The levels of edit, second edition

NASA Technical Reports Server (NTRS)

Vanburen, R.; Buehler, M. F.

1980-01-01

The editorial process is analyzed, and five levels of edit are identified. These levels represent cumulative combinations of nine types of edit: Coordination, Policy, Integrity, Screening, Copy Clarification, Format, Mechanical Style, Language, and Substantive. The levels and types of edit, although developed for specific use with external reports at the Jet Propulsion Laboratory, cover the general range of technical editing, especially as it applies to an in-house technical publications organization. Each type of edit is set forth in terms of groups of actions to be performed by editor. The edit-level concept has enhanced understanding and communication among editors, authors, and publications managers concerning the specific editorial work to be done on each manuscript. It has also proved useful as a management tool for estimating and monitoring cost.

The Landscape of A-to-I RNA Editome Is Shaped by Both Positive and Purifying Selection

PubMed Central

Kong, Yimeng; Pan, Bohu; Chen, Longxian; Wang, Hongbing; Hao, Pei; Li, Xuan

2016-01-01

The hydrolytic deamination of adenosine to inosine (A-to-I editing) in precursor mRNA induces variable gene products at the post-transcription level. How and to what extent A-to-I RNA editing diversifies transcriptome is not fully characterized in the evolution, and very little is known about the selective constraints that drive the evolution of RNA editing events. Here we present a study on A-to-I RNA editing, by generating a global profile of A-to-I editing for a phylogeny of seven Drosophila species, a model system spanning an evolutionary timeframe of approximately 45 million years. Of totally 9281 editing events identified, 5150 (55.5%) are located in the coding sequences (CDS) of 2734 genes. Phylogenetic analysis places these genes into 1,526 homologous families, about 5% of total gene families in the fly lineages. Based on conservation of the editing sites, the editing events in CDS are categorized into three distinct types, representing events on singleton genes (type I), and events not conserved (type II) or conserved (type III) within multi-gene families. While both type I and II events are subject to purifying selection, notably type III events are positively selected, and highly enriched in the components and functions of the nervous system. The tissue profiles are documented for three editing types, and their critical roles are further implicated by their shifting patterns during holometabolous development and in post-mating response. In conclusion, three A-to-I RNA editing types are found to have distinct evolutionary dynamics. It appears that nervous system functions are mainly tested to determine if an A-to-I editing is beneficial for an organism. The coding plasticity enabled by A-to-I editing creates a new class of binary variations, which is a superior alternative to maintain heterozygosity of expressed genes in a diploid mating system. PMID:27467689

A binary linear programming formulation of the graph edit distance.

PubMed

Justice, Derek; Hero, Alfred

2006-08-01

A binary linear programming formulation of the graph edit distance for unweighted, undirected graphs with vertex attributes is derived and applied to a graph recognition problem. A general formulation for editing graphs is used to derive a graph edit distance that is proven to be a metric, provided the cost function for individual edit operations is a metric. Then, a binary linear program is developed for computing this graph edit distance, and polynomial time methods for determining upper and lower bounds on the solution of the binary program are derived by applying solution methods for standard linear programming and the assignment problem. A recognition problem of comparing a sample input graph to a database of known prototype graphs in the context of a chemical information system is presented as an application of the new method. The costs associated with various edit operations are chosen by using a minimum normalized variance criterion applied to pairwise distances between nearest neighbors in the database of prototypes. The new metric is shown to perform quite well in comparison to existing metrics when applied to a database of chemical graphs.

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,…

The levels of edit. [technical writing in science

NASA Technical Reports Server (NTRS)

Vanburen, R.; Buehler, M. F.; Wallenbrock, D. (Editor)

1976-01-01

The editorial process is analyzed, and five levels of edit are identified. These levels represent cumulative combinations of nine types of edit: (1) coordination, (2) policy, (3) integrity, (4) screening, (5) copy clarification, (6) Mechanical Style, (7) Language, and (9) substantive. The levels and types of edit, although developed for specific use with external reports at the Jet Propulsion Laboratory, cover the general range of technical editing, especially as it applies to an in-house technical publications organization. Each type of edit is set forth in terms of groups of actions to be performed by the editor. The edit-level concept has enhanced understanding and communication among editors, authors, and publications managers concerning the specific editorial work to be done on each manuscript. It has also proved useful as a management tool for estimating and monitoring cost.

PONDEROSA, an automated 3D-NOESY peak picking program, enables automated protein structure determination.

PubMed

Lee, Woonghee; Kim, Jin Hae; Westler, William M; Markley, John L

2011-06-15

PONDEROSA (Peak-picking Of Noe Data Enabled by Restriction of Shift Assignments) accepts input information consisting of a protein sequence, backbone and sidechain NMR resonance assignments, and 3D-NOESY ((13)C-edited and/or (15)N-edited) spectra, and returns assignments of NOESY crosspeaks, distance and angle constraints, and a reliable NMR structure represented by a family of conformers. PONDEROSA incorporates and integrates external software packages (TALOS+, STRIDE and CYANA) to carry out different steps in the structure determination. PONDEROSA implements internal functions that identify and validate NOESY peak assignments and assess the quality of the calculated three-dimensional structure of the protein. The robustness of the analysis results from PONDEROSA's hierarchical processing steps that involve iterative interaction among the internal and external modules. PONDEROSA supports a variety of input formats: SPARKY assignment table (.shifts) and spectrum file formats (.ucsf), XEASY proton file format (.prot), and NMR-STAR format (.star). To demonstrate the utility of PONDEROSA, we used the package to determine 3D structures of two proteins: human ubiquitin and Escherichia coli iron-sulfur scaffold protein variant IscU(D39A). The automatically generated structural constraints and ensembles of conformers were as good as or better than those determined previously by much less automated means. The program, in the form of binary code along with tutorials and reference manuals, is available at http://ponderosa.nmrfam.wisc.edu/.

Computer aided field editing in the DHS context: the Turkey experiment.

PubMed

Cushing, J; Loaiza, E

1994-01-01

"In this study two types of field editing used during the Turkey Demographic and Health Survey are compared. These two types of editing are computer aided field editing and manual editing. It is known that manual editing by field editors is a tedious job in which errors especially on skip questions can be missed; however, with the aid of computers field editors could quickly find all occasions on which an interviewer incorrectly followed a skip instruction. At the end of the experiment it has been found...that the field editing done with the aid of a notebook computer was consistently better than that done in the standard manual manner." (SUMMARY IN TUR) excerpt

Complete 13C NMR chemical shifts assignment for cholesterol crystals by combined CP-MAS spectral editing and ab initio GIPAW calculations with dispersion forces.

PubMed

Küçükbenli, Emine; Sonkar, Kanchan; Sinha, Neeraj; de Gironcoli, Stefano

2012-04-12

We report here the first fully ab initio determination of (13)C NMR spectra for several crystal structures of cholesterol, observed in various biomaterials. We combine Gauge-Including Projector Augmented Waves (GIPAW) calculations at relaxed structures, fully including dispersion forces, with Magic Angle Spinning Solid State NMR experiments and spectral editing to achieve a detailed interpretation of the complex NMR spectra of cholesterol crystals. By introducing an environment-dependent secondary referencing scheme in our calculations, not only do we reproduce the characteristic spectral features of the different crystalline polymorphs, thus clearly discriminating among them, but also closely represent the spectrum in the region of several highly overlapping peaks. This, in combination with spectral editing, allows us to provide a complete peak assignment for monohydrate (ChM) and low-temperature anhydrous (ChAl) crystal polymorphs. Our results show that the synergy between ab initio calculations and refined experimental techniques can be exploited for an accurate and efficient NMR crystallography of complex systems of great interest for biomaterial studies. The method is general in nature and can be applied for studies of various complex biomaterials.

A biochemical landscape of A-to-I RNA editing in the human brain transcriptome

PubMed Central

Sakurai, Masayuki; Ueda, Hiroki; Yano, Takanori; Okada, Shunpei; Terajima, Hideki; Mitsuyama, Toutai; Toyoda, Atsushi; Fujiyama, Asao; Kawabata, Hitomi; Suzuki, Tsutomu

2014-01-01

Inosine is an abundant RNA modification in the human transcriptome and is essential for many biological processes in modulating gene expression at the post-transcriptional level. Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosines to inosines (A-to-I editing) in double-stranded regions. We previously established a biochemical method called “inosine chemical erasing” (ICE) to directly identify inosines on RNA strands with high reliability. Here, we have applied the ICE method combined with deep sequencing (ICE-seq) to conduct an unbiased genome-wide screening of A-to-I editing sites in the transcriptome of human adult brain. Taken together with the sites identified by the conventional ICE method, we mapped 19,791 novel sites and newly found 1258 edited mRNAs, including 66 novel sites in coding regions, 41 of which cause altered amino acid assignment. ICE-seq detected novel editing sites in various repeat elements as well as in short hairpins. Gene ontology analysis revealed that these edited mRNAs are associated with transcription, energy metabolism, and neurological disorders, providing new insights into various aspects of human brain functions. PMID:24407955

Kazachstania Zubkova (1971)

USDA-ARS?s Scientific Manuscript database

This chapter describes the ascomycete yeast genus Kazachstania and is to be published in "The Yeasts, A Taxonomic Study, 5th edition." The genus Kazachstania is newly described and was constructed from certain species previously assigned to the genera Saccharomyces, Kluyveromyces and Arxozyma follo...

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

PubMed Central

Wang, Yumeng; Xu, Xiaoyan; Yu, Shuangxing; Jeong, Kang Jin; Zhou, Zhicheng; Han, Leng; Tsang, Yiu Huen; Li, Jun; Chen, Hu; Mangala, Lingegowda S.; Yuan, Yuan; Eterovic, A. Karina; Lu, Yiling; Sood, Anil K.; Scott, Kenneth L.; Mills, Gordon B.; Liang, Han

2017-01-01

RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy. PMID:28411194

Articles as Assignments - Modalities and Experiences of Wikipedia Use in University Courses

NASA Astrophysics Data System (ADS)

Wannemacher, Klaus

In spite of perceived quality deficits, Wikipedia is a popular information resource among students. Instructors increasingly take advantage of the positive student attitude through actively integrating Wikipedia as a learning tool into university courses. The contribution raises the question if Wikipedia assignments in university courses are suited to make complex research, editing and bibliographic processes through which scholarship is produced transparent to students and to effectively improve their research and writing skills.

Saccharomycopsis Schionning (1903)

USDA-ARS?s Scientific Manuscript database

This chapter describes the ascomycete yeast genus Saccharomycopsis and is to be published in The Yeasts, A Taxonomic Study, 5th edition. The genus Saccharomycopsis has 11 assigned species, many worldwide in distribution. Certain species, such as S. fibuligera, are commonly found in fermented, cere...

PONDEROSA, an automated 3D-NOESY peak picking program, enables automated protein structure determination

PubMed Central

Lee, Woonghee; Kim, Jin Hae; Westler, William M.; Markley, John L.

2011-01-01

Summary: PONDEROSA (Peak-picking Of Noe Data Enabled by Restriction of Shift Assignments) accepts input information consisting of a protein sequence, backbone and sidechain NMR resonance assignments, and 3D-NOESY (13C-edited and/or 15N-edited) spectra, and returns assignments of NOESY crosspeaks, distance and angle constraints, and a reliable NMR structure represented by a family of conformers. PONDEROSA incorporates and integrates external software packages (TALOS+, STRIDE and CYANA) to carry out different steps in the structure determination. PONDEROSA implements internal functions that identify and validate NOESY peak assignments and assess the quality of the calculated three-dimensional structure of the protein. The robustness of the analysis results from PONDEROSA's hierarchical processing steps that involve iterative interaction among the internal and external modules. PONDEROSA supports a variety of input formats: SPARKY assignment table (.shifts) and spectrum file formats (.ucsf), XEASY proton file format (.prot), and NMR-STAR format (.star). To demonstrate the utility of PONDEROSA, we used the package to determine 3D structures of two proteins: human ubiquitin and Escherichia coli iron-sulfur scaffold protein variant IscU(D39A). The automatically generated structural constraints and ensembles of conformers were as good as or better than those determined previously by much less automated means. Availability: The program, in the form of binary code along with tutorials and reference manuals, is available at http://ponderosa.nmrfam.wisc.edu/. Contact: whlee@nmrfam.wisc.edu; markley@nmrfam.wisc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21511715

RNA editing with CRISPR-Cas13.

PubMed

Cox, David B T; Gootenberg, Jonathan S; Abudayyeh, Omar O; Franklin, Brian; Kellner, Max J; Joung, Julia; Zhang, Feng

2017-11-24

Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI CRISPR-Cas systems contain the programmable single-effector RNA-guided ribonuclease Cas13. We profiled type VI systems in order to engineer a Cas13 ortholog capable of robust knockdown and demonstrated RNA editing by using catalytically inactive Cas13 (dCas13) to direct adenosine-to-inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), which has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineered this system to create a high-specificity variant and minimized the system to facilitate viral delivery. REPAIR presents a promising RNA-editing platform with broad applicability for research, therapeutics, and biotechnology. Copyright © 2017, American Association for the Advancement of Science.

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers.

PubMed

Wang, Yumeng; Xu, Xiaoyan; Yu, Shuangxing; Jeong, Kang Jin; Zhou, Zhicheng; Han, Leng; Tsang, Yiu Huen; Li, Jun; Chen, Hu; Mangala, Lingegowda S; Yuan, Yuan; Eterovic, A Karina; Lu, Yiling; Sood, Anil K; Scott, Kenneth L; Mills, Gordon B; Liang, Han

2017-07-01

RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR , a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy. © 2017 Wang et al.; Published by Cold Spring Harbor Laboratory Press.

Basic Facialist. Teacher Edition. Cosmetology Series.

ERIC Educational Resources Information Center

Rogers, Jeanette A.

This Oklahoma curriculum guide contains six units. Each instructional unit includes some or all of these basic components: performance objectives; suggested activities for the teacher; pretest; handouts; information sheets; transparency masters; assignment sheets; job sheets; practical tests; written tests; and answers to pretest, assignment…

Microwave. Instructor's Edition. Louisiana Vocational-Technical Education.

ERIC Educational Resources Information Center

Blanton, William

This publication contains related study assignments and job sheets for a course in microwave technology. The course is organized into 12 units covering the following topics: introduction to microwave, microwave systems, microwave oscillators, microwave modulators, microwave transmission lines, transmission lines, detectors and mixers, microwave…

Software Assists in Extensive Environmental Auditing

NASA Technical Reports Server (NTRS)

Callac, Christopher; Matherne, Charlie

2002-01-01

The Base Enivronmental Management System (BEMS) is a Web-based application program for managing and tracking audits by the Environmental Office of Stennis Space Center in conformity with standard 14001 of the International Organization for Standardization (ISO 14001). (This standard specifies requirements for an environmental-management system.) BEMS saves time by partly automating what were previously manual processes for creating audit checklists; recording and tracking audit results; issuing, tracking, and implementing corrective-action requests (CARs); tracking continuous improvements (CIs); and tracking audit results and statistics. BEMS consists on an administration module and an auditor module. As its name suggests, the administration module is used to administer the audit. It helps administrators to edit the list of audit questions; edit the list of audit locations; assign manditory questions to locations; track, approve, and edit CARs; and edit completed audits. The auditor module is used by auditors to perform audits and record audit results: It helps the auditors to create audit checklists, complete audits, view completed audits, create CARs, record and acknowledge CIs, and generate reports from audit results.

Software Assists in Extensive Environmental Auditing

NASA Technical Reports Server (NTRS)

Callac, Christopher; Matherne, Charlie

2003-01-01

The Base Environmental Management System (BEMS) is a Web-based application program for managing and tracking audits by the Environmental Office of Stennis Space Center in conformity with standard 14001 of the International Organization for Standardization (ISO 14001). (This standard specifies requirements for an environmental-management system.) BEMS saves time by partly automating what were previously manual processes for creating audit checklists; recording and tracking audit results; issuing, tracking, and implementing corrective-action requests (CARs); tracking continuous improvements (CIs); and tracking audit results and statistics. BEMS consists of an administration module and an auditor module. As its name suggests, the administration module is used to administer the audit. It helps administrators to edit the list of audit questions; edit the list of audit locations; assign mandatory questions to locations; track, approve, and edit CARs; and edit completed audits. The auditor module is used by auditors to perform audits and record audit results: it helps the auditors to create audit checklists, complete audits, view completed audits, create CARs, record and acknowledge CIs, and generate reports from audit results.

Software Assists in Extensive Environmental Auditing

NASA Technical Reports Server (NTRS)

Callac, Christopher; Matherne, Charlie; Selinsky, T.

2002-01-01

The Base Environmental Management System (BEMS) is a Web-based application program for managing and tracking audits by the Environmental Office of Stennis Space Center in conformity with standard 14001 of the International Organization for Standardization (ISO 14001). (This standard specifies requirements for an environmental-management system.) BEMS saves time by partly automating what were previously manual processes for creating audit checklists; recording and tracking audit results; issuing, tracking, and implementing corrective-action requests (CARs); tracking continuous improvements (CIs); and tracking audit results and statistics. BEMS consists of an administration module and an auditor module. As its name suggests, the administration module is used to administer the audit. It helps administrators to edit the list of audit questions; edit the list of audit locations; assign mandatory questions to locations; track, approve, and edit CARs; and edit completed audits. The auditor module is used by auditors to perform audits and record audit results: it helps the auditors to create audit checklists, complete audits, view completed audits, create CARs, record and acknowledge CIs, and generate reports from audit results.

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

Priceomyuces M. Suzuki & Kurtzman (2010)

USDA-ARS?s Scientific Manuscript database

This chapter describes the ascomycete yeast genus Priceomyces and is to be published in "The Yeasts, A Taxonomic Study, 5th edition." The genus Priceomyces has five described species that were earlier assigned to the genus Pichia, but gene sequence analysis showed that the species, now reclassified...

Ethical Issues in Editing Scholarly Journals.

ERIC Educational Resources Information Center

Stryker, Sheldon

1990-01-01

Discusses ethical issues that arise when serving as an editor of a scholarly journal. Suggests treating these issues using paradigm-based decisions; decisions based on personal sociological predilections and commitments; and reasonable referee-assignment policies. Notes how conflicts of interest inevitably accompanying such a position. (NL)

One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension.

PubMed

Riddle, M C; Yki-Järvinen, H; Bolli, G B; Ziemen, M; Muehlen-Bartmer, I; Cissokho, S; Home, P D

2015-09-01

To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial. EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed. Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c -0.17 [95% confidence interval (CI) -0.30 to -0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89-0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75-0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent. During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between treatments. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Identifying the Machine Translation Error Types with the Greatest Impact on Post-editing Effort

PubMed Central

Daems, Joke; Vandepitte, Sonia; Hartsuiker, Robert J.; Macken, Lieve

2017-01-01

Translation Environment Tools make translators’ work easier by providing them with term lists, translation memories and machine translation output. Ideally, such tools automatically predict whether it is more effortful to post-edit than to translate from scratch, and determine whether or not to provide translators with machine translation output. Current machine translation quality estimation systems heavily rely on automatic metrics, even though they do not accurately capture actual post-editing effort. In addition, these systems do not take translator experience into account, even though novices’ translation processes are different from those of professional translators. In this paper, we report on the impact of machine translation errors on various types of post-editing effort indicators, for professional translators as well as student translators. We compare the impact of MT quality on a product effort indicator (HTER) with that on various process effort indicators. The translation and post-editing process of student translators and professional translators was logged with a combination of keystroke logging and eye-tracking, and the MT output was analyzed with a fine-grained translation quality assessment approach. We find that most post-editing effort indicators (product as well as process) are influenced by machine translation quality, but that different error types affect different post-editing effort indicators, confirming that a more fine-grained MT quality analysis is needed to correctly estimate actual post-editing effort. Coherence, meaning shifts, and structural issues are shown to be good indicators of post-editing effort. The additional impact of experience on these interactions between MT quality and post-editing effort is smaller than expected. PMID:28824482

Identifying the Machine Translation Error Types with the Greatest Impact on Post-editing Effort.

PubMed

Daems, Joke; Vandepitte, Sonia; Hartsuiker, Robert J; Macken, Lieve

2017-01-01

Translation Environment Tools make translators' work easier by providing them with term lists, translation memories and machine translation output. Ideally, such tools automatically predict whether it is more effortful to post-edit than to translate from scratch, and determine whether or not to provide translators with machine translation output. Current machine translation quality estimation systems heavily rely on automatic metrics, even though they do not accurately capture actual post-editing effort. In addition, these systems do not take translator experience into account, even though novices' translation processes are different from those of professional translators. In this paper, we report on the impact of machine translation errors on various types of post-editing effort indicators, for professional translators as well as student translators. We compare the impact of MT quality on a product effort indicator (HTER) with that on various process effort indicators. The translation and post-editing process of student translators and professional translators was logged with a combination of keystroke logging and eye-tracking, and the MT output was analyzed with a fine-grained translation quality assessment approach. We find that most post-editing effort indicators (product as well as process) are influenced by machine translation quality, but that different error types affect different post-editing effort indicators, confirming that a more fine-grained MT quality analysis is needed to correctly estimate actual post-editing effort. Coherence, meaning shifts, and structural issues are shown to be good indicators of post-editing effort. The additional impact of experience on these interactions between MT quality and post-editing effort is smaller than expected.

From course assignment paper to publishable manuscript.

PubMed

Rew, Lynn

2012-12-01

Both undergraduate and graduate nursing students are expected to write numerous papers in their educational programs; however, most of these papers are never published. Many students and faculty lack the skills needed to convert a course assignment paper to a publishable manuscript. The purpose of this article is to describe 10 steps that can transform a course assignment paper into a publishable manuscript. These steps include outlining, clarifying the topic, clearly stating the purpose, identifying an appropriate audience, revising with faculty's feedback, querying journal editors, revising to conform to journal's author guidelines, requesting and responding to peer feedback, and finally editing and proofreading prior to submitting the manuscript. Faculty members are encouraged to make writing assignments that students can then convert to publishable manuscripts. Such publications form an essential cornerstone of professional holistic nursing.

Wikipedia: Friend, Not Foe

ERIC Educational Resources Information Center

Crovitz, Darren; Smoot, W. Scott

2009-01-01

As online research has become an increasingly standard activity for middle school and high school students, Wikipedia (http://www.wikipedia.org) has simultaneously emerged as the bane of many teachers who include research-focused assignments in their courses. An online encyclopedia that allows anyone to edit its entries, Wikipedia has educators…

36 CFR 1206.22 - What type of proposal is eligible for a publications grant?

Code of Federal Regulations, 2012 CFR

2012-07-01

... records; (2) Microfilm editions consisting of organized collections of images of original sources, usually... images of original editions. Electronic editions may include transcriptions and/or annotations and other...

Condition-specific RNA editing in the coral symbiont Symbiodinium microadriaticum

PubMed Central

Li, Yong

2017-01-01

RNA editing is a rare post-transcriptional event that provides cells with an additional level of gene expression regulation. It has been implicated in various processes including adaptation, viral defence and RNA interference; however, its potential role as a mechanism in acclimatization has just recently been recognised. Here, we show that RNA editing occurs in 1.6% of all nuclear-encoded genes of Symbiodinium microadriaticum, a dinoflagellate symbiont of reef-building corals. All base-substitution edit types were present, and statistically significant motifs were associated with three edit types. Strikingly, a subset of genes exhibited condition-specific editing patterns in response to different stressors that resulted in significant increases of non-synonymous changes. We posit that this previously unrecognised mechanism extends this organism’s capability to respond to stress beyond what is encoded by the genome. This in turn may provide further acclimatization capacity to these organisms, and by extension, their coral hosts. PMID:28245292

Library Instruction Handbook. Revised Edition.

ERIC Educational Resources Information Center

Marsh, Sheila; Goff, Linda

The purpose of this handbook is to familiarize the user with the organization of the California State University-Sacramento (CSUS) library. As part of a course requirement, the handbook is designed to provide the student with information necessary to perform assignments in the library independently of librarians and support staff, and as a…

Using Wikis to Develop Collaborative Communities in an Environmental Chemistry Course

ERIC Educational Resources Information Center

Pence, Laura E.; Pence, Harry E.

2015-01-01

Group construction of wikis in an environmental chemistry course provided an effective framework for students to develop and to manage collaborative communities, characterized by interactive projects designed to deepen learning. A sequence of assignments facilitated improvement of the students' wiki construction and editing skills and these…

Yearbook Production, English, Journalism: 5116.153.

ERIC Educational Resources Information Center

Miller, Alfreda R.

An authorized course of instruction for the Quinmester Program in Dade County (Florida) public schools is given for yearbook production. This advanced class is for staff who assign and supervise all photography, write and edit all copy, sell advertising and subscriptions, and handle the publication finances. Specific teaching strategies are given…

Manual for Librarians in Small Hospitals. Sixth Edition.

ERIC Educational Resources Information Center

Graham, Elaine, Ed.; Kesti, Julie, Ed.

This manual is designed to aid the inexperienced person assigned to a hospital library and given the responsibility of ordering library materials, organizing the collection, borrowing from other libraries, and seeking information. Following a brief introduction, the manual is divided into 10 chapters: (1) Organization and Administration of the…

Models in the Teaching of Playwriting.

ERIC Educational Resources Information Center

Delgado, Ramon

One of the best means to create student awareness of play structure is through assigned reading and classroom discussion of successful plays used as models. Various plays from the 1982 edition of "Best Short Plays" are appropriate for discussion of the following structures and techniques: (1) development of conflict and action, suspense,…

ACC Study Guide Series (Revised Edition).

ERIC Educational Resources Information Center

Staples, Katherine; And Others

Designed for the beginning college student who needs to search for information, prepare written assignments, or take tests, the ACC (Austin Community College) Study Guide Series comprises 17 one-page study guides. Printed on card stock with colored headings, the guides are highlighted with cartoon illustrations and are intended to provide…

Wood Condition Assessment Manual: Second Edition

Treesearch

Robert J. Ross; Robert H. White

2014-01-01

This report summarizes information on condition assessment of in-service wood, including visual inspection of wood and timbers, use of ultrasound and probing/boring techniques for inspection, and assessment of wood and timbers that have been exposed to fire. The report also includes information on assigning allowable design values for in-service wood.

