek, Stefan Andreas; Lipps, Hans-Joachim

    2018-06-12

    During sexual reproduction in the unicellular ciliate Stylonychia somatic macronuclei differentiate from germline micronuclei. Thereby, programmed sequence reduction takes place, leading to the elimination of > 95% of germline sequences, which priorly adopt heterochromatin structure via H3K27me3. Simultaneously, 27nt-ncRNAs become synthesized from parental transcripts and are bound by the Argonaute protein PIWI1. These 27nt-ncRNAs cover sequences destined to the developing macronucleus and are thought to protect them from degradation. We provide evidence and propose that RNA/DNA base-pairing guides PIWI1/27nt-RNA complexes to complementary macronucleus-destined DNA target sequences, hence transiently causing locally stalled replication during polytene chromosome formation. This spatiotemporal delay enables the selective deposition of temporarily available histone H3.4K27me3 nucleosomes at all other sequences being continuously replicated, thus dictating their prospective heterochromatin structure before becoming developmentally eliminated. Concomitantly, 27nt-RNA-covered sites remain protected. We introduce the concept of 'RNA-induced DNA replication interference' and explain how the parental functional genome partition could become transmitted to the progeny.

  15. Internal Medicine Point-of-Care Ultrasound Curriculum: Consensus Recommendations from the Canadian Internal Medicine Ultrasound (CIMUS) Group.

    PubMed

    Ma, Irene W Y; Arishenkoff, Shane; Wiseman, Jeffrey; Desy, Janeve; Ailon, Jonathan; Martin, Leslie; Otremba, Mirek; Halman, Samantha; Willemot, Patrick; Blouw, Marcus

    2017-09-01

    Bedside point-of-care ultrasound (POCUS) is increasingly used to assess medical patients. At present, no consensus exists for what POCUS curriculum is appropriate for internal medicine residency training programs. This document details the consensus-based recommendations by the Canadian Internal Medicine Ultrasound (CIMUS) group, comprising 39 members, representing 14 institutions across Canada. Guiding principles for selecting curricular content were determined a priori. Consensus was defined as agreement by at least 80% of the members on POCUS applications deemed appropriate for teaching and assessment of trainees in the core (internal medicine postgraduate years [PGY] 1-3) and expanded (general internal medicine PGY 4-5) training programs. We recommend four POCUS applications for the core PGY 1-3 curriculum (inferior vena cava, lung B lines, pleural effusion, and abdominal free fluid) and three ultrasound-guided procedures (central venous catheterization, thoracentesis, and paracentesis). For the expanded PGY 4-5 curriculum, we recommend an additional seven applications (internal jugular vein, lung consolidation, pneumothorax, knee effusion, gross left ventricular systolic function, pericardial effusion, and right ventricular strain) and four ultrasound-guided procedures (knee arthrocentesis, arterial line insertion, arterial blood gas sampling, and peripheral venous catheterization). These recommendations will provide a framework for training programs at a national level.

  16. Model Training Guide. Firefighter I.

    ERIC Educational Resources Information Center

    Hagevig, William A.; Gallagher, Leigh S.

    This firefighter training guide for a 180-hour course was developed to assist training officers in planning training with emphasis on conformance to recommended National Fire Protection Association (NFPA 1001) standards. The material in the guide is referenced to current editions of the International Fire Service Training Association manuals and…

  17. 75 FR 22674 - U.S. Department of State Advisory Committee on Private International Law Study Group Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Intellectual Property (IP) The Department of State, Office of the Legal Adviser, Private International Law and... rights in intellectual property, as well as possible future work in UNCITRAL on an IP licensing guide.../689), as well as the draft text of the IP supplement to the Guide (A/CN.9/700 and Add. 1-7) that will...

  18. Protein Information Resource: a community resource for expert annotation of protein data

    PubMed Central

    Barker, Winona C.; Garavelli, John S.; Hou, Zhenglin; Huang, Hongzhan; Ledley, Robert S.; McGarvey, Peter B.; Mewes, Hans-Werner; Orcutt, Bruce C.; Pfeiffer, Friedhelm; Tsugita, Akira; Vinayaka, C. R.; Xiao, Chunlin; Yeh, Lai-Su L.; Wu, Cathy

    2001-01-01

    The Protein Information Resource, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the most comprehensive and expertly annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database. To provide timely and high quality annotation and promote database interoperability, the PIR-International employs rule-based and classification-driven procedures based on controlled vocabulary and standard nomenclature and includes status tags to distinguish experimentally determined from predicted protein features. The database contains about 200 000 non-redundant protein sequences, which are classified into families and superfamilies and their domains and motifs identified. Entries are extensively cross-referenced to other sequence, classification, genome, structure and activity databases. The PIR web site features search engines that use sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. The PIR-Inter­national databases and search tools are accessible on the PIR web site at http://pir.georgetown.edu/ and at the MIPS web site at http://www.mips.biochem.mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP. PMID:11125041

  19. Argonaute-based programmable RNase as a tool for cleavage of highly-structured RNA.

    PubMed

    Dayeh, Daniel M; Cantara, William A; Kitzrow, Jonathan P; Musier-Forsyth, Karin; Nakanishi, Kotaro

    2018-06-12

    The recent identification and development of RNA-guided enzymes for programmable cleavage of target nucleic acids offers exciting possibilities for both therapeutic and biotechnological applications. However, critical challenges such as expensive guide RNAs and inability to predict the efficiency of target recognition, especially for highly-structured RNAs, remain to be addressed. Here, we introduce a programmable RNA restriction enzyme, based on a budding yeast Argonaute (AGO), programmed with cost-effective 23-nucleotide (nt) single-stranded DNAs as guides. DNA guides offer the advantage that diverse sequences can be easily designed and purchased, enabling high-throughput screening to identify optimal recognition sites in the target RNA. Using this DNA-induced slicing complex (DISC) programmed with 11 different guide DNAs designed to span the sequence, sites of cleavage were identified in the 352-nt human immunodeficiency virus type 1 5'-untranslated region. This assay, coupled with primer extension and capillary electrophoresis, allows detection and relative quantification of all DISC-cleavage sites simultaneously in a single reaction. Comparison between DISC cleavage and RNase H cleavage reveals that DISC not only cleaves solvent-exposed sites, but also sites that become more accessible upon DISC binding. This study demonstrates the advantages of the DISC system for programmable cleavage of highly-structured, functional RNAs.

  20. Sequential addition of short DNA oligos in DNA-polymerase-based synthesis reactions

    DOEpatents

    Gardner, Shea N; Mariella, Jr., Raymond P; Christian, Allen T; Young, Jennifer A; Clague, David S

    2013-06-25

    A method of preselecting a multiplicity of DNA sequence segments that will comprise the DNA molecule of user-defined sequence, separating the DNA sequence segments temporally, and combining the multiplicity of DNA sequence segments with at least one polymerase enzyme wherein the multiplicity of DNA sequence segments join to produce the DNA molecule of user-defined sequence. Sequence segments may be of length n, where n is an odd integer. In one embodiment the length of desired hybridizing overlap is specified by the user and the sequences and the protocol for combining them are guided by computational (bioinformatics) predictions. In one embodiment sequence segments are combined from multiple reading frames to span the same region of a sequence, so that multiple desired hybridizations may occur with different overlap lengths.

  1. Draft Genome Sequences of Several Fungal Strains Selected for Exposure to Microgravity at the International Space Station.

    PubMed

    Singh, Nitin K; Blachowicz, Adriana; Romsdahl, Jillian; Wang, Clay; Torok, Tamas; Venkateswaran, Kasthuri

    2017-04-13

    The whole-genome sequences of eight fungal strains that were selected for exposure to microgravity at the International Space Station are presented here. These baseline sequences will help to understand the observed production of novel bioactive compounds. Copyright © 2017 Singh et al.

  2. Regulatory Facility Guide for Tennessee

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

    Anderson, S.S.; Bock, R.E.; Francis, M.W.

    1994-02-28

    This guide provides detailed compilations of international, federal, and state transportation related regulations applicable to shipments originating at or destined to Tennessee facilities. Information on preferred routes is also given.

  3. Introduction to Engineering. Course I: Challenges of Engineering. Course II: Engineering Projects.

    ERIC Educational Resources Information Center

    Barrier, Lynn P.

    This guide, which is designed to be used in a two-course sequence, is intended to prepare college-bound high school juniors and seniors for engineering and related courses at the college level. The guide was developed as part of an experimental competency-based curriculum that integrates the high-tech applications of mathematics and science…

  4. The Heart of Matter: A Nuclear Chemistry Module. Teacher's Guide.

    ERIC Educational Resources Information Center

    Viola, Vic; Hearle, Robert

    This teacher's guide is designed to provide science teachers with the necessary guidance and suggestions for teaching nuclear chemistry. In this book, the fundamental concepts of nuclear science and the applications of nuclear energy are discussed. The material in this book can be integrated with the other modules in a sequence that helps students…

  5. Conservation for Children [Levels 1-6 and an All-Levels Supplement].

    ERIC Educational Resources Information Center

    Cupertino Union School District, CA.

    Developed to promote conservation awareness in elementary students, each of the six grade-level-sequenced activity guides provides: (1) a list of conservation concepts; (2) a criterion-referenced test; (3) a class record sheet; (4) a content guide; and (5) 90 student worksheets (40 for language arts, 20 for mathematics, 20 for social studies and…

  6. Elementary Art Constructions: A Supplement to the Elementary Art Guide 1968.

    ERIC Educational Resources Information Center

    Lundman, Donald; And Others

    GRADES OR AGES: K-6. SUBJECT MATTER: Elementary Art--Constructions. ORGANIZATION AND PHYSICAL APPEARANCE: After a brief introduction and a scope and sequence chart, the guide is divided into seven sections, one for each grade covered, and these sections contain details for between three and nine projects, including the making of cheese boards,…

  7. Crawling and/or Squatting: A Saleable Work Skill. Occupation Simulation Packet. Grades K-2nd.

    ERIC Educational Resources Information Center

    Montgomery, Margery

    This teacher's guide for grades K-2 contains simulated work experiences for students using the isolated skill concept, crawling and/or squatting. Teacher instructions include objectives, evaluation, and sequence of activities. The guide contains pre-tests and post-tests with instructions and answer keys. Three pre-skill activities are suggested,…

  8. Health Education Resource Guide, Grades 1-3.

    ERIC Educational Resources Information Center

    Federal Way School District 210, WA.

    As part of a health education program for K-12, these curriculum guides for grades one, two and three provide: (1) a short overview of health education; (2) a scope and sequence chart which lists specific topics to teach on mental health, physical health, community health, and safety that are appropriate at different grade levels; (3) a list of…

  9. Grain, Feed, Seed, and Farm Supply Technology. A Suggested 2-Year Post High School Curriculum.

    ERIC Educational Resources Information Center

    Office of Education (DHEW), Washington, DC.

    The increasing need for skilled agricultural technicians for the grain, feed, seed, and farm supply industry resulted in preparation of this suggested curriculum guide to aid in planning, developing, and evaluating post-high school programs. The guide includes: (1) suggested course outlines with examples of texts and references, (2) sequence of…

  10. Elementary Science Curriculum, Grade 5.

    ERIC Educational Resources Information Center

    Stoneham Public Schools, MA.

    This is one of a set of curriculum guides for the Stoneham Elementary School Science Program (see SE 012 153 - SE 012 158). Each guide contains a chart illustrating the scope and sequence of the physical, life, and earth sciences introduced at each grade level. For each of the topics introduced at this grade level an overview of the topic, a list…

  11. Classroom Archaeology: An Archaeology Activity Guide for Teachers. Third Edition.

    ERIC Educational Resources Information Center

    Hawkins, Nancy W.

    This guide describes archaeology activities appropriate for middle school students, but some activities can be used in intermediate and primary grades or high school and college classes. The activities range in length from less than one hour to 15 hours. A sequence of activities may be used together as a unit on archaeology, or individual…

  12. Access: A Guide to Finding Community Services. Project STEPS (Sequenced Transition to Education in the Public Schools).

    ERIC Educational Resources Information Center

    Byrd, Rita, Comp.; And Others

    This guide is intended to help Kentucky families of children with disabilities or other special needs to find services in their communities. Introductory information offers guidance in selecting services, applying for services, obtaining services, and organizing to obtain unavailable services. A question-and-answer format is used, with space…

  13. Elementary Science Curriculum, Grade 6.

    ERIC Educational Resources Information Center

    Stoneham Public Schools, MA.

    This is one of a set of curriculum guides for the Stoneham Elementary School Science Program (see SE 012 153 - SE 012 158). Each guide contains a chart illustrating the scope and sequence of the physical, life, and earth sciences introduced at each grade level. For each of the topics introduced at this grade level an overview of the topic, a list…

  14. Health Education Resource Guide, Junior High.

    ERIC Educational Resources Information Center

    Federal Way School District 210, WA.

    As part of a health education program for K-12, this curriculum guide for grade eight provides: (1) a short overview of health education; (2) a scope and sequence chart which lists specific topics to teach on mental health, physical health, community health, and safety that are appropriate at different grade levels; (3) a list of objectives; and…

  15. Oral Persuasion: A Saleable Work Skill. Occupation Simulation Packet. Grades 5th-6th.

    ERIC Educational Resources Information Center

    Lee, Dennis W.

    This teacher's guide contains simulated work experiences for 5th and 6th grade students using the isolated skill concept - oral persuasion. Teacher instructions include objectives, evaluation, and sequence of activities. The guide contains pre-tests and post-tests with instructions and answer keys. Two pre-skill activities are suggested, such as…

  16. Form and Function: An Organic Chemistry Module. Teacher's Guide.

    ERIC Educational Resources Information Center

    Jarvis, Bruce; Mazzocchi, Paul; Hearle, Robert

    This teacher's guide is designed to provide science teachers with the necessary guidance and suggestions for teaching organic chemistry. In this book, the diverse field of organic chemistry modules is introduced. The material in this book can be integrated with the other modules in a sequence that helps students to see that chemistry is a unified…

  17. Confronting Global Issues: A Multipurpose IR Simulation

    ERIC Educational Resources Information Center

    Shellman, Stephen M.; Turan, Kursad

    2006-01-01

    This article describes an international relations simulation that focuses on threats of transnational insurgent organizations, the future of the Iraqi regime, and the effect of globalization on foreign policies. It contains both the Simulation Director's Guide and the Participant's Guide. The guides explain the steps taken to run the simulation…

  18. Transpersonal Psychology: Guiding Image for the Advancement of International Adult Education.

    ERIC Educational Resources Information Center

    Boucouvalas, Marcie

    1984-01-01

    The importance of guiding images is examined, along with analyses of the images of humankind and worldviews previously offered by psychology and adopted by society-at-large. The article focuses on the contribution of transpersonal psychology, the discipline's fourth force, which integrates and extends prior guiding images. (CT)

  19. Vertical decomposition with Genetic Algorithm for Multiple Sequence Alignment

    PubMed Central

    2011-01-01

    Background Many Bioinformatics studies begin with a multiple sequence alignment as the foundation for their research. This is because multiple sequence alignment can be a useful technique for studying molecular evolution and analyzing sequence structure relationships. Results In this paper, we have proposed a Vertical Decomposition with Genetic Algorithm (VDGA) for Multiple Sequence Alignment (MSA). In VDGA, we divide the sequences vertically into two or more subsequences, and then solve them individually using a guide tree approach. Finally, we combine all the subsequences to generate a new multiple sequence alignment. This technique is applied on the solutions of the initial generation and of each child generation within VDGA. We have used two mechanisms to generate an initial population in this research: the first mechanism is to generate guide trees with randomly selected sequences and the second is shuffling the sequences inside such trees. Two different genetic operators have been implemented with VDGA. To test the performance of our algorithm, we have compared it with existing well-known methods, namely PRRP, CLUSTALX, DIALIGN, HMMT, SB_PIMA, ML_PIMA, MULTALIGN, and PILEUP8, and also other methods, based on Genetic Algorithms (GA), such as SAGA, MSA-GA and RBT-GA, by solving a number of benchmark datasets from BAliBase 2.0. Conclusions The experimental results showed that the VDGA with three vertical divisions was the most successful variant for most of the test cases in comparison to other divisions considered with VDGA. The experimental results also confirmed that VDGA outperformed the other methods considered in this research. PMID:21867510

  20. A Graph-Centric Approach for Metagenome-Guided Peptide and Protein Identification in Metaproteomics

    PubMed Central

    Tang, Haixu; Li, Sujun; Ye, Yuzhen

    2016-01-01

    Metaproteomic studies adopt the common bottom-up proteomics approach to investigate the protein composition and the dynamics of protein expression in microbial communities. When matched metagenomic and/or metatranscriptomic data of the microbial communities are available, metaproteomic data analyses often employ a metagenome-guided approach, in which complete or fragmental protein-coding genes are first directly predicted from metagenomic (and/or metatranscriptomic) sequences or from their assemblies, and the resulting protein sequences are then used as the reference database for peptide/protein identification from MS/MS spectra. This approach is often limited because protein coding genes predicted from metagenomes are incomplete and fragmental. In this paper, we present a graph-centric approach to improving metagenome-guided peptide and protein identification in metaproteomics. Our method exploits the de Bruijn graph structure reported by metagenome assembly algorithms to generate a comprehensive database of protein sequences encoded in the community. We tested our method using several public metaproteomic datasets with matched metagenomic and metatranscriptomic sequencing data acquired from complex microbial communities in a biological wastewater treatment plant. The results showed that many more peptides and proteins can be identified when assembly graphs were utilized, improving the characterization of the proteins expressed in the microbial communities. The additional proteins we identified contribute to the characterization of important pathways such as those involved in degradation of chemical hazards. Our tools are released as open-source software on github at https://github.com/COL-IU/Graph2Pro. PMID:27918579

  1. Avoidance of truncated proteins from unintended ribosome binding sites within heterologous protein coding sequences.

    PubMed

    Whitaker, Weston R; Lee, Hanson; Arkin, Adam P; Dueber, John E

    2015-03-20

    Genetic sequences ported into non-native hosts for synthetic biology applications can gain unexpected properties. In this study, we explored sequences functioning as ribosome binding sites (RBSs) within protein coding DNA sequences (CDSs) that cause internal translation, resulting in truncated proteins. Genome-wide prediction of bacterial RBSs, based on biophysical calculations employed by the RBS calculator, suggests a selection against internal RBSs within CDSs in Escherichia coli, but not those in Saccharomyces cerevisiae. Based on these calculations, silent mutations aimed at removing internal RBSs can effectively reduce truncation products from internal translation. However, a solution for complete elimination of internal translation initiation is not always feasible due to constraints of available coding sequences. Fluorescence assays and Western blot analysis showed that in genes with internal RBSs, increasing the strength of the intended upstream RBS had little influence on the internal translation strength. Another strategy to minimize truncated products from an internal RBS is to increase the relative strength of the upstream RBS with a concomitant reduction in promoter strength to achieve the same protein expression level. Unfortunately, lower transcription levels result in increased noise at the single cell level due to stochasticity in gene expression. At the low expression regimes desired for many synthetic biology applications, this problem becomes particularly pronounced. We found that balancing promoter strengths and upstream RBS strengths to intermediate levels can achieve the target protein concentration while avoiding both excessive noise and truncated protein.

  2. Tidying Up International Nucleotide Sequence Databases: Ecological, Geographical and Sequence Quality Annotation of ITS Sequences of Mycorrhizal Fungi

    PubMed Central

    Tedersoo, Leho; Abarenkov, Kessy; Nilsson, R. Henrik; Schüssler, Arthur; Grelet, Gwen-Aëlle; Kohout, Petr; Oja, Jane; Bonito, Gregory M.; Veldre, Vilmar; Jairus, Teele; Ryberg, Martin; Larsson, Karl-Henrik; Kõljalg, Urmas

    2011-01-01

    Sequence analysis of the ribosomal RNA operon, particularly the internal transcribed spacer (ITS) region, provides a powerful tool for identification of mycorrhizal fungi. The sequence data deposited in the International Nucleotide Sequence Databases (INSD) are, however, unfiltered for quality and are often poorly annotated with metadata. To detect chimeric and low-quality sequences and assign the ectomycorrhizal fungi to phylogenetic lineages, fungal ITS sequences were downloaded from INSD, aligned within family-level groups, and examined through phylogenetic analyses and BLAST searches. By combining the fungal sequence database UNITE and the annotation and search tool PlutoF, we also added metadata from the literature to these accessions. Altogether 35,632 sequences belonged to mycorrhizal fungi or originated from ericoid and orchid mycorrhizal roots. Of these sequences, 677 were considered chimeric and 2,174 of low read quality. Information detailing country of collection, geographical coordinates, interacting taxon and isolation source were supplemented to cover 78.0%, 33.0%, 41.7% and 96.4% of the sequences, respectively. These annotated sequences are publicly available via UNITE (http://unite.ut.ee/) for downstream biogeographic, ecological and taxonomic analyses. In European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena/), the annotated sequences have a special link-out to UNITE. We intend to expand the data annotation to additional genes and all taxonomic groups and functional guilds of fungi. PMID:21949797

  3. Quality of Widely Available Video Instructional Materials for Point-of-Care Ultrasound-Guided Procedure Training in Internal Medicine.