A New Feature, New Assignment, and Fresh Perspective Worth Noting

ERIC Educational Resources Information Center

Dean, Tomalee

2017-01-01

The author, the new associate university librarian at Arizona State University (ASU) Library, discusses the "New Media Consortium Horizon Report: 2017 Higher Education Edition," an annual report that identifies and describes emerging technologies for learning and teaching. She highlights a major theme of the report--digital equity--and…

Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish

PubMed Central

Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

2018-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites (tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system. PMID:29295818

High-throughput detection and screening of plants modified by gene editing using quantitative real-time polymerase chain reaction.

PubMed

Peng, Cheng; Wang, Hua; Xu, Xiaoli; Wang, Xiaofu; Chen, Xiaoyun; Wei, Wei; Lai, Yongmin; Liu, Guoquan; Godwin, Ian Douglas; Li, Jieqin; Zhang, Ling; Xu, Junfeng

2018-05-15

Gene editing techniques are becoming powerful tools for modifying target genes in organisms. Although several methods have been developed to detect gene-edited organisms, these techniques are time and labour intensive. Meanwhile, few studies have investigated high-throughput detection and screening strategies for plants modified by gene editing. In this study, we developed a simple, sensitive and high-throughput quantitative real-time (qPCR)-based method. The qPCR-based method exploits two differently labelled probes that are placed within one amplicon at the gene editing target site to simultaneously detect the wild-type and a gene-edited mutant. We showed that the qPCR-based method can accurately distinguish CRISPR/Cas9-induced mutants from the wild-type in several different plant species, such as Oryza sativa, Arabidopsis thaliana, Sorghum bicolor, and Zea mays. Moreover, the method can subsequently determine the mutation type by direct sequencing of the qPCR products of mutations due to gene editing. The qPCR-based method is also sufficiently sensitive to distinguish between heterozygous and homozygous mutations in T 0 transgenic plants. In a 384-well plate format, the method enabled the simultaneous analysis of up to 128 samples in three replicates without handling the post-polymerase chain reaction (PCR) products. Thus, we propose that our method is an ideal choice for screening plants modified by gene editing from many candidates in T 0 transgenic plants, which will be widely used in the area of plant gene editing. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Beyond "Trimming the Fat": The Sub-Editing Stage of Newswriting

ERIC Educational Resources Information Center

Vandendaele, Astrid; De Cuypere, Ludovic; Van Praet, Ellen

2015-01-01

Thus far, professional editing has not been researched extensively in writing research. This article zooms in on sub-editing in newswriting as a form of professional editing, addressing three research questions: (a) What are the ways in which a news article's text is altered?, (b) Are some types of news article altered more significantly than…

Assessing the Relationship between Different Types of Student Feedback and the Quality of Revised Writing

ERIC Educational Resources Information Center

Diab, Nuwar Mawlawi

2011-01-01

This paper reports on a quasi-experimental study comparing the effects of peer-editing to self-editing on improving students' revised drafts. The study involved two intact classes (experimental and control groups) of an English course. The experimental group practiced peer-editing while the control group engaged in self-editing. After receiving…

Material-specific retroactive interference effects of the Wechsler Adult Intelligence Scale-Fourth Edition on the Wechsler Memory Scale-Fourth Edition in a nonclinical sample.

PubMed

Ingram, Nicolette S; Diakoumakos, Jessica V; Sinclair, Erin R; Crowe, Simon F

2016-01-01

This study investigated proactive and retroactive interference effects between the Wechsler Memory Scale-Fourth Edition (WMS-IV) using the flexible approach, and the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). One hundred and eighty nonclinical participants were assigned to a four (visual interference, verbal interference, visual and verbal interference, vs. no interference) by two (retroactive vs. proactive) between-subjects design. The administration order of the tests was counterbalanced (i.e., administration of the WAIS-IV prior to the WMS-IV, and the WAIS-IV administered during the delay interval of the WMS-IV). The WAIS-IV produced significant retroactive interference effects on the WMS-IV; however, no proactive interference effect was observed. The retroactive interference effect was dependent on material specificity. The results indicate that material presented within the delay of the WMS-IV can have a significant effect on subsequent delayed recall. Clinicians should carefully consider the effects associated with carry-over effects of these tests when using them in combination.

RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

PubMed

Zhang, Jinyao; Chen, Zhaoli; Tang, Zefang; Huang, Jianbing; Hu, Xueda; He, Jie

2017-07-01

In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function.

PubMed

Rayon-Estrada, Violeta; Harjanto, Dewi; Hamilton, Claire E; Berchiche, Yamina A; Gantman, Emily Conn; Sakmar, Thomas P; Bulloch, Karen; Gagnidze, Khatuna; Harroch, Sheila; McEwen, Bruce S; Papavasiliou, F Nina

2017-12-12

Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues. The majority of editing events alter the sequence of the 3'UTR of targeted transcripts, and we focus on one cell type (monocytes) and on a small set of highly edited transcripts within it to show that editing alters gene expression by modulating translation (but not RNA stability or localization). We further show that specific cellular processes (phagocytosis and transendothelial migration) are enriched for transcripts that are targets of editing and that editing alters their function. Finally, we survey bone marrow progenitors and demonstrate that common monocyte progenitor cells express high levels of APOBEC1 and are susceptible to loss of the editing enzyme. Overall, APOBEC1-mediated transcriptome diversification is required for the fine-tuning of protein expression in monocytes, suggesting an epitranscriptomic mechanism for the proper maintenance of homeostasis in innate immune cells. Copyright © 2017 the Author(s). Published by PNAS.

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases.

PubMed

Song, Chunzi; Sakurai, Masayuki; Shiromoto, Yusuke; Nishikura, Kazuko

2016-12-17

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1's actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases.

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases

PubMed Central

Song, Chunzi; Sakurai, Masayuki; Shiromoto, Yusuke; Nishikura, Kazuko

2016-01-01

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1′s actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases. PMID:27999332

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

PubMed Central

Gu, Tongjun; Gatti, Daniel M.; Srivastava, Anuj; Snyder, Elizabeth M.; Raghupathy, Narayanan; Simecek, Petr; Svenson, Karen L.; Dotu, Ivan; Chuang, Jeffrey H.; Keller, Mark P.; Attie, Alan D.; Braun, Robert E.; Churchill, Gary A.

2016-01-01

RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing. PMID:26614740

What Consultation and Freelance Writing Can Do for You and for Your Students.

ERIC Educational Resources Information Center

Muller, John A.

This paper advises teachers of technical writing to "practice what they preach" by occasionally doing field work in technical communication. The possibilities for off-campus work include consultation, perhaps for an in-house manual of technical writing procedures and skills, editing assignments for businesses and public agencies, and freelance…

Laboratory Manual (For Concrete Instruction Course); Instructor's Guide, Pilot Program Edition.

ERIC Educational Resources Information Center

Portland Cement Association, Cleveland, OH.

This laboratory manual, prepared for a 2-year program in junior colleges and technical institutes, is designed to accompany the instructional materials to train persons for employment as technicians in the cement and concrete industries. Included are 16 laboratory assignments for each of the following: (1) Principles of Concrete, (2) Concrete in…

The Role of Graphic and Sanitized Violence in the Enjoyment of Television Dramas

ERIC Educational Resources Information Center

Weaver, Andrew J.; Wilson, Barbara J.

2009-01-01

This experiment explores the relationship between television violence and viewer enjoyment. Over 400 participants were randomly assigned to one of 15 conditions that were created by editing five TV programs into three versions each: A graphically violent version, a sanitized violent version, and a nonviolent version. After viewing, participants…

Solar Energy Education Packet for Elementary & Secondary Students. Revised Edition.

ERIC Educational Resources Information Center

Center for Renewable Resources, Washington, DC.

The arrangement of this packet is essentially evolutionary, with a conscious effort to alternate reading assignments, activities and experiments. It begins with solar energy facts and terminology as background to introduce the reader to basic concepts. It progresses into a discussion of passive solar systems. This is followed by several projects…

Assigning Students to Edit Wikipedia: Four Case Studies

ERIC Educational Resources Information Center

Carver, Brian W.; Davis, Rochelle; Kelley, Robin T.; Obar, Jonathan A.; Davis, Lianna L.

2012-01-01

During the 2010-11 academic year, the Wikimedia Foundation, the nonprofit organization that supports Wikipedia, worked with professors at universities across the United States who were interested in using Wikipedia as a teaching tool in their classrooms through a pilot version of the Wikipedia Education Program. This article presents a case study…

Women's Work: Up From .878: Report on the DOT Research Project.

ERIC Educational Resources Information Center

Witt, Mary; Naherny, Patricia K.

The document presents results of a research project that reviewed, analyzed, and assessed the United States Department of Labor's Dictionary of Occupational Titles (DOT) in terms of its analysis of traditional female occupations. The current edition of the DOT assesses the tasks of 21,741 salaried occupations, and assigns to each a…

Building 21st Century Writers

ERIC Educational Resources Information Center

Demski, Jennifer

2012-01-01

During what might have in the distant past been called "quiet time" in Arlene Anderson's fourth-grade classroom, many of her students are glued to their netbooks. The intense, enthusiastic focus and the hushed chatter amongst the students are all about high scores and strategy. Students are revising and editing their writing assignments within a…

Action Biology for the First Year. First Edition.

ERIC Educational Resources Information Center

Davis, Mary Pitt

The effectiveness of science experiments often are partly dependent upon the amount of classroom time available for implementation. This factor alone has frustrated many teachers who attempt to complete laboratory assignments in the allotted time period. This document provides experiments that were designed for the middle year in a 3-year biology…

Preparing Students for Jobs: Managing and Writing for Specialized Magazines.

ERIC Educational Resources Information Center

Eynon, Derry

In this paper, two magazine courses offered at Colorado State University as part of the Technical-Business Journalism concentration are described in terms of course content, class assignments, and course objectives. The course entitled "Writing for Specialized Audiences" assumes that the majority of magazines published today are edited for readers…

Drafting. Technology Learning Activity. Teacher Edition. Technology Education Series.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This packet of technology learning activity (TLA) materials for drafting for students in grades 6-10 consists of an instructor's section and student materials. The instructor's section contains background information, suggested activities, and a list of suggested resources. A lesson plan for the 8-day module includes assignments; equipment, tools,…

News Production: Professional Assignments for Broadcast Journalism Students in an Educational Setting.

ERIC Educational Resources Information Center

Reppert, James E.

There is great inherent educational value in teaching broadcast journalism students the proper techniques in videography, editing, writing, and producing. That is why Advanced Electronic News gathering students at Southern Arkansas University (SAU) are expected to do more than just point a camera and shoot. The ability to produce university news…

Residential Construction. Technology Learning Activity. Teacher Edition. Technology Education Series.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This packet of technology learning activity (TLA) materials for residential construction for students in grades 6-10 consists of an instructor's section and student materials. The instructor's section contains background information, suggested activities, and a list of suggested resources. A lesson plan for the 10-day module includes assignments;…

Your Reading: A Booklist for Junior High and Middle School Students. Eighth Edition.

ERIC Educational Resources Information Center

Nilsen, Alleen Pace, Ed.

This annotated bibliography for junior high and middle school students describes nearly 1,200 recent books to read for pleasure, for school assignments, or to satisfy curiosity. Books included are divided into six major sections (the first three contain mostly fiction and biographies): Connections, Understandings, Imaginings, Contemporary Poetry…

Medical Impairment and Computational Reduction to a Single Whole Person Impairment (WPI) Rating Value

NASA Astrophysics Data System (ADS)

Artz, Jerry; Alchemy, John; Weilepp, Anne; Bongiovanni, Michael; Siddhartha, Kumar

2014-03-01

A medical, biophysics, engineering collaboration has produced a standardized cloud-based application for creating automated WPI ratings. The project assigns numerical values to injuries/illness in accordance with the American Medical Association Guides to the Evaluation of Permanent Impairment, Fifth Edition, AMA Press handbook, 5th edition (with 63 medical contributors and 89 medical reviewers). The AMA Guide serves as the industry standard for assigning impairment values for 32 US states and 190 other countries. Clinical medical data is collected using a menu-driven user interface which is computationally combined into a single numeric value. A medical doctor performs a biometric analysis and enters the quantitative data into a mobile device. The data is analyzed using proprietary validation algorithms, and a WPI Impairment rating is created. The findings are imbedded into a formalized medicolegal report in a matter of minutes. This particular presentation will concentrate upon the WPI rating of the spine--cervical, thoracic, and lumbar. Both common rating techniques will be presented--i.e., Diagnosis Related Estimates (DRE) and Range of Motion (ROM).

36 CFR 1206.22 - What type of proposal is eligible for a publications grant?

Code of Federal Regulations, 2014 CFR

2014-07-01

... projects include the production of: (1) Documentary editions that involve collecting, compiling... records; (2) Microfilm editions consisting of organized collections of images of original sources, usually without transcription and annotations; (3) Electronic editions consisting of organized collections of...

36 CFR 1206.22 - What type of proposal is eligible for a publications grant?

Code of Federal Regulations, 2011 CFR

2011-07-01

... projects include the production of: (1) Documentary editions that involve collecting, compiling... records; (2) Microfilm editions consisting of organized collections of images of original sources, usually without transcription and annotations; (3) Electronic editions consisting of organized collections of...

36 CFR § 1206.22 - What type of proposal is eligible for a publications grant?

Code of Federal Regulations, 2013 CFR

2013-07-01

... projects include the production of: (1) Documentary editions that involve collecting, compiling... records; (2) Microfilm editions consisting of organized collections of images of original sources, usually without transcription and annotations; (3) Electronic editions consisting of organized collections of...

RNA Editing with CRISPR-Cas13

PubMed Central

Cox, David B.T.; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Franklin, Brian; Kellner, Max J.; Joung, Julia; Zhang, Feng

2017-01-01

Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI CRISPR-Cas systems contain the programmable single-effector RNA-guided RNases Cas13. Here, we profile Type VI systems to engineer a Cas13 ortholog capable of robust knockdown and demonstrate RNA editing by using catalytically-inactive Cas13 (dCas13) to direct adenosine to inosine deaminase activity by ADAR2 to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineer this system to create a high specificity variant, REPAIRv2, that is 919 times more specific than REPAIRv1 as well as minimize the system to ease viral delivery. REPAIR presents a promising RNA editing platform with broad applicability for research, therapeutics, and biotechnology. PMID:29070703

First Season Catfish Farming. A Workbook for Beginning Pond and Cage Culture of Channel Catfish. Teacher Edition and Student Edition.

ERIC Educational Resources Information Center

Oklahoma State Board of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This workbook, comprised of both the teacher and student editions, presents guidelines useful for first-year catfish farmers in Oklahoma using pond or cage cultures to raise channel catfish. The teacher edition is a set of unit guidelines only. Contents include a list of suggested readings, important addresses with types of information available…

Efficient engineering of a bacteriophage genome using the type I-E CRISPR-Cas system.

PubMed

Kiro, Ruth; Shitrit, Dror; Qimron, Udi

2014-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system has recently been used to engineer genomes of various organisms, but surprisingly, not those of bacteriophages (phages). Here we present a method to genetically engineer the Escherichia coli phage T7 using the type I-E CRISPR-Cas system. T7 phage genome is edited by homologous recombination with a DNA sequence flanked by sequences homologous to the desired location. Non-edited genomes are targeted by the CRISPR-Cas system, thus enabling isolation of the desired recombinant phages. This method broadens CRISPR Cas-based editing to phages and uses a CRISPR-Cas type other than type II. The method may be adjusted to genetically engineer any bacteriophage genome.

The Chloroplast Genome of Pellia endiviifolia: Gene Content, RNA-Editing Pattern, and the Origin of Chloroplast Editing

PubMed Central

Grosche, Christopher; Funk, Helena T.; Maier, Uwe G.; Zauner, Stefan

2012-01-01

RNA editing is a post-transcriptional process that can act upon transcripts from mitochondrial, nuclear, and chloroplast genomes. In chloroplasts, single-nucleotide conversions in mRNAs via RNA editing occur at different frequencies across the plant kingdom. These range from several hundred edited sites in some mosses and ferns to lower frequencies in seed plants and the complete lack of RNA editing in the liverwort Marchantia polymorpha. Here, we report the sequence and edited sites of the chloroplast genome from the liverwort Pellia endiviifolia. The type and frequency of chloroplast RNA editing display a pattern highly similar to that in seed plants. Analyses of the C to U conversions and the genomic context in which the editing sites are embedded provide evidence in favor of the hypothesis that chloroplast RNA editing evolved to compensate mutations in the first land plants. PMID:23221608

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension).

PubMed

Terauchi, Y; Koyama, M; Cheng, X; Sumi, M; Riddle, M C; Bolli, G B; Hirose, T

2017-10-01

To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed. The 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA 1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00-05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish.

PubMed

Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

2018-03-02

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites ( tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system. Copyright © 2018 Hu et al.

Massive Gene Transfer and Extensive RNA Editing of a Symbiotic Dinoflagellate Plastid Genome

PubMed Central

Mungpakdee, Sutada; Shinzato, Chuya; Takeuchi, Takeshi; Kawashima, Takeshi; Koyanagi, Ryo; Hisata, Kanako; Tanaka, Makiko; Goto, Hiroki; Fujie, Manabu; Lin, Senjie; Satoh, Nori; Shoguchi, Eiichi

2014-01-01

Genome sequencing of Symbiodinium minutum revealed that 95 of 109 plastid-associated genes have been transferred to the nuclear genome and subsequently expanded by gene duplication. Only 14 genes remain in plastids and occur as DNA minicircles. Each minicircle (1.8–3.3 kb) contains one gene and a conserved noncoding region containing putative promoters and RNA-binding sites. Nine types of RNA editing, including a novel G/U type, were discovered in minicircle transcripts but not in genes transferred to the nucleus. In contrast to DNA editing sites in dinoflagellate mitochondria, which tend to be highly conserved across all taxa, editing sites employed in DNA minicircles are highly variable from species to species. Editing is crucial for core photosystem protein function. It restores evolutionarily conserved amino acids and increases peptidyl hydropathy. It also increases protein plasticity necessary to initiate photosystem complex assembly. PMID:24881086

[Discussion on several contents of textbook Acupuncture and Moxibustion (New Century 4th Edition)].

PubMed

Tian, Kaiyu

2018-02-12

The textbook Acupuncture and Moxibustion (New Century 4th Edition) was published by China Press of Traditional Chinese Medicine in August of 2016. The author proposed several discussions in the textbook. The information, including the issue date of China national standard Standardized Manipulations of Acupuncture and Moxibustion , the number of foreign countries where China medical teams were assigned, and the number of acupuncture indications recommended by WHO, was not accurate. The content, including several methods of acupoint location, specification of filiform needles, rotating angle of needle, disinfection of needles and skin, locations and indications of scalp acupuncture, etc. should be corrected. Besides, the writing of textbooks should follow national or industry standards.

Harnessing the native type I-B CRISPR-Cas for genome editing in a polyploid archaeon.

PubMed

Cheng, Feiyue; Gong, Luyao; Zhao, Dahe; Yang, Haibo; Zhou, Jian; Li, Ming; Xiang, Hua

2017-11-20

Research on CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated protein) systems has led to the revolutionary CRISPR/Cas9 genome editing technique. However, for most archaea and half of bacteria, exploitation of their native CRISPR-Cas machineries may be more straightforward and convenient. In this study, we harnessed the native type I-B CRISPR-Cas system for precise genome editing in the polyploid haloarchaeon Haloarcula hispanica. After testing different designs, the editing tool was optimized to be a single plasmid that carries both the self-targeting mini-CRISPR and a 600-800 bp donor. Significantly, chromosomal modifications, such as gene deletion, gene tagging or single nucleotide substitution, were precisely introduced into the vast majority of the transformants. Moreover, we showed that simultaneous editing of two genomic loci could also be readily achieved by one step. In summary, our data demonstrate that the haloarchaeal CRISPR-Cas system can be harnessed for genome editing in this polyploid archaeon, and highlight the convenience and efficiency of the native CRISPR-based genome editing strategy. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Automated sequence analysis and editing software for HIV drug resistance testing.

PubMed

Struck, Daniel; Wallis, Carole L; Denisov, Gennady; Lambert, Christine; Servais, Jean-Yves; Viana, Raquel V; Letsoalo, Esrom; Bronze, Michelle; Aitken, Sue C; Schuurman, Rob; Stevens, Wendy; Schmit, Jean Claude; Rinke de Wit, Tobias; Perez Bercoff, Danielle

2012-05-01

Access to antiretroviral treatment in resource-limited-settings is inevitably paralleled by the emergence of HIV drug resistance. Monitoring treatment efficacy and HIV drugs resistance testing are therefore of increasing importance in resource-limited settings. Yet low-cost technologies and procedures suited to the particular context and constraints of such settings are still lacking. The ART-A (Affordable Resistance Testing for Africa) consortium brought together public and private partners to address this issue. To develop an automated sequence analysis and editing software to support high throughput automated sequencing. The ART-A Software was designed to automatically process and edit ABI chromatograms or FASTA files from HIV-1 isolates. The ART-A Software performs the basecalling, assigns quality values, aligns query sequences against a set reference, infers a consensus sequence, identifies the HIV type and subtype, translates the nucleotide sequence to amino acids and reports insertions/deletions, premature stop codons, ambiguities and mixed calls. The results can be automatically exported to Excel to identify mutations. Automated analysis was compared to manual analysis using a panel of 1624 PR-RT sequences generated in 3 different laboratories. Discrepancies between manual and automated sequence analysis were 0.69% at the nucleotide level and 0.57% at the amino acid level (668,047 AA analyzed), and discordances at major resistance mutations were recorded in 62 cases (4.83% of differences, 0.04% of all AA) for PR and 171 (6.18% of differences, 0.03% of all AA) cases for RT. The ART-A Software is a time-sparing tool for pre-analyzing HIV and viral quasispecies sequences in high throughput laboratories and highlighting positions requiring attention. Copyright © 2012 Elsevier B.V. All rights reserved.

Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.

PubMed

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N

2016-11-01

Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies.

Your Reading: A Booklist for Junior High and Middle School Students. Seventh Edition.

ERIC Educational Resources Information Center

Davis, James E., Ed.; Davis, Hazel K., Ed.

This annotated bibliography, for junior high and middle school students, describes nearly 2,000 books to read for pleasure, for school assignments, or merely to satisfy curiosity. Books included have been published mostly in the last five years and are divided into six major sections: fiction, drama, picture books for older readers, poetry, short…

Computer Literacy for the Middle Grades. A Teacher's Guide. Revised Edition.

ERIC Educational Resources Information Center

Abington School District, PA.

This guide was planned for a program to acquaint seventh and eighth grade students with the importance of the computer in society and to ensure uniformity of instructional objectives among teachers assigned to teach a beginning-level course in computer literacy. It includes the history of the computer, operating and controlling the computer,…

Solar Energy Education. Humanities: activities and teacher's guide. Field test edition

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

Not Available

1982-01-01

Activities are outlined to introduce students to information on solar energy while performing ordinary classroom work. In this teaching manual solar energy is integrated with the humanities. The activities include such things as stories, newspapers, writing assignments, and art and musical presentations all filled with energy related terms. An energy glossary is provided. (BCS)

Using Desktop Publishing in an Editing Class--The Lessons Learned and Students' Assessments.

ERIC Educational Resources Information Center

Tharp, Marty; Zimmerman, Don

1992-01-01

Reports students' perceptions of learning desktop publishing (DTP) systems. Finds that (1) students learned the foundations of DTP in under 60 hours of hands-on experience; (2) the incremental introduction of DTP functions and practice sessions before assignments were the most effective teaching strategy; and (3) use of DTP encouraged nonartistic…

Using Separate Answer Sheets with Grade 3 Students

ERIC Educational Resources Information Center

Brooks, Thomas; O'Malley, Kimberly; Ragland, Shelley; Young, Michael; Kirkpatrick, Rob

2014-01-01

The authors compared the performance of third-grade students testing on answer sheets with those testing on machine-scored test booklets. The 1,832 students in the nationally representative sample were assigned at the campus level to complete the Stanford Achievement Test Series, Tenth Edition in 1 of 4 conditions: (a) Form A answer sheet, (b)…

Testing Structural Models of DSM-IV Symptoms of Common Forms of Child and Adolescent Psychopathology

ERIC Educational Resources Information Center

Lahey, Benjamin B.; Rathouz, Paul J.; Van Hulle, Carol; Urbano, Richard C.; Krueger, Robert F.; Applegate, Brooks; Garriock, Holly A.; Chapman, Derek A.; Waldman, Irwin D.

2008-01-01

Confirmatory factor analyses were conducted of "Diagnostic and Statistical Manual of Mental Disorders", Fourth Edition (DSM-IV) symptoms of common mental disorders derived from structured interviews of a representative sample of 4,049 twin children and adolescents and their adult caretakers. A dimensional model based on the assignment of symptoms…

Conditioning attentional skills: examining the effects of the pace of television editing on children's attention.

PubMed

Cooper, N R; Uller, C; Pettifer, J; Stolc, F C

2009-10-01

There is increasing concern about the behavioural and cognitive effects of watching television in childhood. Numerous studies have examined the effects of the amount of viewing time; however, to our knowledge, only one study has investigated whether the speed of editing of a programme may have an effect on behaviour. The purpose of the present study was to examine this question using a novel experimental paradigm. School children (aged 4-7 years) were randomly assigned to one of two groups. Each group was presented with either a fast- or slow-edit 3.5-min film of a narrator reading a children's story. Immediately following film presentation, both groups were presented with a continuous test of attention. Performance varied according to experimental group and age. In particular, we found that children's orienting networks and error rates can be affected by a very short exposure to television. Just 3.5 min of watching television can have a differential effect on the viewer depending on the pacing of the film editing. These findings highlight the potential of experimentally manipulating television exposure in children and emphasize the need for more research in this previously under-explored topic.