    PubMed

    Khandelwal, Aditi; Devine, Luke A; Otremba, Mirek

    2017-07-01

    Many instructional materials for point-of-care ultrasound (US)-guided procedures exist; however, their quality is unknown. This study assessed widely available educational videos for point-of-care US-guided procedures relevant to internal medicine: central venous catheterization, thoracentesis, and paracentesis. We searched Ovid MEDLINE, YouTube, and Google to identify videos for point-of-care US-guided paracentesis, thoracentesis, and central venous catheterization. Videos were evaluated with a 5-point scale assessing the global educational value and a checklist based on consensus guidelines for competencies in point-of-care US-guided procedures. For point-of-care US-guided central venous catheterization, 12 videos were found, with an average global educational value score ± SD of 4.5 ± 0.7. Indications to abort the procedure were discussed in only 3 videos. Five videos described the indications and contraindications for performing central venous catheterization. For point-of-care US-guided thoracentesis, 8 videos were identified, with an average global educational value score of 4.0 ± 0.9. Only one video discussed indications to abort the procedure, and 3 videos discussed sterile technique. For point-of-care US-guided paracentesis, 7 videos were included, with an average global educational value score of 4.1 ± 0.9. Only 1 video discussed indications to abort the procedure, and 2 described the location of the inferior epigastric artery. The 27 videos reviewed contained good-quality general instruction. However, we noted a lack of safety-related information in most of the available videos. Further development of resources is required to teach internal medicine trainees skills that focus on the safety of point-of-care US guidance. © 2017 by the American Institute of Ultrasound in Medicine.

  4. DNA Commission of the International Society for Forensic Genetics: revised and extended guidelines for mitochondrial DNA typing.

    PubMed

    Parson, W; Gusmão, L; Hares, D R; Irwin, J A; Mayr, W R; Morling, N; Pokorak, E; Prinz, M; Salas, A; Schneider, P M; Parsons, T J

    2014-11-01

    The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the question of human identification. Previous recommendations published in 2000 addressed the analysis and interpretation of mitochondrial DNA (mtDNA) in forensic casework. While the foundations set forth in the earlier recommendations still apply, new approaches to the quality control, alignment and nomenclature of mitochondrial sequences, as well as the establishment of mtDNA reference population databases, have been developed. Here, we describe these developments and discuss their application to both mtDNA casework and mtDNA reference population databasing applications. While the generation of mtDNA for forensic casework has always been guided by specific standards, it is now well-established that data of the same quality are required for the mtDNA reference population data used to assess the statistical weight of the evidence. As a result, we introduce guidelines regarding sequence generation, as well as quality control measures based on the known worldwide mtDNA phylogeny, that can be applied to ensure the highest quality population data possible. For both casework and reference population databasing applications, the alignment and nomenclature of haplotypes is revised here and the phylogenetic alignment proffered as acceptable standard. In addition, the interpretation of heteroplasmy in the forensic context is updated, and the utility of alignment-free database searches for unbiased probability estimates is highlighted. Finally, we discuss statistical issues and define minimal standards for mtDNA database searches. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Transition to Science Teacher Educator: Tensions Experienced While Learning to Teach Lesson Sequencing

    ERIC Educational Resources Information Center

    Wiebke, Heidi; Park Rogers, Meredith

    2014-01-01

    This self-study investigated the tensions that I (Heidi) encountered when teaching elementary preservice teachers how to develop a coherent sequence of five science lessons. Four lesson planning components guided me in developing a series of lessons to support the preservice teachers with this exercise. Employing self-study methodology, data…

  6. Filter Presses. Sludge Treatment and Disposal Course #166. Instructor's Guide [and] Student Workbook.

    ERIC Educational Resources Information Center

    Alloway, Rawle A.

    This lesson is an introduction to the operation of filter presses. Two basic types of presses, their components, the sequence of operation, operational controls, sampling, and testing are discussed. The instructor's manual contains a description of the lesson, estimated presentation time, instructional materials list, suggested sequence of…

  7. TU-AB-BRA-07: Distortion-Free 3D Diffusion MRI On An MRI-Guided Radiotherapy System for Longitudinal Tumor Response Assessment

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

    Gao, Y; Yang, Y; Rangwala, N

    Purpose: To develop a reliable, 3D distortion-free diffusion MRI technique for longitudinal tumor response assessment and MRI-guided adaptive radiotherapy(RT). Methods: A diffusion prepared 3D turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) sequence in a commercially available diffusion phantom, and one head-and-neck and one brain cancer patient on an MRI-guided RT system (ViewRay). In phantom study, the geometric fidelity was quantified as the ratio between the left-right (RL) and anterior-posterior (AP) dimension. Ten slices were measured on DP-TSE, DW-ssEPI and standard TSE images where the later was used as the geometricmore » reference. ADC accuracy was verified at both 0°C (reference ADC available) and room temperature with a range of diffusivity between 0.35 and 2.0*10{sup −3}mm{sup 2}/s. The ADC reproducibility was assessed based on 8 room-temperature measurements on 6 different days. In the pilot single-slice in-vivo study, CT images were used as the geometric reference, and ADC maps from both diffusion sequences were compared. Results: Distortion and susceptive-related artifact were severe in DW-ssEPI, with significantly lower RL/AP ratio (0.9579±0.0163) than DP-TSE (0.9990±0.0031) and TSE (0.9995±0.0031). ADCs from the two diffusion sequences both matched well with the vendor-provided values at 0°C; however DW-ssEPI fails to provide accurate ADC for high diffusivity vials at room temperature due to high noise level (10 times higher than DP-TSE). The DP-TSE sequence had excellent ADC reproducibility with <4% ADC variation among 8 separate measurements. In patient study, DP-TSE exhibited substantially improved geometric reliability. ROI analysis in ADC maps generated from DP-TSE and DW-ssEPI showed <5% difference where high b-value images were excluded from the latter approach due to excessive noise level. Conclusion: A diffusion MRI sequence with excellent geometric fidelity, accurate and highly reproducible ADC measurements was proposed for longitudinal tumor response assessment using an MRI-guided RT system. Yu Gao acknowledges research support from ViewRay.« less

  8. Functional DNA quantification guides accurate next-generation sequencing mutation detection in formalin-fixed, paraffin-embedded tumor biopsies

    PubMed Central

    2013-01-01

    The formalin-fixed, paraffin-embedded (FFPE) biopsy is a challenging sample for molecular assays such as targeted next-generation sequencing (NGS). We compared three methods for FFPE DNA quantification, including a novel PCR assay (‘QFI-PCR’) that measures the absolute copy number of amplifiable DNA, across 165 residual clinical specimens. The results reveal the limitations of commonly used approaches, and demonstrate the value of an integrated workflow using QFI-PCR to improve the accuracy of NGS mutation detection and guide changes in input that can rescue low quality FFPE DNA. These findings address a growing need for improved quality measures in NGS-based patient testing. PMID:24001039

  9. Genomic Sequence of the WHO International Standard for Hepatitis A Virus RNA.

    PubMed

    Jenkins, Adrian; Minhas, Rehan; Morris, Clare; Berry, Neil

    2018-05-10

    The World Health Organization (WHO) international standard for hepatitis A virus (HAV) RNA nucleic acid assays was characterized by complete genome sequencing. The entire coding sequence and noncoding regions were assigned HAV genotype IB. This information will aid the design, development, and evaluation of HAV RNA amplification assays. Copyright © 2018 Jenkins et al.

  10. International guide to prescribing psychotropic medication for the management of problem behaviours in adults with intellectual disabilities

    PubMed Central

    DEB, SHOUMITRO; KWOK, HENRY; BERTELLI, MARCO; SALVADOR-CARULLA, LUIS; BRADLEY, ELSPETH; TORR, JENNIFER; BARNHILL, JARRET

    2009-01-01

    Psychotropic medications are used regularly to manage problem behaviours among people with intellectual disabilities. This causes concern because often these medications are used out of their licensed indications in this context. The WPA Section on Psychiatry of Intellectual Disability has recently developed an evidence and consensus-based international guide for practitioners for the use of psychotropic medications for problem behaviours among adults with intellectual disabilities. This guide advises on assessment of behaviours, producing a formulation, initiation of treatment, assessment of out-come and adverse effects, follow-up arrangements, and possibility of discontinuation of treatment. PMID:19812757

  11. The Case for Representative Democracy: What Americans Should Know about Their Legislatures.

    ERIC Educational Resources Information Center

    Rosenthal, Alan; Kurtz, Karl T.; Hibbing, John; Loomis, Burdett

    This guide is a revised and adapted version of a previous monograph, "A New Public Perspective on Representative Democracy: A Guide for Legislative Interns." The guide focuses on civic perspective: how citizens view the political institutions, processes, and people that are fundamental to representative democracy in the United States. It…

  12. 76 FR 62374 - Proposed Information Collection; Comment Request; Alaska Recreational Charter Vessel Guide and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    ... charter vessels in the guided halibut sport fishery in International Pacific Halibut Commission Areas 2C... Pacific halibut is allocated between the guided sport (i.e., the charter sector) and the commercial... Fisheries Science Center proposes to conduct a survey of charter vessel owners to collect annual cost and...

  13. International Student Guide to U.S. Community Colleges, 2007-2008

    ERIC Educational Resources Information Center

    American Association of Community Colleges (NJ1), 2007

    2007-01-01

    This guide was produced for prospective students considering studying in the United States. The guide is organized to help students through all stages of the process, including learning about the U.S. higher education system, finding the right college, benefits of attending community college, obtaining a student visa, estimating expenses, living…

  14. Assessment of progressively delayed prompts on guided skill learning in rats.

    PubMed

    Reid, Alliston K; Futch, Sara E; Ball, Katherine M; Knight, Aubrey G; Tucker, Martha

    2017-03-01

    We examined the controlling factors that allow a prompted skill to become autonomous in a discrete-trials implementation of Touchette's (1971) progressively delayed prompting procedure, but our subjects were rats rather than children with disabilities. Our prompted skill was a left-right lever-press sequence guided by two panel lights. We manipulated (a) the effectiveness of the guiding lights prompt and (b) the presence or absence of a progressively delayed prompt in four groups of rats. The less effective prompt yielded greater autonomy than the more effective prompt. The ability of the progressively delayed prompt procedure to produce behavioral autonomy depended upon characteristics of the obtained delay (trial duration) rather than on the pending prompt. Sequence accuracy was reliably higher in unprompted trials than in prompted trials, and this difference was maintained in the 2 groups that received no prompts but yielded equivalent trial durations. Overall sequence accuracy decreased systematically as trial duration increased. Shorter trials and their greater accuracy were correlated with higher overall reinforcement rates for faster responding. Waiting for delayed prompts (even if no actual prompt was provided) was associated with lower overall reinforcement rate by decreasing accuracy and by lengthening trials. These findings extend results from previous studies regarding the controlling factors in delayed prompting procedures applied to children with disabilities.

  15. Energy--Structure--Life. A Learning System for Understanding Science, Book Two.

    ERIC Educational Resources Information Center

    Bixby, Louis W.; And Others

    This learning guide contains materials for the second year of Energy/Structure/ Life, a two year high school program in integrated science. The guide is programed to permit the student to proceed on his own at a self-determined pace. The two year course is a sequence of physics, chemistry, and biology with the chemical (continued from the first…

  16. The Incredible Egg. 4-H Classroom Curriculum Guide for Grade Levels 4-5.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Cooperative Extension Service.

    This curriculum guide integrates the concepts of chick embryology into mathematics, science, and language arts lesson plans for Grades 4 and 5. The four lessons comprising the unit can be utilized in sequence or as independent lessons within the classroom curriculum. Lesson 1 enables students to identify the parts of an egg. Lesson 2 examines the…

  17. Image Display And Manipulation System (IDAMS), user's guide

    NASA Technical Reports Server (NTRS)

    Cecil, R. W.

    1972-01-01

    A combination operator's guide and user's handbook for the Image Display and Manipulation System (IDAMS) is reported. Information is presented to define how to operate the computer equipment, how to structure a run deck, and how to select parameters necessary for executing a sequence of IDAMS task routines. If more detailed information is needed on any IDAMS program, see the IDAMS program documentation.

  18. GROUNDWARS 4.2 Reference Guide

    DTIC Science & Technology

    1991-12-01

    land duel , homogeneous forces, TANKWARS, target acquisition, combat survivability 19. ABSTRACT (Continue on reverse if necessary and identify by block...number) GROUNDWARS is a stochastic, two-sided, event-sequenced weapon systems effectiveness model which provides the results of a land duel between two...GROUNDWARS 4.2 REFERENCE GUIDE I. INTRODUCTION Groundwars is a weapon systems effectiveness model which provides the results of a land duel between

  19. Madison Public Schools. La Follette Careers Program. Tenth Grade Social Studies Guide.

    ERIC Educational Resources Information Center

    Morrissey, Jim; Waity, Charles

    A social studies course for a tenth grade career program is outlined in this curriculum and teaching guide. A calendar plots the time sequence for the nine units which cover prehistory to the present. The format of each unit is in three sections. The interrelated concepts, behavior goals, and teaching methods and learning activities are presented,…

  20. From Cooks to Carpenters: Measuring - A Saleable Work Skill. Occupation Simulation Packet. Grades 5th-6th.

    ERIC Educational Resources Information Center

    Kennedy, Helena

    This teacher's guide contains simulated work experiences for 5th and 6th grade students using the isolated skill concept - measuring. Teacher instructions include objectives, evaluation, and sequence of activities. The guide contains pre-tests and post-tests with instructions and answer keys. Three pre-skill activities are suggested, such as…

  1. Genreflecting: A Guide to Reading Interests in Genre Fiction. Fourth Edition.

    ERIC Educational Resources Information Center

    Herald, Diana Tixier

    Neither a bibliography nor a history of genres through historical sequences of listings by author, this book is a guide for those who help readers identify genre authors and titles of desired types in both libraries and bookstores. A secondary purpose of the book is as a text for library school students, aimed at familiarizing them with the common…

  2. A user's guide to quantitative and comparative analysis of metagenomic datasets.

    PubMed

    Luo, Chengwei; Rodriguez-R, Luis M; Konstantinidis, Konstantinos T

    2013-01-01

    Metagenomics has revolutionized microbiological studies during the past decade and provided new insights into the diversity, dynamics, and metabolic potential of natural microbial communities. However, metagenomics still represents a field in development, and standardized tools and approaches to handle and compare metagenomes have not been established yet. An important reason accounting for the latter is the continuous changes in the type of sequencing data available, for example, long versus short sequencing reads. Here, we provide a guide to bioinformatic pipelines developed to accomplish the following tasks, focusing primarily on those developed by our team: (i) assemble a metagenomic dataset; (ii) determine the level of sequence coverage obtained and the amount of sequencing required to obtain complete coverage; (iii) identify the taxonomic affiliation of a metagenomic read or assembled contig; and (iv) determine differentially abundant genes, pathways, and species between different datasets. Most of these pipelines do not depend on the type of sequences available or can be easily adjusted to fit different types of sequences, and are freely available (for instance, through our lab Web site: http://www.enve-omics.gatech.edu/). The limitations of current approaches, as well as the computational aspects that can be further improved, will also be briefly discussed. The work presented here provides practical guidelines on how to perform metagenomic analysis of microbial communities characterized by varied levels of diversity and establishes approaches to handle the resulting data, independent of the sequencing platform employed. © 2013 Elsevier Inc. All rights reserved.

  3. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders

    PubMed Central

    Soden, Sarah E.; Saunders, Carol J.; Willig, Laurel K.; Farrow, Emily G.; Smith, Laurie D.; Petrikin, Josh E.; LePichon, Jean-Baptiste; Miller, Neil A.; Thiffault, Isabelle; Dinwiddie, Darrell L.; Twist, Greyson; Noll, Aaron; Heese, Bryce A.; Zellmer, Lee; Atherton, Andrea M.; Abdelmoity, Ahmed T.; Safina, Nicole; Nyp, Sarah S.; Zuccarelli, Britton; Larson, Ingrid A.; Modrcin, Ann; Herd, Suzanne; Creed, Mitchell; Ye, Zhaohui; Yuan, Xuan; Brodsky, Robert A.; Kingsmore, Stephen F.

    2014-01-01

    Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients. PMID:25473036

  4. Field guide to Cretaceous-tertiary boundary sections in northeastern Mexico

    NASA Technical Reports Server (NTRS)

    Keller, Gerta; Stinnesbeck, Wolfgang; Adatte, Thierry; Macleod, Norman; Lowe, Donald R.

    1994-01-01

    This guide was prepared for the field trip to the KT elastic sequence of northeastern Mexico, 5-8 February 1994, in conjunction with the Conference on New Developments Regarding the KT Event and Other Catastrophes in Earth History, held in Houston, Texas. The four-day excursion offers an invaluable opportunity to visit three key outcrops: Arroyo El Mimbral, La Lajilla, and El Pinon. These and other outcrops of this sequence have recently been interpreted as tsunami deposits produced by the meteorite impact event that produced the 200 to 300-km Chicxulub basin in Yucatan, and distributed ejecta around the world approximately 65 m.y. ago that today is recorded as a thin clay layer found at the K/T boundary. The impact tsunami interpretation for these rocks has not gone unchallenged, and others examining the outcrops arrive at quite different conclusions: not tsunami deposits but turbidites; not KT at all but 'upper Cretaceous.' Indeed, it is in hopes of resolving this debate through field discussion, outcrop evaluation, and sampling that led the organizers of the conference to sanction this field trip. This field guide provides participants with background information on the KT clastic sequence outcrops and is divided into two sections. The first section provides regional and logistical context for the outcrops and a description of the clastic sequence. The second section presents three representative interpretations of the outcrops by their advocates. There is clearly no way that these models can be reconciled and so two, if not all three, must be fundamentally wrong. Readers of this guide should keep in mind that many basic outcrop observations that these models are based upon remain unresolved. While great measures were taken to ensure that the information in the description section was as objective as possible, many observations are rooted in interpretations and the emphasis placed on certain observations depends to some degree upon the perspective of the author.

  5. Technical Report and User's Guide for the Program for International Student Assessment (PISA): 2009 Data Files and Database with U.S. Specific Variables. NCES 2011-025

    ERIC Educational Resources Information Center

    Hopstock, Paul J.; Pelczar, Marisa P.

    2011-01-01

    This technical report and user's guide is designed to provide researchers with an overview of the design and implementation of the 2009 Program for International Student Assessment (PISA), as well as with information on how to access the PISA 2009 data. This information is meant to supplement that presented in Organization for Economic Cooperation…

  6. Internet Protocol Implementation Guide.

    DTIC Science & Technology

    1982-08-01

    RD-R153 624 INTERNET PROTOCOL IMPLEMENTATION GIDE(U) SRI 1/2 INTERNATIONAL MENLO PARK CA NETWORK INFORMATION CENTER AUG 82 DCA2e-83-C-8e25 N... INTERNET PROTOCOL S IMPLEMENTATION GUIDE August 1982 DTICFL. !.ECTE .-" MAY 1 31985 ;z B Q.. Network Information Center SRI International Menlo Park...this is more information than the receiving Internet * module needs. The specified procedure is to take the return route recorded in the first

  7. 75 FR 32834 - U.S. Department of State Advisory Committee on Private International Law Study Group Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-09

    ... Intellectual Property (IP) The Department of State, Office of the Legal Adviser, Private International Law and... IP licensing guide. The meeting will take place on Thursday, June 17, 2010 from 2:30 p.m. to 4 p.m... in New York (A/CN.9/689), as well as the draft text of the IP supplement to the Guide (A/CN.9/700 and...

  8. Intravenous phage display identifies peptide sequences that target the burn-injured intestine.

    PubMed

    Costantini, Todd W; Eliceiri, Brian P; Putnam, James G; Bansal, Vishal; Baird, Andrew; Coimbra, Raul

    2012-11-01

    The injured intestine is responsible for significant morbidity and mortality after severe trauma and burn; however, targeting the intestine with therapeutics aimed at decreasing injury has proven difficult. We hypothesized that we could use intravenous phage display technology to identify peptide sequences that target the injured intestinal mucosa in a murine model, and then confirm the cross-reactivity of this peptide sequence with ex vivo human gut. Four hours following 30% TBSA burn we performed an in vivo, intravenous systemic administration of phage library containing 10(12) phage in balb/c mice to biopan for gut-targeting peptides. In vivo assessment of the candidate peptide sequences identified after 4 rounds of internalization was performed by injecting 1×10(12) copies of each selected phage clone into sham or burned animals. Internalization into the gut was assessed using quantitative polymerase chain reaction. We then incubated this gut-targeting peptide sequence with human intestine and visualized fluorescence using confocal microscopy. We identified 3 gut-targeting peptide sequences which caused collapse of the phage library (4-1: SGHQLLLNKMP, 4-5: ILANDLTAPGPR, 4-11: SFKPSGLPAQSL). Sequence 4-5 was internalized into the intestinal mucosa of burned animals 9.3-fold higher than sham animals injected with the same sequence (2.9×10(5)vs. 3.1×10(4) particles per mg tissue). Sequences 4-1 and 4-11 were both internalized into the gut, but did not demonstrate specificity for the injured mucosa. Phage sequence 4-11 demonstrated cross-reactivity with human intestine. In the future, this gut-targeting peptide sequence could serve as a platform for the delivery of biotherapeutics. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Sunshine School's S.O.P.: Sequenced Objectives for Preschoolers. An Evaluation and Instruction Guide for Working with the Developmentally Delayed.

    ERIC Educational Resources Information Center

    Sunshine School, Gainesville, FL.