Digitization of a geologic map for the Quebec-Maine-Gulf of Maine global geoscience transect

USGS Publications Warehouse

Wright, Bruce E.; Stewart, David B.

1990-01-01

The Bedrock Geologic Map of Maine was digitized and combined with digital geologic data for Quebec and the Gulf of Maine for the Quebec-Maine-Gulf of Maine Geologic Transect Project. This map is being combined with digital geophysical data to produce three-dimensional depictions of the subsurface geology and to produce cross sections of the Earth's crust. It is an essential component of a transect that stretches from the craton near Quebec City, Quebec, to the Atlantic Ocean Basin south of Georges Bank. The transect is part of the Global Geosciences Transect Project of the International Lithosphere Program. The Digital Line Graph format is used for storage of the digitized data. A coding scheme similar to that used for base category planimetric data was developed to assign numeric codes to the digitized geologic data. These codes were used to assign attributes to polygon and line features to describe rock type, age, name, tectonic setting of original deposition, mineralogy, and composition of igneous plutonic rocks, as well as faults and other linear features. The digital geologic data can be readily edited, rescaled, and reprojected. The attribute codes allow generalization and selective retrieval of the geologic features. The codes allow assignment of map colors based on age, lithology, or other attribute. The Digital Line Graph format is a general transfer format that is supported by many software vendors and is easily transferred between systems.

Eduard Jaeger's Test-Types (Schrift-Scalen) and the historical development of vision tests.

PubMed Central

Runge, P E

2000-01-01

PURPOSE: Eduard Jaeger's original Test-Types were carefully evaluated: (1) to determine whether Jaeger had maintained a consistent standard, (2) to establish the correct Snellen equivalent for Jaeger's Test-Types, (3) to answer the question of why and how the standard was lost, and (4) to compare the visual angle of optotypes to lines of continuous text. METHODS: All original Viennese editions of Jaeger's Test-Types, as well as first generation United Kingdom (UK) and United States (US) versions, were evaluated. Data were collected objectively using a microruler with a 20X loupe and subjectively using a laser distance-measuring device. The data were analyzed using Microsoft Excel. All previous measurements of Jaeger's Test-Types, objective and subjective, collected over the past 133 years were compared to the current data and to each other. RESULTS: The correct Snellen equivalent of Jaeger's Test-Types was determined. The visual angle created from the measurement of the height of lowercase letters, without ascenders or descenders, provides an accurate method of assigning a visual angle of a line of continuous text. Comparing the typefaces used in printing first generation UK and US versions of Jaeger's Test-Types to the Viennese editions provided an explanation for the absence of a consistent standard for Jaeger's Test-Types today. CONCLUSIONS: All 10 versions of Jaeger's original Test-Types are virtually identical and established a gold standard for reading vision tests. Jaeger's standard was lost when his Test-Types were first printed in the UK and the US using local typefaces. The Jaeger standard has been re-established. Visual angles determined using continuous text are comparable to those obtained by using optotypes. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7C FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19A FIGURE 19B p409-a FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 26 FIGURE 27 FIGURE 28A FIGURE 28B FIGURE 28C FIGURE 29 FIGURE 30 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36A FIGURE 37 FIGURE 38 FIGURE 39 PMID:11190034

Learning chronobiology by improving Wikipedia.

PubMed

Chiang, C D; Lewis, C L; Wright, M D E; Agapova, S; Akers, B; Azad, T D; Banerjee, K; Carrera, P; Chen, A; Chen, J; Chi, X; Chiou, J; Cooper, J; Czurylo, M; Downs, C; Ebstein, S Y; Fahey, P G; Goldman, J W; Grieff, A; Hsiung, S; Hu, R; Huang, Y; Kapuria, A; Li, K; Marcu, I; Moore, S H; Moseley, A C; Nauman, N; Ness, K M; Ngai, D M; Panzer, A; Peters, P; Qin, E Y; Sadhu, S; Sariol, A; Schellhase, A; Schoer, M B; Steinberg, M; Surick, G; Tsai, C A; Underwood, K; Wang, A; Wang, M H; Wang, V M; Westrich, D; Yockey, L J; Zhang, L; Herzog, E D

2012-08-01

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.

Highlighting entanglement of cultures via ranking of multilingual Wikipedia articles.

PubMed

Eom, Young-Ho; Shepelyansky, Dima L

2013-01-01

How different cultures evaluate a person? Is an important person in one culture is also important in the other culture? We address these questions via ranking of multilingual Wikipedia articles. With three ranking algorithms based on network structure of Wikipedia, we assign ranking to all articles in 9 multilingual editions of Wikipedia and investigate general ranking structure of PageRank, CheiRank and 2DRank. In particular, we focus on articles related to persons, identify top 30 persons for each rank among different editions and analyze distinctions of their distributions over activity fields such as politics, art, science, religion, sport for each edition. We find that local heroes are dominant but also global heroes exist and create an effective network representing entanglement of cultures. The Google matrix analysis of network of cultures shows signs of the Zipf law distribution. This approach allows to examine diversity and shared characteristics of knowledge organization between cultures. The developed computational, data driven approach highlights cultural interconnections in a new perspective. Dated: June 26, 2013.

Highlighting Entanglement of Cultures via Ranking of Multilingual Wikipedia Articles

PubMed Central

Eom, Young-Ho; Shepelyansky, Dima L.

2013-01-01

How different cultures evaluate a person? Is an important person in one culture is also important in the other culture? We address these questions via ranking of multilingual Wikipedia articles. With three ranking algorithms based on network structure of Wikipedia, we assign ranking to all articles in 9 multilingual editions of Wikipedia and investigate general ranking structure of PageRank, CheiRank and 2DRank. In particular, we focus on articles related to persons, identify top 30 persons for each rank among different editions and analyze distinctions of their distributions over activity fields such as politics, art, science, religion, sport for each edition. We find that local heroes are dominant but also global heroes exist and create an effective network representing entanglement of cultures. The Google matrix analysis of network of cultures shows signs of the Zipf law distribution. This approach allows to examine diversity and shared characteristics of knowledge organization between cultures. The developed computational, data driven approach highlights cultural interconnections in a new perspective. Dated: June 26, 2013 PMID:24098338

An Exact Algorithm to Compute the Double-Cut-and-Join Distance for Genomes with Duplicate Genes.

PubMed

Shao, Mingfu; Lin, Yu; Moret, Bernard M E

2015-05-01

Computing the edit distance between two genomes is a basic problem in the study of genome evolution. The double-cut-and-join (DCJ) model has formed the basis for most algorithmic research on rearrangements over the last few years. The edit distance under the DCJ model can be computed in linear time for genomes without duplicate genes, while the problem becomes NP-hard in the presence of duplicate genes. In this article, we propose an integer linear programming (ILP) formulation to compute the DCJ distance between two genomes with duplicate genes. We also provide an efficient preprocessing approach to simplify the ILP formulation while preserving optimality. Comparison on simulated genomes demonstrates that our method outperforms MSOAR in computing the edit distance, especially when the genomes contain long duplicated segments. We also apply our method to assign orthologous gene pairs among human, mouse, and rat genomes, where once again our method outperforms MSOAR.

Beyond Word Processing.

ERIC Educational Resources Information Center

Haight, Larry

1989-01-01

Types of specialty software that can help in computer editing are discussed, including programs for file transformation, optical character recognition, facsimile transmission, spell-checking, style assistance, editing, indexing, and headline-writing. (MSE)

The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers | Office of Cancer Genomics

Cancer.gov

Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting.

PubMed

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D

2017-04-07

Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR-Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR-Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting

PubMed Central

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D.

2017-01-01

Bacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification. PMID:28387220

Designing Successful Transitions: A Guide for Orienting Students to College. 3rd Edition. The First-Year Experience Monograph Series No. 13

ERIC Educational Resources Information Center

Ward-Roof, Jeanine A., Ed.

2010-01-01

The 2010 edition of this monograph addresses many topics (e.g., administration of orientation programs, family involvement, student characteristics and needs, assessment, and orientation for specific student populations and institutional types) that were included in previous editions but approaches them with new information, updated data, and…

Genome Editing of Monogenic Neuromuscular Diseases

PubMed Central

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N.

2017-01-01

IMPORTANCE Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. OBJECTIVES To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. EVIDENCE REVIEW PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, andmyotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9–mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. FINDINGS Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing–meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. CONCLUSIONS AND RELEVANCE Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies. PMID:27668807

RepeatsDB-lite: a web server for unit annotation of tandem repeat proteins.

PubMed

Hirsh, Layla; Paladin, Lisanna; Piovesan, Damiano; Tosatto, Silvio C E

2018-05-09

RepeatsDB-lite (http://protein.bio.unipd.it/repeatsdb-lite) is a web server for the prediction of repetitive structural elements and units in tandem repeat (TR) proteins. TRs are a widespread but poorly annotated class of non-globular proteins carrying heterogeneous functions. RepeatsDB-lite extends the prediction to all TR types and strongly improves the performance both in terms of computational time and accuracy over previous methods, with precision above 95% for solenoid structures. The algorithm exploits an improved TR unit library derived from the RepeatsDB database to perform an iterative structural search and assignment. The web interface provides tools for analyzing the evolutionary relationships between units and manually refine the prediction by changing unit positions and protein classification. An all-against-all structure-based sequence similarity matrix is calculated and visualized in real-time for every user edit. Reviewed predictions can be submitted to RepeatsDB for review and inclusion.

Global analysis of A-to-I RNA editing reveals association with common disease variants

PubMed Central

Jain, Rajeev; Jain, Anamika; Betsholtz, Christer; Giannarelli, Chiara; Kovacic, Jason C.; Ruusalepp, Arno; Skogsberg, Josefin; Hao, Ke; Schadt, Eric E.

2018-01-01

RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN. Twenty-five genes, including LRP11 and PLIN5, had editing sites that were associated with plasma lipid levels. Our findings provide new insights into the genetic regulation of RNA editing and establish a rich catalogue for further exploration of this process. PMID:29527417

2015 Edition Health Information Technology (Health IT) Certification Criteria, 2015 Edition Base Electronic Health Record (EHR) Definition, and ONC Health IT Certification Program Modifications. Final rule.

PubMed

2015-10-16

This final rule finalizes a new edition of certification criteria (the 2015 Edition health IT certification criteria or "2015 Edition'') and a new 2015 Edition Base Electronic Health Record (EHR) definition, while also modifying the ONC Health IT Certification Program to make it open and accessible to more types of health IT and health IT that supports various care and practice settings. The 2015 Edition establishes the capabilities and specifies the related standards and implementation specifications that Certified Electronic Health Record Technology (CEHRT) would need to include to, at a minimum, support the achievement of meaningful use by eligible professionals (EPs), eligible hospitals, and critical access hospitals (CAHs) under the Medicare and Medicaid EHR Incentive Programs (EHR Incentive Programs) when such edition is required for use under these programs.

Statistical Physics Approaches to RNA Editing

NASA Astrophysics Data System (ADS)

Bundschuh, Ralf

2012-02-01

The central dogma of molecular Biology states that DNA is transcribed base by base into RNA which is in turn translated into proteins. However, some organisms edit their RNA before translation by inserting, deleting, or substituting individual or short stretches of bases. In many instances the mechanisms by which an organism recognizes the positions at which to edit or by which it performs the actual editing are unknown. One model system that stands out by its very high rate of on average one out of 25 bases being edited are the Myxomycetes, a class of slime molds. In this talk we will show how the computational methods and concepts from statistical Physics can be used to analyze DNA and protein sequence data to predict editing sites in these slime molds and to guide experiments that identified previously unknown types of editing as well as the complete set of editing events in the slime mold Physarum polycephalum.

Mister Rogers' Plan & Play Book: Activities from Mister Rogers' Neighborhood for Parents & Child Care Providers. Fourth Edition.

ERIC Educational Resources Information Center

Family Communications, Inc., Pittsburgh, PA.

Intended for both childcare professionals and parents, this book lists activities from episodes of Mister Rogers' Neighborhood television program, and can be used with or without watching the program. Each activity is assigned a number which corresponds to the television episode in which the activity is featured, and a national PBS Broadcast…

PROGRAMMED INSTRUCTION IN WEST AFRICA AND THE ARAB STATES, A REPORT ON TWO TRAINING WORKSHOPS. EDUCATIONAL STUDIES AND DOCUMENTS, NO. 52.

ERIC Educational Resources Information Center

KOMOSKI, P. KENNETH; GREEN, EDWARD J.

DURING THE SUMMER OF 1963 NINETEEN PERSONS IN RAMALLAH, JORDAN AND THIRTY-SEVEN PERSONS IN IBADAN, NIGERIA TOOK A SIX WEEK TRAINING WORKSHOP COURSE IN PROGRAMED INSTRUCTION. THE COURSE CONSISTED OF LECTURES, GROUP DISCUSSIONS, READING ASSIGNMENTS, INDIVIDUAL CONFERENCES, PROGRAM WRITING, EDITING, AND STUDENT TRIALS. THE TRAINEES MADE COMMENDABLE…

Strategies for Searching. A Self-Paced Workbook for Basic Library Skills. Second Edition.

ERIC Educational Resources Information Center

Hales, Celia; And Others

This self-paced workbook is designed to help students at the University of North Carolina-Charlotte acquire basic skills in using a university library. The workbook, which is used in conjuction with course assignments, is divided into six sections: (l) Introduction; (2) How to Locate Background Information; (3) How to Locate Books; (4) How to…

America is in Trouble, National Wildlife Federation's 1970 National EQ Index.

ERIC Educational Resources Information Center

National Wildlife Federation, Washington, DC.

This is the second annual edition of the EQ (Environmental Quality) Index and is reprinted from the October-November, 1970 National Wildlife Magazine. The index is an attempt "to assign some values and form some judgements on those vital factors that make up the quality of our life--and to decide whether we were winning or losing the pollution…

Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia | Office of Cancer Genomics

Cancer.gov

NCI's TARGET Initiative reported the discovery of a novel genetic marker for children with acute lymphoblastic leukemia (ALL) in the January 7, 2009, advance online edition of The New England Journal of Medicine. The genetic alteration identified, IKZF1, should improve clinicians' ability to identify high-risk patients and better assign these patients to appropriate therapy.

Massive gene transfer and extensive RNA editing of a symbiotic dinoflagellate plastid genome.

PubMed

Mungpakdee, Sutada; Shinzato, Chuya; Takeuchi, Takeshi; Kawashima, Takeshi; Koyanagi, Ryo; Hisata, Kanako; Tanaka, Makiko; Goto, Hiroki; Fujie, Manabu; Lin, Senjie; Satoh, Nori; Shoguchi, Eiichi

2014-05-31

Genome sequencing of Symbiodinium minutum revealed that 95 of 109 plastid-associated genes have been transferred to the nuclear genome and subsequently expanded by gene duplication. Only 14 genes remain in plastids and occur as DNA minicircles. Each minicircle (1.8-3.3 kb) contains one gene and a conserved noncoding region containing putative promoters and RNA-binding sites. Nine types of RNA editing, including a novel G/U type, were discovered in minicircle transcripts but not in genes transferred to the nucleus. In contrast to DNA editing sites in dinoflagellate mitochondria, which tend to be highly conserved across all taxa, editing sites employed in DNA minicircles are highly variable from species to species. Editing is crucial for core photosystem protein function. It restores evolutionarily conserved amino acids and increases peptidyl hydropathy. It also increases protein plasticity necessary to initiate photosystem complex assembly. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

A comparison of the affect of two types of student behavior with manipulatives on the development of projective spatial structures

NASA Astrophysics Data System (ADS)

Cohen, Herbert

The primary problem investigated was whether examining materials from a variety of perspecitives enhances the development of projective spatial abilities more than examining materials from a single perspective. A secondary consideration dealt with gender effects. One hundred and five (56 females and 49 males) fifth grade students were randomly assigned to one of four groups. Two teachers taught two classes apiece-one receiving instruction encouraging examination of materials from a single perspective, the other from multiple perspectives. All four groups received instruction consisting of access to manipulatives-SCIIS, 2nd edition, Level 5. Instruction occurred twice a week, 45 minutes per session, for 6 weeks. The experimental design was the Solomon Four Group Design. A Battery of 8 Piagetian-type tasks were used to assess possession of the projective groupings. The main and interactive effects of pretesting were determined to be negligible, while the treatment was determined to have a statistically significant effect on the development on projective spatial abilities. Gender was determined to have no direct effect on the dependent variables.

C-to-U editing and site-directed RNA editing for the correction of genetic mutations.

PubMed

Vu, Luyen Thi; Tsukahara, Toshifumi

2017-07-24

Cytidine to uridine (C-to-U) editing is one type of substitutional RNA editing. It occurs in both mammals and plants. The molecular mechanism of C-to-U editing involves the hydrolytic deamination of a cytosine to a uracil base. C-to-U editing is mediated by RNA-specific cytidine deaminases and several complementation factors, which have not been completely identified. Here, we review recent findings related to the regulation and enzymatic basis of C-to-U RNA editing. More importantly, when C-to-U editing occurs in coding regions, it has the power to reprogram genetic information on the RNA level, therefore it has great potential for applications in transcript repair (diseases related to thymidine to cytidine (T>C) or adenosine to guanosine (A>G) point mutations). If it is possible to manipulate or mimic C-to-U editing, T>C or A>G genetic mutation-related diseases could be treated. Enzymatic and non-enzymatic site-directed RNA editing are two different approaches for mimicking C-to-U editing. For enzymatic site-directed RNA editing, C-to-U editing has not yet been successfully performed, and in theory, adenosine to inosine (A-to-I) editing involves the same strategy as C-to-U editing. Therefore, in this review, for applications in transcript repair, we will provide a detailed overview of enzymatic site-directed RNA editing, with a focus on A-to-I editing and non-enzymatic site-directed C-to-U editing.

Non-Homologous End Joining and Homology Directed DNA Repair Frequency of Double-Stranded Breaks Introduced by Genome Editing Reagents.

PubMed

Zaboikin, Michail; Zaboikina, Tatiana; Freter, Carl; Srinivasakumar, Narasimhachar

2017-01-01

Genome editing using transcription-activator like effector nucleases or RNA guided nucleases allows one to precisely engineer desired changes within a given target sequence. The genome editing reagents introduce double stranded breaks (DSBs) at the target site which can then undergo DNA repair by non-homologous end joining (NHEJ) or homology directed recombination (HDR) when a template DNA molecule is available. NHEJ repair results in indel mutations at the target site. As PCR amplified products from mutant target regions are likely to exhibit different melting profiles than PCR products amplified from wild type target region, we designed a high resolution melting analysis (HRMA) for rapid identification of efficient genome editing reagents. We also designed TaqMan assays using probes situated across the cut site to discriminate wild type from mutant sequences present after genome editing. The experiments revealed that the sensitivity of the assays to detect NHEJ-mediated DNA repair could be enhanced by selection of transfected cells to reduce the contribution of unmodified genomic DNA from untransfected cells to the DNA melting profile. The presence of donor template DNA lacking the target sequence at the time of genome editing further enhanced the sensitivity of the assays for detection of mutant DNA molecules by excluding the wild-type sequences modified by HDR. A second TaqMan probe that bound to an adjacent site, outside of the primary target cut site, was used to directly determine the contribution of HDR to DNA repair in the presence of the donor template sequence. The TaqMan qPCR assay, designed to measure the contribution of NHEJ and HDR in DNA repair, corroborated the results from HRMA. The data indicated that genome editing reagents can produce DSBs at high efficiency in HEK293T cells but a significant proportion of these are likely masked by reversion to wild type as a result of HDR. Supplying a donor plasmid to provide a template for HDR (that eliminates a PCR amplifiable target) revealed these cryptic DSBs and facilitated the determination of the true efficacy of genome editing reagents. The results indicated that in HEK293T cells, approximately 40% of the DSBs introduced by genome editing, were available for participation in HDR.

Accurate detection for a wide range of mutation and editing sites of microRNAs from small RNA high-throughput sequencing profiles

PubMed Central

Zheng, Yun; Ji, Bo; Song, Renhua; Wang, Shengpeng; Li, Ting; Zhang, Xiaotuo; Chen, Kun; Li, Tianqing; Li, Jinyan

2016-01-01

Various types of mutation and editing (M/E) events in microRNAs (miRNAs) can change the stabilities of pre-miRNAs and/or complementarities between miRNAs and their targets. Small RNA (sRNA) high-throughput sequencing (HTS) profiles can contain many mutated and edited miRNAs. Systematic detection of miRNA mutation and editing sites from the huge volume of sRNA HTS profiles is computationally difficult, as high sensitivity and low false positive rate (FPR) are both required. We propose a novel method (named MiRME) for an accurate and fast detection of miRNA M/E sites using a progressive sequence alignment approach which refines sensitivity and improves FPR step-by-step. From 70 sRNA HTS profiles with over 1.3 billion reads, MiRME has detected thousands of statistically significant M/E sites, including 3′-editing sites, 57 A-to-I editing sites (of which 32 are novel), as well as some putative non-canonical editing sites. We demonstrated that a few non-canonical editing sites were not resulted from mutations in genome by integrating the analysis of genome HTS profiles of two human cell lines, suggesting the existence of new editing types to further diversify the functions of miRNAs. Compared with six existing studies or methods, MiRME has shown much superior performance for the identification and visualization of the M/E sites of miRNAs from the ever-increasing sRNA HTS profiles. PMID:27229138

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice‐daily basal insulin to once‐daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis)

PubMed Central

d'Emden, Michael C.; Fisher, Miles; Ampudia‐Blasco, F. Javier; Stella, Peter; Bizet, Florence; Cali, Anna M. G.; Wysham, Carol H.

2017-01-01

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla‐300) and glargine 100 U/mL (Gla‐100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice‐daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice‐daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla‐300 or Gla‐100 (least squares mean difference −0.01%; 95% confidence interval [CI] −0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI −0.25 to 0.57, in EDITION 2). Participants previously receiving twice‐daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla‐300 vs Gla‐100 at night (00:00–05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla‐300 provided similar glycaemic control with less hypoglycaemia compared with Gla‐100 in people with T2DM switching from twice‐daily to once‐daily basal insulin. PMID:28736942

Reference and Information Services: An Introduction. Third Edition. Library and Information Science Text Series.

ERIC Educational Resources Information Center

Bopp, Richard E., Ed.; Smith, Linda C., Ed.

Like the first two editions, this third edition is designed primarily to provide the beginning student of library and information science with an overview both of the concepts and processes behind today's reference services and of the most important sources consulted in answering common types of reference questions. The first 12 chapters deal with…

Adenosine-to-Inosine Editing of MicroRNA-487b Alters Target Gene Selection After Ischemia and Promotes Neovascularization.

PubMed

van der Kwast, Reginald V C T; van Ingen, Eva; Parma, Laura; Peters, Hendrika A B; Quax, Paul H A; Nossent, A Yaël

2018-02-02

Adenosine-to-inosine editing of microRNAs has the potential to cause a shift in target site selection. 2'-O-ribose-methylation of adenosine residues, however, has been shown to inhibit adenosine-to-inosine editing. To investigate whether angiomiR miR487b is subject to adenosine-to-inosine editing or 2'-O-ribose-methylation during neovascularization. Complementary DNA was prepared from C57BL/6-mice subjected to hindlimb ischemia. Using Sanger sequencing and endonuclease digestion, we identified and validated adenosine-to-inosine editing of the miR487b seed sequence. In the gastrocnemius muscle, pri-miR487b editing increased from 6.7±0.4% before to 11.7±1.6% ( P =0.02) 1 day after ischemia. Edited pri-miR487b is processed into a novel microRNA, edited miR487b, which is also upregulated after ischemia. We confirmed editing of miR487b in multiple human primary vascular cell types. Short interfering RNA-mediated knockdown demonstrated that editing is adenosine deaminase acting on RNA 1 and 2 dependent. Using reverse-transcription at low dNTP concentrations followed by quantitative-PCR, we found that the same adenosine residue is methylated in mice and human primary cells. In the murine gastrocnemius, the estimated methylation fraction increased from 32.8±14% before to 53.6±12% 1 day after ischemia. Short interfering RNA knockdown confirmed that methylation is fibrillarin dependent. Although we could not confirm that methylation directly inhibits editing, we do show that adenosine deaminase acting on RNA 1 and 2 and fibrillarin negatively influence each other's expression. Using multiple luciferase reporter gene assays, we could demonstrate that editing results in a complete switch of target site selection. In human primary cells, we confirmed the shift in miR487b targeting after editing, resulting in a edited miR487b targetome that is enriched for multiple proangiogenic pathways. Furthermore, overexpression of edited miR487b, but not wild-type miR487b, stimulates angiogenesis in both in vitro and ex vivo assays. MiR487b is edited in the seed sequence in mice and humans, resulting in a novel, proangiogenic microRNA with a unique targetome. The rate of miR487b editing, as well as 2'-O-ribose-methylation, is increased in murine muscle tissue during postischemic neovascularization. Our findings suggest miR487b editing plays an intricate role in postischemic neovascularization. © 2017 American Heart Association, Inc.

Rapid analysis of protein backbone resonance assignments using cryogenic probes, a distributed Linux-based computing architecture, and an integrated set of spectral analysis tools.

PubMed

Monleón, Daniel; Colson, Kimberly; Moseley, Hunter N B; Anklin, Clemens; Oswald, Robert; Szyperski, Thomas; Montelione, Gaetano T

2002-01-01

Rapid data collection, spectral referencing, processing by time domain deconvolution, peak picking and editing, and assignment of NMR spectra are necessary components of any efficient integrated system for protein NMR structure analysis. We have developed a set of software tools designated AutoProc, AutoPeak, and AutoAssign, which function together with the data processing and peak-picking programs NMRPipe and Sparky, to provide an integrated software system for rapid analysis of protein backbone resonance assignments. In this paper we demonstrate that these tools, together with high-sensitivity triple resonance NMR cryoprobes for data collection and a Linux-based computer cluster architecture, can be combined to provide nearly complete backbone resonance assignments and secondary structures (based on chemical shift data) for a 59-residue protein in less than 30 hours of data collection and processing time. In this optimum case of a small protein providing excellent spectra, extensive backbone resonance assignments could also be obtained using less than 6 hours of data collection and processing time. These results demonstrate the feasibility of high throughput triple resonance NMR for determining resonance assignments and secondary structures of small proteins, and the potential for applying NMR in large scale structural proteomics projects.

Auditing the Assignments of Top-Level Semantic Types in the UMLS Semantic Network to UMLS Concepts

PubMed Central

He, Zhe; Perl, Yehoshua; Elhanan, Gai; Chen, Yan; Geller, James; Bian, Jiang

2018-01-01

The Unified Medical Language System (UMLS) is an important terminological system. By the policy of its curators, each concept of the UMLS should be assigned the most specific Semantic Types (STs) in the UMLS Semantic Network (SN). Hence, the Semantic Types of most UMLS concepts are assigned at or near the bottom (leaves) of the UMLS Semantic Network. While most ST assignments are correct, some errors do occur. Therefore, Quality Assurance efforts of UMLS curators for ST assignments should concentrate on automatically detected sets of UMLS concepts with higher error rates than random sets. In this paper, we investigate the assignments of top-level semantic types in the UMLS semantic network to concepts, identify potential erroneous assignments, define four categories of errors, and thus provide assistance to curators of the UMLS to avoid these assignments errors. Human experts analyzed samples of concepts assigned 10 of the top-level semantic types and categorized the erroneous ST assignments into these four logical categories. Two thirds of the concepts assigned these 10 top-level semantic types are erroneous. Our results demonstrate that reviewing top-level semantic type assignments to concepts provides an effective way for UMLS quality assurance, comparing to reviewing a random selection of semantic type assignments. PMID:29375930

Auditing the Assignments of Top-Level Semantic Types in the UMLS Semantic Network to UMLS Concepts.

PubMed

He, Zhe; Perl, Yehoshua; Elhanan, Gai; Chen, Yan; Geller, James; Bian, Jiang

2017-11-01

The Unified Medical Language System (UMLS) is an important terminological system. By the policy of its curators, each concept of the UMLS should be assigned the most specific Semantic Types (STs) in the UMLS Semantic Network (SN). Hence, the Semantic Types of most UMLS concepts are assigned at or near the bottom (leaves) of the UMLS Semantic Network. While most ST assignments are correct, some errors do occur. Therefore, Quality Assurance efforts of UMLS curators for ST assignments should concentrate on automatically detected sets of UMLS concepts with higher error rates than random sets. In this paper, we investigate the assignments of top-level semantic types in the UMLS semantic network to concepts, identify potential erroneous assignments, define four categories of errors, and thus provide assistance to curators of the UMLS to avoid these assignments errors. Human experts analyzed samples of concepts assigned 10 of the top-level semantic types and categorized the erroneous ST assignments into these four logical categories. Two thirds of the concepts assigned these 10 top-level semantic types are erroneous. Our results demonstrate that reviewing top-level semantic type assignments to concepts provides an effective way for UMLS quality assurance, comparing to reviewing a random selection of semantic type assignments.

Systematic quantification of HDR and NHEJ reveals effects of locus, nuclease, and cell type on genome-editing.

PubMed

Miyaoka, Yuichiro; Berman, Jennifer R; Cooper, Samantha B; Mayerl, Steven J; Chan, Amanda H; Zhang, Bin; Karlin-Neumann, George A; Conklin, Bruce R

2016-03-31

Precise genome-editing relies on the repair of sequence-specific nuclease-induced DNA nicking or double-strand breaks (DSBs) by homology-directed repair (HDR). However, nonhomologous end-joining (NHEJ), an error-prone repair, acts concurrently, reducing the rate of high-fidelity edits. The identification of genome-editing conditions that favor HDR over NHEJ has been hindered by the lack of a simple method to measure HDR and NHEJ directly and simultaneously at endogenous loci. To overcome this challenge, we developed a novel, rapid, digital PCR-based assay that can simultaneously detect one HDR or NHEJ event out of 1,000 copies of the genome. Using this assay, we systematically monitored genome-editing outcomes of CRISPR-associated protein 9 (Cas9), Cas9 nickases, catalytically dead Cas9 fused to FokI, and transcription activator-like effector nuclease at three disease-associated endogenous gene loci in HEK293T cells, HeLa cells, and human induced pluripotent stem cells. Although it is widely thought that NHEJ generally occurs more often than HDR, we found that more HDR than NHEJ was induced under multiple conditions. Surprisingly, the HDR/NHEJ ratios were highly dependent on gene locus, nuclease platform, and cell type. The new assay system, and our findings based on it, will enable mechanistic studies of genome-editing and help improve genome-editing technology.

Effect of Making an Audio Recording of a Term Paper on Writing Quality

ERIC Educational Resources Information Center

Taxis, Tasia M.; Lannin, Amy A.; Selting, Bonita R.; Lamberson, William R.

2014-01-01

Writing-to-learn assignments engage students with a problem while they develop writing skills. It is difficult in large classes to provide training in proofreading and editing techniques. The purpose of this project was to determine if a term paper was improved after making an audio recording of a draft of the paper. Data from 2 years of papers…

Children's Struggles with the Writing Process: Exploring Storytelling, Visual Arts, and Keyboarding to Promote Narrative Story Writing

ERIC Educational Resources Information Center

Dunn, Michael W.; Finley, Susan

2010-01-01

Composing text is an essential skill for students. Assignments, tests, and emailing are a few examples of the many tasks which require students to generate thoughts and put them into prose. For many students, choosing a topic, creating an outline, generating an initial draft, and making edits to produce a final copy is a fluid process which poses…

Towards a comprehensive picture of C-to-U RNA editing sites in angiosperm mitochondria.

PubMed

Edera, Alejandro A; Gandini, Carolina L; Sanchez-Puerta, M Virginia

2018-05-14

Our understanding of the dynamic and evolution of RNA editing in angiosperms is in part limited by the few editing sites identified to date. This study identified 10,217 editing sites from 17 diverse angiosperms. Our analyses confirmed the universality of certain features of RNA editing, and offer new evidence behind the loss of editing sites in angiosperms. RNA editing is a post-transcriptional process that substitutes cytidines (C) for uridines (U) in organellar transcripts of angiosperms. These substitutions mostly take place in mitochondrial messenger RNAs at specific positions called editing sites. By means of publicly available RNA-seq data, this study identified 10,217 editing sites in mitochondrial protein-coding genes of 17 diverse angiosperms. Even though other types of mismatches were also identified, we did not find evidence of non-canonical editing processes. The results showed an uneven distribution of editing sites among species, genes, and codon positions. The analyses revealed that editing sites were conserved across angiosperms but there were some species-specific sites. Non-synonymous editing sites were particularly highly conserved (~ 80%) across the plant species and were efficiently edited (80% editing extent). In contrast, editing sites at third codon positions were poorly conserved (~ 30%) and only partially edited (~ 40% editing extent). We found that the loss of editing sites along angiosperm evolution is mainly occurring by replacing editing sites with thymidines, instead of a degradation of the editing recognition motif around editing sites. Consecutive and highly conserved editing sites had been replaced by thymidines as result of retroprocessing, by which edited transcripts are reverse transcribed to cDNA and then integrated into the genome by homologous recombination. This phenomenon was more pronounced in eudicots, and in the gene cox1. These results suggest that retroprocessing is a widespread driving force underlying the loss of editing sites in angiosperm mitochondria.

Tuning of RNA editing by ADAR is required in Drosophila

PubMed Central

Keegan, Liam P; Brindle, James; Gallo, Angela; Leroy, Anne; Reenan, Robert A; O'Connell, Mary A

2005-01-01

RNA editing increases during development in more than 20 transcripts encoding proteins involved in rapid synaptic neurotransmission in Drosophila central nervous system and muscle. Adar (adenosine deaminase acting on RNA) mutant flies expressing only genome-encoded, unedited isoforms of ion-channel subunits are viable but show severe locomotion defects. The Adar transcript itself is edited in adult wild-type flies to generate an isoform with a serine to glycine substitution close to the ADAR active site. We show that editing restricts ADAR function since the edited isoform of ADAR is less active in vitro and in vivo than the genome-encoded, unedited isoform. Ubiquitous expression in embryos and larvae of an Adar transcript that is resistant to editing is lethal. Expression of this transcript in embryonic muscle is also lethal, with above-normal, adult-like levels of editing at sites in a transcript encoding a muscle voltage-gated calcium channel. PMID:15920480

Non-viral delivery of genome-editing nucleases for gene therapy.

PubMed

Wang, M; Glass, Z A; Xu, Q

2017-03-01

Manipulating the genetic makeup of mammalian cells using programmable nuclease-based genome-editing technology has recently evolved into a powerful avenue that holds great potential for treating genetic disorders. There are four types of genome-editing nucleases, including meganucleases, zinc finger nucleases, transcription activator-like effector nucleases and clustered, regularly interspaced, short palindromic repeat-associated nucleases such as Cas9. These nucleases have been harnessed to introduce precise and specific changes of the genome sequence at virtually any genome locus of interest. The therapeutic relevance of these genome-editing technologies, however, is challenged by the safe and efficient delivery of nuclease into targeted cells. Herein, we summarize recent advances that have been made on non-viral delivery of genome-editing nucleases. In particular, we focus on non-viral delivery of Cas9/sgRNA ribonucleoproteins for genome editing. In addition, the future direction for developing non-viral delivery of programmable nucleases for genome editing is discussed.

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis).

PubMed

Roussel, Ronan; d'Emden, Michael C; Fisher, Miles; Ampudia-Blasco, F Javier; Stella, Peter; Bizet, Florence; Cali, Anna M G; Wysham, Carol H

2018-02-01

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Efficient Generation and Editing of Feeder-free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System.

PubMed

Nandal, Anjali; Mallon, Barbara; Telugu, Bhanu P

2017-11-08

Embryonic and induced pluripotent stem cells can self-renew and differentiate into multiple cell types of the body. The pluripotent cells are thus coveted for research in regenerative medicine and are currently in clinical trials for eye diseases, diabetes, heart diseases, and other disorders. The potential to differentiate into specialized cell types coupled with the recent advances in genome editing technologies including the CRISPR/Cas system have provided additional opportunities for tailoring the genome of iPSC for varied applications including disease modeling, gene therapy, and biasing pathways of differentiation, to name a few. Among the available editing technologies, the CRISPR/Cas9 from Streptococcus pyogenes has emerged as a tool of choice for site-specific editing of the eukaryotic genome. The CRISPRs are easily accessible, inexpensive, and highly efficient in engineering targeted edits. The system requires a Cas9 nuclease and a guide sequence (20-mer) specific to the genomic target abutting a 3-nucleotide "NGG" protospacer-adjacent-motif (PAM) for targeting Cas9 to the desired genomic locus, alongside a universal Cas9 binding tracer RNA (together called single guide RNA or sgRNA). Here we present a step-by-step protocol for efficient generation of feeder-independent and footprint-free iPSC and describe methodologies for genome editing of iPSC using the Cas9 ribonucleoprotein (RNP) complexes. The genome editing protocol is effective and can be easily multiplexed by pre-complexing sgRNAs for more than one target with the Cas9 protein and simultaneously delivering into the cells. Finally, we describe a simplified approach for identification and characterization of iPSCs with desired edits. Taken together, the outlined strategies are expected to streamline generation and editing of iPSC for manifold applications.

Changing genetic information through RNA editing

NASA Technical Reports Server (NTRS)

Maas, S.; Rich, A.

2000-01-01

RNA editing, the post-transcriptional alteration of a gene-encoded sequence, is a widespread phenomenon in eukaryotes. As a consequence of RNA editing, functionally distinct proteins can be produced from a single gene. The molecular mechanisms involved include single or multiple base insertions or deletions as well as base substitutions. In mammals, one type of substitutional RNA editing, characterized by site-specific base-modification, was shown to modulate important physiological processes. The underlying reaction mechanism of substitutional RNA editing involves hydrolytic deamination of cytosine or adenosine bases to uracil or inosine, respectively. Protein factors have been characterized that are able to induce RNA editing in vitro. A supergene family of RNA-dependent deaminases has emerged with the recent addition of adenosine deaminases specific for tRNA. Here we review the developments that have substantially increased our understanding of base-modification RNA editing over the past few years, with an emphasis on mechanistic differences, evolutionary aspects and the first insights into the regulation of editing activity.

The New Peabody Picture Vocabulary Test-III: An Illusion of Unbiased Assessment?

PubMed

Stockman, Ida J

2000-10-01

This article examines whether changes in the ethnic minority composition of the standardization sample for the latest edition of the Peabody Picture Vocabulary Test (PPVT-III, Dunn & Dunn, 1997) can be used as the sole explanation for children's better test scores when compared to an earlier edition, the Peabody Picture Vocabulary Test-Revised (PPVT-R, Dunn & Dunn, 1981). Results from a comparative analysis of these two test editions suggest that other factors may explain improved performances. Among these factors are the number of words and age levels sampled, the types of words and pictures used, and characteristics of the standardization sample other than its ethnic minority composition. This analysis also raises questions regarding the usefulness of converting scores from one edition to the other and the type of criteria that could be used to evaluate whether the PPVT-III is an unbiased test of vocabulary for children from diverse cultural and linguistic backgrounds.

Efficient genome editing of differentiated renal epithelial cells.

PubMed

Hofherr, Alexis; Busch, Tilman; Huber, Nora; Nold, Andreas; Bohn, Albert; Viau, Amandine; Bienaimé, Frank; Kuehn, E Wolfgang; Arnold, Sebastian J; Köttgen, Michael

2017-02-01

Recent advances in genome editing technologies have enabled the rapid and precise manipulation of genomes, including the targeted introduction, alteration, and removal of genomic sequences. However, respective methods have been described mainly in non-differentiated or haploid cell types. Genome editing of well-differentiated renal epithelial cells has been hampered by a range of technological issues, including optimal design, efficient expression of multiple genome editing constructs, attainable mutation rates, and best screening strategies. Here, we present an easily implementable workflow for the rapid generation of targeted heterozygous and homozygous genomic sequence alterations in renal cells using transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeat (CRISPR) system. We demonstrate the versatility of established protocols by generating novel cellular models for studying autosomal dominant polycystic kidney disease (ADPKD). Furthermore, we show that cell culture-validated genetic modifications can be readily applied to mouse embryonic stem cells (mESCs) for the generation of corresponding mouse models. The described procedure for efficient genome editing can be applied to any cell type to study physiological and pathophysiological functions in the context of precisely engineered genotypes.

Transcriptogenomics identification and characterization of RNA editing sites in human primary monocytes using high-depth next generation sequencing data.

PubMed

Leong, Wai-Mun; Ripen, Adiratna Mat; Mirsafian, Hoda; Mohamad, Saharuddin Bin; Merican, Amir Feisal

2018-06-07

High-depth next generation sequencing data provide valuable insights into the number and distribution of RNA editing events. Here, we report the RNA editing events at cellular level of human primary monocyte using high-depth whole genomic and transcriptomic sequencing data. We identified over a ten thousand putative RNA editing sites and 69% of the sites were A-to-I editing sites. The sites enriched in repetitive sequences and intronic regions. High-depth sequencing datasets revealed that 90% of the canonical sites were edited at lower frequencies (<0.7). Single and multiple human monocytes and brain tissues samples were analyzed through genome sequence independent approach. The later approach was observed to identify more editing sites. Monocytes was observed to contain more C-to-U editing sites compared to brain tissues. Our results establish comparable pipeline that can address current limitations as well as demonstrate the potential for highly sensitive detection of RNA editing events in single cell type. Copyright © 2018 Elsevier Inc. All rights reserved.

Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets

PubMed Central

Pinto, Yishay; Buchumenski, Ilana

2018-01-01

Abstract A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation by miRNAs and its behavior in human cancers is still unknown. Here we systematically characterized miRNA editing in 10 593 human samples across 32 cancer types and normal controls. We find that the majority of previously reported sites show little to no evidence for editing in this dataset, compile a list of 58 reliable miRNA editing sites, and study them across normal and cancer samples. Edited miRNA versions tend to suppress expression of known oncogenes, and, consistently, we observe a clear global tendency for hypo-editing in tumors, in strike contrast to the behavior for mRNA editing, allowing an accurate classification of normal/tumor samples based on their miRNA editing profile. In many cancers this profile correlates with patients' survival. Finally, thousands of miRNA binding sites are differentially edited in cancer. Our study thus establishes the important effect of RNA editing on miRNA-regulation in the tumor cell, with prospects for diagnostic and prognostic applications. PMID:29165639

AQME: A forensic mitochondrial DNA analysis tool for next-generation sequencing data.

PubMed

Sturk-Andreaggi, Kimberly; Peck, Michelle A; Boysen, Cecilie; Dekker, Patrick; McMahon, Timothy P; Marshall, Charla K

2017-11-01

The feasibility of generating mitochondrial DNA (mtDNA) data has expanded considerably with the advent of next-generation sequencing (NGS), specifically in the generation of entire mtDNA genome (mitogenome) sequences. However, the analysis of these data has emerged as the greatest challenge to implementation in forensics. To address this need, a custom toolkit for use in the CLC Genomics Workbench (QIAGEN, Hilden, Germany) was developed through a collaborative effort between the Armed Forces Medical Examiner System - Armed Forces DNA Identification Laboratory (AFMES-AFDIL) and QIAGEN Bioinformatics. The AFDIL-QIAGEN mtDNA Expert, or AQME, generates an editable mtDNA profile that employs forensic conventions and includes the interpretation range required for mtDNA data reporting. AQME also integrates an mtDNA haplogroup estimate into the analysis workflow, which provides the analyst with phylogenetic nomenclature guidance and a profile quality check without the use of an external tool. Supplemental AQME outputs such as nucleotide-per-position metrics, configurable export files, and an audit trail are produced to assist the analyst during review. AQME is applied to standard CLC outputs and thus can be incorporated into any mtDNA bioinformatics pipeline within CLC regardless of sample type, library preparation or NGS platform. An evaluation of AQME was performed to demonstrate its functionality and reliability for the analysis of mitogenome NGS data. The study analyzed Illumina mitogenome data from 21 samples (including associated controls) of varying quality and sample preparations with the AQME toolkit. A total of 211 tool edits were automatically applied to 130 of the 698 total variants reported in an effort to adhere to forensic nomenclature. Although additional manual edits were required for three samples, supplemental tools such as mtDNA haplogroup estimation assisted in identifying and guiding these necessary modifications to the AQME-generated profile. Along with profile generation, AQME reported accurate haplogroups for 18 of the 19 samples analyzed. The single errant haplogroup assignment, although phylogenetically close, identified a bug that only affects partial mitogenome data. Future adjustments to AQME's haplogrouping tool will address this bug as well as enhance the overall scoring strategy to better refine and automate haplogroup assignments. As NGS enables broader use of the mtDNA locus in forensics, the availability of AQME and other forensic-focused mtDNA analysis tools will ease the transition and further support mitogenome analysis within routine casework. Toward this end, the AFMES-AFDIL has utilized the AQME toolbox in conjunction with the CLC Genomics Workbench to successfully validate and implement two NGS mitogenome methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Detailed analysis of targeted gene mutations caused by the Platinum-Fungal TALENs in Aspergillus oryzae RIB40 strain and a ligD disruptant.

PubMed

Mizutani, Osamu; Arazoe, Takayuki; Toshida, Kenji; Hayashi, Risa; Ohsato, Shuichi; Sakuma, Tetsushi; Yamamoto, Takashi; Kuwata, Shigeru; Yamada, Osamu

2017-03-01

Transcription activator-like effector nucleases (TALENs), which can generate DNA double-strand breaks at specific sites in the desired genome locus, have been used in many organisms as a tool for genome editing. In Aspergilli, including Aspergillus oryzae, however, the use of TALENs has not been validated. In this study, we performed genome editing of A. oryzae wild-type strain via error of nonhomologous end-joining (NHEJ) repair by transient expression of high-efficiency Platinum-Fungal TALENs (PtFg TALENs). Targeted mutations were observed as various mutation patterns. In particular, approximately half of the PtFg TALEN-mediated deletion mutants had deletions larger than 1 kb in the TALEN-targeting region. We also conducted PtFg TALEN-based genome editing in A. oryzae ligD disruptant (ΔligD) lacking the ligD gene involved in the final step of the NHEJ repair and found that mutations were still obtained as well as wild-type. In this case, the ratio of the large deletions reduced compared to PtFg TALEN-based genome editing in the wild-type. In conclusion, we demonstrate that PtFg TALENs are sufficiently functional to cause genome editing via error of NHEJ in A. oryzae. In addition, we reveal that genome editing using TALENs in A. oryzae tends to cause large deletions at the target region, which were partly suppressed by deletion of ligD. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Dynamic landscape and regulation of RNA editing in mammals

PubMed Central

Tan, Meng How; Li, Qin; Shanmugam, Raghuvaran; Piskol, Robert; Kohler, Jennefer; Young, Amy N.; Liu, Kaiwen Ivy; Zhang, Rui; Ramaswami, Gokul; Ariyoshi, Kentaro; Gupte, Ankita; Keegan, Liam P.; George, Cyril X.; Ramu, Avinash; Huang, Ni; Pollina, Elizabeth A.; Leeman, Dena S.; Rustighi, Alessandra; Sharon Goh, Y. P.; Chawla, Ajay; Del Sal, Giannino; Peltz, Gary; Brunet, Anne; Conrad, Donald F.; Samuel, Charles E.; O’Connell, Mary A.; Walkley, Carl R.; Nishikura, Kazuko; Li, Jin Billy

2017-01-01

Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules1. Although many editing sites have recently been discovered2–7, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood8–10. Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples. We show that editing levels in non-repetitive coding regions vary more between tissues than editing levels in repetitive regions. Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 is the primary editor of non-repetitive coding sites, whereas the catalytically inactive ADAR3 predominantly acts as an inhibitor of editing. Cross-species analysis of RNA editing in several tissues revealed that species, rather than tissue type, is the primary determinant of editing levels, suggesting stronger cis-directed regulation of RNA editing for most sites, although the small set of conserved coding sites is under stronger trans-regulation. In addition, we curated an extensive set of ADAR1 and ADAR2 targets and showed that many editing sites display distinct tissue-specific regulation by the ADAR enzymes in vivo. Further analysis of the GTEx data revealed several potential regulators of editing, such as AIMP2, which reduces editing in muscles by enhancing the degradation of the ADAR proteins. Collectively, our work provides insights into the complex cis- and trans-regulation of A-to-I editing. PMID:29022589

Dynamic landscape and regulation of RNA editing in mammals.

PubMed

Tan, Meng How; Li, Qin; Shanmugam, Raghuvaran; Piskol, Robert; Kohler, Jennefer; Young, Amy N; Liu, Kaiwen Ivy; Zhang, Rui; Ramaswami, Gokul; Ariyoshi, Kentaro; Gupte, Ankita; Keegan, Liam P; George, Cyril X; Ramu, Avinash; Huang, Ni; Pollina, Elizabeth A; Leeman, Dena S; Rustighi, Alessandra; Goh, Y P Sharon; Chawla, Ajay; Del Sal, Giannino; Peltz, Gary; Brunet, Anne; Conrad, Donald F; Samuel, Charles E; O'Connell, Mary A; Walkley, Carl R; Nishikura, Kazuko; Li, Jin Billy

2017-10-11

Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules. Although many editing sites have recently been discovered, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood. Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples. We show that editing levels in non-repetitive coding regions vary more between tissues than editing levels in repetitive regions. Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 is the primary editor of non-repetitive coding sites, whereas the catalytically inactive ADAR3 predominantly acts as an inhibitor of editing. Cross-species analysis of RNA editing in several tissues revealed that species, rather than tissue type, is the primary determinant of editing levels, suggesting stronger cis-directed regulation of RNA editing for most sites, although the small set of conserved coding sites is under stronger trans-regulation. In addition, we curated an extensive set of ADAR1 and ADAR2 targets and showed that many editing sites display distinct tissue-specific regulation by the ADAR enzymes in vivo. Further analysis of the GTEx data revealed several potential regulators of editing, such as AIMP2, which reduces editing in muscles by enhancing the degradation of the ADAR proteins. Collectively, our work provides insights into the complex cis- and trans-regulation of A-to-I editing.

Area Handbook Series: Soviet Union: A Country Study

DTIC Science & Technology

1989-05-01

War, edited by Harriet F. Scott and William F. Scott, is a judicious combination of the editors’ commentaries and of excerpts from translated writ...equipped the Soviet armed forces to capably fulfill their assigned missions. The single most complete work on the Soviet armed forces is Harriet F. Scott and...Hague: Martinus Nijhoff, 1969. _ _ Russian Intellectual History: An Anthology. New York: Hu- manities Press, 1978. Riasanovsky, Nicholas. A History of

Army Library Institute V: Product/Marketing/Service - Volume 2, Supplementary Data

DTIC Science & Technology

1981-11-01

Rinctlons OCLC for Beginners Performance Standards Screening Panel Session 4, Thursday, 21 May 1981 Task Force Group Meetings ADP/Networking...for Library Functions W OCLC for Beginners X Career Programs and Position Classification Standards Y Screening Panel...is non-DLC a librarian will examine it, assign a call number, and do any other editing. For a flowchart , see Appendix 6, but remember that this is a

United States Air Force Statistical Digest, Fiscal Year 1959. Fourteenth Edition

DTIC Science & Technology

1959-09-30

Support Forces for fiscal year 1959 consist of Air Refueling; Strategic Support; Airborne Early Warning and Control; Radar Evaluation ;.He11cop~er...missions. (EI) Test: Aircraft assigned to evaluate the aircraft and/or its components installed as standard equipment. (EH) Test Support: Aircraft... consumables under two AF-GEN sub-projects: PROJECT SEAWEED and PROJECT NIGHT LIFE & FLYAWAY KITS. Also included in this section is data on ammunition

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.…

ADAR2 induces reproducible changes in sequence and abundance of mature microRNAs in the mouse brain

PubMed Central

Vesely, Cornelia; Tauber, Stefanie; Sedlazeck, Fritz J.; Tajaddod, Mansoureh; von Haeseler, Arndt; Jantsch, Michael F.