    Developed by professional educational staff, the curriculum of developmentally sequenced objectives for preschoolers (SOP) is designed for use in infant stimulation programs, for preschool training for all levels of retardation, with severely and profoundly retarded school age children, and for trainable and educable children during the earlier…

  10. Physics First: An Informational Guide for Teachers, School Administrators, Parents, Scientists, and the Public

    ERIC Educational Resources Information Center

    American Association of Physics Teachers (NJ1), 2009

    2009-01-01

    Physics First represents an organizational alternative to the traditional high school science sequence. It calls for a re-sequencing of high school courses so that students study physics before chemistry and biology. The purpose of this pamphlet is to provide: (1) Basic information and rationale for the Physics First curriculum; (2) Strategies for…

  11. Sludge Lagoons. Sludge Treatment and Disposal Course #166. Instructor's Guide [and] Student Workbook.

    ERIC Educational Resources Information Center

    Sharman, Ronald M.

    This lesson describes three different types of sludge lagoons: (1) drying lagoons; (2) facultative lagoons; and (3) anaerobic lagoons. Normal operating sequence and equipment are also described. The lesson is designed to be used in sequence with the complete Sludge Treatment and Disposal Course #166 or as an independent lesson. The instructor's…

  12. A Guide to Analyzing Message-Response Sequences and Group Interaction Patterns in Computer-Mediated Communication

    ERIC Educational Resources Information Center

    Jeong, Allan

    2005-01-01

    This paper proposes a set of methods and a framework for evaluating, modeling, and predicting group interactions in computer-mediated communication. The method of sequential analysis is described along with specific software tools and techniques to facilitate the analysis of message-response sequences. In addition, the Dialogic Theory and its…

  13. Planning a Teaching Sequence for the Teaching of Chemical Bonding

    ERIC Educational Resources Information Center

    Sibanda, Doras; Hobden, Paul

    2015-01-01

    The current study seeks to examine how teachers plan teaching sequences to teach chemical bonding in the senior secondary phase of schooling. The study employs a learning demand tool as interpretive framework. A mixed method was used to guide the collection of data. Data were collected through a survey instrument with 227 practising physical…

  14. SU-F-E-02: A Feasibility Study for Application of Metal Artifact Reduction Techniques in MR-Guided Brachytherapy Gynecological Cancer with Titanium Applicators

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

    Kadbi, M

    Purpose: Utilization of Titanium Tandem and Ring (T&R) applicators in MR-guided brachytherapy has become widespread for gynecological cancer treatment. However, Titanium causes magnetic field disturbance and susceptibility artifact, which complicate image interpretation. In this study, metal artifact reduction techniques were employed to improve the image quality and reduce the metal related artifacts. Methods: Several techniques were employed to reduce the metal artifact caused by titanium T&R applicator. These techniques include Metal Artifact Reduction Sequence (MARS), View Angle Tilting (VAT) to correct in-plane distortion, and Slice Encoding for Metal Artifact Correction (SEMAC) for through-plane artifact correction. Moreover, MARS can be combinedmore » with VAT to further reduce the in-plane artifact by reapplying the selection gradients during the readout (MARS+VAT). SEMAC uses a slice selective excitation but acquires additional z-encodings in order to resolve off-resonant signal and to reduce through-plane distortions. Results: Comparison between the clinical sequences revealed that increasing the bandwidth reduces the error in measured diameter of T&R. However, the error is larger than 4mm for the best case with highest bandwidth and spatial resolution. MARS+VAT with isotropic resolution of 1mm reduced the error to 1.9mm which is the least among the examined 2D sequences. The measured diameter of tandem from SEMAC+VAT has the closest value to the actual diameter of tandem (3.2mm) and the error was reduced to less than 1mm. In addition, SEMAC+VAT significantly reduces the blooming artifact in the ring compared to clinical sequences. Conclusion: A higher bandwidth and spatial resolution sequence reduces the artifact and diameter of applicator with a slight compromise in SNR. Metal artifact reduction sequences decrease the distortion associated with titanium applicator. SEMAC+VAT sequence in combination with VAT revealed promising results for titanium imaging and can be utilized for MR-guided brachytherapy in gynecological cancer. The author is employee with Philips Healthcare.« less

  15. The PiGeOn project: protocol of a longitudinal study examining psychosocial and ethical issues and outcomes in germline genomic sequencing for cancer.

    PubMed

    Best, Megan; Newson, Ainsley J; Meiser, Bettina; Juraskova, Ilona; Goldstein, David; Tucker, Kathy; Ballinger, Mandy L; Hess, Dominique; Schlub, Timothy E; Biesecker, Barbara; Vines, Richard; Vines, Kate; Thomas, David; Young, Mary-Anne; Savard, Jacqueline; Jacobs, Chris; Butow, Phyllis

    2018-04-23

    Advances in genomics offer promise for earlier detection or prevention of cancer, by personalisation of medical care tailored to an individual's genomic risk status. However genome sequencing can generate an unprecedented volume of results for the patient to process with potential implications for their families and reproductive choices. This paper describes a protocol for a study (PiGeOn) that aims to explore how patients and their blood relatives experience germline genomic sequencing, to help guide the appropriate future implementation of genome sequencing into routine clinical practice. We have designed a mixed-methods, prospective, cohort sub-study of a germline genomic sequencing study that targets adults with cancer suggestive of a genetic aetiology. One thousand probands and 2000 of their blood relatives will undergo germline genomic sequencing as part of the parent study in Sydney, Australia between 2016 and 2020. Test results are expected within12-15 months of recruitment. For the PiGeOn sub-study, participants will be invited to complete surveys at baseline, three months and twelve months after baseline using self-administered questionnaires, to assess the experience of long waits for results (despite being informed that results may not be returned) and expectations of receiving them. Subsets of both probands and blood relatives will be purposively sampled and invited to participate in three semi-structured qualitative interviews (at baseline and each follow-up) to triangulate the data. Ethical themes identified in the data will be used to inform critical revisions of normative ethical concepts or frameworks. This will be one of the first studies internationally to follow the psychosocial impact on probands and their blood relatives who undergo germline genome sequencing, over time. Study results will inform ongoing ethical debates on issues such as informed consent for genomic sequencing, and informing participants and their relatives of specific results. The study will also provide important outcome data concerning the psychological impact of prolonged waiting for germline genomic sequencing. These data are needed to ensure that when germline genomic sequencing is introduced into standard clinical settings, ethical concepts are embedded, and patients and their relatives are adequately prepared and supported during and after the testing process.

  16. StrainSeeker: fast identification of bacterial strains from raw sequencing reads using user-provided guide trees.

    PubMed

    Roosaare, Märt; Vaher, Mihkel; Kaplinski, Lauris; Möls, Märt; Andreson, Reidar; Lepamets, Maarja; Kõressaar, Triinu; Naaber, Paul; Kõljalg, Siiri; Remm, Maido

    2017-01-01

    Fast, accurate and high-throughput identification of bacterial isolates is in great demand. The present work was conducted to investigate the possibility of identifying isolates from unassembled next-generation sequencing reads using custom-made guide trees. A tool named StrainSeeker was developed that constructs a list of specific k -mers for each node of any given Newick-format tree and enables the identification of bacterial isolates in 1-2 min. It uses a novel algorithm, which analyses the observed and expected fractions of node-specific k -mers to test the presence of each node in the sample. This allows StrainSeeker to determine where the isolate branches off the guide tree and assign it to a clade whereas other tools assign each read to a reference genome. Using a dataset of 100 Escherichia coli isolates, we demonstrate that StrainSeeker can predict the clades of E. coli with 92% accuracy and correct tree branch assignment with 98% accuracy. Twenty-five thousand Illumina HiSeq reads are sufficient for identification of the strain. StrainSeeker is a software program that identifies bacterial isolates by assigning them to nodes or leaves of a custom-made guide tree. StrainSeeker's web interface and pre-computed guide trees are available at http://bioinfo.ut.ee/strainseeker. Source code is stored at GitHub: https://github.com/bioinfo-ut/StrainSeeker.

  17. Refinement of a Conceptual Model for Adolescent Readiness to Engage in End-of-Life Discussions.

    PubMed

    Bell, Cynthia J; Zimet, Gregory D; Hinds, Pamela S; Broome, Marion E; McDaniel, Anna M; Mays, Rose M; Champion, Victoria L

    Adolescents living with incurable cancer require ongoing support to process grief, emotions, and information as disease progresses including treatment options (phase 1 clinical trials and/or hospice/palliative care). Little is known about how adolescents become ready for such discussions. The purpose of this study was to explore the process of adolescent readiness for end-of-life preparedness discussions, generating a theoretical understanding for guiding clinical conversations when curative options are limited. We explored 2 in-depth cases across time using case-study methodology. An à priori conceptual model based on current end-of-life research guided data collection and analysis. Multiple sources including in-depth adolescent interviews generated data collection on model constructs. Analysis followed a logical sequence establishing a chain of evidence linking raw data to study conclusions. Synthesis and data triangulation across cases and time led to theoretical generalizations. Initially, we proposed a linear process of readiness with 3 domains: a cognitive domain (awareness), an emotional domain (acceptance), and a behavioral domain (willingness), which preceded preparedness. Findings led to conceptual model refinement showing readiness is a dynamic internal process that interacts with preparedness. Current awareness context facilitates the type of preparedness discussions (cognitive or emotional). Furthermore, social constraint inhibits discussions. Data support theoretical understanding of the dynamism of readiness. Future research that validates adolescent conceptualization will ensure age-appropriate readiness representation. Understanding the dynamic process of readiness for engaging in end-of-life preparedness provides clinician insight for guiding discussions that facilitate shared decision making and promote quality of life for adolescents and their families.

  18. Development of a quantitative-competitive PCR for quantification of human cytomegalovirus load and comparison with antigenaemia, viraemia and pp67 RNA detection by nucleic acid sequence-based amplification.

    PubMed

    Bergallo, M; Costa, C; Tarallo, S; Daniele, R; Merlino, C; Segoloni, G P; Negro Ponzi, A; Cavallo, R

    2006-06-01

    The human cytomegalovirus (HCMV) is an important pathogen in immunocompromised patients, such as transplant recipients. The use of sensitive and rapid diagnostic assays can have a great impact on antiviral prophylaxis and therapy monitoring and diagnosing active disease. Quantification of HCMV DNA may additionally have prognostic value and guide routine management. The aim of this study was to develop a reliable internally-controlled quantitative-competitive PCR (QC-PCR) for the detection and quantification of HCMV DNA viral load in peripheral blood and compare it with other methods: the HCMV pp65 antigenaemia assay in leukocyte fraction, the HCMV viraemia, both routinely employed in our laboratory, and the nucleic acid sequence-based amplification (NASBA) for detection of HCMV pp67-mRNA. Quantitative-competitive PCR is a procedure for nucleic acid quantification based on co-amplification of competitive templates, the target DNA and a competitor functioning as internal standard. In particular, a standard curve is generated by amplifying 10(2) to 10(5) copies of target pCMV-435 plasmid with 10(4) copies of competitor pCMV-C plasmid. Clinical samples derived from 40 kidney transplant patients were tested by spiking 10(4) copies of pCMV-C into the PCR mix as internal control, and comparing results with the standard curve. Of the 40 patients studied, 39 (97.5%) were positive for HCMV DNA by QC-PCR. While the correlation between the number of pp65-positive cells and the number of HCMV DNA genome copies/mL and the former and the pp67mRNA-positivity were statistically significant, there was no significant correlation between HCMV DNA viral load assayed by QC-PCR and HCMV viraemia. The QC-PCR assay could detect from 10(2) to over 10(7) copies of HCMV DNA with a range of linearity between 10(2) and 10(5) genomes.

  19. ICCS 2009 User Guide for the International Database. Supplement 1: International Version of the ICCS 2009 Questionnaires

    ERIC Educational Resources Information Center

    Brese, Falk; Jung, Michael; Mirazchiyski, Plamen; Schulz, Wolfram; Zuehlke, Olaf

    2011-01-01

    This document presents Supplement 1 of "The International Civic and Citizenship Education Study (ICCS) 2009 International Database," which includes data for all questionnaires administered as part of the ICCS 2009 assessment. This supplement contains the international version of the ICCS 2009 questionnaires in the following seven…

  20. New International School Library Guidelines

    ERIC Educational Resources Information Center

    Oberg, Dianne

    2018-01-01

    The publication in 2015 of new international school library guidelines was the culmination of a two-year process involving a wide network of contributors. The process was guided by the Joint Committee of the International Federation of Library Associations (IFLA) School Libraries Section and the International Association of School Librarianship…

  1. International Women and Health Resource Guide.

    ERIC Educational Resources Information Center

    Women's International and Communication Service, Carouge (Switzerland).

    Information on women and health from around the world is provided in this guide. So far, no country has formal mechanisms through which women themselves can create the policies and practices so critical to their own health and that of their families. A major purpose of the guide is to assist the many women's initiatives attempting to change this…

  2. Resilience Guide: A Collection of Resources on Resilience in Children and Families.

    ERIC Educational Resources Information Center

    Cesarone, Bernard, Ed.

    This guide offers a collection of resources gathered as part of the effort to create the ResilienceNet Web site on the resilience of children and families. The introduction to the guide describes the partnership between ASSIST INTERNATIONAL, INC. and the ERIC Clearinghouse on Elementary and Early Childhood Education that led to the development of…

  3. Inside the Global Economy: Preview Guide to the Telecourse.

    ERIC Educational Resources Information Center

    Rabin, Steven

    This document contains samples only of just the print components of a telecourse that includes: 13 videotapes, 2 videodiscs, a recommended textbook, a case-study reader and review guide, a text study guide, a faculty manual with text bank; and a computer softrware tutorial. This telecourse examines international global economies by means of 13…

  4. Shipping: The World Connection. Student Guide and Teacher Guide. OEAGLS Investigation 12.

    ERIC Educational Resources Information Center

    Fortner, Rosanne; Pauken, Ray

    This unit investigates through three activities the importance of the Great Lakes in international trade. A student workbook and a teaching guide are provided. Included in the teacher's manual are an overview of the unit, a materials list, objectives, teaching suggestions, evaluation items, and answer keys to student activities. In the first…

  5. Cloning and Identification of Recombinant Argonaute-Bound Small RNAs Using Next-Generation Sequencing.

    PubMed

    Gangras, Pooja; Dayeh, Daniel M; Mabin, Justin W; Nakanishi, Kotaro; Singh, Guramrit

    2018-01-01

    Argonaute proteins (AGOs) are loaded with small RNAs as guides to recognize target mRNAs. Since the target specificity heavily depends on the base complementarity between two strands, it is important to identify small guide and long target RNAs bound to AGOs. For this purpose, next-generation sequencing (NGS) technologies have extended our appreciation truly to the nucleotide level. However, the identification of RNAs via NGS from scarce RNA samples remains a challenge. Further, most commercial and published methods are compatible with either small RNAs or long RNAs, but are not equally applicable to both. Therefore, a single method that yields quantitative, bias-free NGS libraries to identify small and long RNAs from low levels of input will be of wide interest. Here, we introduce such a procedure that is based on several modifications of two published protocols and allows robust, sensitive, and reproducible cloning and sequencing of small amounts of RNAs of variable lengths. The method was applied to the identification of small RNAs bound to a purified eukaryotic AGO. Following ligation of a DNA adapter to RNA 3'-end, the key feature of this method is to use the adapter for priming reverse transcription (RT) wherein biotinylated deoxyribonucleotides specifically incorporated into the extended complementary DNA. Such RT products are enriched on streptavidin beads, circularized while immobilized on beads and directly used for PCR amplification. We provide a stepwise guide to generate RNA-Seq libraries, their purification, quantification, validation, and preparation for next-generation sequencing. We also provide basic steps in post-NGS data analyses using Galaxy, an open-source, web-based platform.

  6. MIPS: a database for protein sequences, homology data and yeast genome information.

    PubMed Central

    Mewes, H W; Albermann, K; Heumann, K; Liebl, S; Pfeiffer, F

    1997-01-01

    The MIPS group (Martinsried Institute for Protein Sequences) at the Max-Planck-Institute for Biochemistry, Martinsried near Munich, Germany, collects, processes and distributes protein sequence data within the framework of the tripartite association of the PIR-International Protein Sequence Database (,). MIPS contributes nearly 50% of the data input to the PIR-International Protein Sequence Database. The database is distributed on CD-ROM together with PATCHX, an exhaustive supplement of unique, unverified protein sequences from external sources compiled by MIPS. Through its WWW server (http://www.mips.biochem.mpg.de/ ) MIPS permits internet access to sequence databases, homology data and to yeast genome information. (i) Sequence similarity results from the FASTA program () are stored in the FASTA database for all proteins from PIR-International and PATCHX. The database is dynamically maintained and permits instant access to FASTA results. (ii) Starting with FASTA database queries, proteins have been classified into families and superfamilies (PROT-FAM). (iii) The HPT (hashed position tree) data structure () developed at MIPS is a new approach for rapid sequence and pattern searching. (iv) MIPS provides access to the sequence and annotation of the complete yeast genome (), the functional classification of yeast genes (FunCat) and its graphical display, the 'Genome Browser' (). A CD-ROM based on the JAVA programming language providing dynamic interactive access to the yeast genome and the related protein sequences has been compiled and is available on request. PMID:9016498

  7. Inhibition of Escherichia coli viability by external guide sequences complementary to two essential genes

    PubMed Central

    McKinney, Jeffrey; Guerrier-Takada, Cecilia; Wesolowski, Donna; Altman, Sidney

    2001-01-01

    Narrow spectrum antimicrobial activity has been designed to reduce the expression of two essential genes, one coding for the protein subunit of RNase P (C5 protein) and one for gyrase (gyrase A). In both cases, external guide sequences (EGS) have been designed to complex with either mRNA. Using the EGS technology, the level of microbial viability is reduced to less than 10% of the wild-type strain. The EGSs are additive when used together and depend on the number of nucleotides paired when attacking gyrase A mRNA. In the case of gyrase A, three nucleotides unpaired out of a 15-mer EGS still favor complete inhibition by the EGS but five unpaired nucleotides do not. PMID:11381134

  8. Tour Recommendation Guide- Personalized travel sequence recommendation

    NASA Astrophysics Data System (ADS)

    Sivakumar, Akshitha; Prabadevi, B.

    2017-11-01

    Presents a personalized travel sequence for the given area the individual wants to visit. It not only helps to personalize the travel but also recommend a travel sequence based on the area mentioned. Firstly the frequently visited routes are ranked then top ranked routes are chosen based on previous travel records. The data is being collected using data mining and the famous routes are ranked based on user and the route. It helps in bridging the gap between user travel preference and routes.

  9. Chemistry of Living Matter, Energy Capture & Growth, Parts Three & Four of an Integrated Science Sequence, Student Guide, 1971 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This student guide is divided into two sections, "Chemistry of Living Matter" and "Energy Capture and Growth," constituting parts three and four of the third year of the Portland Project, a three-year high school integrated science curriculum. The underlying intention of the third year is to study energy and its importance to…

  10. Motion and Energy Chemical Reactions, Parts One & Two of an Integrated Science Sequence, Student Guide, 1971 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This student guide is for the second year of the Portland Project, a three-year integrated secondary school science curriculum. "Motion and Energy," the first of the two parts in this volume, begins with the study of motion, going from the quantitative description of motion to a consideration of what causes motion and a discussion of…

  11. Newton's method: A link between continuous and discrete solutions of nonlinear problems

    NASA Technical Reports Server (NTRS)

    Thurston, G. A.

    1980-01-01

    Newton's method for nonlinear mechanics problems replaces the governing nonlinear equations by an iterative sequence of linear equations. When the linear equations are linear differential equations, the equations are usually solved by numerical methods. The iterative sequence in Newton's method can exhibit poor convergence properties when the nonlinear problem has multiple solutions for a fixed set of parameters, unless the iterative sequences are aimed at solving for each solution separately. The theory of the linear differential operators is often a better guide for solution strategies in applying Newton's method than the theory of linear algebra associated with the numerical analogs of the differential operators. In fact, the theory for the differential operators can suggest the choice of numerical linear operators. In this paper the method of variation of parameters from the theory of linear ordinary differential equations is examined in detail in the context of Newton's method to demonstrate how it might be used as a guide for numerical solutions.

  12. Chromatin accessibility and guide sequence secondary structure affect CRISPR-Cas9 gene editing efficiency.

    PubMed

    Jensen, Kristopher Torp; Fløe, Lasse; Petersen, Trine Skov; Huang, Jinrong; Xu, Fengping; Bolund, Lars; Luo, Yonglun; Lin, Lin

    2017-07-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) systems have emerged as the method of choice for genome editing, but large variations in on-target efficiencies continue to limit their applicability. Here, we investigate the effect of chromatin accessibility on Cas9-mediated gene editing efficiency for 20 gRNAs targeting 10 genomic loci in HEK293T cells using both SpCas9 and the eSpCas9(1.1) variant. Our study indicates that gene editing is more efficient in euchromatin than in heterochromatin, and we validate this finding in HeLa cells and in human fibroblasts. Furthermore, we investigate the gRNA sequence determinants of CRISPR-Cas9 activity using a surrogate reporter system and find that the efficiency of Cas9-mediated gene editing is dependent on guide sequence secondary structure formation. This knowledge can aid in the further improvement of tools for gRNA design. © 2017 Federation of European Biochemical Societies.

  13. Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.