2014-01-01

Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in double-stranded RNAs including miRNA precursors. A to I editing is widespread and required for normal life. By comparing deep sequencing data of brain miRNAs from wild-type and ADAR2 deficient mouse strains, we detect editing sites and altered miRNA processing at high sensitivity. We detect 48 novel editing events in miRNAs. Some editing events reach frequencies of up to 80%. About half of all editing events depend on ADAR2 while some miRNAs are preferentially edited by ADAR1. Sixty-four percent of all editing events are located within the seed region of mature miRNAs. For the highly edited miR-3099, we experimentally prove retargeting of the edited miRNA to novel 3′ UTRs. We show further that an abundant editing event in miR-497 promotes processing by Drosha of the corresponding pri-miRNA. We also detect reproducible changes in the abundance of specific miRNAs in ADAR2-deficient mice that occur independent of adjacent A to I editing events. This indicates that ADAR2 binding but not editing of miRNA precursors may influence their processing. Correlating with changes in miRNA abundance we find misregulation of putative targets of these miRNAs in the presence or absence of ADAR2. PMID:25260591

Assessing health risk behaviors among adolescents: the effect of question wording and appeals for honesty.

PubMed

Brener, Nancy D; Grunbaum, Jo Anne; Kann, Laura; McManus, Tim; Ross, Jim

2004-08-01

To understand how methodological factors influence prevalence estimates of health-risk behaviors obtained from surveys, we examined the effect of varying question wording and honesty appeals while holding other aspects of the surveys constant. A convenience sample of students (n = 4140) in grades 9 through 12 was randomly assigned to complete one of six versions of a paper-and-pencil questionnaire in classrooms. Each questionnaire version represented a different combination of honesty appeal (standard vs. strong) and questionnaire type. The questionnaire types varied in wording and in the number of questions assessing particular types of behaviors. The questionnaires were based on those used in three national surveys--the Youth Risk Behavior Survey, Monitoring the Future, and the National Household Survey on Drug Abuse. Logistic regression analyses examined how responses to each survey question assessing behavior were associated with questionnaire type, honesty appeal, and the interaction of those two variables. Among 32 behaviors with different question wording across questionnaire types, 12 showed a significant effect of questionnaire type. Among 45 behaviors with identical question wording across questionnaire types, five showed a significant main effect of questionnaire type. Among all 77 behaviors, one showed a significant main effect for honesty appeal and two showed a significant interaction between honesty appeal and questionnaire type. When population, setting, questionnaire context, mode of administration, and data-editing protocols are held constant, differences in question wording can create statistically significant differences in some prevalence estimates. Varying honesty appeals does not have an effect on prevalence estimates.

3D Human Motion Editing and Synthesis: A Survey

PubMed Central

Wang, Xin; Chen, Qiudi; Wang, Wanliang

2014-01-01

The ways to compute the kinematics and dynamic quantities of human bodies in motion have been studied in many biomedical papers. This paper presents a comprehensive survey of 3D human motion editing and synthesis techniques. Firstly, four types of methods for 3D human motion synthesis are introduced and compared. Secondly, motion capture data representation, motion editing, and motion synthesis are reviewed successively. Finally, future research directions are suggested. PMID:25045395

Speech Recognition as a Transcription Aid: A Randomized Comparison With Standard Transcription

PubMed Central

Mohr, David N.; Turner, David W.; Pond, Gregory R.; Kamath, Joseph S.; De Vos, Cathy B.; Carpenter, Paul C.

2003-01-01

Objective. Speech recognition promises to reduce information entry costs for clinical information systems. It is most likely to be accepted across an organization if physicians can dictate without concerning themselves with real-time recognition and editing; assistants can then edit and process the computer-generated document. Our objective was to evaluate the use of speech-recognition technology in a randomized controlled trial using our institutional infrastructure. Design. Clinical note dictations from physicians in two specialty divisions were randomized to either a standard transcription process or a speech-recognition process. Secretaries and transcriptionists also were assigned randomly to each of these processes. Measurements. The duration of each dictation was measured. The amount of time spent processing a dictation to yield a finished document also was measured. Secretarial and transcriptionist productivity, defined as hours of secretary work per minute of dictation processed, was determined for speech recognition and standard transcription. Results. Secretaries in the endocrinology division were 87.3% (confidence interval, 83.3%, 92.3%) as productive with the speech-recognition technology as implemented in this study as they were using standard transcription. Psychiatry transcriptionists and secretaries were similarly less productive. Author, secretary, and type of clinical note were significant (p < 0.05) predictors of productivity. Conclusion. When implemented in an organization with an existing document-processing infrastructure (which included training and interfaces of the speech-recognition editor with the existing document entry application), speech recognition did not improve the productivity of secretaries or transcriptionists. PMID:12509359

A Novel RNA Editing Sensor Tool and a Specific Agonist Determine Neuronal Protein Expression of RNA-Edited Glycine Receptors and Identify a Genomic APOBEC1 Dimorphism as a New Genetic Risk Factor of Epilepsy

PubMed Central

Kankowski, Svenja; Förstera, Benjamin; Winkelmann, Aline; Knauff, Pina; Wanker, Erich E.; You, Xintian A.; Semtner, Marcus; Hetsch, Florian; Meier, Jochen C.

2018-01-01

C-to-U RNA editing of glycine receptors (GlyR) can play an important role in disease progression of temporal lobe epilepsy (TLE) as it may contribute in a neuron type-specific way to neuropsychiatric symptoms of the disease. It is therefore necessary to develop tools that allow identification of neuron types that express RNA-edited GlyR protein. In this study, we identify NH4 as agonist of C-to-U RNA edited GlyRs. Furthermore, we generated a new molecular C-to-U RNA editing sensor tool that detects Apobec-1- dependent RNA editing in HEPG2 cells and rat primary hippocampal neurons. Using this sensor combined with NH4 application, we were able to identify C-to-U RNA editing-competent neurons and expression of C-to-U RNA-edited GlyR protein in neurons. Bioinformatic analysis of 1,000 Genome Project Phase 3 allele frequencies coding for human Apobec-1 80M and 80I variants showed differences between populations, and the results revealed a preference of the 80I variant to generate RNA-edited GlyR protein. Finally, we established a new PCR-based restriction fragment length polymorphism (RFLP) approach to profile mRNA expression with regard to the genetic APOBEC1 dimorphism of patients with intractable temporal lobe epilepsy (iTLE) and found that the patients fall into two groups. Patients with expression of the Apobec-1 80I variant mostly suffered from simple or complex partial seizures, whereas patients with 80M expression exhibited secondarily generalized seizure activity. Thus, our method allows the characterization of Apobec-1 80M and 80l variants in the brain and provides a new way to epidemiologically and semiologically classify iTLE according to the two different APOBEC1 alleles. Together, these results demonstrate Apobec-1-dependent expression of RNA-edited GlyR protein in neurons and identify the APOBEC1 80I/M-coding alleles as new genetic risk factors for iTLE patients. PMID:29375302

[Application of CRISPR/Cas9 mediated genome editing in farm animals].

PubMed

Xing, Yu-yun; Yang, Qiang; Ren, Jun

2016-03-01

CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) is an acquired immune system found in bacteria and archaea that fight against invasion of viruses or plasmids. CRISPR/Cas systems are currently classified into three main types: I, II and III, of which type II has relatively simple components. The CRISPR/Cas9 technology modified from type II CRISPR/Cas system has been developed as an efficient genome editing tool. Since the initial application of the CRISPR/Cas9 technology in mammals in 2013, the reports of this system for genomic editing has skyrocketed. Farm animals are not only economically important animals, but also ideal animal models for human diseases and biomedical studies. In this review, we summarize the applications of CRISPR/Cas9 in farm animals, briefly describe the off-target effects and the main solutions, and finally highlight the future perspectives of this technology.

Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer.

PubMed

Hong, HuiQi; An, Omer; Chan, Tim H M; Ng, Vanessa H E; Kwok, Hui Si; Lin, Jaymie S; Qi, Lihua; Han, Jian; Tay, Daryl J T; Tang, Sze Jing; Yang, Henry; Song, Yangyang; Bellido Molias, Fernando; Tenen, Daniel G; Chen, Leilei

2018-05-18

Adenosine-to-inosine (A-to-I) RNA editing entails the enzymatic deamination of adenosines to inosines by adenosine deaminases acting on RNA (ADARs). Dysregulated A-to-I editing has been implicated in various diseases, including cancers. However, the precise factors governing the A-to-I editing and their physiopathological implications remain as a long-standing question. Herein, we unravel that DEAH box helicase 9 (DHX9), at least partially dependent of its helicase activity, functions as a bidirectional regulator of A-to-I editing in cancer cells. Intriguingly, the ADAR substrate specificity determines the opposing effects of DHX9 on editing as DHX9 silencing preferentially represses editing of ADAR1-specific substrates, whereas augments ADAR2-specific substrate editing. Analysis of 11 cancer types from The Cancer Genome Atlas (TCGA) reveals a striking overexpression of DHX9 in tumors. Further, tumorigenicity studies demonstrate a helicase-dependent oncogenic role of DHX9 in cancer development. In sum, DHX9 constitutes a bidirectional regulatory mode in A-to-I editing, which is in part responsible for the dysregulated editome profile in cancer.

An evaluation of the quality of obstetric morbidity coding using an objective assessment tool, the Performance Indicators For Coding Quality (PICQ).

PubMed

Lamb, Mary K; Innes, Kerry; Saad, Patricia; Rust, Julie; Dimitropoulos, Vera; Cumerlato, Megan

The Performance Indicators for Coding Quality (PICQ) is a data quality assessment tool developed by Australia's National Centre for Classification in Health (NCCH). PICQ consists of a number of indicators covering all ICD-10-AM disease chapters, some procedure chapters from the Australian Classification of Health Intervention (ACHI) and some Australian Coding Standards (ACS). The indicators can be used to assess the coding quality of hospital morbidity data by monitoring compliance of coding conventions and ACS; this enables the identification of particular records that may be incorrectly coded, thus providing a measure of data quality. There are 31 obstetric indicators available for the ICD-10-AM Fourth Edition. Twenty of these 31 indicators were classified as Fatal, nine as Warning and two Relative. These indicators were used to examine coding quality of obstetric records in the 2004-2005 financial year Australian national hospital morbidity dataset. Records with obstetric disease or procedure codes listed anywhere in the code string were extracted and exported from the SPSS source file. Data were then imported into a Microsoft Access database table as per PICQ instructions, and run against all Fatal and Warning and Relative (N=31) obstetric PICQ 2006 Fourth Edition Indicators v.5 for the ICD-10- AM Fourth Edition. There were 689,905 gynaecological and obstetric records in the 2004-2005 financial year, of which 1.14% were found to have triggered Fatal degree errors, 3.78% Warning degree errors and 8.35% Relative degree errors. The types of errors include completeness, redundancy, specificity and sequencing problems. It was found that PICQ is a useful initial screening tool for the assessment of ICD-10-AM/ACHI coding quality. The overall quality of codes assigned to obstetric records in the 2004- 2005 Australian national morbidity dataset is of fair quality.

Edited synoptic cloud reports from ships and land stations over the globe, 1982--1991

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

Hahn, C.J.; Warren, S.G.; London, J.

1996-02-01

Surface synoptic weather reports for the entire globe for the 10-year period from December 1981 through November 1991 have been processed, edited, and rewritten to provide a data set designed for use in cloud analyses. The information in these reports relating to clouds, including the present weather information, was extracted and put through a series of quality control checks. Correctable inconsistencies within reports were edited for consistency, so that the ``edited cloud report`` can be used for cloud analysis. Cases of ``sky obscured`` were interpreted by reference to the present weather code as to whether they indicated fog, rain ormore » snow and were given appropriate cloud type designations. Nimbostratus clouds were also given a special designation. Changes made to an original report are indicated in the edited report so that the original report can be reconstructed if desired. While low cloud amount is normally given directly in the synoptic report, the edited cloud report also includes the amounts, either directly reported or inferred, of middle and high clouds, both the non-overlapped amounts and the ``actual`` amounts. Since illumination from the moon is important for the adequate detection of clouds at night, both the relative lunar illuminance and the solar altitude are given; well as a parameter that indicates whether our recommended illuminance criterion was satisfied. This data set contains 124 million reports from land stations and 15 million reports from ships. Each report is 56 characters in length. The archive consists of 240 files, one file for each month of data for land and ocean separately. With this data set a user can develop a climatology for any particular cloud type or group of types, for any geographical region and any spatial and temporal resolution desired.« less

Targeting Anti-Insulin B Cell Receptors Improves Receptor Editing in Type 1 Diabetes-Prone Mice1, 2, 3

PubMed Central

Bonami, Rachel H.; Thomas, James W.

2015-01-01

Autoreactive B lymphocytes that commonly arise in the developing repertoire can be salvaged by receptor editing, a central tolerance mechanism that alters BCR specificity through continued L chain rearrangement. It is unknown whether autoantigens with weak cross-linking potential, such as insulin, elicit receptor editing, or if this process is dysregulated in related autoimmunity. To resolve these issues, an editing-competent model was developed in which anti-insulin Vκ125 was targeted to the Igκ locus and paired with anti-insulin VH125Tg. Physiologic, circulating insulin increased RAG-2 expression and was associated with BCR replacement that eliminated autoantigen recognition in a proportion of developing anti-insulin B lymphocytes. The proportion of anti-insulin B cells that underwent receptor editing was reduced in the type 1 diabetes-prone NOD strain relative to a non-autoimmune strain. Resistance to editing was associated with increased surface IgM expression on immature (but not transitional or mature) anti-insulin B cells in the NOD strain. The actions of mAb123 on central tolerance were also investigated, as selective targeting of insulin-occupied BCR by mAb123 eliminates anti-insulin B lymphocytes and prevents type 1 diabetes. Autoantigen-targeting by mAb123 increased RAG-2 expression and dramatically enhanced BCR replacement in newly developed B lymphocytes. Administering F(ab’)2123 induced IgM downregulation and reduced the frequency of anti-insulin B lymphocytes within the polyclonal repertoire of VH125Tg/NOD mice, suggesting enhanced central tolerance by direct BCR interaction. These findings indicate that weak or faulty checkpoints for central tolerance can be overcome by autoantigen-specific immunomodulatory therapy. PMID:26432895

Cell-type-specific genome editing with a microRNA-responsive CRISPR–Cas9 switch

PubMed Central

Hirosawa, Moe; Fujita, Yoshihiko; Parr, Callum J. C.; Hayashi, Karin; Kashida, Shunnichi; Hotta, Akitsu; Woltjen, Knut

2017-01-01

Abstract The CRISPR–Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR–Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells. Moreover, the miR-Cas9 switches could differentially control the genome editing by sensing endogenous miRNA activities within a heterogeneous cell population. Our miR-Cas9 switch system provides a promising framework for cell-type selective genome editing and cell engineering based on intracellular miRNA information. PMID:28525578

The Impact of a Horse Riding Intervention on the Social Functioning of Children with Autism Spectrum Disorder

PubMed Central

Harris, Androulla; Williams, Joanne M.

2017-01-01

This paper reports a case-control study of a horse riding intervention for children with autism spectrum disorder (ASD). A sample of 26 children, aged 6 to 9 years, were assigned to either the intervention (n = 12) or control group conditions (n = 14). Pre- and post-tests were carried out using the Childhood Autism Rating Scale, Second Edition (CARS2) and the Aberrant Behaviour Checklist-Community Edition (ABC-C). An observational measure of compliance and behaviour during the horse riding sessions was completed for the intervention group. There was a significant reduction in the severity of ASD symptoms and hyperactivity from pre- to post-test for the intervention group only. These results indicate that the intervention improves some aspects of social functioning for children with ASD. PMID:28708075

The Impact of Continuity Editing in Narrative Film on Event Segmentation

PubMed Central

Magliano, Joseph P.; Zacks, Jeffrey M.

2011-01-01

Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events while brain activity was recorded with functional MRI. We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and provided evidence that specialized mechanisms in higher-order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location. PMID:21972849

The HLA dictionary 2008: a summary of HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens.

PubMed

Holdsworth, R; Hurley, C K; Marsh, S G E; Lau, M; Noreen, H J; Kempenich, J H; Setterholm, M; Maiers, M

2009-02-01

The 2008 report of the human leukocyte antigen (HLA) data dictionary presents serologic equivalents of HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, and -DQB1 alleles. The dictionary is an update of the one published in 2004. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for Factors of the HLA System, the International Cell Exchange, UCLA, the National Marrow Donor Program, recent publications, and individual laboratories. The 2008 edition includes information on 832 new alleles (685 class I and 147 class II) and updated information on 766 previously listed alleles (577 class I and 189 class II). The tables list the alleles with remarks on the serologic patterns and the equivalents. The serological equivalents are listed as expert assigned types, and the data are useful for identifying potential stem cell donors who were typed by either serology or DNA-based methods. The tables with HLA equivalents are available as a searchable form on the IMGT/HLA database Web site (http://www.ebi.ac.uk/imgt/hla/dictionary.html).

Modern Genome Editing Technologies in Huntington's Disease Research.

PubMed

Malankhanova, Tuyana B; Malakhova, Anastasia A; Medvedev, Sergey P; Zakian, Suren M

2017-01-01

The development of new revolutionary technologies for directed gene editing has made it possible to thoroughly model and study NgAgo human diseases at the cellular and molecular levels. Gene editing tools like ZFN, TALEN, CRISPR-based systems, NgAgo and SGN can introduce different modifications. In gene sequences and regulate gene expression in different types of cells including induced pluripotent stem cells (iPSCs). These tools can be successfully used for Huntington's disease (HD) modeling, for example, to generate isogenic cell lines bearing different numbers of CAG repeats or to correct the mutation causing the disease. This review presents common genome editing technologies and summarizes the progress made in using them in HD and other hereditary diseases. Furthermore, we will discuss prospects and limitations of genome editing in understanding HD pathology.

Genome editing for crop improvement: Challenges and opportunities

PubMed Central

Abdallah, Naglaa A; Prakash, Channapatna S; McHughen, Alan G

2015-01-01

ABSTRACT Genome or gene editing includes several new techniques to help scientists precisely modify genome sequences. The techniques also enables us to alter the regulation of gene expression patterns in a pre-determined region and facilitates novel insights into the functional genomics of an organism. Emergence of genome editing has brought considerable excitement especially among agricultural scientists because of its simplicity, precision and power as it offers new opportunities to develop improved crop varieties with clear-cut addition of valuable traits or removal of undesirable traits. Research is underway to improve crop varieties with higher yields, strengthen stress tolerance, disease and pest resistance, decrease input costs, and increase nutritional value. Genome editing encompasses a wide variety of tools using either a site-specific recombinase (SSR) or a site-specific nuclease (SSN) system. Both systems require recognition of a known sequence. The SSN system generates single or double strand DNA breaks and activates endogenous DNA repair pathways. SSR technology, such as Cre/loxP and Flp/FRT mediated systems, are able to knockdown or knock-in genes in the genome of eukaryotes, depending on the orientation of the specific sites (loxP, FLP, etc.) flanking the target site. There are 4 main classes of SSN developed to cleave genomic sequences, mega-nucleases (homing endonuclease), zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and the CRISPR/Cas nuclease system (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein). The recombinase mediated genome engineering depends on recombinase (sub-) family and target-site and induces high frequencies of homologous recombination. Improving crops with gene editing provides a range of options: by altering only a few nucleotides from billions found in the genomes of living cells, altering the full allele or by inserting a new gene in a targeted region of the genome. Due to its precision, gene editing is more precise than either conventional crop breeding methods or standard genetic engineering methods. Thus this technology is a very powerful tool that can be used toward securing the world's food supply. In addition to improving the nutritional value of crops, it is the most effective way to produce crops that can resist pests and thrive in tough climates. There are 3 types of modifications produced by genome editing; Type I includes altering a few nucleotides, Type II involves replacing an allele with a pre-existing one and Type III allows for the insertion of new gene(s) in predetermined regions in the genome. Because most genome-editing techniques can leave behind traces of DNA alterations evident in a small number of nucleotides, crops created through gene editing could avoid the stringent regulation procedures commonly associated with GM crop development. For this reason many scientists believe plants improved with the more precise gene editing techniques will be more acceptable to the public than transgenic plants. With genome editing comes the promise of new crops being developed more rapidly with a very low risk of off-target effects. It can be performed in any laboratory with any crop, even those that have complex genomes and are not easily bred using conventional methods. PMID:26930114

Spectrally edited 2D 13Csbnd 13C NMR spectra without diagonal ridge for characterizing 13C-enriched low-temperature carbon materials

NASA Astrophysics Data System (ADS)

Johnson, Robert L.; Anderson, Jason M.; Shanks, Brent H.; Fang, Xiaowen; Hong, Mei; Schmidt-Rohr, Klaus

2013-09-01

Two robust combinations of spectral editing techniques with 2D 13Csbnd 13C NMR have been developed for characterizing the aromatic components of 13C-enriched low-temperature carbon materials. One method (exchange with protonated and nonprotonated spectral editing, EXPANSE) selects cross peaks of protonated and nearby nonprotonated carbons, while the other technique, dipolar-dephased double-quantum/single-quantum (DQ/SQ) NMR, selects signals of bonded nonprotonated carbons. Both spectra are free of a diagonal ridge, which has many advantages: Cross peaks on the diagonal or of small intensity can be detected, and residual spinning sidebands or truncation artifacts associated with the diagonal ridge are avoided. In the DQ/SQ experiment, dipolar dephasing of the double-quantum coherence removes protonated-carbon signals; this approach also eliminates the need for high-power proton decoupling. The initial magnetization is generated with minimal fluctuation by combining direct polarization, cross polarization, and equilibration by 13C spin diffusion. The dipolar dephased DQ/SQ spectrum shows signals from all linkages between aromatic rings, including a distinctive peak from polycondensed aromatics. In EXPANSE NMR, signals of protonated carbons are selected in the first spectral dimension by short cross polarization combined with dipolar dephasing difference. This removes ambiguities of peak assignment to overlapping signals of nonprotonated and protonated aromatic carbons, e.g. near 125 ppm. Spin diffusion is enhanced by dipolar-assisted rotational resonance. Before detection, Csbnd H dipolar dephasing by gated decoupling is applied, which selects signals of nonprotonated carbons. Thus, only cross peaks due to magnetization originating from protonated C and ending on nearby nonprotonated C are retained. Combined with the chemical shifts deduced from the cross-peak position, this double spectral editing defines the bonding environment of aromatic, COO, and Cdbnd O carbons, which is particularly useful for identifying furan and arene rings. The Cdbnd O carbons, whose chemical shifts vary strongly (between 212 and 165 ppm) and systematically depend on their two bonding partners, show particularly informative cross peaks, given that one bonding partner is defined by the other frequency coordinate of the cross peak. The new techniques and the information content of the resulting spectra are validated on sulfuric-acid treated low-temperature carbon materials and on products of the Maillard reaction. The crucial need for spectral editing for correct peak assignment is demonstrated in an example.

Genome-Wide Analysis of A-to-I RNA Editing.

PubMed

Savva, Yiannis A; Laurent, Georges St; Reenan, Robert A

2016-01-01

Adenosine (A)-to-inosine (I) RNA editing is a fundamental posttranscriptional modification that ensures the deamination of A-to-I in double-stranded (ds) RNA molecules. Intriguingly, the A-to-I RNA editing system is particularly active in the nervous system of higher eukaryotes, altering a plethora of noncoding and coding sequences. Abnormal RNA editing is highly associated with many neurological phenotypes and neurodevelopmental disorders. However, the molecular mechanisms underlying RNA editing-mediated pathogenesis still remain enigmatic and have attracted increasing attention from researchers. Over the last decade, methods available to perform genome-wide transcriptome analysis, have evolved rapidly. Within the RNA editing field researchers have adopted next-generation sequencing technologies to identify RNA-editing sites within genomes and to elucidate the underlying process. However, technical challenges associated with editing site discovery have hindered efforts to uncover comprehensive editing site datasets, resulting in the general perception that the collections of annotated editing sites represent only a small minority of the total number of sites in a given organism, tissue, or cell type of interest. Additionally to doubts about sensitivity, existing RNA-editing site lists often contain high percentages of false positives, leading to uncertainty about their validity and usefulness in downstream studies. An accurate investigation of A-to-I editing requires properly validated datasets of editing sites with demonstrated and transparent levels of sensitivity and specificity. Here, we describe a high signal-to-noise method for RNA-editing site detection using single-molecule sequencing (SMS). With this method, authentic RNA-editing sites may be differentiated from artifacts. Machine learning approaches provide a procedure to improve upon and experimentally validate sequencing outcomes through use of computationally predicted, iterative feedback loops. Subsequent use of extensive Sanger sequencing validations can generate accurate editing site lists. This approach has broad application and accurate genome-wide editing analysis of various tissues from clinical specimens or various experimental organisms is now a possibility.

Comparison of Insertional RNA Editing in Myxomycetes

PubMed Central

Chen, Cai; Frankhouser, David; Bundschuh, Ralf

2012-01-01

RNA editing describes the process in which individual or short stretches of nucleotides in a messenger or structural RNA are inserted, deleted, or substituted. A high level of RNA editing has been observed in the mitochondrial genome of Physarum polycephalum. The most frequent editing type in Physarum is the insertion of individual Cs. RNA editing is extremely accurate in Physarum; however, little is known about its mechanism. Here, we demonstrate how analyzing two organisms from the Myxomycetes, namely Physarum polycephalum and Didymium iridis, allows us to test hypotheses about the editing mechanism that can not be tested from a single organism alone. First, we show that using the recently determined full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium. We use this approach to predict genes in the mitochondrial genome of Didymium and identify six new edited genes as well as one new gene that appears unedited. Next we investigate sequence conservation in the vicinity of editing sites between the two organisms in order to identify sites that harbor the information for the location of editing sites based on increased conservation. Our results imply that the information contained within only nine or ten nucleotides on either side of the editing site (a distance previously suggested through experiments) is not enough to locate the editing sites. Finally, we show that the codon position bias in C insertional RNA editing of these two organisms is correlated with the selection pressure on the respective genes thereby directly testing an evolutionary theory on the origin of this codon bias. Beyond revealing interesting properties of insertional RNA editing in Myxomycetes, our work suggests possible approaches to be used when finding sequence motifs for any biological process fails. PMID:22383871

Recognizing and managing depression in primary care: a standardized patient study.