    PubMed

    Heler, Robert; Wright, Addison V; Vucelja, Marija; Bikard, David; Doudna, Jennifer A; Marraffini, Luciano A

    2017-01-05

    CRISPR loci and their associated (Cas) proteins encode a prokaryotic immune system that protects against viruses and plasmids. Upon infection, a low fraction of cells acquire short DNA sequences from the invader. These sequences (spacers) are integrated in between the repeats of the CRISPR locus and immunize the host against the matching invader. Spacers specify the targets of the CRISPR immune response through transcription into short RNA guides that direct Cas nucleases to the invading DNA molecules. Here we performed random mutagenesis of the RNA-guided Cas9 nuclease to look for variants that provide enhanced immunity against viral infection. We identified a mutation, I473F, that increases the rate of spacer acquisition by more than two orders of magnitude. Our results highlight the role of Cas9 during CRISPR immunization and provide a useful tool to study this rare process and develop it as a biotechnological application. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Beyond the International Year of Astronomy: The Universe Discovery Guides

    NASA Astrophysics Data System (ADS)

    Lawton, B.; Berendsen, M.; Gurton, S.; Smith, D.; NASA SMD Astrophysics EPO Community

    2014-07-01

    Developed for informal educators and their audiences, the 12 Universe Discovery Guides (UDGs, one per month) are adapted from the Discovery Guides that were developed for the International Year of Astronomy in 2009. The UDGs showcase education and public outreach resources from across more than 30 NASA astrophysics missions and programs. Via collaboration through scientist and educator partnerships, the UDGs aim to increase the impact of individual missions and programs, put their efforts into context, and extend their reach to new audiences. Each of the UDGs has a science topic, an interpretive story, a sky object to view with finding charts, hands-on activities, and connections to recent NASA science discoveries. The UDGs are modular; informal educators can take resources from the guides that they find most useful for their audiences. Attention is being given to audience needs, and field-testing is ongoing. The UDGs are available via downloadable PDFs.

  15. Transretroperitoneal CT-guided Embolization of Growing Internal Iliac Artery Aneurysm after Repair of Abdominal Aortic Aneurysm: A Transretroperitoneal Approach with Intramuscular Lidocaine Injection Technique

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

    Park, Joon Young, E-mail: pjy1331@hanmail.net; Kim, Shin Jung, E-mail: witdd2@hanmail.net; Kim, Hyoung Ook, E-mail: chaos821209@hanmail.net

    This study was designed to evaluate the efficacy and safety of CT-guided embolization of internal iliac artery aneurysm (IIAA) after repair of abdominal aortic aneurysm by transretroperitoneal approach using the lidocaine injection technique to iliacus muscle, making window for safe needle path for three patients for whom CT-guided embolization of IIAA was performed by transretroperitoneal approach with intramuscular lidocaine injection technique. Transretroperitoneal access to the IIAA was successful in all three patients. In all three patients, the IIAA was first embolized using microcoils. The aneurysmal sac was then embolized with glue and coils without complication. With a mean follow-up ofmore » 7 months, the volume of the IIAAs remained stable without residual endoleaks. Transretroperitoneal CT-guided embolization of IIAA using intramuscular lidocaine injection technique is effective, safe, and results in good outcome.« less

  16. Rapid Identification of Cell-Specific, Internalizing RNA Aptamers with Bioinformatics Analyses of a Cell-Based Aptamer Selection

    PubMed Central

    Thiel, William H.; Bair, Thomas; Peek, Andrew S.; Liu, Xiuying; Dassie, Justin; Stockdale, Katie R.; Behlke, Mark A.; Miller, Francis J.; Giangrande, Paloma H.

    2012-01-01

    Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. Methodology/Principal Findings We demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. Conclusions and Significance We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies. PMID:22962591

  17. Internal wire guide for GTAW welding

    NASA Technical Reports Server (NTRS)

    Morgan, Gene E. (Inventor); Dyer, Gerald E. (Inventor)

    1989-01-01

    A welding torch for gas tungsten arc welding apparatus has a filler metal wire guide positioned within the torch, and within the shielding gas nozzle. The wire guide is adjacent to the tungsten electrode and has a ceramic liner through which the wire is fed. This reduces the size of the torch and eliminates the outside clearance problems that exit with external wire guides. Additionally, since the wire is always within the shielding gas, oxidizing of the wire is eliminated.

  18. A new adjustable parallel drill guide for internal fixation of femoral neck fracture: a developmental and experimental study.

    PubMed

    Yuenyongviwat, Varah; Tuntarattanapong, Pakjai; Tangtrakulwanich, Boonsin

    2016-01-11

    Internal fixation is one treatment for femoral neck fracture. Some devices and techniques reported improved accuracy and decreased fluoroscopic time. However, these are not widely used nowadays due to the lack of available special instruments and techniques. To improve the surgical procedure, the authors designed a new adjustable drill guide and tested the efficacy of the device. The authors developed a new adjustable drill guide for cannulated screw guide wire insertion for multiple screw fixation. Eight orthopaedic surgeons performed the experimental study to evaluate the efficacy of this device. Each surgeon performed guide wire insertion for multiple screw fixation in six synthetic femurs: three times with the new device and three times with the conventional technique. The fluoroscopic time, operative time and surgeon satisfaction were evaluated. In the operations with the new adjustable drill guide, the fluoroscopic and operative times were significantly lower than the operations with the conventional technique (p < 0.05). The mean score for the level of satisfaction of this device was also statistically significantly better (p = 0.02) than the conventional technique. The fluoroscopic and operative times with the new adjustable drill guide were reduced for multiple screw fixation of femoral neck fracture and the satisfaction of the surgeons was good.

  19. Sequencing of a QTL-rich region of the Theobroma cacao genome using pooled BACs and the identification of trait specific candidate genes

    USDA-ARS?s Scientific Manuscript database

    Background: BAC-based physical maps provide for sequencing across an entire genome or selected sub-genome regions of biological interest. Using the minimum tiling path as a guide, it is possible to select specific BAC clones from prioritized genome sections such as a genetically defined QTL interv...

  20. From Arithmetic to Algebra: Sequences and Patterns as an Introductory Lesson in Seventh Grade Mathematics

    ERIC Educational Resources Information Center

    Aniban, Diana Grace; Chua, Von Christopher; Garcia, Jellen; Elipane, Levi Esteban

    2014-01-01

    Guided by the principles of lesson study as applied to microteaching, this paper discusses the results and conclusions of a series of activities done by some graduate students of De La Salle University, Philippines, in an attempt to test the applicability of the lesson--Sequence and Patterns--to facilitate the transition of seventh graders from…

  1. Genome Sequence of Mycobacterium hassiacum DSM 44199, a Rare Source of Heat-Stable Mycobacterial Proteins

    PubMed Central

    Tiago, Igor; Maranha, Ana; Mendes, Vitor; Alarico, Susana; Moynihan, Patrick J.; Clarke, Anthony J.; Macedo-Ribeiro, Sandra; Pereira, Pedro J. B.

    2012-01-01

    Mycobacterium hassiacum is a rapidly growing mycobacterium isolated from human urine and so far the most thermophilic among mycobacterial species. Its thermotolerance and phylogenetic relationship to M. tuberculosis render its proteins attractive tools for crystallization and structure-guided drug design. We report the draft genome sequence of M. hassiacum DSM 44199. PMID:23209251

  2. Mississippi Curriculum Framework for Banking & Finance Technology (Program CIP: 52.0803--Banking and Related Financial Programs, Other). Postsecondary Programs.

    ERIC Educational Resources Information Center

    Mississippi Research and Curriculum Unit for Vocational and Technical Education, State College.

    This document, which is intended for use by community and junior colleges throughout Mississippi, contains curriculum frameworks for the course sequences in the banking and finance technology program. Presented in the introduction are a program description and suggested course sequence. Section I is a curriculum guide consisting of outlines for…

  3. in silico Whole Genome Sequencer & Analyzer (iWGS): a computational pipeline to guide the design and analysis of de novo genome sequencing studies

    USDA-ARS?s Scientific Manuscript database

    The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding it...

  4. Development of shared decision-making resources to help inform difficult healthcare decisions: An example focused on dysvascular partial foot and transtibial amputations.

    PubMed

    Quigley, Matthew; Dillon, Michael P; Fatone, Stefania

    2018-02-01

    Shared decision making is a consultative process designed to encourage patient participation in decision making by providing accurate information about the treatment options and supporting deliberation with the clinicians about treatment options. The process can be supported by resources such as decision aids and discussion guides designed to inform and facilitate often difficult conversations. As this process increases in use, there is opportunity to raise awareness of shared decision making and the international standards used to guide the development of quality resources for use in areas of prosthetic/orthotic care. To describe the process used to develop shared decision-making resources, using an illustrative example focused on decisions about the level of dysvascular partial foot amputation or transtibial amputation. Development process: The International Patient Decision Aid Standards were used to guide the development of the decision aid and discussion guide focused on decisions about the level of dysvascular partial foot amputation or transtibial amputation. Examples from these shared decision-making resources help illuminate the stages of development including scoping and design, research synthesis, iterative development of a prototype, and preliminary testing with patients and clinicians not involved in the development process. Lessons learnt through the process, such as using the International Patient Decision Aid Standards checklist and development guidelines, may help inform others wanting to develop similar shared decision-making resources given the applicability of shared decision making to many areas of prosthetic-/orthotic-related practice. Clinical relevance Shared decision making is a process designed to guide conversations that help patients make an informed decision about their healthcare. Raising awareness of shared decision making and the international standards for development of high-quality decision aids and discussion guides is important as the approach is introduced in prosthetic-/orthotic-related practice.

  5. Draft Genome Sequences of Biosafety Level 2 Opportunistic Pathogens Isolated from the Environmental Surfaces of the International Space Station.

    PubMed

    Checinska Sielaff, Aleksandra; Singh, Nitin K; Allen, Jonathan E; Thissen, James; Jaing, Crystal; Venkateswaran, Kasthuri

    2016-12-29

    The draft genome sequences of 20 biosafety level 2 (BSL-2) opportunistic pathogens isolated from the environmental surfaces of the International Space Station (ISS) were presented. These genomic sequences will help in understanding the influence of microgravity on the pathogenicity and virulence of these strains when compared with Earth strains. Copyright © 2016 Checinska Sielaff et al.

  6. RNAcentral: an international database of ncRNA sequences

    DOE PAGES

    Williams, Kelly Porter

    2014-10-28

    The field of non-coding RNA biology has been hampered by the lack of availability of a comprehensive, up-to-date collection of accessioned RNA sequences. Here we present the first release of RNAcentral, a database that collates and integrates information from an international consortium of established RNA sequence databases. The initial release contains over 8.1 million sequences, including representatives of all major functional classes. A web portal (http://rnacentral.org) provides free access to data, search functionality, cross-references, source code and an integrated genome browser for selected species.

  7. 75 FR 56903 - Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels in Alaska

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    .... 100503209-0430-02] RIN 0648-AY85 Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels... program for charter vessels in the guided sport fishery for Pacific halibut in the waters of International... sport fishing for halibut and charter vessels in IPHC Areas 2C and 3A may be found in sections 3, 25...

  8. Draft Genome Sequences of Two Fusarium oxysporum Isolates Cultured from Infected Zinnia hybrida Plants Grown on the International Space Station

    PubMed Central

    Urbaniak, Camilla; Massa, Gioia; Hummerick, Mary; Khodadad, Christina; Schuerger, Andrew

    2018-01-01

    ABSTRACT Here, we present the whole-genome sequences of two Fusarium oxysporum isolates cultured from infected Zinnia hybrida plants that were grown onboard the International Space Station (ISS). PMID:29773617

  9. Sequential addition of short DNA oligos in DNA-polymerase-based synthesis reactions

    DOEpatents

    Gardner, Shea N [San Leandro, CA; Mariella, Jr., Raymond P.; Christian, Allen T [Tracy, CA; Young, Jennifer A [Berkeley, CA; Clague, David S [Livermore, CA

    2011-01-18

    A method of fabricating a DNA molecule of user-defined sequence. The method comprises the steps of preselecting a multiplicity of DNA sequence segments that will comprise the DNA molecule of user-defined sequence, separating the DNA sequence segments temporally, and combining the multiplicity of DNA sequence segments with at least one polymerase enzyme wherein the multiplicity of DNA sequence segments join to produce the DNA molecule of user-defined sequence. Sequence segments may be of length n, where n is an even or odd integer. In one embodiment the length of desired hybridizing overlap is specified by the user and the sequences and the protocol for combining them are guided by computational (bioinformatics) predictions. In one embodiment sequence segments are combined from multiple reading frames to span the same region of a sequence, so that multiple desired hybridizations may occur with different overlap lengths. In one embodiment starting sequence fragments are of different lengths, n, n+1, n+2, etc.

  10. Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2

    PubMed Central

    De, Nabanita; Young, Lisa; Lau, Pick-Wei; Meisner, Nicole-Claudia; Morrissey, David V.; MacRae, Ian J.

    2013-01-01

    SUMMARY Argonaute proteins use small RNAs to guide the silencing of complementary target RNAs in many eukaryotes. Although small RNA biogenesis pathways are well studied, mechanisms for removal of guide RNAs from Argonaute are poorly understood. Here we show that the Argonaute2 (Ago2) guide RNA complex is extremely stable, with a half-life on the order of days. However, highly complementary target RNAs destabilize the complex and significantly accelerate release of the guide RNA from Ago2. This “unloading” activity can be enhanced by mismatches between the target and the guide 5′ end and attenuated by mismatches to the guide 3′ end. The introduction of 3′ mismatches leads to more potent silencing of abundant mRNAs in mammalian cells. These findings help to explain why the 3′ ends of mammalian microRNAs (miRNAs) rarely match their targets, suggest a mechanism for sequence-specific small RNA turnover, and offer insights for controlling small RNAs in mammalian cells. PMID:23664376

  11. A simplified Sanger sequencing method for full genome sequencing of multiple subtypes of human influenza A viruses.

    PubMed

    Deng, Yi-Mo; Spirason, Natalie; Iannello, Pina; Jelley, Lauren; Lau, Hilda; Barr, Ian G

    2015-07-01

    Full genome sequencing of influenza A viruses (IAV), including those that arise from annual influenza epidemics, is undertaken to determine if reassorting has occurred or if other pathogenic traits are present. Traditionally IAV sequencing has been biased toward the major surface glycoproteins haemagglutinin and neuraminidase, while the internal genes are often ignored. Despite the development of next generation sequencing (NGS), many laboratories are still reliant on conventional Sanger sequencing to sequence IAV. To develop a minimal and robust set of primers for Sanger sequencing of the full genome of IAV currently circulating in humans. A set of 13 primer pairs was designed that enabled amplification of the six internal genes of multiple human IAV subtypes including the recent avian influenza A(H7N9) virus from China. Specific primers were designed to amplify the HA and NA genes of each IAV subtype of interest. Each of the primers also incorporated a binding site at its 5'-end for either a forward or reverse M13 primer, such that only two M13 primers were required for all subsequent sequencing reactions. This minimal set of primers was suitable for sequencing the six internal genes of all currently circulating human seasonal influenza A subtypes as well as the avian A(H7N9) viruses that have infected humans in China. This streamlined Sanger sequencing protocol could be used to generate full genome sequence data more rapidly and easily than existing influenza genome sequencing protocols. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Guide for studying and evaluating internal accounting controls. Oil and gas exploration, development and production

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

    Not Available

    1981-01-01

    One of the most important responsibilities of any company's management is to establish and maintain, via periodic evaluations, is adequate internal accounting controls. Arthur Andersen and Co. approaches this problem as it relates to the oil and gas industry by logically dividing the economic events that affect a given company into four groups of activity termed ''business cycles'': treasury, expenditure, conversion (exploration, development, and production), and revenue activities. Independent public accountants can evaluate a company's existing internal controls much more thoroughly by studying only one category of business transactions at a time. Arthur Andersen's guide to reviewing internal controls coversmore » each step of this ''transaction-flow'' method as applied to a typical oil and gas company.« less

  13. Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

    PubMed Central

    Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

    2009-01-01

    Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease error correction in combination with PIPE cloning. In a sister manuscript we present data on how Gene Composer designed genes and protein constructs can result in improved protein production for structural studies. PMID:19383142

  14. Gene composer: database software for protein construct design, codon engineering, and gene synthesis.

    PubMed

    Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

    2009-04-21

    To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease error correction in combination with PIPE cloning. In a sister manuscript we present data on how Gene Composer designed genes and protein constructs can result in improved protein production for structural studies.

  15. Preservice elementary teachers learning to use curriculum materials to plan and teach science

    NASA Astrophysics Data System (ADS)

    Gunckel, Kristin Lee

    New elementary teachers rely heavily on curriculum materials, but available science curriculum materials do not often support teachers in meeting specified learning goals, engaging students in the inquiry and application practices of science, or leveraging students' intellectual and cultural resources for learning. One approach to supporting new elementary teachers in using available science curriculum materials is to provide frameworks to scaffold preservice teachers' developing lesson planning and teaching practices. The Inquiry-Application Instructional Model (I-AIM) and the Critical Analysis and Planning (CA&P) tool were designed to scaffold preservice teachers' developing practice to use curriculum materials effectively to plan and teach science. The I-AIM identifies functions for each activity in an instructional sequence. The CA&P provides guides preservice teachers in modifying curriculum materials to better fit I-AIM and leverage students' resources for learning. This study followed three elementary preservice teachers in an intern-level science method course as they learned to use the I-AIM and CA&P to plan and teach a science unit in their field placement classrooms. Using a sociocultural perspective, this study focused on the ways that the interns used the tools and the mediators that influenced how they used the tools. A color-coding analysis procedure was developed to identify the teaching patterns in the interns' planned instructional approaches and enacted activity sequences and compare those to the patterns implied by the I-AIM and CA&P tools. Interviews with the interns were also conducted and analyzed, along with the assignments they completed for their science methods course, to gain insight into the meanings the interns made of the tools and their experiences planning and teaching science. The results show that all three interns had some successes using the I-AIM and CA&P to analyze their curriculum materials and to plan and teach science lessons. However, all three interns used the tools in different ways, and some of their ways of using the tools were different from the intentions for the tools. These differences can be accounted for by the variety of mediators that influenced the interns' use of the I-AIM and CA&P tools. These mediators were rooted in the Discourses at play in the various communities in which the interns participated during their teacher preparation program. Some of the practices and resources of these various Discourses interfered with or supported the interns' use of the I-AIM and CA&P tools. Each intern took a different trajectory through these Discourses and encountered different practices that mediated how each used the I-AIM and CA&P tools. The results of this study suggest that the goal of preparing preservice teachers to use the I-AIM and CA&P tools should be to provide preservice teachers with opportunities to use the tools and help them develop the metaknowledge about the tools necessary to critically analyze the affordances and weaknesses of different approaches to teaching science.

  16. Draft Genome Sequences of Two Fusarium oxysporum Isolates Cultured from Infected Zinnia hybrida Plants Grown on the International Space Station.

    PubMed

    Urbaniak, Camilla; Massa, Gioia; Hummerick, Mary; Khodadad, Christina; Schuerger, Andrew; Venkateswaran, Kasthuri

    2018-05-17

    Here, we present the whole-genome sequences of two Fusarium oxysporum isolates cultured from infected Zinnia hybrida plants that were grown onboard the International Space Station (ISS). Copyright © 2018 Urbaniak et al.

  17. A snapshot of the emerging tomato genome sequence

    USDA-ARS?s Scientific Manuscript database

    The genome of tomato (Solanum lycopersicum) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, the Netherlands, France, Japan, Spain, Italy and the United States) as part of a larger initiative called the ‘International Solanaceae Genome Proje...

  18. ATLAS, an integrated structural analysis and design system. Volume 1: ATLAS user's guide

    NASA Technical Reports Server (NTRS)

    Dreisbach, R. L. (Editor)

    1979-01-01

    Some of the many analytical capabilities provided by the ATLAS Version 4.0 System in the logical sequence are described in which model-definition data are prepared and the subsequent computer job is executed. The example data presented and the fundamental technical considerations that are highlighted can be used as guides during the problem solving process. This guide does not describe the details of the ATLAS capabilities, but provides an introduction to the new user of ATLAS to the level at which the complete array of capabilities described in the ATLAS User's Manual can be exploited fully.

  19. Development of Light-Activated CRISPR Using Guide RNAs with Photocleavable Protectors.

    PubMed

    Jain, Piyush K; Ramanan, Vyas; Schepers, Arnout G; Dalvie, Nisha S; Panda, Apekshya; Fleming, Heather E; Bhatia, Sangeeta N

    2016-09-26

    The ability to remotely trigger CRISPR/Cas9 activity would enable new strategies to study cellular events with greater precision and complexity. In this work, we have developed a method to photocage the activity of the guide RNA called "CRISPR-plus" (CRISPR-precise light-mediated unveiling of sgRNAs). The photoactivation capability of our CRISPR-plus method is compatible with the simultaneous targeting of multiple DNA sequences and supports numerous modifications that can enable guide RNA labeling for use in imaging and mechanistic investigations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Simplifying the Process for Finding Research Funding: A Cross-Campus Collaboration at a Large Academic Institution.

    PubMed

    Rosenzweig, Merle; Smith, Judith E; Curtis, Ann; Puffenberger, Amy

    2016-01-01

    This article describes the collaboration between the University of Michigan's M-Library and the University of Michigan Medical School's Office of Research in developing a comprehensive online guide and consultation service. The guide was designed to assist researchers in finding available funding from both internal and external sources and was based on the results of a survey distributed by the Office of Research. Because many of the respondents were unaware of internal funding programs and needed more information on resources external to the university as well, the guide included information on both possibilities in an easy-to-use format that researchers use independently without needing further instruction, although personal consultation was also offered when necessary.

  1. Hanford internal dosimetry program manual

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

    Carbaugh, E.H.; Sula, M.J.; Bihl, D.E.

    1989-10-01

    This document describes the Hanford Internal Dosimetry program. Program Services include administrating the bioassay monitoring program, evaluating and documenting assessments of internal exposure and dose, ensuring that analytical laboratories conform to requirements, selecting and applying appropriate models and procedures for evaluating internal radionuclide deposition and the resulting dose, and technically guiding and supporting Hanford contractors in matters regarding internal dosimetry. 13 refs., 16 figs., 42 tabs.

  2. Nuclide Guide and International Chart of Nuclides - 2008

    NASA Astrophysics Data System (ADS)

    Golashvili, T.

    2009-08-01

    New versions of Nuclide Guide and Chart of the Nuclides were developed as a result of Russian-Chinese collaboration. The Nuclide Guide contains the basic information on more than 3000 radioactive and stable nuclides. The characteristics of isomers with half-lives more than 1 ms are included. For each nuclide spin, parity, mass of nuclide, magnetic moment (if available), mass excess, half-life or abundance, decay modes, branching ratios, emitted particles, energies of most intense gamma-rays and their intensities, decay energies and mean values of radiation energy per decay are given. For stable and natural long-lived nuclides cross-sections of thermal neutron induced activation are indicated. The information presented in the Guide was compiled from 5 sources: 1) ENSDF-2008, 2) atomic mass evaluation-2005 by Audi and Wapstra, 3) interactive data bases at web-sites , , 4) original evaluations of authors, 5) recent publications. The International Chart ot Nuclides was developed on the basis of information presented in Nuclide Guide.

  3. Clinical value of pointwise encoding time reduction with radial acquisition (PETRA) MR sequence in assessing internal derangement of knee.

    PubMed

    Kim, Sung Kwan; Kim, Donghyun; Lee, Sun Joo; Choo, Hye Jung; Oh, Minkyung; Son, Yohan; Paek, MunYoung

    2018-06-01

    The purpose was to evaluate the clinical value of PETRA sequence for the diagnosis of internal derangement of the knee. The major structures of the knee in 34 patients were evaluated and compared among conventional MRI findings, PETRA images, and arthroscopic findings. The specificities of PETRA with 2D FSE sequence were higher for meniscal lesions than those obtained when using 2D FSE alone. Using PETRA images along with conventional 2D FSE images can increase the accuracy of assessing internal derangements of the knee and, specifically, meniscal lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Towards Sustainability: A Guide for Colleges.

    ERIC Educational Resources Information Center

    Khan, Shirley Ali

    This guide, which builds on the Further Education Development Agency's environmental, regional, and economic development initiatives, is intended to help further education (FE) colleges throughout the United Kingdom respond to the sustainable development challenges posed by the International Organization for Standardization's quality environmental…

  5. 7 CFR Exhibit B to Subpart G of... - Development and Implementation of Natural Resource Management Guide

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... resource management guide needs to be developed in full recognition of its role as an internal Agency.... County Supervisors shall contact local officials and shall be responsible for being familiar with and for...

  6. Sequence-specific epigenetic effects of the maternal somatic genome on developmental rearrangements of the zygotic genome in Paramecium primaurelia.

    PubMed Central

    Meyer, E; Butler, A; Dubrana, K; Duharcourt, S; Caron, F

    1997-01-01

    In ciliates, the germ line genome is extensively rearranged during the development of the somatic macronucleus from a mitotic product of the zygotic nucleus. Germ line chromosomes are fragmented in specific regions, and a large number of internal sequence elements are eliminated. It was previously shown that transformation of the vegetative macronucleus of Paramecium primaurelia with a plasmid containing a subtelomeric surface antigen gene can affect the processing of the homologous germ line genomic region during development of a new macronucleus in sexual progeny of transformed clones. The gene and telomere-proximal flanking sequences are deleted from the new macronuclear genome, although the germ line genome remains wild type. Here we show that plasmids containing nonoverlapping segments of the same genomic region are able to induce similar terminal deletions; the locations of deletion end points depend on the particular sequence used. Transformation of the maternal macronucleus with a sequence internal to a macronuclear chromosome also causes the occurrence of internal deletions between short direct repeats composed of alternating thymines and adenines. The epigenetic influence of maternal macronuclear sequences on developmental rearrangements of the zygotic genome thus appears to be both sequence specific and general, suggesting that this trans-nucleus effect is mediated by pairing of homologous sequences. PMID:9199294

  7. [Efficient genome editing in human pluripotent stem cells through CRISPR/Cas9].

    PubMed

    Liu, Gai-gai; Li, Shuang; Wei, Yu-da; Zhang, Yong-xian; Ding, Qiu-rong

    2015-11-01

    The RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)-associated Cas9 nuclease has offered a new platform for genome editing with high efficiency. Here, we report the use of CRISPR/Cas9 technology to target a specific genomic region in human pluripotent stem cells. We show that CRISPR/Cas9 can be used to disrupt a gene by introducing frameshift mutations to gene coding region; to knock in specific sequences (e.g. FLAG tag DNA sequence) to targeted genomic locus via homology directed repair; to induce large genomic deletion through dual-guide multiplex. Our results demonstrate the versatile application of CRISPR/Cas9 in stem cell genome editing, which can be widely utilized for functional studies of genes or genome loci in human pluripotent stem cells.

  8. Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

    PubMed

    Pena, Loren D M; Jiang, Yong-Hui; Schoch, Kelly; Spillmann, Rebecca C; Walley, Nicole; Stong, Nicholas; Rapisardo Horn, Sarah; Sullivan, Jennifer A; McConkie-Rosell, Allyn; Kansagra, Sujay; Smith, Edward C; El-Dairi, Mays; Bellet, Jane; Keels, Martha Ann; Jasien, Joan; Kranz, Peter G; Noel, Richard; Nagaraj, Shashi K; Lark, Robert K; Wechsler, Daniel S G; Del Gaudio, Daniela; Leung, Marco L; Hendon, Laura G; Parker, Collette C; Jones, Kelly L; Goldstein, David B; Shashi, Vandana

    2018-04-01

    PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses.

  9. Internal models for interpreting neural population activity during sensorimotor control

    PubMed Central

    Golub, Matthew D; Yu, Byron M; Chase, Steven M

    2015-01-01

    To successfully guide limb movements, the brain takes in sensory information about the limb, internally tracks the state of the limb, and produces appropriate motor commands. It is widely believed that this process uses an internal model, which describes our prior beliefs about how the limb responds to motor commands. Here, we leveraged a brain-machine interface (BMI) paradigm in rhesus monkeys and novel statistical analyses of neural population activity to gain insight into moment-by-moment internal model computations. We discovered that a mismatch between subjects’ internal models and the actual BMI explains roughly 65% of movement errors, as well as long-standing deficiencies in BMI speed control. We then used the internal models to characterize how the neural population activity changes during BMI learning. More broadly, this work provides an approach for interpreting neural population activity in the context of how prior beliefs guide the transformation of sensory input to motor output. DOI: http://dx.doi.org/10.7554/eLife.10015.001 PMID:26646183

  10. SI (Systeme International). A Metric Workbook for Teachers of Consumer & Homemaking Education.

    ERIC Educational Resources Information Center

    Bielefeld, Carole, Comp.

    The teaching guide for providing instruction in use of the metric system contains materials geared for the daily activities of the home. Contents of the guide are organized into four parts. Part 1 is a brief description of the history of the metric system and reasons for conversion in the United States. The major portion of the guide, part 2…

  11. User Guide to the PDS Dataset for the Cassini Composite Infrared Spectrometer (CIRS)

    NASA Technical Reports Server (NTRS)

    Nixon, Conor A.; Kaelberer, Monte S.; Gorius, Nicolas

    2012-01-01

    This User Guide to the Cassini Composite Infrared Spectrometer (CIRS) has been written with two communities in mind. First and foremost, scientists external to the Cassini Project who seek to use the CIRS data as archived in the Planetary Data System (PDS). In addition, it is intended to be a comprehensive reference guide for those internal to the CIRS team.

  12. PASTA: Ultra-Large Multiple Sequence Alignment for Nucleotide and Amino-Acid Sequences.

    PubMed

    Mirarab, Siavash; Nguyen, Nam; Guo, Sheng; Wang, Li-San; Kim, Junhyong; Warnow, Tandy

    2015-05-01

    We introduce PASTA, a new multiple sequence alignment algorithm. PASTA uses a new technique to produce an alignment given a guide tree that enables it to be both highly scalable and very accurate. We present a study on biological and simulated data with up to 200,000 sequences, showing that PASTA produces highly accurate alignments, improving on the accuracy and scalability of the leading alignment methods (including SATé). We also show that trees estimated on PASTA alignments are highly accurate--slightly better than SATé trees, but with substantial improvements relative to other methods. Finally, PASTA is faster than SATé, highly parallelizable, and requires relatively little memory.

  13. Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by CRISPR-Cas12a.

    PubMed

    Swarts, Daan C; van der Oost, John; Jinek, Martin

    2017-04-20

    The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding. Furthermore, the R-loop complex structure reveals the strand displacement mechanism that facilitates guide-target hybridization and suggests a mechanism for double-stranded DNA cleavage involving a single active site. Together, these insights advance our mechanistic understanding of Cas12a enzymes and may contribute to further development of genome editing technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. An Outbreak of Streptococcus pyogenes in a Mental Health Facility: Advantage of Well-Timed Whole-Genome Sequencing Over emm Typing.

    PubMed

    Bergin, Sarah M; Periaswamy, Balamurugan; Barkham, Timothy; Chua, Hong Choon; Mok, Yee Ming; Fung, Daniel Shuen Sheng; Su, Alex Hsin Chuan; Lee, Yen Ling; Chua, Ming Lai Ivan; Ng, Poh Yong; Soon, Wei Jia Wendy; Chu, Collins Wenhan; Tan, Siyun Lucinda; Meehan, Mary; Ang, Brenda Sze Peng; Leo, Yee Sin; Holden, Matthew T G; De, Partha; Hsu, Li Yang; Chen, Swaine L; de Sessions, Paola Florez; Marimuthu, Kalisvar

    2018-05-09

    OBJECTIVEWe report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.SETTINGA 2,000-bed tertiary-care psychiatric hospital.METHODSActive surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)-based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.RESULTSThe study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1-C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0-5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21-45 and 26-58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.CONCLUSIONSWGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.Infect Control Hosp Epidemiol 2018;1-9.

  15. Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

    PubMed

    Lee, Ciaran M; Davis, Timothy H; Bao, Gang

    2018-04-01

    What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  16. Whole genome analysis of CRISPR Cas9 sgRNA off-target homologies via an efficient computational algorithm.

    PubMed

    Zhou, Hong; Zhou, Michael; Li, Daisy; Manthey, Joseph; Lioutikova, Ekaterina; Wang, Hong; Zeng, Xiao

    2017-11-17

    The beauty and power of the genome editing mechanism, CRISPR Cas9 endonuclease system, lies in the fact that it is RNA-programmable such that Cas9 can be guided to any genomic loci complementary to a 20-nt RNA, single guide RNA (sgRNA), to cleave double stranded DNA, allowing the introduction of wanted mutations. Unfortunately, it has been reported repeatedly that the sgRNA can also guide Cas9 to off-target sites where the DNA sequence is homologous to sgRNA. Using human genome and Streptococcus pyogenes Cas9 (SpCas9) as an example, this article mathematically analyzed the probabilities of off-target homologies of sgRNAs and discovered that for large genome size such as human genome, potential off-target homologies are inevitable for sgRNA selection. A highly efficient computationl algorithm was developed for whole genome sgRNA design and off-target homology searches. By means of a dynamically constructed sequence-indexed database and a simplified sequence alignment method, this algorithm achieves very high efficiency while guaranteeing the identification of all existing potential off-target homologies. Via this algorithm, 1,876,775 sgRNAs were designed for the 19,153 human mRNA genes and only two sgRNAs were found to be free of off-target homology. By means of the novel and efficient sgRNA homology search algorithm introduced in this article, genome wide sgRNA design and off-target analysis were conducted and the results confirmed the mathematical analysis that for a sgRNA sequence, it is almost impossible to escape potential off-target homologies. Future innovations on the CRISPR Cas9 gene editing technology need to focus on how to eliminate the Cas9 off-target activity.

  17. Perinatal and paediatric post-mortem magnetic resonance imaging (PMMR): sequences and technique

    PubMed Central

    Norman, Wendy; Jawad, Noorulhuda; Jones, Rod; Taylor, Andrew M

    2016-01-01

    As post-mortem MRI (PMMR) becomes more widely used for investigation following perinatal and paediatric deaths, the best possible images should be acquired. In this article, we review the most widely used published PMMR sequences, together with outlining our acquisition protocol and sequence parameters for foetal, perinatal and paediatric PMMR. We give examples of both normal and abnormal appearances, so that the reader can understand the logic behind each acquisition step before interpretation, as a useful day-to-day reference guide to performing PMMR. PMID:26916282

  18. Effect of Structured Touch and Guided Imagery for Pain and Anxiety in Elective Joint Replacement Patients--A Randomized Controlled Trial: M-TIJRP.

    PubMed

    Forward, John Brent; Greuter, Nancy Elizabeth; Crisall, Santa J; Lester, Houston F

    2015-01-01

    Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics. Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively. To investigate the effectiveness of the "M" Technique (M), a registered method of structured touch using a set sequence and number of strokes, and a consistent level of pressure on hands and feet, compared with guided imagery and usual care, for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery. Randomized controlled trial: M-TIJRP (MiTechnique and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a community hospital, 225 male and female patients, aged 38 to 90 years, undergoing elective total hip or knee replacement were randomly assigned to 1 of 3 groups (75 patients in each): M, guided imagery, or usual care. They were blinded to their assignment until the intervention. Reduction of pain and anxiety postoperatively. Secondary outcomes measured use of pain medication and patient satisfaction. This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care. M showed the largest predicted decreases in both pain and anxiety between groups. There was no significant difference in narcotic pain medication use between groups. Patient satisfaction survey ratings were highest for M, followed by guided imagery. The benefit of M may be because of the specifically structured sequence of touch by competent caring, trained providers.

  19. Effect of Structured Touch and Guided Imagery for Pain and Anxiety in Elective Joint Replacement Patients—A Randomized Controlled Trial: M-TIJRP

    PubMed Central

    Forward, John Brent; Greuter, Nancy Elizabeth; Crisall, Santa J; Lester, Houston F

    2015-01-01

    Context: Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics. Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively. Objective: To investigate the effectiveness of the “M” Technique (M), a registered method of structured touch using a set sequence and number of strokes, and a consistent level of pressure on hands and feet, compared with guided imagery and usual care, for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery. Methods: Randomized controlled trial: M-TIJRP (MiTechnique and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a community hospital, 225 male and female patients, aged 38 to 90 years, undergoing elective total hip or knee replacement were randomly assigned to 1 of 3 groups (75 patients in each): M, guided imagery, or usual care. They were blinded to their assignment until the intervention. Main Outcome Measures: Reduction of pain and anxiety postoperatively. Secondary outcomes measured use of pain medication and patient satisfaction. Results: This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care. M showed the largest predicted decreases in both pain and anxiety between groups. There was no significant difference in narcotic pain medication use between groups. Patient satisfaction survey ratings were highest for M, followed by guided imagery. Conclusion: The benefit of M may be because of the specifically structured sequence of touch by competent caring, trained providers. PMID:26222093

  20. ITS enhanced bus rapid transit. Research and deployment program. [Draft for comment

    DOT National Transportation Integrated Search

    2000-02-01

    The purpose of this guide is to provide a resource on worldwide transportation libraries and information centers for domestic and international professionals in the highway transportation field. This guide, Volume 1, is part of a multi-volume set of ...

  1. A Developmental Sequence Model to University Adjustment of International Undergraduate Students

    ERIC Educational Resources Information Center

    Chavoshi, Saeid; Wintre, Maxine Gallander; Dentakos, Stella; Wright, Lorna

    2017-01-01

    The current study proposes a Developmental Sequence Model to University Adjustment and uses a multifaceted measure, including academic, social and psychological adjustment, to examine factors predictive of undergraduate international student adjustment. A hierarchic regression model is carried out on the Student Adaptation to College Questionnaire…

  2. TIMSS 2011 User Guide for the International Database. Supplement 1: International Version of the TIMSS 2011 Background and Curriculum Questionnaires

    ERIC Educational Resources Information Center

    Foy, Pierre, Ed.; Arora, Alka, Ed.; Stanco, Gabrielle M., Ed.

    2013-01-01

    The TIMSS 2011 International Database includes data for all questionnaires administered as part of the TIMSS 2011 assessment. This supplement contains the international version of the TIMSS 2011 background questionnaires and curriculum questionnaires in the following 10 sections: (1) Fourth Grade Student Questionnaire; (2) Fourth Grade Home…

  3. TEDS-M 2008 User Guide for the International Database. Supplement 1: International Version of the TEDS-M Questionnaires

    ERIC Educational Resources Information Center

    Brese, Falk, Ed.

    2012-01-01

    The Teacher Education Study in Mathematics (TEDS-M) International Database includes data for all questionnaires administered as part of the TEDS-M study. These consisted of questionnaires administered to future teachers, educators, and institutions with teacher preparation programs. This supplement contains the international version of the TEDS-M…

  4. Teaching International Economics and Trade--Concepts in International Relations

    ERIC Educational Resources Information Center

    Starbird, Caroline; DeBoer, Dale; Pettit, Jenny

    2004-01-01

    The purpose of this book is to introduce students to real-life issues in international economics. The sections of the book are: (1) The Advantages of Trade; (2) Judging NAFTA; (3) Does Globalization Benefit Poor Countries?; (4) Pocket Guide to International Financial Institutions; (5) What Do You Know about the WTO?; (6) Free Trade and Shifting…

  5. 76 FR 46841 - Certain Products Containing Interactive Program Guides and Parental Controls Technology; Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-747] Certain Products Containing.... International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has determined not to review the presiding administrative law judge's (``ALJ'') initial...

  6. 75 FR 5351 - Proposed Revisions to Accounting Guide for LSC Recipients

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-02

    ... elements of an adequate accounting and financial reporting system, including the use of specific internal... checklist of accounting procedures and internal controls. The proposed revisions update the checklist to... accounting procedures and internal controls to reflect current best practices; (7) updated and new references...

  7. 75 FR 42786 - Accounting Guide for LSC Recipients (2010 Edition)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... adequate accounting and financial reporting system, including the use of specific internal controls and... the Accounting Procedures and Internal Control Checklist in Appendix VII. Sections G2, G3, and M of... the responsibilities of a recipient to maintain adequate accounting records and internal control...

  8. Health Education a Conceptual Approach. Growing and Developing, Interacting, Decision Making. Concept 2: Growing and Developing Follows a Predictable Sequence, Yet is Unique for Each Individual. Teacher-Student Resources.

    ERIC Educational Resources Information Center

    Creswell, William H., Jr.; And Others

    The following resource guide is one in a series which presents extensive bibliographic material oriented around a specific concept, in this guide, the predictability and uniqueness of growing and developing. A section is devoted to selected materials related to the concept; grade levels for which each resource might be useful are indicated beside…

  9. Ways to Experience Literature: A Reading-Communicating Program for High School Students. Guidebook II: Literature to Understand Others, Literature to Change Society, Literature to Discover Beauty.

    ERIC Educational Resources Information Center

    Kahn, Norma B.