PubMed

Carney, P A; Dietrich, A J; Eliassen, M S; Owen, M; Badger, L W

1999-12-01

Guidelines for recognition and management of depression in primary care provide a framework for detailed exploration of physician practice patterns. Our objective was to explore physician diagnosis and management approaches to depressive disorders according to type (major vs. minor) and presenting complaint (difficulty sleeping and concentrating vs. headache). The participants were community primary care internists and family physicians in northern New England, Washington, and Alabama (N = 149) who were randomly assigned to receive a visit from an unannounced actor portraying a standardized patient in 1 of 2 depression scenarios: (A) insomnia and poor concentration meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for major depressive disorder; or (B) tension headaches meeting the criteria for minor depression. All physicians who were assigned to the standardized patients presenting with scenario A recognized depression, and 49% (38 of 78) of those assigned to scenario B patients diagnosed depression. Of those recognizing depression, 72% and 42% queried patients about anhedonia and mood, respectively. For both scenarios, if fewer than 2 DSM-III-R criteria were explored, depression was not diagnosed. Management for scenario A was compatible with Agency for Health Care Policy and Research guidelines, including the prescription of an antidepressant (94%), scheduling of a follow-up visit within 2 weeks (61%), and exploration of suicidal ideation (69.4%). For scenario B, management included over-the-counter analgesics for the headache (84%), exercise (63%), prescription for an antidepressant (53%), recommendation for ongoing counseling (100%), and follow-up within 2 weeks (42%). Major depression is recognized in primary care at a very high rate. Guidelines for recognizing and managing depression are often followed in primary care. Patients' presentations of depression influence its recognition and management.

Novel modes of RNA editing in mitochondria

PubMed Central

Moreira, Sandrine; Valach, Matus; Aoulad-Aissa, Mohamed; Otto, Christian; Burger, Gertraud

2016-01-01

Abstract Gene structure and expression in diplonemid mitochondria are unparalleled. Genes are fragmented in pieces (modules) that are separately transcribed, followed by the joining of module transcripts to contiguous RNAs. Some instances of unique uridine insertion RNA editing at module boundaries were noted, but the extent and potential occurrence of other editing types remained unknown. Comparative analysis of deep transcriptome and genome data from Diplonema papillatum mitochondria reveals ∼220 post-transcriptional insertions of uridines, but no insertions of other nucleotides nor deletions. In addition, we detect in total 114 substitutions of cytosine by uridine and adenosine by inosine, amassed into unusually compact clusters. Inosines in transcripts were confirmed experimentally. This is the first report of adenosine-to-inosine editing of mRNAs and ribosomal RNAs in mitochondria. In mRNAs, editing causes mostly amino-acid additions and non-synonymous substitutions; in ribosomal RNAs, it permits formation of canonical secondary structures. Two extensively edited transcripts were compared across four diplonemids. The pattern of uridine-insertion editing is strictly conserved, whereas substitution editing has diverged dramatically, but still rendering diplonemid proteins more similar to other eukaryotic orthologs. We posit that RNA editing not only compensates but also sustains, or even accelerates, ultra-rapid evolution of genome structure and sequence in diplonemid mitochondria. PMID:27001515

Food Production, Management and Services: Service. Teacher Edition. Second Edition.

ERIC Educational Resources Information Center

Palan, Earl

This food production, management, and services teacher guide contains nine units: (1) orientation; (2) types of service; (3) table settings; (4) dining room personnel; (5) dining room procedures; (6) side work; (7) guest/employee relationships; (8) sales techniques; and (9) safety and sanitation. Suggestions are included to increase reinforcement…

Basics of Desktop Publishing. Second Edition.

ERIC Educational Resources Information Center

Beeby, Ellen; Crummett, Jerrie

This document contains teacher and student materials for a basic course in desktop publishing. Six units of instruction cover the following: (1) introduction to desktop publishing; (2) desktop publishing systems; (3) software; (4) type selection; (5) document design; and (6) layout. The teacher edition contains some or all of the following…

RNA editing: trypanosomes rewrite the genetic code.

PubMed

Stuart, K

1998-01-01

The understanding of how genetic information is stored and expressed has advanced considerably since the "central dogma" asserted that genetic information flows from the nucleotide sequence of DNA to that of messenger RNA (mRNA) which in turn specifies the amino acid sequence of a protein. It was found that genetic information can be stored as RNA (e.g. in RNA viruses) and can flow from RNA to DNA by reverse transcriptase enzyme activity. In addition, some genes contain introns, nucleotide sequences that are removed from their RNA (by RNA splicing) and thus are not represented in the resultant protein. Furthermore, alternative splicing was found to produce variant proteins from a single gene. More recently, the study of trypanosome parasites revealed an unexpected and indeed counter-intuitive genetic complexity. Genetic information for a single protein can be dispersed among several (DNA) genes in these organisms. One of these genes specifies an encrypted precursor mRNA that is converted to a functional mRNA by a process called RNA editing that inserts and deletes uridylate nucleotides. The sequence of the edited mRNA is specified by multiple small RNAs, named guide RNAs, (gRNAs) each of which is encoded in a separate gene. Thus, edited mRNA sequences are assembled from multiple genes by the transfer of information from one type of RNA to another. The existence of editing was surprising but has stimulated the discovery of other types of RNA editing. The Stuart laboratory has been exploring RNA editing in trypanosomes from the time of its discovery. They found dramatic differences between the mitochondrial gene sequences and those of the corresponding mRNAs, which indicated editing by the insertion and deletion of uridylates. Some editing was modest; simply eliminating shifts in sequence register of minimally extending the protein coding sequence. However, editing of many mRNAs was startingly extensive. The RNA sequence was essentially entirely remodeled with its sequence more the result of editing than the gene sequence. The identities of genes for such extensively edited RNA were not recognizable from the DNA sequence but they were readily identifiable from the edited mRNA sequence. Thus, despite the complex and extensive editing the resultant mRNA sequence is precise. Characterization of partially edited RNAs indicated that editing proceeds in the direction opposite to that used to specify the protein which reflects the use of the gRNAs. The numerous gRNAs that are used for editing are encoded in the DNA molecules whose role was previously a mystery. Using information gained in our earlier studies, the Stuart group developed an in vitro system that reproduces the fundamental process of editing in order to resolve the mechanism by which it occurs. They determined that editing entails a series of enzymatic steps rather than the mechanism used in RNA splicing. They also showed that chimeric gRNA-mRNA molecules are aberrant by-products of editing rather than intermediates in the process as had been proposed. Additional studies are exploring precisely how the number of added and deleted uridylates is specified by the gRNA. The Stuart laboratory showed that editing is performed by an aggregation of enzymes that catalyze the separate steps of editing. It also developed a method to purify this multimolecule complex that contains several, perhaps tens of, proteins. This will allow the study of its composition and the functions of its component parts. Indeed, the gene for one component has been identified and its detailed characterization begun. These studies are developing tools to explore related processes. An early finding in the lab was that the various mRNAs are differentially edited during the life cycle of the parasite. The pattern of this editing indicates that editing serves to regulate the alternation between two modes of energy generation. This regulation is coordinated with other events that are occurring during the life c

The impact of continuity editing in narrative film on event segmentation.

PubMed

Magliano, Joseph P; Zacks, Jeffrey M

2011-01-01

Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events, while brain activity was recorded with functional magnetic resonance imaging (MRI). We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation, and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and they provided evidence that specialized mechanisms in higher order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location. Copyright © 2011 Cognitive Science Society, Inc.

Basic list of veterinary medical serials, third edition: using a decision matrix to update the core list of veterinary journals.

PubMed

Ugaz, Ana G; Boyd, C Trenton; Croft, Vicki F; Carrigan, Esther E; Anderson, Katherine M

2010-10-01

This paper presents the methods and results of a study designed to produce the third edition of the "Basic List of Veterinary Medical Serials," which was established by the Veterinary Medical Libraries Section in 1976 and last updated in 1986. A set of 238 titles were evaluated using a decision matrix in order to systematically assign points for both objective and subjective criteria and determine an overall score for each journal. Criteria included: coverage in four major indexes, scholarly impact rank as tracked in two sources, identification as a recommended journal in preparing for specialty board examinations, and a veterinary librarian survey rating. Of the 238 titles considered, a minimum scoring threshold determined the 123 (52%) journals that constituted the final list. The 36 subject categories represented on the list include general and specialty disciplines in veterinary medicine. A ranked list of journals and a list by subject category were produced. Serials appearing on the third edition of the "Basic List of Veterinary Medical Serials" met expanded objective measures of quality and impact as well as subjective perceptions of value by both librarians and veterinary practitioners.

Basic list of veterinary medical serials, third edition: using a decision matrix to update the core list of veterinary journals

PubMed Central

Ugaz, Ana G; Boyd, C. Trenton; Croft, Vicki F; Carrigan, Esther E; Anderson, Katherine M

2010-01-01

Objective: This paper presents the methods and results of a study designed to produce the third edition of the “Basic List of Veterinary Medical Serials,” which was established by the Veterinary Medical Libraries Section in 1976 and last updated in 1986. Methods: A set of 238 titles were evaluated using a decision matrix in order to systematically assign points for both objective and subjective criteria and determine an overall score for each journal. Criteria included: coverage in four major indexes, scholarly impact rank as tracked in two sources, identification as a recommended journal in preparing for specialty board examinations, and a veterinary librarian survey rating. Results: Of the 238 titles considered, a minimum scoring threshold determined the 123 (52%) journals that constituted the final list. The 36 subject categories represented on the list include general and specialty disciplines in veterinary medicine. A ranked list of journals and a list by subject category were produced. Conclusion: Serials appearing on the third edition of the “Basic List of Veterinary Medical Serials” met expanded objective measures of quality and impact as well as subjective perceptions of value by both librarians and veterinary practitioners. PMID:20936066

Decreased A-to-I RNA editing as a source of keratinocytes' dsRNA in psoriasis.

PubMed

Shallev, Lea; Kopel, Eli; Feiglin, Ariel; Leichner, Gil S; Avni, Dror; Sidi, Yechezkel; Eisenberg, Eli; Barzilai, Aviv; Levanon, Erez Y; Greenberger, Shoshana

2018-06-01

Recognition of dsRNA molecules activates the MDA5-MAVS pathway and plays a critical role in stimulating type-I interferon responses in psoriasis. However, the source of the dsRNA accumulation in psoriatic keratinocytes remains largely unknown. A-to-I RNA editing is a common co- or post-transcriptional modification that diversifies adenosine in dsRNA, and leads to unwinding of dsRNA structures. Thus, impaired RNA editing activity can result in an increased load of endogenous dsRNAs. Here we provide a transcriptome-wide analysis of RNA editing across dozens of psoriasis patients, and we demonstrate a global editing reduction in psoriatic lesions. In addition to the global alteration, we also detect editing changes in functional recoding sites located in the IGFBP7 , COPA , and FLNA genes. Accretion of dsRNA activates autoimmune responses, and therefore the results presented here, linking for the first time an autoimmune disease to reduction in global editing level, are relevant to a wide range of autoimmune diseases. © 2018 Shallev et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Towards social acceptance of plant breeding by genome editing.

PubMed

Araki, Motoko; Ishii, Tetsuya

2015-03-01

Although genome-editing technologies facilitate efficient plant breeding without introducing a transgene, it is creating indistinct boundaries in the regulation of genetically modified organisms (GMOs). Rapid advances in plant breeding by genome-editing require the establishment of a new global policy for the new biotechnology, while filling the gap between process-based and product-based GMO regulations. In this Opinion article we review recent developments in producing major crops using genome-editing, and we propose a regulatory model that takes into account the various methodologies to achieve genetic modifications as well as the resulting types of mutation. Moreover, we discuss the future integration of genome-editing crops into society, specifically a possible response to the 'Right to Know' movement which demands labeling of food that contains genetically engineered ingredients. Copyright © 2015 Elsevier Ltd. All rights reserved.

BiCluE - Exact and heuristic algorithms for weighted bi-cluster editing of biomedical data

PubMed Central

2013-01-01

Background The explosion of biological data has dramatically reformed today's biology research. The biggest challenge to biologists and bioinformaticians is the integration and analysis of large quantity of data to provide meaningful insights. One major problem is the combined analysis of data from different types. Bi-cluster editing, as a special case of clustering, which partitions two different types of data simultaneously, might be used for several biomedical scenarios. However, the underlying algorithmic problem is NP-hard. Results Here we contribute with BiCluE, a software package designed to solve the weighted bi-cluster editing problem. It implements (1) an exact algorithm based on fixed-parameter tractability and (2) a polynomial-time greedy heuristics based on solving the hardest part, edge deletions, first. We evaluated its performance on artificial graphs. Afterwards we exemplarily applied our implementation on real world biomedical data, GWAS data in this case. BiCluE generally works on any kind of data types that can be modeled as (weighted or unweighted) bipartite graphs. Conclusions To our knowledge, this is the first software package solving the weighted bi-cluster editing problem. BiCluE as well as the supplementary results are available online at http://biclue.mpi-inf.mpg.de. PMID:24565035

TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

PubMed

Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

2010-11-01

TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs.

TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites

PubMed Central

Ammerman, Michelle L.; Presnyak, Vladimir; Fisk, John C.; Foda, Bardees M.; Read, Laurie K.

2010-01-01

TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5′ ends of pan-edited RNAs than at their 3′ ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3′ to 5′ progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3′ ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA–RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3′ to 5′ progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

Cell-type-specific genome editing with a microRNA-responsive CRISPR-Cas9 switch.

PubMed

Hirosawa, Moe; Fujita, Yoshihiko; Parr, Callum J C; Hayashi, Karin; Kashida, Shunnichi; Hotta, Akitsu; Woltjen, Knut; Saito, Hirohide

2017-07-27

The CRISPR-Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR-Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells. Moreover, the miR-Cas9 switches could differentially control the genome editing by sensing endogenous miRNA activities within a heterogeneous cell population. Our miR-Cas9 switch system provides a promising framework for cell-type selective genome editing and cell engineering based on intracellular miRNA information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Receptor-Mediated Delivery of CRISPR-Cas9 Endonuclease for Cell-Type-Specific Gene Editing.

PubMed

Rouet, Romain; Thuma, Benjamin A; Roy, Marc D; Lintner, Nathanael G; Rubitski, David M; Finley, James E; Wisniewska, Hanna M; Mendonsa, Rima; Hirsh, Ariana; de Oñate, Lorena; Compte Barrón, Joan; McLellan, Thomas J; Bellenger, Justin; Feng, Xidong; Varghese, Alison; Chrunyk, Boris A; Borzilleri, Kris; Hesp, Kevin D; Zhou, Kaihong; Ma, Nannan; Tu, Meihua; Dullea, Robert; McClure, Kim F; Wilson, Ross C; Liras, Spiros; Mascitti, Vincent; Doudna, Jennifer A

2018-05-30

CRISPR-Cas RNA-guided endonucleases hold great promise for disrupting or correcting genomic sequences through site-specific DNA cleavage and repair. However, the lack of methods for cell- and tissue-selective delivery currently limits both research and clinical uses of these enzymes. We report the design and in vitro evaluation of S. pyogenes Cas9 proteins harboring asialoglycoprotein receptor ligands (ASGPrL). In particular, we demonstrate that the resulting ribonucleoproteins (Cas9-ASGPrL RNP) can be engineered to be preferentially internalized into cells expressing the corresponding receptor on their surface. Uptake of such fluorescently labeled proteins in liver-derived cell lines HEPG2 (ASGPr+) and SKHEP (control; diminished ASGPr) was studied by live cell imaging and demonstrates increased accumulation of Cas9-ASGPrL RNP in HEPG2 cells as a result of effective ASGPr-mediated endocytosis. When uptake occurred in the presence of a peptide with endosomolytic properties, we observed receptor-facilitated and cell-type specific gene editing that did not rely on electroporation or the use of transfection reagents. Overall, these in vitro results validate the receptor-mediated delivery of genome-editing enzymes as an approach for cell-selective gene editing and provide a framework for future potential applications to hepatoselective gene editing in vivo.

Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis

PubMed Central

Liddicoat, Brian J.; Hartner, Jochen C.; Piskol, Robert; Ramaswami, Gokul; Chalk, Alistair M.; Kingsley, Paul D.; Sankaran, Vijay G.; Wall, Meaghan; Purton, Louise E.; Seeburg, Peter H.; Palis, James; Orkin, Stuart H.; Lu, Jun; Li, Jin Billy; Walkley, Carl R.

2016-01-01

Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in double-stranded RNA. In vivo, ADAR1 is essential for the maintenance of hematopoietic stem/progenitors. Whether other hematopoietic cell types also require ADAR1 has not been assessed. Using erythroid- and myeloid-restricted deletion of Adar1, we demonstrate that ADAR1 is dispensable for myelopoiesis but is essential for normal erythropoiesis. Adar1-deficient erythroid cells display a profound activation of innate immune signaling and high levels of cell death. No changes in microRNA levels were found in ADAR1-deficient erythroid cells. Using an editing-deficient allele, we demonstrate that RNA editing is the essential function of ADAR1 during erythropoiesis. Mapping of adenosine-to-inosine editing in purified erythroid cells identified clusters of hyperedited adenosines located in long 3’-untranslated regions of erythroid-specific transcripts and these are ADAR1-specific editing events. ADAR1-mediated RNA editing is essential for normal erythropoiesis. PMID:27373493

Production of Purified CasRNPs for Efficacious Genome Editing.

PubMed

Lingeman, Emily; Jeans, Chris; Corn, Jacob E

2017-10-02

CRISPR-Cas systems have been harnessed as modular genome editing reagents for functional genomics and show promise to cure genetic diseases. Directed by a guide RNA, a Cas effector introduces a double stranded break in DNA and host cell DNA repair leads to the introduction of errors (e.g., to knockout a gene) or a programmed change. Introduction of a Cas effector and guide RNA as a purified Cas ribonucleoprotein complex (CasRNP) has recently emerged as a powerful approach to alter cell types and organisms. Not only does CasRNP editing exhibit increased efficacy and specificity, it avoids optimization and iteration of species-specific factors such as codon usage, promoters, and terminators. CasRNP editing has been rapidly adopted for research use in many contexts and is quickly becoming a popular method to edit primary cells for therapeutic application. This article describes how to make a Cas9 RNP and outlines its use for gene editing in human cells. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Measuring the Diagnostic Features of Social (Pragmatic) Communication Disorder: An Exploratory Study.

PubMed

Yuan, Haiying; Dollaghan, Christine

2018-03-27

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition introduced a new neurodevelopmental disorder, social (pragmatic) communication disorder (SPCD), that is characterized by deficits in 4 areas of communication. Although descriptions of these areas are provided, no assessment tools for SPCD are recommended. The purpose of this study was to examine the extent to which items from measurement tools commonly used in assessing pragmatic language impairment and related disorders might be useful in assessing the characteristics of social communication that define SPCD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Based on a literature search, 594 items from assessment tools commonly used to measure social communication abilities in people with pragmatic language impairment were identified. The first author judged whether each item reflected 1, more than 1, or none of the 4 SPCD diagnostic characteristics. After a brief training process, 5 second raters independently mapped subsets of items to the 6 categories. We calculated the percentage of agreement and Cohen's kappa for each pair of raters in assigning items to categories. Percentages of agreement ranged from 76% to 82%, and Cohen's kappa values ranged from .69 to .76, indicating substantial agreement. Sources and item numbers for the 206 items that both raters assigned to the same SPCD feature are provided. These items may provide guidance in assessing SPCD and in designing standardized screening and diagnostic measures for SPCD.

Primary Airway Epithelial Cell Gene Editing Using CRISPR-Cas9.

PubMed

Everman, Jamie L; Rios, Cydney; Seibold, Max A

2018-01-01

The adaptation of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated endonuclease 9 (CRISPR-Cas9) machinery from prokaryotic organisms has resulted in a gene editing system that is highly versatile, easily constructed, and can be leveraged to generate human cells knocked out (KO) for a specific gene. While standard transfection techniques can be used for the introduction of CRISPR-Cas9 expression cassettes to many cell types, delivery by this method is not efficient in many primary cell types, including primary human airway epithelial cells (AECs). More efficient delivery in AECs can be achieved through lentiviral-mediated transduction, allowing the CRISPR-Cas9 system to be integrated into the genome of the cell, resulting in stable expression of the nuclease machinery and increasing editing rates. In parallel, advancements have been made in the culture, expansion, selection, and differentiation of AECs, which allow the robust generation of a bulk edited AEC population from transduced cells. Applying these methods, we detail here our latest protocol to generate mucociliary epithelial cultures knocked out for a specific gene from donor-isolated primary human basal airway epithelial cells. This protocol includes methods to: (1) design and generate lentivirus which targets a specific gene for KO with CRISPR-Cas9 machinery, (2) efficiently transduce AECs, (3) culture and select for a bulk edited AEC population, (4) molecularly screen AECs for Cas9 cutting and specific sequence edits, and (5) further expand and differentiate edited cells to a mucociliary airway epithelial culture. The AEC knockouts generated using this protocol provide an excellent primary cell model system with which to characterize the function of genes involved in airway dysfunction and disease.

Seamless editing of the chloroplast genome in plants.

PubMed

Martin Avila, Elena; Gisby, Martin F; Day, Anil

2016-07-29

Gene editing technologies enable the precise insertion of favourable mutations and performance enhancing trait genes into chromosomes whilst excluding all excess DNA from modified genomes. The technology gives rise to a new class of biotech crops which is likely to have widespread applications in agriculture. Despite progress in the nucleus, the seamless insertions of point mutations and non-selectable foreign genes into the organelle genomes of crops have not been described. The chloroplast genome is an attractive target to improve photosynthesis and crop performance. Current chloroplast genome engineering technologies for introducing point mutations into native chloroplast genes leave DNA scars, such as the target sites for recombination enzymes. Seamless editing methods to modify chloroplast genes need to address reversal of site-directed point mutations by template mediated repair with the vast excess of wild type chloroplast genomes that are present early in the transformation process. Using tobacco, we developed an efficient two-step method to edit a chloroplast gene by replacing the wild type sequence with a transient intermediate. This was resolved to the final edited gene by recombination between imperfect direct repeats. Six out of 11 transplastomic plants isolated contained the desired intermediate and at the second step this was resolved to the edited chloroplast gene in five of six plants tested. Maintenance of a single base deletion mutation in an imperfect direct repeat of the native chloroplast rbcL gene showed the limited influence of biased repair back to the wild type sequence. The deletion caused a frameshift, which replaced the five C-terminal amino acids of the Rubisco large subunit with 16 alternative residues resulting in a ~30-fold reduction in its accumulation. We monitored the process in vivo by engineering an overlapping gusA gene downstream of the edited rbcL gene. Translational coupling between the overlapping rbcL and gusA genes resulted in relatively high GUS accumulation (~0.5 % of leaf protein). Editing chloroplast genomes using transient imperfect direct repeats provides an efficient method for introducing point mutations into chloroplast genes. Moreover, we describe the first synthetic operon allowing expression of a downstream overlapping gene by translational coupling in chloroplasts. Overlapping genes provide a new mechanism for co-ordinating the translation of foreign proteins in chloroplasts.

Expected and unexpected evolution of plant RNA editing factors CLB19, CRR28 and RARE1: retention of CLB19 despite a phylogenetically deep loss of its two known editing targets in Poaceae.

PubMed

Hein, Anke; Knoop, Volker

2018-06-07

C-to-U RNA editing in mitochondria and chloroplasts and the nuclear-encoded, RNA-binding PPR proteins acting as editing factors present a wide field of co-evolution between the different genetic systems in a plant cell. Recent studies on chloroplast editing factors RARE1 and CRR28 addressing one or two chloroplast editing sites, respectively, found them strictly conserved among 65 flowering plants as long as one of their RNA editing targets remained present. Extending the earlier sampling to 117 angiosperms with high-quality genome or transcriptome data, we find more evidence confirming previous conclusions but now also identify cases for expected evolutionary transition states such as retention of RARE1 despite loss of its editing target or the degeneration of CRR28 truncating its carboxyterminal DYW domain. The extended angiosperm set was now used to explore CLB19, an "E+"-type PPR editing factor targeting two chloroplast editing sites, rpoAeU200SF and clpPeU559HY, in Arabidopsis thaliana. We found CLB19 consistently conserved if one of the two targets was retained and three independent losses of CLB19 after elimination of both targets. The Ericales show independent regains of the ancestrally lost clpPeU559HY editing, further explaining why multiple-target editing factors are lost much more rarely than single target factors like RARE1. The retention of CLB19 despite loss of both editing targets in some Ericaceae, Apocynaceae and in Camptotheca (Nyssaceae) likely represents evolutionary transitions. However, the retention of CLB19 after a phylogenetic deep loss in the Poaceae rather suggests a yet unrecognized further editing target, for which we suggest editing event ndhAeU473SL. Extending the scope of studies on plant organelle RNA editing to further taxa and additional nuclear cofactors reveals expected evolutionary transitions, strikingly different evolutionary dynamics for multiple-target editing factors like CLB19 and CRR28 and suggests additional functions for editing factor CLB19 among the Poaceae.

Identification of genomic sites for CRISPR/Cas9-based genome editing in the Vitis vinifera genome.