    This guide focuses on literature to understand others, literature to change society, and literature to discover beauty. Designed primarily for independent use by students, several of the literary selections in each section of the guide are followed by the same sequence of questions so that students can develop a pattern for questioning themselves.…

  10. Ultrasonography-guided central venous catheterisation in haematological patients with severe thrombocytopenia

    PubMed Central

    Napolitano, Mariasanta; Malato, Alessandra; Raffaele, Francesco; Palazzolo, Manuela; Iacono, Giorgio Lo; Pinna, Roberto; Geraci, Girolamo; Modica, Giuseppe; Saccullo, Giorgia; Siragusa, Sergio; Cajozzo, Massimo

    2013-01-01

    Background Cannulation of the internal jugular vein (CVC) is a blind surface landmark-guided technique that could be potentially dangerous in patients with very low platelet counts. In such patients, ultrasonography (US)-guided CVC may be a valid approach. There is a lack of published data on the efficacy and safety of urgent US-guided CVC performed in haematological patients with severe thrombocytopenia. Materials and methods We retrospectively studied the safety of urgent CVC procedures in haematological patients including those with severe thrombocytopenia (platelet count <30×109/L). From January 1999 to June 2009, 431 CVC insertional procedures in 431 consecutive patients were evaluated. Patients were included in the study if they had a haematological disorder and required urgent CVC insertion. Patients were placed in Trendelenburg's position, an 18-gauge needle and guide-wire were advanced under real-time US guidance into the last part of the internal jugular vein; central venous cannulation of the internal jugular vein was performed using the Seldinger technique in all the procedures. Major and minor procedure-related complications were recorded. Results All 431 patients studied had haematological disorders: 39 had severe thrombocytopenia, refractory to platelet transfusion (group 1), while 392 did not have severe thrombocytopenia (group 2). The general characteristics of the patients in the two groups differed only for platelet count. The average time taken to perform the procedure was 4 minutes. Success rates were 97.4% and 97.9% in group 1 and group 2, respectively. No major complications occurred in either group. Discussion US-guided CVC is a safe and effective approach in haematological patients with severe thrombocytopenia requiring urgent cannulation for life support, plasma-exchange, chemotherapy and transfusion. PMID:23399356

  11. Clinical evaluation of panel testing by next-generation sequencing (NGS) for gene mutations in myeloid neoplasms.

    PubMed

    Au, Chun Hang; Wa, Anna; Ho, Dona N; Chan, Tsun Leung; Ma, Edmond S K

    2016-01-22

    Genomic techniques in recent years have allowed the identification of many mutated genes important in the pathogenesis of acute myeloid leukemia (AML). Together with cytogenetic aberrations, these gene mutations are powerful prognostic markers in AML and can be used to guide patient management, for example selection of optimal post-remission therapy. The mutated genes also hold promise as therapeutic targets themselves. We evaluated the applicability of a gene panel for the detection of AML mutations in a diagnostic molecular pathology laboratory. Fifty patient samples comprising 46 AML and 4 other myeloid neoplasms were accrued for the study. They consisted of 19 males and 31 females at a median age of 60 years (range: 18-88 years). A total of 54 genes (full coding exons of 15 genes and exonic hotspots of 39 genes) were targeted by 568 amplicons that ranged from 225 to 275 bp. The combined coverage was 141 kb in sequence length. Amplicon libraries were prepared by TruSight myeloid sequencing panel (Illumina, CA) and paired-end sequencing runs were performed on a MiSeq (Illumina) genome sequencer. Sequences obtained were analyzed by in-house bioinformatics pipeline, namely BWA-MEM, Samtools, GATK, Pindel, Ensembl Variant Effect Predictor and a novel algorithm ITDseek. The mean count of sequencing reads obtained per sample was 3.81 million and the mean sequencing depth was over 3000X. Seventy-seven mutations in 24 genes were detected in 37 of 50 samples (74 %). On average, 2 mutations (range 1-5) were detected per positive sample. TP53 gene mutations were found in 3 out of 4 patients with complex and unfavorable cytogenetics. Comparing NGS results with that of conventional molecular testing showed a concordance rate of 95.5 %. After further resolution and application of a novel bioinformatics algorithm ITDseek to aid the detection of FLT3 internal tandem duplication (ITD), the concordance rate was revised to 98.2 %. Gene panel testing by NGS approach was applicable for sensitive and accurate detection of actionable AML gene mutations in the clinical laboratory to individualize patient management. A novel algorithm ITDseek was presented that improved the detection of FLT3-ITD of varying length, position and at low allelic burden.

  12. A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

    PubMed

    Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

    2017-04-01

    After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

  13. Young Children's Development of Scientific Knowledge Through the Combination of Teacher-Guided Play and Child-Guided Play

    NASA Astrophysics Data System (ADS)

    Sliogeris, Marija; Almeida, Sylvia Christine

    2017-09-01

    Play-based approaches to science learning allow children to meaningfully draw on their everyday experiences and activities as they explore science concepts in context. Acknowledging the crucial role of the teacher in facilitating science learning through play, the purpose of this qualitative study was to examine how teacher-guided play, in conjunction with child-guided play, supports children's development of science concepts. While previous research on play-based science learning has mainly focused on preschool settings, this study explores the possibilities of play-based approaches to science in primary school contexts. Using a qualitative methodology grounded in the cultural-historical theoretical perspective, children's learning was examined during a science learning sequence that combined teacher-guided and child-guided play. This study revealed that the teacher-guided play explicitly introduced science concepts which children then used and explored in subsequent child-guided play. However, intentional teaching during the child-guided play continued to be important. Play-based approaches to science allowed children to make sense of the science concepts using familiar, everyday knowledge and activities. It became evident that the expectations and values communicated through classroom practices influenced children's learning through play.

  14. Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol.

    PubMed

    Bielinski, Suzette J; Olson, Janet E; Pathak, Jyotishman; Weinshilboum, Richard M; Wang, Liewei; Lyke, Kelly J; Ryu, Euijung; Targonski, Paul V; Van Norstrand, Michael D; Hathcock, Matthew A; Takahashi, Paul Y; McCormick, Jennifer B; Johnson, Kiley J; Maschke, Karen J; Rohrer Vitek, Carolyn R; Ellingson, Marissa S; Wieben, Eric D; Farrugia, Gianrico; Morrisette, Jody A; Kruckeberg, Keri J; Bruflat, Jamie K; Peterson, Lisa M; Blommel, Joseph H; Skierka, Jennifer M; Ferber, Matthew J; Black, John L; Baudhuin, Linnea M; Klee, Eric W; Ross, Jason L; Veldhuizen, Tamra L; Schultz, Cloann G; Caraballo, Pedro J; Freimuth, Robert R; Chute, Christopher G; Kullo, Iftikhar J

    2014-01-01

    To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR). We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. A 3-dimensional-printed patient-specific guide system for minimally invasive plate osteosynthesis of a comminuted mid-diaphyseal humeral fracture in a cat.

    PubMed

    Oxley, Bill

    2018-04-01

    To report the use of a 3-dimensional (3D)-printed patient-specific reduction guide system to facilitate minimally invasive plate osteosynthesis (MIPO) of a humeral fracture in a cat. Case report. A 9-year-old male neutered domestic short hair cat weighing 4.4 kg. A 9-year-old male domestic short hair cat was presented with a comminuted, mid-diaphyseal left humeral fracture. Computed tomographic data were processed to yield 3D mesh representations of both humeri and subsequently manipulated in computer-aided design software. The mirrored, intact humerus was used as a template for appropriate spatial orientation of the major proximal and distal fracture fragments. Patient-specific Ellis pin orientation guides and a reduction guide were designed and 3D printed. The guide system was used intraoperatively to align the major fracture fragments before application of locking internal fixation via standard MIPO surgical portals. Internal fixation of the fracture resulted in appropriate bone alignment. Recovery was uncomplicated, with early return to normal limb function and radiographic evidence of advanced fracture healing after 4 months. A 3D-printed patient-specific reduction guide system facilitated accurate alignment of a comminuted humeral fracture during MIPO without intraoperative imaging. © 2018 The American College of Veterinary Surgeons.

  16. Industrial Education. "Small Engines".

    ERIC Educational Resources Information Center

    Parma City School District, OH.

    Part of a series of curriculum guides dealing with industrial education in junior high schools, this guide provides the student with information and manipulative experiences on small gasoline engines. Included are sections on shop adjustment, safety, small engines, internal combustion, engine construction, four stroke engines, two stroke engines,…

  17. Recommendations from the 4th International Conference on Environmental Education, Ahmedabad, India

    ERIC Educational Resources Information Center

    Journal of Education for Sustainable Development, 2008

    2008-01-01

    The first set of international recommendations to guide environmental education (EE) was developed in Tbilisi, Georgia, in 1977. Ten years later, in 1987, a conference in Moscow, Russia, reviewed progress and focused on institutional strategies and action plans to strengthen environmental education. A third international environmental education…

  18. Internationally Yours: Writing and Communicating Successfully in Today's Global Marketplace.

    ERIC Educational Resources Information Center

    De Vries, Mary A.

    Intended to help international business people create business documents of style and substance for correspondents in many different cultures (correspondents whose second or even third language is English), this guide is extremely useful for the millions who travel internationally, work abroad, and correspond with business people in other…

  19. 78 FR 49766 - Certain Products Containing Interactive Program Guide and Parental Control Technology; Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-15

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-845] Certain Products Containing... a Final Initial Determination Finding No Violation of Section 337 AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has...

  20. Your International Business Plan. A Workbook.

    ERIC Educational Resources Information Center

    Otis, John W., Comp.

    Designed for firms who are seriously interested in expanding their business into international trade and who want to evaluate their prospects and potential for success, this workbook guides the reader through the steps in preparing an international business plan. Introductory sections explain how to use the workbook, offer a summary outline of an…

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

    NASA Astrophysics Data System (ADS)

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

    2018-04-01

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

  2. A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.

    PubMed

    Haque, Ashraful; Engel, Jessica; Teichmann, Sarah A; Lönnberg, Tapio

    2017-08-18

    RNA sequencing (RNA-seq) is a genomic approach for the detection and quantitative analysis of messenger RNA molecules in a biological sample and is useful for studying cellular responses. RNA-seq has fueled much discovery and innovation in medicine over recent years. For practical reasons, the technique is usually conducted on samples comprising thousands to millions of cells. However, this has hindered direct assessment of the fundamental unit of biology-the cell. Since the first single-cell RNA-sequencing (scRNA-seq) study was published in 2009, many more have been conducted, mostly by specialist laboratories with unique skills in wet-lab single-cell genomics, bioinformatics, and computation. However, with the increasing commercial availability of scRNA-seq platforms, and the rapid ongoing maturation of bioinformatics approaches, a point has been reached where any biomedical researcher or clinician can use scRNA-seq to make exciting discoveries. In this review, we present a practical guide to help researchers design their first scRNA-seq studies, including introductory information on experimental hardware, protocol choice, quality control, data analysis and biological interpretation.

  3. SILVA tree viewer: interactive web browsing of the SILVA phylogenetic guide trees.

    PubMed

    Beccati, Alan; Gerken, Jan; Quast, Christian; Yilmaz, Pelin; Glöckner, Frank Oliver

    2017-09-30

    Phylogenetic trees are an important tool to study the evolutionary relationships among organisms. The huge amount of available taxa poses difficulties in their interactive visualization. This hampers the interaction with the users to provide feedback for the further improvement of the taxonomic framework. The SILVA Tree Viewer is a web application designed for visualizing large phylogenetic trees without requiring the download of any software tool or data files. The SILVA Tree Viewer is based on Web Geographic Information Systems (Web-GIS) technology with a PostgreSQL backend. It enables zoom and pan functionalities similar to Google Maps. The SILVA Tree Viewer enables access to two phylogenetic (guide) trees provided by the SILVA database: the SSU Ref NR99 inferred from high-quality, full-length small subunit sequences, clustered at 99% sequence identity and the LSU Ref inferred from high-quality, full-length large subunit sequences. The Tree Viewer provides tree navigation, search and browse tools as well as an interactive feedback system to collect any kinds of requests ranging from taxonomy to data curation and improving the tool itself.

  4. Folding and Stabilization of Native-Sequence-Reversed Proteins

    PubMed Central

    Zhang, Yuanzhao; Weber, Jeffrey K; Zhou, Ruhong

    2016-01-01

    Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we investigate how the reverse-sequences of native proteins might fold by examining a series of small proteins of increasing structural complexity (α-helix, β-hairpin, α-helix bundle, and α/β-protein). Employing a tandem protein structure prediction algorithmic and molecular dynamics simulation approach, we find that the ability of reverse sequences to adopt native-like folds is strongly influenced by protein size and the flexibility of the native hydrophobic core. For β-hairpins with reverse-sequences that fail to fold, we employ a simple mutational strategy for guiding stable hairpin formation that involves the insertion of amino acids into the β-turn region. This systematic look at reverse sequence duality sheds new light on the problem of protein sequence-structure mapping and may serve to inspire new protein design and protein structure prediction protocols. PMID:27113844

  5. Folding and Stabilization of Native-Sequence-Reversed Proteins

    NASA Astrophysics Data System (ADS)

    Zhang, Yuanzhao; Weber, Jeffrey K.; Zhou, Ruhong

    2016-04-01

    Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we investigate how the reverse-sequences of native proteins might fold by examining a series of small proteins of increasing structural complexity (α-helix, β-hairpin, α-helix bundle, and α/β-protein). Employing a tandem protein structure prediction algorithmic and molecular dynamics simulation approach, we find that the ability of reverse sequences to adopt native-like folds is strongly influenced by protein size and the flexibility of the native hydrophobic core. For β-hairpins with reverse-sequences that fail to fold, we employ a simple mutational strategy for guiding stable hairpin formation that involves the insertion of amino acids into the β-turn region. This systematic look at reverse sequence duality sheds new light on the problem of protein sequence-structure mapping and may serve to inspire new protein design and protein structure prediction protocols.

  6. The diploid genome sequence of an Asian individual

    PubMed Central

    Wang, Jun; Wang, Wei; Li, Ruiqiang; Li, Yingrui; Tian, Geng; Goodman, Laurie; Fan, Wei; Zhang, Junqing; Li, Jun; Zhang, Juanbin; Guo, Yiran; Feng, Binxiao; Li, Heng; Lu, Yao; Fang, Xiaodong; Liang, Huiqing; Du, Zhenglin; Li, Dong; Zhao, Yiqing; Hu, Yujie; Yang, Zhenzhen; Zheng, Hancheng; Hellmann, Ines; Inouye, Michael; Pool, John; Yi, Xin; Zhao, Jing; Duan, Jinjie; Zhou, Yan; Qin, Junjie; Ma, Lijia; Li, Guoqing; Yang, Zhentao; Zhang, Guojie; Yang, Bin; Yu, Chang; Liang, Fang; Li, Wenjie; Li, Shaochuan; Li, Dawei; Ni, Peixiang; Ruan, Jue; Li, Qibin; Zhu, Hongmei; Liu, Dongyuan; Lu, Zhike; Li, Ning; Guo, Guangwu; Zhang, Jianguo; Ye, Jia; Fang, Lin; Hao, Qin; Chen, Quan; Liang, Yu; Su, Yeyang; san, A.; Ping, Cuo; Yang, Shuang; Chen, Fang; Li, Li; Zhou, Ke; Zheng, Hongkun; Ren, Yuanyuan; Yang, Ling; Gao, Yang; Yang, Guohua; Li, Zhuo; Feng, Xiaoli; Kristiansen, Karsten; Wong, Gane Ka-Shu; Nielsen, Rasmus; Durbin, Richard; Bolund, Lars; Zhang, Xiuqing; Li, Songgang; Yang, Huanming; Wang, Jian

    2009-01-01

    Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics. PMID:18987735

  7. Spread Spectrum Receiver Electromagnetic Interference (EMI) Test Guide

    NASA Technical Reports Server (NTRS)

    Wheeler, Mark L.

    1998-01-01

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

  8. Confirmatory factor analysis of teaching and learning guiding principles instrument among teacher educators in higher education institutions

    NASA Astrophysics Data System (ADS)

    Masuwai, Azwani; Tajudin, Nor'ain Mohd; Saad, Noor Shah

    2017-05-01

    The purpose of this study is to develop and establish the validity and reliability of an instrument to generate teaching and learning guiding principles using Teaching and Learning Guiding Principles Instrument (TLGPI). Participants consisted of 171 Malaysian teacher educators. It is an essential instrument to reflect in generating the teaching and learning guiding principles in higher education level in Malaysia. Confirmatory Factor Analysis has validated all 19 items of TLGPI whereby all items indicated high reliability and internal consistency. A Confirmatory Factor Analysis also confirmed that a single factor model was used to generate teaching and learning guiding principles.

  9. Analysis of sequence repeats of proteins in the PDB.

    PubMed

    Mary Rajathei, David; Selvaraj, Samuel

    2013-12-01

    Internal repeats in protein sequences play a significant role in the evolution of protein structure and function. Applications of different bioinformatics tools help in the identification and characterization of these repeats. In the present study, we analyzed sequence repeats in a non-redundant set of proteins available in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a protein, PDBeFOLD for assessing structural similarity, PDBsum for finding functional involvement and Pfam for domain assignment of the repeats in a protein. Through the analysis of sequence repeats, we found that identity of the sequence repeats falls in the range of 20-40% and, the superimposed structures of the most of the sequence repeats maintain similar overall folding. Analysis sequence repeats at the functional level reveals that most of the sequence repeats are involved in the function of the protein through functionally involved residues in the repeat regions. We also found that sequence repeats in single and two domain proteins often contained conserved sequence motifs for the function of the domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Assessment of phylogenetic relationship of rare plant species collected from Saudi Arabia using internal transcribed spacer sequences of nuclear ribosomal DNA.

    PubMed

    Al-Qurainy, F; Khan, S; Nadeem, M; Tarroum, M; Alaklabi, A

    2013-03-11

    The rare and endangered plants of any country are important genetic resources that often require urgent conservation measures. Assessment of phylogenetic relationships and evaluation of genetic diversity is very important prior to implementation of conservation strategies for saving rare and endangered plant species. We used internal transcribed spacer sequences of nuclear ribosomal DNA for the evaluation of sequence identity from the available taxa in the GenBank database by using the Basic Local Alignment Search Tool (BLAST). Two rare plant species viz, Heliotropium strigosum claded with H. pilosum (98% branch support) and Pancratium tortuosum claded with P. tenuifolium (61% branch support) clearly. However, some species, viz Scadoxus multiflorus, Commiphora myrrha and Senecio hadiensis showed close relationships with more than one species. We conclude that nuclear ribosomal internal transcribed spacer sequences are useful markers for phylogenetic study of these rare plant species in Saudi Arabia.

  11. Rational Protein Engineering Guided by Deep Mutational Scanning

    PubMed Central

    Shin, HyeonSeok; Cho, Byung-Kwan

    2015-01-01

    Sequence–function relationship in a protein is commonly determined by the three-dimensional protein structure followed by various biochemical experiments. However, with the explosive increase in the number of genome sequences, facilitated by recent advances in sequencing technology, the gap between protein sequences available and three-dimensional structures is rapidly widening. A recently developed method termed deep mutational scanning explores the functional phenotype of thousands of mutants via massive sequencing. Coupled with a highly efficient screening system, this approach assesses the phenotypic changes made by the substitution of each amino acid sequence that constitutes a protein. Such an informational resource provides the functional role of each amino acid sequence, thereby providing sufficient rationale for selecting target residues for protein engineering. Here, we discuss the current applications of deep mutational scanning and consider experimental design. PMID:26404267

  12. Teaching Time Concepts to Young Children.

    ERIC Educational Resources Information Center

    Muir, Sharon Pray

    1986-01-01

    Presents many activity ideas for teaching young children about time using chronological events, clocks, and calendars. Jerome Bruner's enactive-iconic-symbolic sequence of concept development is used as a guide for these learning experiences. (LP)

  13. PIRLS 2011 User Guide for the International Database. Supplement 1: International Version of the PIRLS 2011, Background Questionnaires and Curriculum Questionnaire

    ERIC Educational Resources Information Center

    Foy, Pierre, Ed.; Drucker, Kathleen T., Ed.

    2013-01-01

    The PIRLS 2011 international database includes data for all questionnaires administered as part of the PIRLS 2011 assessment. This supplement contains the international version of the PIRLS 2011 background questionnaires and curriculum questionnaires in the following 5 sections: (1) Student Questionnaire; (2) Home Questionnaire (Learning to Read…

  14. Programmable DNA-Guided Artificial Restriction Enzymes.

    PubMed

    Enghiad, Behnam; Zhao, Huimin

    2017-05-19

    Restriction enzymes are essential tools for recombinant DNA technology that have revolutionized modern biological research. However, they have limited sequence specificity and availability. Here we report a Pyrococcus furiosus Argonaute (PfAgo) based platform for generating artificial restriction enzymes (AREs) capable of recognizing and cleaving DNA sequences at virtually any arbitrary site and generating defined sticky ends of varying length. Short DNA guides are used to direct PfAgo to target sites for cleavage at high temperatures (>87 °C) followed by reannealing of the cleaved single stranded DNAs. We used this platform to generate over 18 AREs for DNA fingerprinting and molecular cloning of PCR-amplified or genomic DNAs. These AREs work as efficiently as their naturally occurring counterparts, and some of them even do not have any naturally occurring counterparts, demonstrating easy programmability, generality, versatility, and high efficiency for this new technology.

  15. Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans.

    PubMed

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-10-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy. Here, we review recent CRISPR/Cas9-based approaches to combat specific human viruses in humans and discuss challenges that need to be overcome before CRISPR/Cas9 may be used in the clinic as an antiviral strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Preliminary investigation of flow dynamics during the start-up of a bulb turbine model

    NASA Astrophysics Data System (ADS)

    Coulaud, M.; Fraser, R.; Lemay, J.; Duquesne, P.; Aeschlimann, V.; Deschênes, C.

    2016-11-01

    Nowadays, the electricity network undergoes more perturbations due to the market demand. Additionally, an increase of the production from alternative resources such as wind or solar also induces important variations on the grid. Hydraulic power plants are used to respond quickly to these variations to stabilize the network. Hydraulic turbines have to face more frequent start-up and stop sequences that might shorten significantly their life time. In this context, an experimental analysis of start-up sequences has been conducted on the bulb turbine model of the BulbT project at the Hydraulic Machines Laboratory (LAMH) of Laval University. Maintaining a constant head, guide vanes are opened from 0 ° to 30 °. Three guide vanes opening speed have been chosen from 5 °/s to 20 °/s. Several repetitions were done for each guide vanes opening speed. During these sequences, synchronous time resolved measurements have been performed. Pressure signals were recorded at the runner inlet and outlet and along the draft tube. Also, 25 pressure measurements and strain measurements were obtained on the runner blades. Time resolved particle image velocimetry were used to evaluate flowrate during start-up for some repetitions. Torque fluctuations at shaft were also monitored. This paper presents the experimental set-up and start-up conditions chosen to simulate a prototype start-up. Transient flowrate methodology is explained and validation measurements are detailed. The preliminary results of global performances and runner pressure measurements are presented.

  17. The Benefits of Guided Facility Self-Assessments

    ERIC Educational Resources Information Center

    O'Leary, Keith

    2012-01-01

    A growing number of educational institutions have discovered that a guided self-assessment solution helps them to consistently and cost-effectively obtain facility condition information and make better-informed capital planning decisions. Facility self-assessment employs a consistent, repeatable process for internal staff to quickly assess assets…

  18. Capturing the 'ome': the expanding molecular toolbox for RNA and DNA library construction.

    PubMed

    Boone, Morgane; De Koker, Andries; Callewaert, Nico

    2018-04-06

    All sequencing experiments and most functional genomics screens rely on the generation of libraries to comprehensively capture pools of targeted sequences. In the past decade especially, driven by the progress in the field of massively parallel sequencing, numerous studies have comprehensively assessed the impact of particular manipulations on library complexity and quality, and characterized the activities and specificities of several key enzymes used in library construction. Fortunately, careful protocol design and reagent choice can substantially mitigate many of these biases, and enable reliable representation of sequences in libraries. This review aims to guide the reader through the vast expanse of literature on the subject to promote informed library generation, independent of the application.

  19. PASTA: Ultra-Large Multiple Sequence Alignment for Nucleotide and Amino-Acid Sequences

    PubMed Central

    Mirarab, Siavash; Nguyen, Nam; Guo, Sheng; Wang, Li-San; Kim, Junhyong

    2015-01-01

    Abstract We introduce PASTA, a new multiple sequence alignment algorithm. PASTA uses a new technique to produce an alignment given a guide tree that enables it to be both highly scalable and very accurate. We present a study on biological and simulated data with up to 200,000 sequences, showing that PASTA produces highly accurate alignments, improving on the accuracy and scalability of the leading alignment methods (including SATé). We also show that trees estimated on PASTA alignments are highly accurate—slightly better than SATé trees, but with substantial improvements relative to other methods. Finally, PASTA is faster than SATé, highly parallelizable, and requires relatively little memory. PMID:25549288

  20. Single-Cell RNA-Sequencing in Glioma.

    PubMed

    Johnson, Eli; Dickerson, Katherine L; Connolly, Ian D; Hayden Gephart, Melanie

    2018-04-10

    In this review, we seek to summarize the literature concerning the use of single-cell RNA-sequencing for CNS gliomas. Single-cell analysis has revealed complex tumor heterogeneity, subpopulations of proliferating stem-like cells and expanded our view of tumor microenvironment influence in the disease process. Although bulk RNA-sequencing has guided our initial understanding of glioma genetics, this method does not accurately define the heterogeneous subpopulations found within these tumors. Single-cell techniques have appealing applications in cancer research, as diverse cell types and the tumor microenvironment have important implications in therapy. High cost and difficult protocols prevent widespread use of single-cell RNA-sequencing; however, continued innovation will improve accessibility and expand our of knowledge gliomas.

  1. "Visual Learning Is the Best Learning--It Lets You Be Creative while Learning": Exploring Ways to Begin Guided Writing in Second Language Learning through the Use of Comics

    ERIC Educational Resources Information Center

    Rossetto, Marietta; Chiera-Macchia, Antonella

    2011-01-01

    This study investigated the use of comics (Cary, 2004) in a guided writing experience in secondary school Italian language learning. The main focus of the peer group interaction task included the exploration of visual sequencing and visual integration (Bailey, O'Grady-Jones, & McGown, 1995) using image and text to create a comic strip narrative in…

  2. Spread Spectrum Receiver Electromagnetic Interference (EMI) Test Guide

    NASA Technical Reports Server (NTRS)

    Wheeler, M. L.

    1998-01-01

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

  3. Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona

    PubMed Central

    Gandhi, Shashank; Haeussler, Maximilian; Razy-Krajka, Florian; Christiaen, Lionel; Stolfi, Alberto

    2017-01-01

    The CRISPR/Cas9 system has emerged as an important tool for various genome engineering applications. A current obstacle to high throughput applications of CRISPR/Cas9 is the imprecise prediction of highly active single guide RNAs (sgRNAs). We previously implemented the CRISPR/Cas9 system to induce tissue-specific mutations in the tunicate Ciona. In the present study, we designed and tested 83 single guide RNA (sgRNA) vectors targeting 23 genes expressed in the cardiopharyngeal progenitors and surrounding tissues of Ciona embryo. Using high-throughput sequencing of mutagenized alleles, we identified guide sequences that correlate with sgRNA mutagenesis activity and used this information for the rational design of all possible sgRNAs targeting the Ciona transcriptome. We also describe a one-step cloning-free protocol for the assembly of sgRNA expression cassettes. These cassettes can be directly electroporated as unpurified PCR products into Ciona embryos for sgRNA expression in vivo, resulting in high frequency of CRISPR/Cas9-mediated mutagenesis in somatic cells of electroporated embryos. We found a strong correlation between the frequency of an Ebf loss-of-function phenotype and the mutagenesis efficacies of individual Ebf-targeting sgRNAs tested using this method. We anticipate that our approach can be scaled up to systematically design and deliver highly efficient sgRNAs for the tissue-specific investigation of gene functions in Ciona. PMID:28341547

  4. Metagenome assembly through clustering of next-generation sequencing data using protein sequences.

    PubMed

    Sim, Mikang; Kim, Jaebum

    2015-02-01

    The study of environmental microbial communities, called metagenomics, has gained a lot of attention because of the recent advances in next-generation sequencing (NGS) technologies. Microbes play a critical role in changing their environments, and the mode of their effect can be solved by investigating metagenomes. However, the difficulty of metagenomes, such as the combination of multiple microbes and different species abundance, makes metagenome assembly tasks more challenging. In this paper, we developed a new metagenome assembly method by utilizing protein sequences, in addition to the NGS read sequences. Our method (i) builds read clusters by using mapping information against available protein sequences, and (ii) creates contig sequences by finding consensus sequences through probabilistic choices from the read clusters. By using simulated NGS read sequences from real microbial genome sequences, we evaluated our method in comparison with four existing assembly programs. We found that our method could generate relatively long and accurate metagenome assemblies, indicating that the idea of using protein sequences, as a guide for the assembly, is promising. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction

    PubMed Central

    Guda, Swaroopa; Brendel, Christian; Renella, Raffaele; Du, Peng; Bauer, Daniel E; Canver, Matthew C; Grenier, Jennifer K; Grimson, Andrew W; Kamran, Sophia C; Thornton, James; de Boer, Helen; Root, David E; Milsom, Michael D; Orkin, Stuart H; Gregory, Richard I; Williams, David A

    2015-01-01

    RNA interference (RNAi) technology using short hairpin RNAs (shRNAs) expressed via RNA polymerase (pol) III promoters has been widely exploited to modulate gene expression in a variety of mammalian cell types. For certain applications, such as lineage-specific knockdown, embedding targeting sequences into pol II-driven microRNA (miRNA) architecture is required. Here, using the potential therapeutic target BCL11A, we demonstrate that pol III-driven shRNAs lead to significantly increased knockdown but also increased cytotoxcity in comparison to pol II-driven miRNA adapted shRNAs (shRNAmiR) in multiple hematopoietic cell lines. We show that the two expression systems yield mature guide strand sequences that differ by a 4 bp shift. This results in alternate seed sequences and consequently influences the efficacy of target gene knockdown. Incorporating a corresponding 4 bp shift into the guide strand of shRNAmiRs resulted in improved knockdown efficiency of BCL11A. This was associated with a significant de-repression of the hemoglobin target of BCL11A, human γ-globin or the murine homolog Hbb-y. Our results suggest the requirement for optimization of shRNA sequences upon incorporation into a miRNA backbone. These findings have important implications in future design of shRNAmiRs for RNAi-based therapy in hemoglobinopathies and other diseases requiring lineage-specific expression of gene silencing sequences. PMID:26080908

  6. 15 CFR 287.2 - Definitions. 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... International Organization for Standardization (ISO)/International Electrotechnical Commission (IEC), Guide 2 (1996). In certain industrial sectors, it is recognized that organizations other than ISO or IEC may...; supplier's declaration of conformity; certification; and quality and environmental management system...

  7. Active Learning in PhysicsTechnology and Research-based Techniques Emphasizing Interactive Lecture Demonstrations

    NASA Astrophysics Data System (ADS)

    Thornton, Ronald

    2010-10-01

    Physics education research has shown that learning environments that engage students and allow them to take an active part in their learning can lead to large conceptual gains compared to traditional instruction. Examples of successful curricula and methods include Peer Instruction, Just in Time Teaching, RealTime Physics, Workshop Physics, Scale-Up, and Interactive Lecture Demonstrations (ILDs). An active learning environment is often difficult to achieve in lecture sessions. This presentation will demonstrate the use of sequences of Interactive Lecture Demonstrations (ILDs) that use real experiments often involving real-time data collection and display combined with student interaction to create an active learning environment in large or small lecture classes. Interactive lecture demonstrations will be done in the area of mechanics using real-time motion probes and the Visualizer. A video tape of students involved in interactive lecture demonstrations will be shown. The results of a number of research studies at various institutions (including international) to measure the effectiveness of ILDs and guided inquiry conceptual laboratories will be presented.

  8. Progress toward studies of bubble-geometry Bose-Einstein condensates in microgravity with a ground-based prototype of NASA CAL

    NASA Astrophysics Data System (ADS)

    Lundblad, Nathan; Jarvis, Thomas; Paseltiner, Daniel; Lannert, Courtney

    2016-05-01

    We have proposed using NASA's Cold Atom Laboratory (CAL, launching to the International Space Station in 2017) to generate bubble-geometry Bose-Einstein condensates through radiofrequency dressing of an atom-chip magnetic trap. This geometry has not been truly realized terrestrially due to the perturbing influence of gravity, making it an ideal candidate for microgravity investigation aboard CAL. We report progress in the construction of a functional prototype of the orbital BEC apparatus: a compact atom-chip machine loaded by a 2D+MOT source, conventional 3D MOT, quadrupole trap, and transfer coil. We also present preliminary modeling of the dressed trap uniformity, which will crucially inform the geometric closure of the BEC shell surface as atom number, bubble radius, and bubble aspect ratio are varied. Finally, we discuss plans for experimental sequences to be run aboard CAL guided by intuition from ground-based prototype operation. JPL 1502172.

  9. A sensorimotor theory of temporal tracking and beat induction.

    PubMed

    Todd, N P McAngus; Lee, C S; O'Boyle, D J

    2002-02-01

    In this paper, we develop a theory of the neurobiological basis of temporal tracking and beat induction as a form of sensory-guided action. We propose three principal components for the neurological architecture of temporal tracking: (1) the central auditory system, which represents the temporal information in the input signal in the form of a modulation power spectrum; (2) the musculoskeletal system, which carries out the action and (3) a controller, in the form of a parieto-cerebellar-frontal loop, which carries out the synchronisation between input and output by means of an internal model of the musculoskeletal dynamics. The theory is implemented in the form of a computational algorithm which takes sound samples as input and synchronises a simple linear mass-spring-damper system to simulate audio-motor synchronisation. The model may be applied to both the tracking of isochronous click sequences and beat induction in rhythmic music or speech, and also accounts for the approximate Weberian property of timing.

  10. Improved Atomistic Monte Carlo Simulations Demonstrate that Poly-L-Proline Adopts Heterogeneous Ensembles of Conformations of Semi-Rigid Segments Interrupted by Kinks

    PubMed Central

    Radhakrishnan, Aditya; Vitalis, Andreas; Mao, Albert H.; Steffen, Adam T.; Pappu, Rohit V.

    2012-01-01

    Poly-L-proline (PLP) polymers are useful mimics of biologically relevant proline-rich sequences. Biophysical and computational studies of PLP polymers in aqueous solutions are challenging because of the diversity of length scales and the slow time scales for conformational conversions. We describe an atomistic simulation approach that combines an improved ABSINTH implicit solvation model, with conformational sampling based on standard and novel Metropolis Monte Carlo moves. Refinements to forcefield parameters were guided by published experimental data for proline-rich systems. We assessed the validity of our simulation results through quantitative comparisons to experimental data that were not used in refining the forcefield parameters. Our analysis shows that PLP polymers form heterogeneous ensembles of conformations characterized by semi-rigid, rod-like segments interrupted by kinks, which result from a combination of internal cis peptide bonds, flexible backbone ψ-angles, and the coupling between ring puckering and backbone degrees of freedom. PMID:22329658

  11. Methods for decoding Cas9 protospacer adjacent motif (PAM) sequences: A brief overview.

    PubMed

    Karvelis, Tautvydas; Gasiunas, Giedrius; Siksnys, Virginijus

    2017-05-15

    Recently the Cas9, an RNA guided DNA endonuclease, emerged as a powerful tool for targeted genome manipulations. Cas9 protein can be reprogrammed to cleave, bind or nick any DNA target by simply changing crRNA sequence, however a short nucleotide sequence, termed PAM, is required to initiate crRNA hybridization to the DNA target. PAM sequence is recognized by Cas9 protein and must be determined experimentally for each Cas9 variant. Exploration of Cas9 orthologs could offer a diversity of PAM sequences and novel biochemical properties that may be beneficial for genome editing applications. Here we briefly review and compare Cas9 PAM identification assays that can be adopted for other PAM-dependent CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Motor set in Parkinson's disease.

    PubMed Central

    Robertson, C; Flowers, K A

    1990-01-01

    Three experiments employing a five-choice button-pressing task tested the ability of Parkinsonian patients to learn and generate sequences of movement, and to switch between alternative sequences at will. It was found that patients could learn and generate individual patterns of movement normally, even complex ones involving an incompatible stimulus-response relationship. They had difficulty, however, in maintaining a sequence if two different ones had been learnt and subjects were required to switch spontaneously from one to the other within a trial. Providing external cues at the start of each sequence to guide the ordering of movements improved the stability of patients' performance. Most errors in sequencing consisted of reverting to the alternative pattern of movement. Parkinsonian subjects thus show an impairment in motor set similar to that found previously in cognitive activity. Images PMID:2391523

  13. 2013 Progress Report -- DOE Joint Genome Institute

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

    None

    2013-11-01

    In October 2012, we introduced a 10-Year Strategic Vision [http://bit.ly/JGI-Vision] for the Institute. A central focus of this Strategic Vision is to bridge the gap between sequenced genomes and an understanding of biological functions at the organism and ecosystem level. This involves the continued massive-scale generation of sequence data, complemented by orthogonal new capabilities to functionally annotate these large sequence data sets. Our Strategic Vision lays out a path to guide our decisions and ensure that the evolving set of experimental and computational capabilities available to DOE JGI users will continue to enable groundbreaking science.

  14. A GUIDE TO UNDERSTANDING WORLD AFFAIRS.

    ERIC Educational Resources Information Center

    ROGERS, WILLIAM C.

    WRITTEN IN EVERYDAY ENGLISH, THIS READING BOOK PRESENTS MANY FACTS AND IDEAS ABOUT WORLD AFFAIRS. CHAPTERS COVER INTERNATIONAL LIFE, POWER IN WORLD AFFAIRS, WAR AS INTERNATIONAL CONFLICT, THE MEANS AND VARIETIES OF ARMED CONFLICT, INTERNATIONAL CONFLICT SHORT OF WAR, THE ACCOMMODATION OF CONFLICT IN WORLD AFFAIRS, AND PEACE--WHAT IT IS AND HOW TO…

  15. Politics and Pedagogy: Discursive Constructions in the IB "Theory of Knowledge--Guide"

    ERIC Educational Resources Information Center

    Smith, Nigel V.; Morgan, Mandy

    2010-01-01

    The International Baccalaureate (IB) curriculum is increasingly popular in both national and international secondary education settings. The "Theory of knowledge" (TOK) course is cast as the prime example of the international globalised values the IB Diploma represents. This article argues that such a positioning is contested within the TOK…

  16. Engaging the Discourse of International Language Recognition through ISO 639-3 Signed Language Change Requests

    ERIC Educational Resources Information Center

    Parks, Elizabeth

    2015-01-01

    Linguistic ideologies that are left unquestioned and unexplored, especially as reflected and produced in marginalized language communities, can contribute to inequality made real in decisions about languages and the people who use them. One of the primary bodies of knowledge guiding international language policy is the International Organization…

  17. Think Globally! Enhancing the International Student Experience with LibGuides

    ERIC Educational Resources Information Center

    Han, Ning; Hall, Susan L.

    2012-01-01

    Enrollment of international students in colleges and universities across the United States is growing. The relocation process can be arduous for international students as they face many barriers transitioning to a new environment. With retention as a key component in the success of academic institutions, what resources and services can academic…

  18. Reflections of Single Turkish International Graduate Students: Studies on Life at a Midwestern University

    ERIC Educational Resources Information Center

    Burkholder, Jessica Reno

    2010-01-01

    The research was guided by the research question: How do full-time single Turkish international graduate students conceptualize their experiences as international students? Participants in the study included three doctoral students and three master's students who participated in a series of semi-structured interviews. The data was transcribed and…

  19. 78 FR 35642 - Certain TV Programs, Literary Works for TV Production and Episode Guides Pertaining to Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... INTERNATIONAL TRADE COMMISSION [Docket No 2959] Certain TV Programs, Literary Works for TV... Relating to the Public Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has received a complaint entitled...

  20. International Relations: A Student's Guide to Reference Resources.

    ERIC Educational Resources Information Center

    Silvester, Elizabeth

    Intended for students, this annotated bibliography describes reference materials in International Relations that may be found in either the McLennan or Law Library of McGill University. Scope includes political science, international law, and related areas in the social and behavioral sciences, but titles which relate to the foreign relations of a…

  1. Manual for Building an International Education Program in the Community College.

    ERIC Educational Resources Information Center

    Campion, William J.; Bostic, Don

    Designed as a resource guide for establishing an international education program at a community college, this handbook provides descriptions of procedures and sample forms utilized in the establishment of an Office of International Education (OIE) at Central Florida Community College (CFCC). The first section, describes the role of the OIE in…

  2. "Tell Me What to Do" vs. "Guide Me through It": Feedback Experiences of International Doctoral Students

    ERIC Educational Resources Information Center

    Wang, Ting; Li, Linda Y.

    2011-01-01

    Despite increasing attention to the challenges of supervising international doctoral students, little research has been conducted to examine supervisory feedback practice with international students and its impact on the thesis writing process. This exploratory qualitative study seeks to fill the gap and contribute to understanding the feedback…

  3. ILGWU Worker-Family Education Program Curriculum Guide, 1989-1990.

    ERIC Educational Resources Information Center

    Freeman, Deidre; LaMar, Maureen

    This teacher's guide for the International Ladies' Garment Workers' Union (ILGWU) educational program provides background information, instructional materials, and instructional techniques for teaching a course in job skills and issues, with emphasis on the development of English language skills. The course is made available to union members and…

  4. Bilingualism and Education in the United States: A Resource Guide.

    ERIC Educational Resources Information Center

    Karski, Joan Leonard

    The guide is intended to introduce education professionals and interested groups to government resources and provide strategies for obtaining information on bilingualism and education in the United States. It consists primarily of annotated listings of federal government publications, but also includes some state and international resources. An…

  5. An Institutional Approach to the Evaluation of Educational Technology.

    ERIC Educational Resources Information Center

    Kennedy, Gregor E.

    2003-01-01

    Outlines an institutional approach that guides the evaluation of educational technology in the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne (Victoria, Australia). Roles for an internal evaluator and educational technology practitioners are proposed, and a conceptual framework that guides the evaluation process…

  6. Softball Guide with Official Rules. January 1972 - January 1974.

    ERIC Educational Resources Information Center

    Claussen, Connie, Ed.

    This guide, published by the Division for Girls and Women's Sports (DGWS) of the American Association for Health, Physical Education, and Recreation (AAHPER) presents a statement of DGWS beliefs, standards in sports, sources of information and international committee rules. It details various affiliated boards of officials and presents the…

  7. Resource Guide for Persons with Speech or Language Impairments.

    ERIC Educational Resources Information Center

    IBM, Atlanta, GA. National Support Center for Persons with Disabilities.

    The resource guide identifies products which assist speech or language impaired individuals in accessing IBM (International Business Machine) Personal Computers or the IBM Personal System/2 family of products. An introduction provides a general overview of ways computers can help persons with speech or language handicaps. The document then…

  8. The Complete Guide to Training Delivery: A Competency-Based Approach.

    ERIC Educational Resources Information Center

    King, Stephen B.; King, Marsha; Rothwell, William J.

    This guide focuses on 14 instructor competencies identified by the International Board of Standards for Training, Performance, and Instruction. It provides examples, job aids, worksheets, case studies, and sample dialogs and contains actual experiences and critical incidents faced by trainers who participated in the survey study. Strategies to…

  9. 78 FR 6765 - Amendment to the International Traffic in Arms Regulations: Revision of U.S. Munitions List...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... revise Category IV (launch vehicles, guided missiles, ballistic missiles, rockets, torpedoes, bombs, and... revises USML Category IV (launch vehicles, guided missiles, ballistic missiles, rockets, torpedoes, bombs... missiles, rockets, torpedoes, bombs, and mines whose jurisdiction would be in doubt based on this revision...

  10. Key Skills Portfolio Assessment: Good Practice Guide

    ERIC Educational Resources Information Center

    Rolfe, Martin; Wilson, Lorraine

    2007-01-01

    This guide offers advice and guidance to key skills managers, coordinators and other practitioners who are responsible for ensuring that the standards of portfolio assessment in their center are consistent across the center and with national standards. It describes and offers advice and guidance on the stages of assessment and internal moderation…

  11. Educators Resource Guide to WP Material for the Classroom.

    ERIC Educational Resources Information Center

    Potts, Peggy J.