PubMed

Wang, Yi; Liu, Xianju; Ren, Chong; Zhong, Gan-Yuan; Yang, Long; Li, Shaohua; Liang, Zhenchang

2016-04-21

CRISPR/Cas9 has been recently demonstrated as an effective and popular genome editing tool for modifying genomes of humans, animals, microorganisms, and plants. Success of such genome editing is highly dependent on the availability of suitable target sites in the genomes to be edited. Many specific target sites for CRISPR/Cas9 have been computationally identified for several annual model and crop species, but such sites have not been reported for perennial, woody fruit species. In this study, we identified and characterized five types of CRISPR/Cas9 target sites in the widely cultivated grape species Vitis vinifera and developed a user-friendly database for editing grape genomes in the future. A total of 35,767,960 potential CRISPR/Cas9 target sites were identified from grape genomes in this study. Among them, 22,597,817 target sites were mapped to specific genomic locations and 7,269,788 were found to be highly specific. Protospacers and PAMs were found to distribute uniformly and abundantly in the grape genomes. They were present in all the structural elements of genes with the coding region having the highest abundance. Five PAM types, TGG, AGG, GGG, CGG and NGG, were observed. With the exception of the NGG type, they were abundantly present in the grape genomes. Synteny analysis of similar genes revealed that the synteny of protospacers matched the synteny of homologous genes. A user-friendly database containing protospacers and detailed information of the sites was developed and is available for public use at the Grape-CRISPR website ( http://biodb.sdau.edu.cn/gc/index.html ). Grape genomes harbour millions of potential CRISPR/Cas9 target sites. These sites are widely distributed among and within chromosomes with predominant abundance in the coding regions of genes. We developed a publicly-accessible Grape-CRISPR database for facilitating the use of the CRISPR/Cas9 system as a genome editing tool for functional studies and molecular breeding of grapes. Among other functions, the database allows users to identify and select multi-protospacers for editing similar sequences in grape genomes simultaneously.

Is Working Memory Involved in the Transcribing and Editing of Texts?

ERIC Educational Resources Information Center

Hayes, John R.; Chenoweth, N. Ann

2006-01-01

Generally, researchers agree that verbal working memory plays an important role in cognitive processes involved in writing. However, there is disagreement about which cognitive processes make use of working memory. Kellogg has proposed that verbal working memory is involved in translating but not in editing or producing (i.e., typing) text. In…

Polyhedron Models for the Classroom. Second Edition.

ERIC Educational Resources Information Center

Wenninger, Magnus J.

This second edition explains the historical background and techniques for constructing various types of polyhedra. Seven center-fold sheets are included, containing full-scale drawings from which nets or templates may be made to construct the models shown and described in the text. Details are provided for construction of the five Platonic solids,…

14 CFR Appendix B to Part 36 - Noise Levels for Transport Category and Jet Airplanes Under § 36.103

Code of Federal Regulations, 2013 CFR

2013-01-01

..., DEPARTMENT OF TRANSPORTATION AIRCRAFT NOISE STANDARDS: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Pt. 36...) Annex 16, Environmental Protection, Volume I, Aircraft Noise, Third Edition, July 1993, Amendment 7..., Environmental Protection, Volume I, Aircraft Noise, Third Edition, July 1993, Amendment 7, effective March 21...

14 CFR Appendix B to Part 36 - Noise Levels for Transport Category and Jet Airplanes Under § 36.103

Code of Federal Regulations, 2012 CFR

2012-01-01

..., DEPARTMENT OF TRANSPORTATION AIRCRAFT NOISE STANDARDS: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Pt. 36...) Annex 16, Environmental Protection, Volume I, Aircraft Noise, Third Edition, July 1993, Amendment 7..., Environmental Protection, Volume I, Aircraft Noise, Third Edition, July 1993, Amendment 7, effective March 21...

14 CFR Appendix B to Part 36 - Noise Levels for Transport Category and Jet Airplanes Under § 36.103

Code of Federal Regulations, 2014 CFR

2014-01-01

..., DEPARTMENT OF TRANSPORTATION AIRCRAFT NOISE STANDARDS: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Pt. 36... Organization (ICAO) Annex 16, Environmental Protection, Volume I, Aircraft Noise, Third Edition, July 1993... (ICAO) Annex 16, Environmental Protection, Volume I, Aircraft Noise, Third Edition, July 1993, Amendment...

The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study.

PubMed

Safarinejad, Mohammad Reza

2010-09-01

To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.

Dynamic hyper-editing underlies temperature adaptation in Drosophila

PubMed Central

Ashwal-Fluss, Reut; Pandey, Varun; Levanon, Erez Y.; Kadener, Sebastian

2017-01-01

In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila. Although there is a higher level of editing at lower temperatures, at 29°C more sites are edited. These sites are less evolutionarily conserved, more disperse, less likely to be involved in secondary structures, and more likely to be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker transcriptional response to temperature changes than wild-type flies and a highly abnormal behavioral response upon temperature increase. In sum, our data shows that ADAR is essential for proper temperature adaptation, a key behavior trait that is essential for survival of flies in the wild. Moreover, our results suggest a more general role of ADAR in regulating RNA secondary structures in vivo. PMID:28746393

A novel technique based on in vitro oocyte injection to improve CRISPR/Cas9 gene editing in zebrafish

PubMed Central

Xie, Shao-Lin; Bian, Wan-Ping; Wang, Chao; Junaid, Muhammad; Zou, Ji-Xing; Pei, De-Sheng

2016-01-01

Contemporary improvements in the type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system offer a convenient way for genome editing in zebrafish. However, the low efficiencies of genome editing and germline transmission require a time-intensive and laborious screening work. Here, we reported a method based on in vitro oocyte storage by injecting oocytes in advance and incubating them in oocyte storage medium to significantly improve the efficiencies of genome editing and germline transmission by in vitro fertilization (IVF) in zebrafish. Compared to conventional methods, the prior micro-injection of zebrafish oocytes improved the efficiency of genome editing, especially for the sgRNAs with low targeting efficiency. Due to high throughputs, simplicity and flexible design, this novel strategy will provide an efficient alternative to increase the speed of generating heritable mutants in zebrafish by using CRISPR/Cas9 system. PMID:27680290

A future scenario of the global regulatory landscape regarding genome-edited crops

PubMed Central

Araki, Motoko

2017-01-01

ABSTRACT The global agricultural landscape regarding the commercial cultivation of genetically modified (GM) crops is mosaic. Meanwhile, a new plant breeding technique, genome editing is expected to make genetic engineering-mediated crop breeding more socially acceptable because it can be used to develop crop varieties without introducing transgenes, which have hampered the regulatory review and public acceptance of GM crops. The present study revealed that product- and process-based concepts have been implemented to regulate GM crops in 30 countries. Moreover, this study analyzed the regulatory responses to genome-edited crops in the USA, Argentina, Sweden and New Zealand. The findings suggested that countries will likely be divided in their policies on genome-edited crops: Some will deregulate transgene-free crops, while others will regulate all types of crops that have been modified by genome editing. These implications are discussed from the viewpoint of public acceptance. PMID:27960622

RNA Editome in Rhesus Macaque Shaped by Purifying Selection

PubMed Central

Yang, Xin-Zhuang; Tan, Bertrand Chin-Ming; Fang, Huaying; Liu, Chu-Jun; Shi, Mingming; Ye, Zhi-Qiang; Zhang, Yong E.; Deng, Minghua; Zhang, Xiuqin; Li, Chuan-Yun

2014-01-01

Understanding of the RNA editing process has been broadened considerably by the next generation sequencing technology; however, several issues regarding this regulatory step remain unresolved – the strategies to accurately delineate the editome, the mechanism by which its profile is maintained, and its evolutionary and functional relevance. Here we report an accurate and quantitative profile of the RNA editome for rhesus macaque, a close relative of human. By combining genome and transcriptome sequencing of multiple tissues from the same animal, we identified 31,250 editing sites, of which 99.8% are A-to-G transitions. We verified 96.6% of editing sites in coding regions and 97.5% of randomly selected sites in non-coding regions, as well as the corresponding levels of editing by multiple independent means, demonstrating the feasibility of our experimental paradigm. Several lines of evidence supported the notion that the adenosine deamination is associated with the macaque editome – A-to-G editing sites were flanked by sequences with the attributes of ADAR substrates, and both the sequence context and the expression profile of ADARs are relevant factors in determining the quantitative variance of RNA editing across different sites and tissue types. In support of the functional relevance of some of these editing sites, substitution valley of decreased divergence was detected around the editing site, suggesting the evolutionary constraint in maintaining some of these editing substrates with their double-stranded structure. These findings thus complement the “continuous probing” model that postulates tinkering-based origination of a small proportion of functional editing sites. In conclusion, the macaque editome reported here highlights RNA editing as a widespread functional regulation in primate evolution, and provides an informative framework for further understanding RNA editing in human. PMID:24722121

Edited Synoptic Cloud Reports from Ships and Land Stations Over the Globe, 1982-1991 (NDP-026B)

DOE Data Explorer

Hahn, Carole J. [University of Arizona; Warren, Stephen G. [University of Washington; London, Julius [University of Colorado

1996-01-01

Surface synoptic weather reports for the entire globe for the 10-year period from December 1981 through November 1991 have been processed, edited, and rewritten to provide a data set designed for use in cloud analyses. The information in these reports relating to clouds, including the present weather information, was extracted and put through a series of quality control checks. Reports not meeting certain quality control standards were rejected, as were reports from buoys and automatic weather stations. Correctable inconsistencies within reports were edited for consistency, so that the "edited cloud report" can be used for cloud analysis without further quality checking. Cases of "sky obscured" were interpreted by reference to the present weather code as to whether they indicated fog, rain or snow and were given appropriate cloud type designations. Nimbostratus clouds, which are not specifically coded for in the standard synoptic code, were also given a special designation. Changes made to an original report are indicated in the edited report so that the original report can be reconstructed if desired. While low cloud amount is normally given directly in the synoptic report, the edited cloud report also includes the amounts, either directly reported or inferred, of middle and high clouds, both the non-overlapped amounts and the "actual" amounts (which may be overlapped). Since illumination from the moon is important for the adequate detection of clouds at night, both the relative lunar illuminance and the solar altitude are given, as well as a parameter that indicates whether our recommended illuminance criterion was satisfied. This data set contains 124 million reports from land stations and 15 million reports from ships. Each report is 56 characters in length. The archive consists of 240 files, one file for each month of data for land and ocean separately. With this data set a user can develop a climatology for any particular cloud type or group of types, for any geographical region and any spatial and temporal resolution desired.

Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa.

PubMed

Shinkuma, Satoru; Guo, Zongyou; Christiano, Angela M

2016-05-17

Genome editing with engineered site-specific endonucleases involves nonhomologous end-joining, leading to reading frame disruption. The approach is applicable to dominant negative disorders, which can be treated simply by knocking out the mutant allele, while leaving the normal allele intact. We applied this strategy to dominant dystrophic epidermolysis bullosa (DDEB), which is caused by a dominant negative mutation in the COL7A1 gene encoding type VII collagen (COL7). We performed genome editing with TALENs and CRISPR/Cas9 targeting the mutation, c.8068_8084delinsGA. We then cotransfected Cas9 and guide RNA expression vectors expressed with GFP and DsRed, respectively, into induced pluripotent stem cells (iPSCs) generated from DDEB fibroblasts. After sorting, 90% of the iPSCs were edited, and we selected four gene-edited iPSC lines for further study. These iPSCs were differentiated into keratinocytes and fibroblasts secreting COL7. RT-PCR and Western blot analyses revealed gene-edited COL7 with frameshift mutations degraded at the protein level. In addition, we confirmed that the gene-edited truncated COL7 could neither associate with normal COL7 nor undergo triple helix formation. Our data establish the feasibility of mutation site-specific genome editing in dominant negative disorders.

Limited Effects Weapons Study: Catalog of Currently Available Weapons and Devices. Edition 1,

DTIC Science & Technology

1995-10-25

1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE 3 . REPORT TYPE AND DATES COVERED 77 20 Oct 95 1st edition 4. TITLE AND SUBTITLE S. FUNDING NUMBERS...special markings in all capitals (e.g. Jan 88). Must cite at least the year. NOFORN, REL, ITAR). Block 3 . Type of Report and Dates Covered. DOD See...RA 88 and MA/RA 83 (Muzzle Launched Rubber Ammunition) 1 No. 15 Stinger" Grenade with Rubber Pellets 3 12 Gauge Flexible Baton Lead Shot Bean Bags 5 12

Reproductive medicine involving genome editing: clinical uncertainties and embryological needs.

PubMed

Ishii, Tetsuya

2017-01-01

Genome editing based on site-directed nucleases facilitated efficient and versatile genetic modifications in human cells. However, recent reports, demonstrating CRISPR/Cas9-mediated genome editing in human embryos have raised profound concerns worldwide. This commentary explores the clinical justification and feasibility of reproductive medicine using germline genome editing. Despite the perceived utility of reproductive medicine for treating intractable infertility, it is difficult to justify germline genome editing from the perspective of the prospective child. As suggested by the UK legalization regarding mitochondrial donation, the prevention of genetic disease in offspring by genome editing might be acceptable in limited cases of serious or life-threatening conditions, where no alternative medicine is available. Nonetheless, the mosaicism underlying human embryos as well as the off-target effect by artificial nucleases will likely hamper preimplantation genetic diagnosis prior to embryo transfer. Such considerations suggest that this type of reproductive medicine should not be developed toward a clinical application. However, the clinical uncertainties underscore the need for embryology that can address fundamental questions regarding germline aneuploidy and mosaicism using genome editing. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Defense Energy Support Center Fact Book, Fiscal Year 2001, Twenty-Fourth Edition

DTIC Science & Technology

2001-01-01

PMA-272). He was assigned to the U.S. European Command in Stuttgart, Germany from 1991 to 1994, serving in the Joint Petroleum Office as the Staff...Air Force Base, Florida from July 1990 to June 1993. He then served as Logistics Officer (G4) at 3rd Corps Support Command in Wiesbaden, Germany from...TURNOVER TO DESC FUEL SALES TO NORWAY AND EXCHANGES OF PRODUCT WITH GERMANY WILL LEAD TO TERMINATION OF AGREEMENTS WITH NORWAY AND DENMARK IN 2002 SOURCE

Defense Energy Support Center Fact Book, Fiscal Year 2000, Twenty-Third Edition

DTIC Science & Technology

2000-01-01

assigned to the U.S. European Command in Stuttgart, Germany from 1991 to 1994, serving in the Joint Petroleum Office as the Staff Petroleum Officer for...from July 1990 to June 1993. He then served as Logistics Officer (G4) at 3rd Corps Support Command in Wiesbaden, Germany from July 1993 to June 1995...successfully used the RDC system to collect fuel requirements for customers in the Germany PC&S and Hawaii PC&S programs. In August 2000, DESC used the

The Effects of Local Exertion and Anticipation on the Performance of a Discrete Skill.

DTIC Science & Technology

1986-01-01

295-298. Davies, B.T. & Ward, H. (1978). The effect of physical work on a subsequent fine manipulative task. Ergonomics , 21, 939-944. Dechovitz, A.B...Lt Jaeger’s next assignment was at the Occupational Measurement Cente r, Lackland AFB, Texas, where for three years he wrote and edited achievement...psychology, and human factors engineering for two years, then was selected for advanced graduate work in ergonomics under the sponsorship of the Air

ICD-11 and DSM-5 personality trait domains capture categorical personality disorders: Finding a common ground.

PubMed

Bach, Bo; Sellbom, Martin; Skjernov, Mathias; Simonsen, Erik

2018-05-01

The five personality disorder trait domains in the proposed International Classification of Diseases, 11th edition and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition are comparable in terms of Negative Affectivity, Detachment, Antagonism/Dissociality and Disinhibition. However, the International Classification of Diseases, 11th edition model includes a separate domain of Anankastia, whereas the Diagnostic and Statistical Manual of Mental Disorders, 5th edition model includes an additional domain of Psychoticism. This study examined associations of International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition trait domains, simultaneously, with categorical personality disorders. Psychiatric outpatients ( N = 226) were administered the Structured Clinical Interview for DSM-IV Axis II Personality Disorders Interview and the Personality Inventory for DSM-5. International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition trait domain scores were obtained using pertinent scoring algorithms for the Personality Inventory for DSM-5. Associations between categorical personality disorders and trait domains were examined using correlation and multiple regression analyses. Both the International Classification of Diseases, 11th edition and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition domain models showed relevant continuity with categorical personality disorders and captured a substantial amount of their information. As expected, the International Classification of Diseases, 11th edition model was superior in capturing obsessive-compulsive personality disorder, whereas the Diagnostic and Statistical Manual of Mental Disorders, 5th edition model was superior in capturing schizotypal personality disorder. These preliminary findings suggest that little information is 'lost' in a transition to trait domain models and potentially adds to narrowing the gap between Diagnostic and Statistical Manual of Mental Disorders, 5th edition and the proposed International Classification of Diseases, 11th edition model. Accordingly, the International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition domain models may be used to delineate one another as well as features of familiar categorical personality disorder types. A preliminary category-to-domain 'cross walk' is provided in the article.

Therapeutic Care. Technology Learning Activity. Teacher Edition. Technology Education Series. Level 2.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This Technology Learning Activity (TLA) for exploring therapeutic care careers is designed for use in eight class periods. It exposes students to the different types of therapeutic care and helps them understand how they can be used to treat and heal. This teacher's edition begins with an overview of technology education. The second section…

Reading: Tests and Assessment Techniques. Second Edition. United Kingdom Reading Association Teaching of Reading Monograph Series.

ERIC Educational Resources Information Center

Pumfrey, Peter D.

The second edition of this British publication provides details of recent developments in the assessment of reading attainments and the analysis of reading processes. The book begins with a description of various types of reading tests and assessment techniques with consideration given to the purposes for which normative, criterion-referenced, and…

Evaluation of a UMLS Auditing Process of Semantic Type Assignments

PubMed Central

Gu, Huanying; Hripcsak, George; Chen, Yan; Morrey, C. Paul; Elhanan, Gai; Cimino, James J.; Geller, James; Perl, Yehoshua

2007-01-01

The UMLS is a terminological system that integrates many source terminologies. Each concept in the UMLS is assigned one or more semantic types from the Semantic Network, an upper level ontology for biomedicine. Due to the complexity of the UMLS, errors exist in the semantic type assignments. Finding assignment errors may unearth modeling errors. Even with sophisticated tools, discovering assignment errors requires manual review. In this paper we describe the evaluation of an auditing project of UMLS semantic type assignments. We studied the performance of the auditors who reviewed potential errors. We found that four auditors, interacting according to a multi-step protocol, identified a high rate of errors (one or more errors in 81% of concepts studied) and that results were sufficiently reliable (0.67 to 0.70) for the two most common types of errors. However, reliability was low for each individual auditor, suggesting that review of potential errors is resource-intensive. PMID:18693845

Efficient CRISPR/Cas9-mediated Targeted Mutagenesis in Populus in the First Generation

PubMed Central

Fan, Di; Liu, Tingting; Li, Chaofeng; Jiao, Bo; Li, Shuang; Hou, Yishu; Luo, Keming

2015-01-01

Recently, RNA-guided genome editing using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) system has been applied to edit the plant genome in several herbaceous plant species. However, it remains unknown whether this system can be used for genome editing in woody plants. In this study, we describe the genome editing and targeted gene mutation in a woody species, Populus tomentosa Carr. via the CRISPR/Cas9 system. Four guide RNAs (gRNAs) were designed to target with distinct poplar genomic sites of the phytoene desaturase gene 8 (PtoPDS) which are followed by the protospacer-adjacent motif (PAM). After Agrobacterium-mediated transformation, obvious albino phenotype was observed in transgenic poplar plants. By analyzing the RNA-guided genome-editing events, 30 out of 59 PCR clones were homozygous mutants, 2 out of 59 were heterozygous mutants and the mutation efficiency at these target sites was estimated to be 51.7%. Our data demonstrate that the Cas9/sgRNA system can be exploited to precisely edit genomic sequence and effectively create knockout mutations in woody plants. PMID:26193631

Mediated Plastid RNA Editing in Plant Immunity

PubMed Central

García-Andrade, Javier; Ramírez, Vicente; López, Ana; Vera, Pablo

2013-01-01

Plant regulatory circuits coordinating nuclear and plastid gene expression have evolved in response to external stimuli. RNA editing is one of such control mechanisms. We determined the Arabidopsis nuclear-encoded homeodomain-containing protein OCP3 is incorporated into the chloroplast, and contributes to control over the extent of ndhB transcript editing. ndhB encodes the B subunit of the chloroplast NADH dehydrogenase-like complex (NDH) involved in cyclic electron flow (CEF) around photosystem I. In ocp3 mutant strains, ndhB editing efficiency decays, CEF is impaired and disease resistance to fungal pathogens substantially enhanced, a process recapitulated in plants defective in editing plastid RNAs encoding NDH complex subunits due to mutations in previously described nuclear-encoded pentatricopeptide-related proteins (i.e. CRR21, CRR2). Furthermore, we observed that following a pathogenic challenge, wild type plants respond with editing inhibition of ndhB transcript. In parallel, rapid destabilization of the plastidial NDH complex is also observed in the plant following perception of a pathogenic cue. Therefore, NDH complex activity and plant immunity appear as interlinked processes. PMID:24204264

46 CFR 42.20-3 - Freeboard assignment: Type “A” vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Freeboard assignment: Type âAâ vessels. 42.20-3 Section 42.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES DOMESTIC AND FOREIGN VOYAGES BY SEA Freeboards § 42.20-3 Freeboard assignment: Type “A” vessels. (a) A Type “A” vessel...

Gene Editing in Human Lymphoid Cells: Role for Donor DNA, Type of Genomic Nuclease and Cell Selection Method.

PubMed

Zotova, Anastasia; Lopatukhina, Elena; Filatov, Alexander; Khaitov, Musa; Mazurov, Dmitriy

2017-11-02

Programmable endonucleases introduce DNA breaks at specific sites, which are repaired by non-homologous end joining (NHEJ) or homology recombination (HDR). Genome editing in human lymphoid cells is challenging as these difficult-to-transfect cells may also inefficiently repair DNA by HDR. Here, we estimated efficiencies and dynamics of knockout (KO) and knockin (KI) generation in human T and B cell lines depending on repair template, target loci and types of genomic endonucleases. Using zinc finger nuclease (ZFN), we have engineered Jurkat and CEM cells with the 8.2 kb human immunodeficiency virus type 1 (HIV-1) ∆Env genome integrated at the adeno-associated virus integration site 1 (AAVS1) locus that stably produce virus particles and mediate infection upon transfection with helper vectors. Knockouts generated by ZFN or clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) double nicking techniques were comparably efficient in lymphoid cells. However, unlike polyclonal sorted cells, gene-edited cells selected by cloning exerted tremendous deviations in functionality as estimated by replication of HIV-1 and human T cell leukemia virus type 1 (HTLV-1) in these cells. Notably, the recently reported high-fidelity eCas9 1.1 when combined to the nickase mutation displayed gene-dependent decrease in on-target activity. Thus, the balance between off-target effects and on-target efficiency of nucleases, as well as choice of the optimal method of edited cell selection should be taken into account for proper gene function validation in lymphoid cells.

Bending the rules: when deaf writers leave college.

PubMed

Biser, Eileen; Rubel, Linda; Toscano, Rose Marie

2007-01-01

On-the-job writing of deaf college graduates at all degree levels was investigated. Institutional databases and questionnaires to alumni and employers were the sources for information. Respondents were asked about editing assistance, sources and types of assistance, and perceptions of such assistance by employers and employees. Results of the study confirmed that deaf employees did considerable writing regardless of degree or type of job. Their self-reports indicated grammar as the major weakness. Additionally, employers stated that clarity, organization, and spelling were serious writing problems. The study also showed that deaf employees asked for and received editing assistance and that employers were willing to support the improvement of writing skills. Because error-free texts are expected in the workplace and editing assistance is sought and received, postsecondary institutions should mimic these practices by providing copyediting services and instruction in the ethics and practices of working with editors.

Selective excitation for spectral editing and assignment in separated local field experiments of oriented membrane proteins

NASA Astrophysics Data System (ADS)

Koroloff, Sophie N.; Nevzorov, Alexander A.

2017-01-01

Spectroscopic assignment of NMR spectra for oriented uniformly labeled membrane proteins embedded in their native-like bilayer environment is essential for their structure determination. However, sequence-specific assignment in oriented-sample (OS) NMR is often complicated by insufficient resolution and spectral crowding. Therefore, the assignment process is usually done by a laborious and expensive "shotgun" method involving multiple selective labeling of amino acid residues. Presented here is a strategy to overcome poor spectral resolution in crowded regions of 2D spectra by selecting resolved "seed" residues via soft Gaussian pulses inserted into spin-exchange separated local-field experiments. The Gaussian pulse places the selected polarization along the z-axis while dephasing the other signals before the evolution of the 1H-15N dipolar couplings. The transfer of magnetization is accomplished via mismatched Hartmann-Hahn conditions to the nearest-neighbor peaks via the proton bath. By optimizing the length and amplitude of the Gaussian pulse, one can also achieve a phase inversion of the closest peaks, thus providing an additional phase contrast. From the superposition of the selective spin-exchanged SAMPI4 onto the fully excited SAMPI4 spectrum, the 15N sites that are directly adjacent to the selectively excited residues can be easily identified, thereby providing a straightforward method for initiating the assignment process in oriented membrane proteins.

U-insertion/deletion RNA editing multiprotein complexes and mitochondrial ribosomes in Leishmania tarentolae are located in antipodal nodes adjacent to the kinetoplast DNA.

PubMed

Wong, Richard G; Kazane, Katelynn; Maslov, Dmitri A; Rogers, Kestrel; Aphasizhev, Ruslan; Simpson, Larry

2015-11-01

We studied the intramitochondrial localization of several multiprotein complexes involved in U-insertion/deletion RNA editing in trypanosome mitochondria. The editing complexes are located in one or two antipodal nodes adjacent to the kinetoplast DNA (kDNA) disk, which are distinct from but associated with the minicircle catenation nodes. In some cases the proteins are in a bilateral sheet configuration. We also found that mitoribosomes have a nodal configuration. This type of organization is consistent with evidence for protein and RNA interactions of multiple editing complexes to form an ~40S editosome and also an interaction of editosomes with mitochondrial ribosomes. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

PubMed Central

Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

2009-01-01

Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4+ T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5′ untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1. PMID:19651874

What! I Have To Give a Speech? 2nd Edition.

ERIC Educational Resources Information Center

Snyder, Kenneth; Murphy, Thomas J.