    This guide lists materials to be used in the classroom instruction of word processing technology. A listing of international, national, and regional word processing associations is followed by an annotated enumeration of resources under nine headings: (1) booklets and brochures, (2) books, (3) films, (4) handbooks, (5) machine transcription…

  12. Resources on Civic Education for Democracy: International Perspectives. Yearbook No. 2.

    ERIC Educational Resources Information Center

    Pinhey, Laura A., Ed.; Boyer, Candace L., Ed.

    This resource guide is intended to facilitate cooperation and exchange of knowledge among civic educators around the world. The guide is divided into six parts. Part 1 consists of three civic education papers: "Education and Democratic Citizenship: Where We Stand" (Albert Shanker); "Civil Society and Democracy Reconsidered"…

  13. 33 CFR 156.111 - Incorporation by reference.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html..., England. Ship to Ship Transfer Guide (Petroleum), Second Edition, 1988—156.330. International Chamber of Shipping 12 Carthusian Street, London EC1M 6EB, England. Guide to Helicopter/Ship Operations, Third Edition...

  14. 33 CFR 156.111 - Incorporation by reference.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html..., England. Ship to Ship Transfer Guide (Petroleum), Second Edition, 1988—156.330. International Chamber of Shipping 12 Carthusian Street, London EC1M 6EB, England. Guide to Helicopter/Ship Operations, Third Edition...

  15. 33 CFR 156.111 - Incorporation by reference.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html..., England. Ship to Ship Transfer Guide (Petroleum), Second Edition, 1988—156.330. International Chamber of Shipping 12 Carthusian Street, London EC1M 6EB, England. Guide to Helicopter/Ship Operations, Third Edition...

  16. 33 CFR 156.111 - Incorporation by reference.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html..., England. Ship to Ship Transfer Guide (Petroleum), Second Edition, 1988—156.330. International Chamber of Shipping 12 Carthusian Street, London EC1M 6EB, England. Guide to Helicopter/Ship Operations, Third Edition...

  17. 33 CFR 156.111 - Incorporation by reference.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html..., England. Ship to Ship Transfer Guide (Petroleum), Second Edition, 1988—156.330. International Chamber of Shipping 12 Carthusian Street, London EC1M 6EB, England. Guide to Helicopter/Ship Operations, Third Edition...

  18. Learning about Leadership from a Visit to the Art Museum

    ERIC Educational Resources Information Center

    Kaimal, Girija; Drescher, Jon; Fairbank, Holly; Gonzaga, Adele M. L.; Junkin, Janelle S.; White, George P.

    2016-01-01

    This qualitative study presents an analysis of how guided visits to an art museum can provide leadership lessons for developing school leaders. The principal interns participated in teaching artists-facilitated guided arts engagement sessions at a large metropolitan museum. The sessions included art-making, observations of portraiture in the…

  19. Y.E.S. International Entomology Resource Guide. Second Edition. Special Publication No. 2.

    ERIC Educational Resources Information Center

    Dunn, Gary A., Comp.

    This resource guide is designed to provide Young Entomologists' Society (Y.E.S.) members and other interested entomologists with information on people and companies that sell entomological equipment, supplies, services, preserved and dried specimens, livestock, books, publications, slides and other visuals, gift or novelty items, and…

  20. Helping Students Overcome Depression and Anxiety: A Practical Guide. Second Edition

    ERIC Educational Resources Information Center

    Merrell, Kenneth W.

    2008-01-01

    This guide provides expert information and clear-cut strategies for assessing and treating internalizing problems in school settings. More than 40 specific psychoeducational and psychosocial intervention techniques are detailed, with a focus on approaches that are evidence based, broadly applicable, and easy to implement. Including 26…

  1. Asian Higher Education: An International Handbook and Reference Guide.

    ERIC Educational Resources Information Center

    Postiglione, Gerard A., Ed.; Mak, Grace C., Ed.

    This book is a guide to the present academic systems of twenty Asian countries and political units. Data provided in each chapter include a historical overview, description of the current system, funding support, enrollment rates, and overall organization of higher education. The chapters include: (1) "Bangladesh" (Kowsar P. Chowdhury);…

  2. Wheat for Kids! [and] Teacher's Guide.

    ERIC Educational Resources Information Center

    Idaho Wheat Commission, Boise.

    "Wheat for Kids" contains information at the elementary school level about: the structure of the wheat kernel; varieties of wheat and their uses; growing wheat; making wheat dough; the U.S. Department of Agriculture Food Guide Pyramid and nutrition; Idaho's part of the international wheat market; recipes; and word games based on the…

  3. 75 FR 22424 - Avalotis Corp.; Grant of a Permanent Variance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-28

    ... International, LLC, and Matrix Service Industrial Contractors, Inc.), and 71 FR 10557 (Commonwealth Dynamics... of damage or defects at all times. (b) Guide rope fastening and alignment tension. The employer must fasten one end of each guide rope securely to the overhead support, with appropriate tension applied at...

  4. Further Food for Thought on the "ABS Guide"

    ERIC Educational Resources Information Center

    Hussain, Simon

    2012-01-01

    This paper replies to points raised by the editors of the "ABS Guide", Huw Morris, Charles Harvey, Aidan Kelly and Michael Rowlinson (2011) "Accounting Education: an international journal", 20(6), pp. 561-573) in response to a paper published in a previous issue of "Accounting Education" (Hussain, S. (2011)…

  5. Planetarium Educator's Workshop Guide. International Planetarium Society Special Report No. 10.

    ERIC Educational Resources Information Center

    Friedman, Alan; And Others

    Presented is a workshop guide for planetarium educators. Seven modules and four appendices focus on organizational patterns, learning theories, questioning strategies, activities for the planetarium, and incorporating all of the above into teaching. The four appendices include a list of the 1978 workshop participants, an annotated bibliography for…

  6. Success rate and complications of internal jugular vein catheterization with and without ultrasonography guide.

    PubMed

    Karimi-Sari, Hamidreza; Faraji, Mehrdad; Mohazzab Torabi, Saman; Asjodi, Gholamreza

    2014-12-01

    Central venous catheterization (CVC) is an important procedure in emergency departments (EDs). Despite existence of ultrasonography (US) devices in every ED, CVC is done using anatomical landmarks in many EDs in Iran. This study aimed to compare the traditional landmark method vs. US-guided method of CVC placement in terms of complications and success rate. In this randomized controlled trial, patients who were candidate for internal jugular vein catheterization, and referred to Baqiyatallah Hospital ED were randomly allocated into US-guided CVC and anatomical landmarks guided CVC groups. Central vein access time, number of attempts, success rate, and complications in each group were evaluated. Mann-Whitney U, chi-square and Fisher exact tests along with Pearson and Spearman correlation coefficients were used to analyze the data. Out of 100 patients, 56 were male and 44 were female. No significant differences were found between the US-guided and traditional landmark methods of CVC insertion in terms of age, gender, BMI, and site of catheter insertion. The mean access time was significantly lower in the US-guided group (37.12 ± 17.33 s vs. 63.42 ± 35.19 s, P < 0.001). The mean number of attempts was also significantly lower in the US-guided group (1.12 ± 0.3 vs. 1.58 ± 0.64 times, P < 0.001). Eighty-eight percent of patients in the US-guided group were catheterized in the first attempt, while 50% of patients in the traditional landmark group were catheterized in the second or more attempts (P < 0.001). The success rate was 100% in the US-guided group, while it was 88% in the landmark group (P = 0.013). Moreover, the rate of complications was significantly lower in the US-guided group (4% vs. 24%, P = 0.004). The US-guided method for CVC placement was superior to the traditional landmark method in terms of access time, number of attempts, success rate, and fewer complications.

  7. The Clinical Use of Hypnotic Regression and Progression in Psychotherapy.

    ERIC Educational Resources Information Center

    Goldberg, Bruce

    1990-01-01

    Discusses concept of time in therapy, presenting theoretical and clinical foundations to illustrate the validity of guiding patients into past lives and future lifetimes through hypnosis to resolve self-defeating sequences. (Author/TE)

  8. Draft Genome Sequences of Two Aspergillus fumigatus Strains, Isolated from the International Space Station.

    PubMed

    Singh, Nitin Kumar; Blachowicz, Adriana; Checinska, Aleksandra; Wang, Clay; Venkateswaran, Kasthuri

    2016-07-14

    Draft genome sequences of Aspergillus fumigatus strains (ISSFT-021 and IF1SW-F4), opportunistic pathogens isolated from the International Space Station (ISS), were assembled to facilitate investigations of the nature of the virulence characteristics of the ISS strains to other clinical strains isolated on Earth. Copyright © 2016 Singh et al.

  9. CATH-Gene3D: Generation of the Resource and Its Use in Obtaining Structural and Functional Annotations for Protein Sequences.

    PubMed

    Dawson, Natalie L; Sillitoe, Ian; Lees, Jonathan G; Lam, Su Datt; Orengo, Christine A

    2017-01-01

    This chapter describes the generation of the data in the CATH-Gene3D online resource and how it can be used to study protein domains and their evolutionary relationships. Methods will be presented for: comparing protein structures, recognizing homologs, predicting domain structures within protein sequences, and subclassifying superfamilies into functionally pure families, together with a guide on using the webpages.

  10. Genomic Sequence Variation Markup Language (GSVML).

    PubMed

    Nakaya, Jun; Kimura, Michio; Hiroi, Kaei; Ido, Keisuke; Yang, Woosung; Tanaka, Hiroshi

    2010-02-01

    With the aim of making good use of internationally accumulated genomic sequence variation data, which is increasing rapidly due to the explosive amount of genomic research at present, the development of an interoperable data exchange format and its international standardization are necessary. Genomic Sequence Variation Markup Language (GSVML) will focus on genomic sequence variation data and human health applications, such as gene based medicine or pharmacogenomics. We developed GSVML through eight steps, based on case analysis and domain investigations. By focusing on the design scope to human health applications and genomic sequence variation, we attempted to eliminate ambiguity and to ensure practicability. We intended to satisfy the requirements derived from the use case analysis of human-based clinical genomic applications. Based on database investigations, we attempted to minimize the redundancy of the data format, while maximizing the data covering range. We also attempted to ensure communication and interface ability with other Markup Languages, for exchange of omics data among various omics researchers or facilities. The interface ability with developing clinical standards, such as the Health Level Seven Genotype Information model, was analyzed. We developed the human health-oriented GSVML comprising variation data, direct annotation, and indirect annotation categories; the variation data category is required, while the direct and indirect annotation categories are optional. The annotation categories contain omics and clinical information, and have internal relationships. For designing, we examined 6 cases for three criteria as human health application and 15 data elements for three criteria as data formats for genomic sequence variation data exchange. The data format of five international SNP databases and six Markup Languages and the interface ability to the Health Level Seven Genotype Model in terms of 317 items were investigated. GSVML was developed as a potential data exchanging format for genomic sequence variation data exchange focusing on human health applications. The international standardization of GSVML is necessary, and is currently underway. GSVML can be applied to enhance the utilization of genomic sequence variation data worldwide by providing a communicable platform between clinical and research applications. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  11. Addiction Science: A Rationale and Tools for a Public Health Response to Drug Abuse

    PubMed Central

    Rawson, Richard A.; Rieckmann, Traci; Gust, Steven W.

    2014-01-01

    New scientific knowledge and effective, evidence-based interventions have provided health leaders and policymakers a remarkable paradigm to guide the development of addiction treatment services around the world. The definition of addiction as a brain disease, validated screening and assessment tools, medication-assisted treatment, and effective behavioral treatments have served as vehicles for both the United States and other countries to guide the transformation of their substance abuse treatment systems. Seeking to expand international research and infrastructure, the National Institute on Drug Abuse (NIDA)'s International Program has engaged international investigators and institutions in addiction research to promote dissemination of addiction science globally. This paper presents three mixed-methods case studies to exemplify the use of advancements in evidence-based practice in addiction treatment as guides and tools for the creation or further development of treatment systems in three countries, Vietnam, Lebanon, and Abu Dhabi. Results indicate that a framework of evidence-based medicine and empirical science creates a necessary platform from which objective conversations about addictions may begin. Other facilitative factors that help create treatment programs internationally include: a receptive and supportive government, support from international donors and technical experts, networking and interest from other international organizations, and often a synergistic and concerted effort by multiple entities and partners. Despite substantial differences in the circumstances that generated these initiatives and the varying scope of the services, common themes across these efforts have been the implementation of science-based approaches to systems transformation and support for a public health approach to addressing drug abuse and addiction. PMID:26752803

  12. GuideLiner™ as guide catheter extension for the unreachable mammary bypass graft.

    PubMed

    Vishnevsky, Alec; Savage, Michael P; Fischman, David L

    2018-03-09

    Percutaneous coronary intervention (PCI) of mammary artery bypass grafts through a trans-radial (TR) approach can present unique challenges, including coaxial vessel engagement of the guiding catheter, adequate visualization of the target lesion, sufficient backup support for equipment delivery, and the ability to reach very distal lesions. The GuideLiner catheter, a rapid exchange monorail mother-in-daughter system, facilitates successful interventions in such challenging anatomy. We present a case of a patient undergoing PCI of a right internal mammary artery (RIMA) graft via TR access in whom the graft could not be engaged with any guiding catheter. Using a balloon tracking technique over a guidewire, a GuideLiner was placed as an extension of the guiding catheter and facilitated TR-PCI by overcoming technical challenges associated with difficult anatomy. © 2018 Wiley Periodicals, Inc.

  13. Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group.

    PubMed

    Gray, Stacy W; Martins, Yolanda; Feuerman, Lindsay Z; Bernhardt, Barbara A; Biesecker, Barbara B; Christensen, Kurt D; Joffe, Steven; Rini, Christine; Veenstra, David; McGuire, Amy L

    2014-10-01

    The routine use of genomic sequencing in clinical medicine has the potential to dramatically alter patient care and medical outcomes. To fully understand the psychosocial and behavioral impact of sequencing integration into clinical practice, it is imperative that we identify the factors that influence sequencing-related decision making and patient outcomes. In an effort to develop a collaborative and conceptually grounded approach to studying sequencing adoption, members of the National Human Genome Research Institute's Clinical Sequencing Exploratory Research Consortium formed the Outcomes and Measures Working Group. Here we highlight the priority areas of investigation and psychosocial and behavioral outcomes identified by the Working Group. We also review some of the anticipated challenges to measurement in social and behavioral research related to genomic sequencing; opportunities for instrument development; and the importance of qualitative, quantitative, and mixed-method approaches. This work represents the early, shared efforts of multiple research teams as we strive to understand individuals' experiences with genomic sequencing. The resulting body of knowledge will guide recommendations for the optimal use of sequencing in clinical practice.

  14. Manufacturing Planning Guide

    NASA Technical Reports Server (NTRS)

    Waid, Michael

    2011-01-01

    Manufacturing process, milestones and inputs are unknowns to first-time users of the manufacturing facilities. The Manufacturing Planning Guide aids in establishing expectations for both NASA and non-NASA facility customers. The potential audience for this guide includes both internal and commercial spaceflight hardware/software developers. It is intended to assist their project engineering personnel in manufacturing planning and execution. Material covered includes a roadmap of the manufacturing process, roles and responsibilities of facility and user, major milestones, facility capabilities, and inputs required by the facility. Samples of deliverables, products, and inputs necessary to define test scope, cost, and schedule are included as an appendix to the guide.

  15. SOBA: sequence ontology bioinformatics analysis.

    PubMed

    Moore, Barry; Fan, Guozhen; Eilbeck, Karen

    2010-07-01

    The advent of cheaper, faster sequencing technologies has pushed the task of sequence annotation from the exclusive domain of large-scale multi-national sequencing projects to that of research laboratories and small consortia. The bioinformatics burden placed on these laboratories, some with very little programming experience can be daunting. Fortunately, there exist software libraries and pipelines designed with these groups in mind, to ease the transition from an assembled genome to an annotated and accessible genome resource. We have developed the Sequence Ontology Bioinformatics Analysis (SOBA) tool to provide a simple statistical and graphical summary of an annotated genome. We envisage its use during annotation jamborees, genome comparison and for use by developers for rapid feedback during annotation software development and testing. SOBA also provides annotation consistency feedback to ensure correct use of terminology within annotations, and guides users to add new terms to the Sequence Ontology when required. SOBA is available at http://www.sequenceontology.org/cgi-bin/soba.cgi.

  16. A decade of aeroacoustic research at NASA Ames Research Center

    NASA Technical Reports Server (NTRS)

    Schmitz, Frederic H.; Mosher, M.; Kitaplioglu, Cahit; Cross, J.; Chang, I.

    1988-01-01

    The rotorcraft aeroacoustic research accomplishments of the past decade at Ames Research Center are reviewed. These include an extensive sequence of flight, ground, and wind tunnel tests that have utilized the facilities to guide and pioneer theoretical research. Many of these experiments were of benchmark quality. The experiments were used to isolate the inadequacies of linear theory in high-speed impulsive noise research, have led to the development of theoretical approaches, and have guided the emerging discipline of computational fluid dynamics to rotorcraft aeroacoustic problems.

  17. Deep learning improves prediction of CRISPR-Cpf1 guide RNA activity.

    PubMed

    Kim, Hui Kwon; Min, Seonwoo; Song, Myungjae; Jung, Soobin; Choi, Jae Woo; Kim, Younggwang; Lee, Sangeun; Yoon, Sungroh; Kim, Hyongbum Henry

    2018-03-01

    We present two algorithms to predict the activity of AsCpf1 guide RNAs. Indel frequencies for 15,000 target sequences were used in a deep-learning framework based on a convolutional neural network to train Seq-deepCpf1. We then incorporated chromatin accessibility information to create the better-performing DeepCpf1 algorithm for cell lines for which such information is available and show that both algorithms outperform previous machine learning algorithms on our own and published data sets.

  18. Construction Strategy for an Internal Amplification Control for Real-Time Diagnostic Assays Using Nucleic Acid Sequence-Based Amplification: Development and Clinical Application

    PubMed Central

    Rodríguez-Lázaro, David; D'Agostino, Martin; Pla, Maria; Cook, Nigel

    2004-01-01

    An important analytical control in molecular amplification-based methods is an internal amplification control (IAC), which should be included in each reaction mixture. An IAC is a nontarget nucleic acid sequence which is coamplified simultaneously with the target sequence. With negative results for the target nucleic acid, the absence of an IAC signal indicates that amplification has failed. A general strategy for the construction of an IAC for inclusion in molecular beacon-based real-time nucleic acid sequence-based amplification (NASBA) assays is presented. Construction proceeds in two phases. In the first phase, a double-stranded DNA molecule that contains nontarget sequences flanked by target sequences complementary to the NASBA primers is produced. At the 5′ end of this DNA molecule is a T7 RNA polymerase binding sequence. In the second phase of construction, RNA transcripts are produced from the DNA by T7 RNA polymerase. This RNA is the IAC; it is amplified by the target NASBA primers and is detected by a molecular beacon probe complementary to the internal nontarget sequences. As a practical example, an IAC for use in an assay for the detection of Mycobacterium avium subsp. paratuberculosis is described, its incorporation and optimization within the assay are detailed, and its application to spiked and natural clinical samples is shown to illustrate the correct interpretation of the diagnostic results. PMID:15583319

  19. ASFinder: a tool for genome-wide identification of alternatively splicing transcripts from EST-derived sequences.

    PubMed

    Min, Xiang Jia

    2013-01-01

    Expressed Sequence Tags (ESTs) are a rich resource for identifying Alternatively Splicing (AS) genes. The ASFinder webserver is designed to identify AS isoforms from EST-derived sequences. Two approaches are implemented in ASFinder. If no genomic sequences are provided, the server performs a local BLASTN to identify AS isoforms from ESTs having both ends aligned but an internal segment unaligned. Otherwise, ASFinder uses SIM4 to map ESTs to the genome, then the overlapping ESTs that are mapped to the same genomic locus and have internal variable exon/intron boundaries are identified as AS isoforms. The tool is available at http://proteomics.ysu.edu/tools/ASFinder.html.

  20. Intra-Genomic Internal Transcribed Spacer Region Sequence Heterogeneity and Molecular Diagnosis in Clinical Microbiology.

    PubMed

    Zhao, Ying; Tsang, Chi-Ching; Xiao, Meng; Cheng, Jingwei; Xu, Yingchun; Lau, Susanna K P; Woo, Patrick C Y

    2015-10-22

    Internal transcribed spacer region (ITS) sequencing is the most extensively used technology for accurate molecular identification of fungal pathogens in clinical microbiology laboratories. Intra-genomic ITS sequence heterogeneity, which makes fungal identification based on direct sequencing of PCR products difficult, has rarely been reported in pathogenic fungi. During the process of performing ITS sequencing on 71 yeast strains isolated from various clinical specimens, direct sequencing of the PCR products showed ambiguous sequences in six of them. After cloning the PCR products into plasmids for sequencing, interpretable sequencing electropherograms could be obtained. For each of the six isolates, 10-49 clones were selected for sequencing and two to seven intra-genomic ITS copies were detected. The identities of these six isolates were confirmed to be Candida glabrata (n=2), Pichia (Candida) norvegensis (n=2), Candida tropicalis (n=1) and Saccharomyces cerevisiae (n=1). Multiple sequence alignment revealed that one to four intra-genomic ITS polymorphic sites were present in the six isolates, and all these polymorphic sites were located in the ITS1 and/or ITS2 regions. We report and describe the first evidence of intra-genomic ITS sequence heterogeneity in four different pathogenic yeasts, which occurred exclusively in the ITS1 and ITS2 spacer regions for the six isolates in this study.

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