Noting that fear of public speaking is shared by people of all types, the second edition of this book offers practical, easy-to-follow strategies for confident and effective public speaking. The book discusses the following aspects of public speaking: what to talk about; how to research a topic; how to organize a speech; how to keep an audience…

"What Do You Think?" Let Me Tell You: Discourse about Texts and the Literature Classroom

ERIC Educational Resources Information Center

Mason, Jessica; Giovanelli, Marcello

2017-01-01

This article examines the practice of studying texts in secondary school English lessons as a particular type of reading experience. Through a critical stylistic analysis of a popular edition of John Steinbeck's "Of Mice and Men", the article explores how reading the text is framed by educational editions, and how this might present the…

Responsiveness of the Psychoeducational Profile-Third Edition for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Chen, Kuan-Lin; Chiang, Fu-Mei; Tseng, Mei-Hui; Fu, Chung-Pei; Hsieh, Ching-Lin

2011-01-01

The aim of this study was to examine the responsiveness of the Psychoeducational Profile-third edition (PEP-3) in children with Autism Spectrum Disorders (ASD). We investigated the responsiveness in terms of three types of scores (i.e., raw scores, developmental ages, and percentile ranks) of the subtests and composites of the PEP-3 and three…

The Conspicuity of CRISPR-Cpf1 System as a Significant Breakthrough in Genome Editing.

PubMed

Bayat, Hadi; Modarressi, Mohammad Hossein; Rahimpour, Azam

2018-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) is a microbial adaptive immune system. CRISPR-Cas systems are classified into two main classes and six types. Cpf1 is a putative type V (class II) CRISPR effector, which has revolutionized the genome editing approaches through multiple distinct features such as using T-rich protospacer-adjacent motif, applying a short guide RNA lacking trans-activating crRNA, introducing a staggered double-strand break, and possessing RNA processing activity in addition to DNA nuclease activity. In the present review, we attempt to highlight most recent advances in CRISPR-Cpf1 (CRISPR-Cas12a) system in particular, considering ground expeditions of the nature and the biology of this system, introducing novel Cpf1 variants that have broadened the versatility and feasibility of CRISPR-Cpf1 system, and lastly the great impact of the CRISPR-Cpf1 system on the manipulation of the genome of prokaryotic, mammalian, and plant models is summarized. With regard to recent developments in utilizing the CRISPR-Cpf1 system in genome editing of various organisms, it can be concluded with confidence that this system is a reliable molecular toolbox of genome editing approaches.

Rule-based support system for multiple UMLS semantic type assignments

PubMed Central

Geller, James; He, Zhe; Perl, Yehoshua; Morrey, C. Paul; Xu, Julia

2012-01-01

Background When new concepts are inserted into the UMLS, they are assigned one or several semantic types from the UMLS Semantic Network by the UMLS editors. However, not every combination of semantic types is permissible. It was observed that many concepts with rare combinations of semantic types have erroneous semantic type assignments or prohibited combinations of semantic types. The correction of such errors is resource-intensive. Objective We design a computational system to inform UMLS editors as to whether a specific combination of two, three, four, or five semantic types is permissible or prohibited or questionable. Methods We identify a set of inclusion and exclusion instructions in the UMLS Semantic Network documentation and derive corresponding rule-categories as well as rule-categories from the UMLS concept content. We then design an algorithm adviseEditor based on these rule-categories. The algorithm specifies rules for an editor how to proceed when considering a tuple (pair, triple, quadruple, quintuple) of semantic types to be assigned to a concept. Results Eight rule-categories were identified. A Web-based system was developed to implement the adviseEditor algorithm, which returns for an input combination of semantic types whether it is permitted, prohibited or (in a few cases) requires more research. The numbers of semantic type pairs assigned to each rule-category are reported. Interesting examples for each rule-category are illustrated. Cases of semantic type assignments that contradict rules are listed, including recently introduced ones. Conclusion The adviseEditor system implements explicit and implicit knowledge available in the UMLS in a system that informs UMLS editors about the permissibility of a desired combination of semantic types. Using adviseEditor might help accelerate the work of the UMLS editors and prevent erroneous semantic type assignments. PMID:23041716

VizieR Online Data Catalog: Yale Trigonometric Parallaxes Preliminary (van Altena+ 1991)

NASA Astrophysics Data System (ADS)

van Altena, W. F.; Lee, J. T.; Hoffleit, D.

1995-10-01

The preliminary edition of the General Catalogue of Trigonometric Stellar Parallaxes, containing 15349 parallaxes for 7879 stars, has been prepared at the Yale University Observatory. In this edition 1480 stars have been added to those contained in the previous edition of the catalog by Jenkins (1952, 1963). This relatively small increase in the number of stars is more than compensated for by the increased accuracy of the newer trigonometric parallaxes. The authors have attempted to include here all trigonometric parallaxes made available to them by March 1991 and will provide for each listed parallax in the final version the reference to its source of publication. For each star it lists the equatorial coordinates for B1900 and the secular variation for 100 years, the proper motion in x and y, the weighted average absolute parallax and its standard error, the number of parallax observations, the quality of interagreement among the different values, the visual magnitude, and various cross identifications with other catalogs. The B1900 equinox has been maintained to avoid assigning yet another star number. Ancillary information, including UBV photometry, MK spectral types, data on the variability and binary nature of the stars, orbits when available, and miscellaneous information to aid in determining the reliability of the data, will be listed in the final version. The relative parallaxes are corrected to absolute parallax using newly computed corrections that are based on an improved model of the galaxy. An analysis of the resulting absolute parallaxes has been made to study the accidental and systematic errors of the parallaxes. The results of that investigation are used to arrive at a weighting system for the catalog, which then yields weighted absolute parallaxes for each star. The weighting system is still under investigation; therefore, the weighted parallaxes may change a bit in the final version. Printed copies of the catalog will be available from the Yale University Observatory when the work has been completed (late 1993?). See the file cdrom.doc which provides the original documentation by W. van Altena. (1 data file).

Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene.

PubMed

Nerys-Junior, Arildo; Braga-Dias, Luciene P; Pezzuto, Paula; Cotta-de-Almeida, Vinícius; Tanuri, Amilcar

2018-01-01

The human C-C chemokine receptor type-5 (CCR5) is the major transmembrane co-receptor that mediates HIV-1 entry into target CD4+ cells. Gene therapy to knock-out the CCR5 gene has shown encouraging results in providing a functional cure for HIV-1 infection. In gene therapy strategies, the initial region of the CCR5 gene is a hotspot for producing functional gene knock-out. Such target gene editing can be done using programmable endonucleases such as transcription activator-like effector nucleases (TALEN) or clustered regularly interspaced short palindromic repeats (CRISPR-Cas9). These two gene editing approaches are the most modern and effective tools for precise gene modification. However, little is known of potential differences in the efficiencies of TALEN and CRISPR-Cas9 for editing the beginning of the CCR5 gene. To examine which of these two methods is best for gene therapy, we compared the patterns and amount of editing at the beginning of the CCR5 gene using TALEN and CRISPR-Cas9 followed by DNA sequencing. This comparison revealed that CRISPR-Cas9 mediated the sorting of cells that contained 4.8 times more gene editing than TALEN+ transfected cells.

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

PubMed

Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene

PubMed Central

Nerys-Junior, Arildo; Braga-Dias, Luciene P.; Pezzuto, Paula; Cotta-de-Almeida, Vinícius; Tanuri, Amilcar

2018-01-01

Abstract The human C-C chemokine receptor type-5 (CCR5) is the major transmembrane co-receptor that mediates HIV-1 entry into target CD4+ cells. Gene therapy to knock-out the CCR5 gene has shown encouraging results in providing a functional cure for HIV-1 infection. In gene therapy strategies, the initial region of the CCR5 gene is a hotspot for producing functional gene knock-out. Such target gene editing can be done using programmable endonucleases such as transcription activator-like effector nucleases (TALEN) or clustered regularly interspaced short palindromic repeats (CRISPR-Cas9). These two gene editing approaches are the most modern and effective tools for precise gene modification. However, little is known of potential differences in the efficiencies of TALEN and CRISPR-Cas9 for editing the beginning of the CCR5 gene. To examine which of these two methods is best for gene therapy, we compared the patterns and amount of editing at the beginning of the CCR5 gene using TALEN and CRISPR-Cas9 followed by DNA sequencing. This comparison revealed that CRISPR-Cas9 mediated the sorting of cells that contained 4.8 times more gene editing than TALEN+ transfected cells. PMID:29583154

Examining End-Of-Chapter Problems Across Editions of an Introductory Calculus-Based Physics Textbook

NASA Astrophysics Data System (ADS)

Xiao, Bin

End-Of-Chapter (EOC) problems have been part of many physics education studies. Typically, only problems "localized" as relevant to a single chapter were used. This work examines how well this type of problem represents all EOC problems and whether EOC problems found in leading textbooks have changed over the past several decades. To investigate whether EOC problems have connections between chapters, I solved all problems of the E&M; chapters of the most recent edition of a popular introductory level calculus-based textbook and coded the equations used to solve each problem. These results were compared to the first edition of the same text. Also, several relevant problem features were coded for those problems and results were compared for sample chapters across all editions. My findings include two parts. The result of equation usage shows that problems in the E&M; chapters do use equations from both other E&M; chapters and non-E&M; chapters. This out-of-chapter usage increased from the first edition to the last edition. Information about the knowledge structure of E&M; chapters was also revealed. The results of the problem feature study show that most EOC problems have common features but there was an increase of diversity in some of the problem features across editions.

ActionMap: A web-based software that automates loci assignments to framework maps.

PubMed

Albini, Guillaume; Falque, Matthieu; Joets, Johann

2003-07-01

Genetic linkage computation may be a repetitive and time consuming task, especially when numerous loci are assigned to a framework map. We thus developed ActionMap, a web-based software that automates genetic mapping on a fixed framework map without adding the new markers to the map. Using this tool, hundreds of loci may be automatically assigned to the framework in a single process. ActionMap was initially developed to map numerous ESTs with a small plant mapping population and is limited to inbred lines and backcrosses. ActionMap is highly configurable and consists of Perl and PHP scripts that automate command steps for the MapMaker program. A set of web forms were designed for data import and mapping settings. Results of automatic mapping can be displayed as tables or drawings of maps and may be exported. The user may create personal access-restricted projects to store raw data, settings and mapping results. All data may be edited, updated or deleted. ActionMap may be used either online or downloaded for free (http://moulon.inra.fr/~bioinfo/).

ActionMap: a web-based software that automates loci assignments to framework maps

PubMed Central

Albini, Guillaume; Falque, Matthieu; Joets, Johann

2003-01-01

Genetic linkage computation may be a repetitive and time consuming task, especially when numerous loci are assigned to a framework map. We thus developed ActionMap, a web-based software that automates genetic mapping on a fixed framework map without adding the new markers to the map. Using this tool, hundreds of loci may be automatically assigned to the framework in a single process. ActionMap was initially developed to map numerous ESTs with a small plant mapping population and is limited to inbred lines and backcrosses. ActionMap is highly configurable and consists of Perl and PHP scripts that automate command steps for the MapMaker program. A set of web forms were designed for data import and mapping settings. Results of automatic mapping can be displayed as tables or drawings of maps and may be exported. The user may create personal access-restricted projects to store raw data, settings and mapping results. All data may be edited, updated or deleted. ActionMap may be used either online or downloaded for free (http://moulon.inra.fr/~bioinfo/). PMID:12824426

Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

PubMed

Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

2015-10-01

Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

Design and assessment of engineered CRISPR-Cpf1 and its use for genome editing.

PubMed

Li, Bin; Zeng, Chunxi; Dong, Yizhou

2018-05-01

Cpf1, a CRISPR endonuclease discovered in Prevotella and Francisella 1 bacteria, offers an alternative platform for CRISPR-based genome editing beyond the commonly used CRISPR-Cas9 system originally discovered in Streptococcus pyogenes. This protocol enables the design of engineered CRISPR-Cpf1 components, both CRISPR RNAs (crRNAs) to guide the endonuclease and Cpf1 mRNAs to express the endonuclease protein, and provides experimental procedures for effective genome editing using this system. We also describe quantification of genome-editing activity and off-target effects of the engineered CRISPR-Cpf1 in human cell lines using both T7 endonuclease I (T7E1) assay and targeted deep sequencing. This protocol enables rapid construction and identification of engineered crRNAs and Cpf1 mRNAs to enhance genome-editing efficiency using the CRISPR-Cpf1 system, as well as assessment of target specificity within 2 months. This protocol may also be appropriate for fine-tuning other types of CRISPR systems.

Treatment of Dyslipidemia Using CRISPR/Cas9 Genome Editing.

PubMed

Chadwick, Alexandra C; Musunuru, Kiran

2017-07-01

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) has recently emerged as a top genome editing technology and has afforded investigators the ability to more easily study a number of diseases. This review discusses CRISPR/Cas9's advantages and limitations and highlights a few recent reports on genome editing applications for alleviating dyslipidemia through disruption of proprotein convertase subtilisin/kexin type 9 (PCSK9). Targeting of mouse Pcsk9 using CRISPR/Cas9 technology has yielded promising results for lowering total cholesterol levels, and several recent findings are highlighted in this review. Reported on-target mutagenesis efficiency is as high as 90% with a subsequent 40% reduction of blood cholesterol levels in mice, highlighting the potential for use as a therapeutic in human patients. The ability to characterize and treat diseases is becoming easier with the recent advances in genome editing technologies. In this review, we discuss how genome editing strategies can be of use for potential therapeutic applications.

Left-handed Z-DNA: structure and function

NASA Technical Reports Server (NTRS)

Herbert, A.; Rich, A.

1999-01-01

Z-DNA is a high energy conformer of B-DNA that forms in vivo during transcription as a result of torsional strain generated by a moving polymerase. An understanding of the biological role of Z-DNA has advanced with the discovery that the RNA editing enzyme double-stranded RNA adenosine deaminase type I (ADAR1) has motifs specific for the Z-DNA conformation. Editing by ADAR1 requires a double-stranded RNA substrate. In the cases known, the substrate is formed by folding an intron back onto the exon that is targeted for modification. The use of introns to direct processing of exons requires that editing occurs before splicing. Recognition of Z-DNA by ADAR1 may allow editing of nascent transcripts to be initiated immediately after transcription, ensuring that editing and splicing are performed in the correct sequence. Structural characterization of the Z-DNA binding domain indicates that it belongs to the winged helix-turn-helix class of proteins and is similar to the globular domain of histone-H5.

Malnutrition coding 101: financial impact and more.

PubMed

Giannopoulos, Georgia A; Merriman, Louise R; Rumsey, Alissa; Zwiebel, Douglas S

2013-12-01

Recent articles have addressed the characteristics associated with adult malnutrition as published by the Academy of Nutrition and Dietetics (the Academy) and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). This article describes a successful interdisciplinary program developed by the Department of Food and Nutrition at New York-Presbyterian Hospital to maintain and monitor clinical documentation, ensure accurate International Classification of Diseases 9th Edition (ICD-9) coding, and identify subsequent incremental revenue resulting from the early identification, documentation, and treatment of malnutrition in an adult inpatient population. The first step in the process requires registered dietitians to identify patients with malnutrition; then clear and specifically worded diagnostic statements that include the type and severity of malnutrition are documented in the medical record by the physician, nurse practitioner, or physician's assistant. This protocol allows the Heath Information Management/Coding department to accurately assign ICD-9 codes associated with protein-energy malnutrition. Once clinical coding is complete, a final diagnosis related group (DRG) is generated to ensure appropriate hospital reimbursement. Successful interdisciplinary programs such as this can drive optimal care and ensure appropriate reimbursement.

Mathematics Textbooks and the Teaching of Assigned Writing.

ERIC Educational Resources Information Center

Donlan, Dan

This paper initially presents the results of several studies concerning what kind of writing mathematics teachers assign and what kind of writing mathematics textbooks assign. By far, report-research was the most popular type of writing assigned in the surveyed textbooks. The types of reports students were asked to write include biography,…

Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1.

PubMed

Schiroli, Giulia; Ferrari, Samuele; Conway, Anthony; Jacob, Aurelien; Capo, Valentina; Albano, Luisa; Plati, Tiziana; Castiello, Maria C; Sanvito, Francesca; Gennery, Andrew R; Bovolenta, Chiara; Palchaudhuri, Rahul; Scadden, David T; Holmes, Michael C; Villa, Anna; Sitia, Giovanni; Lombardo, Angelo; Genovese, Pietro; Naldini, Luigi

2017-10-11

Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of corrected cells and might affect the feasibility and safety of clinical translation. These concerns need to be addressed in stringent preclinical models and overcome by developing more efficient editing methods. We generated a humanized X-linked severe combined immunodeficiency (SCID-X1) mouse model and evaluated the efficacy and safety of hematopoietic reconstitution from limited input of functional HSPCs, establishing thresholds for full correction upon different types of conditioning. Unexpectedly, conditioning before HSPC infusion was required to protect the mice from lymphoma developing when transplanting small numbers of progenitors. We then designed a one-size-fits-all IL2RG (interleukin-2 receptor common γ-chain) gene correction strategy and, using the same reagents suitable for correction of human HSPC, validated the edited human gene in the disease model in vivo, providing evidence of targeted gene editing in mouse HSPCs and demonstrating the functionality of the IL2RG -edited lymphoid progeny. Finally, we optimized editing reagents and protocol for human HSPCs and attained the threshold of IL2RG editing in long-term repopulating cells predicted to safely rescue the disease, using clinically relevant HSPC sources and highly specific zinc finger nucleases or CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9). Overall, our work establishes the rationale and guiding principles for clinical translation of SCID-X1 gene editing and provides a framework for developing gene correction for other diseases. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer.

PubMed

Cho, Charles J; Jung, Jaeeun; Jiang, Lushang; Lee, Eun Ji; Kim, Dae-Soo; Kim, Byung Sik; Kim, Hee Sung; Jung, Hwoon-Yong; Song, Ho-June; Hwang, Sung Wook; Park, Yangsoon; Jung, Min Kyo; Pack, Chan Gi; Myung, Seung-Jae; Chang, Suhwan

2018-04-25

Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear. This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3' untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs). RNA-sequencing and small RNA-sequencing were performed on AGS and MKN-45 cells with a stable ADAR1 knockdown. Changed frequencies of editing and mRNA and miRNA expression were then identified by bioinformatic analyses. Targets of RNA editing were further validated in patients' samples. In the Alu region of both gastric cell lines, editing was most commonly of the A-to-I type in 3'-UTR or intron. mRNA and protein levels of PHACTR4 increased in ADAR1 knockdown cells, because of the loss of seed sequences in 3'-UTR of PHACTR4 mRNA that are required for miRNA-196a-3p binding. Immunohistochemical analyses of tumor and paired normal samples from 16 gastric cancer patients showed that ADAR1 expression was higher in tumors than in normal tissues and inversely correlated with PHACTR4 staining. On the other hand, decreased miRNA-148a-3p expression in ADAR1 knockdown cells led to increased mRNA and protein expression of NFYA, demonstrating ADAR1's editing-independent function. ADAR1 regulates post-transcriptional gene expression in gastric cancer through both RNA editing-dependent and editing-independent mechanisms.

Intellectual interchanges in the history of the massive online open-editing encyclopedia, Wikipedia

NASA Astrophysics Data System (ADS)

Yun, Jinhyuk; Lee, Sang Hoon; Jeong, Hawoong

2016-01-01

Wikipedia is a free Internet encyclopedia with an enormous amount of content. This encyclopedia is written by volunteers with various backgrounds in a collective fashion; anyone can access and edit most of the articles. This open-editing nature may give us prejudice that Wikipedia is an unstable and unreliable source; yet many studies suggest that Wikipedia is even more accurate and self-consistent than traditional encyclopedias. Scholars have attempted to understand such extraordinary credibility, but usually used the number of edits as the unit of time, without consideration of real time. In this work, we probe the formation of such collective intelligence through a systematic analysis using the entire history of 34 534 110 English Wikipedia articles, between 2001 and 2014. From this massive data set, we observe the universality of both timewise and lengthwise editing scales, which suggests that it is essential to consider the real-time dynamics. By considering real time, we find the existence of distinct growth patterns that are unobserved by utilizing the number of edits as the unit of time. To account for these results, we present a mechanistic model that adopts the article editing dynamics based on both editor-editor and editor-article interactions. The model successfully generates the key properties of real Wikipedia articles such as distinct types of articles for the editing patterns characterized by the interrelationship between the numbers of edits and editors, and the article size. In addition, the model indicates that infrequently referred articles tend to grow faster than frequently referred ones, and articles attracting a high motivation to edit counterintuitively reduce the number of participants. We suggest that this decay of participants eventually brings inequality among the editors, which will become more severe with time.

Intellectual interchanges in the history of the massive online open-editing encyclopedia, Wikipedia.

PubMed

Yun, Jinhyuk; Lee, Sang Hoon; Jeong, Hawoong

2016-01-01

Wikipedia is a free Internet encyclopedia with an enormous amount of content. This encyclopedia is written by volunteers with various backgrounds in a collective fashion; anyone can access and edit most of the articles. This open-editing nature may give us prejudice that Wikipedia is an unstable and unreliable source; yet many studies suggest that Wikipedia is even more accurate and self-consistent than traditional encyclopedias. Scholars have attempted to understand such extraordinary credibility, but usually used the number of edits as the unit of time, without consideration of real time. In this work, we probe the formation of such collective intelligence through a systematic analysis using the entire history of 34534110 English Wikipedia articles, between 2001 and 2014. From this massive data set, we observe the universality of both timewise and lengthwise editing scales, which suggests that it is essential to consider the real-time dynamics. By considering real time, we find the existence of distinct growth patterns that are unobserved by utilizing the number of edits as the unit of time. To account for these results, we present a mechanistic model that adopts the article editing dynamics based on both editor-editor and editor-article interactions. The model successfully generates the key properties of real Wikipedia articles such as distinct types of articles for the editing patterns characterized by the interrelationship between the numbers of edits and editors, and the article size. In addition, the model indicates that infrequently referred articles tend to grow faster than frequently referred ones, and articles attracting a high motivation to edit counterintuitively reduce the number of participants. We suggest that this decay of participants eventually brings inequality among the editors, which will become more severe with time.

Specifications and Construction Methods for Asphalt Concrete and Other Plant-Mix Types, 3rd Edition.

ERIC Educational Resources Information Center

Asphalt Inst., College Park, MD.

The purpose of this publication is to assist engineers in the analysis, design and control of paving projects that use asphalt concrete and other asphalt plant-mixes. The scope of this new third edition has been enlarged, and changes necessitated by advances in asphalt technology have been incorporated. Chapters I and II and Appendices A and B…

Metaphor and Pedagogy in Early Buddhist Literature: An Edition and Study of Two Sutras from the Senior Collection of Gandhari Manuscripts

ERIC Educational Resources Information Center

Marino, Joseph

2017-01-01

This dissertation examines the role of metaphorical language in early Buddhist literature through the lens of two previously unpublished Gandhari sutras on a manuscript from the Robert Senior Collection. At the microscopic level, I offer an edition, translation, and textual analysis of a Buddhist manuscript containing two Sa?yuktagama-type sutras…

46 CFR 110.10-1 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Explosive Gas Atmospheres—Part 15: Type of Protection “n”, Second Edition (2001) (“IEC 60079-15”), 111.105-1..., Part 202: System Design-Protection (1996) (“IEC 92-202”), 111.12-7; 111.50-3; 111.53-1; 111.54-1; (18..., First Edition (1975) (“IEC 92-503”), 111.30-5; (28) IEC 60529 Degrees of Protection Provided by...

46 CFR 110.10-1 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Explosive Gas Atmospheres—Part 15: Type of Protection “n”, Second Edition (2001) (“IEC 60079-15”), 111.105-1..., Part 202: System Design-Protection (1996) (“IEC 92-202”), 111.12-7; 111.50-3; 111.53-1; 111.54-1; (18..., First Edition (1975) (“IEC 92-503”), 111.30-5; (28) IEC 60529 Degrees of Protection Provided by...

From Psychical treatment to psychoanalysis: considerations on the misdating of an early Freud text and on a hitherto overlooked addition to it (here reproduced).

PubMed

Fichtner, Gerhard

2008-08-01

Freud's early paper Psychical (or mental) treatment, first published in a family reference book for educated lay persons, was reproduced in the Gesammelte Werke with a stated publication date of 1905. This date was subsequently called into question owing to certain parts of the subject-matter (the use of hypnosis and suggestion in 'mental treatment'), and the contribution was erroneously assigned, for instance by James Strachey, to the year 1890. This error is corrected in the present paper. Furthermore, the existence of a second edition of this reference book, which contains an addition to Freud's text and appeared in 1918-19, has previously gone unnoticed. The first edition had been published in 1905-6. Freud's contribution must, however, have been written at an appreciably earlier date. The probable time of its genesis is discussed. Freud's new text is reproduced (in English translation) for the first time in an appendix to this paper.

Combining Fourier phase encoding and broadband inversion toward J-edited spectra

NASA Astrophysics Data System (ADS)

Lin, Yulan; Guan, Quanshuai; Su, Jianwei; Chen, Zhong

2018-06-01

Nuclear magnetic resonance (NMR) spectra are often utilized for gathering accurate information relevant to molecular structures and composition assignments. In this study, we develop a homonuclear encoding approach based on imparting a discrete phase modulation of the targeted cross peaks, and combine it with a pure shift experiments (PSYCHE) based J-modulated scheme, providing simple 2D J-edited spectra for accurate measurement of scalar coupling networks. Chemical shifts and J coupling constants of protons coupled to the specific protons are demonstrated along the F2 and F1 dimensions, respectively. Polychromatic pulses by Fourier phase encoding were performed to simultaneously detect several coupling networks. Proton-proton scalar couplings are chosen by a polychromatic pulse and a PSYCHE element. Axis peaks and unwanted couplings are complete eradicated by incorporating a selective COSY block as a preparation period. The theoretical principles and the signal processing procedure are laid out, and experimental observations are rationalized on the basis of theoretical analyses.

Crowdsourcing the Moral Limits of Human Gene Editing?

PubMed

Juengst, Eric T

2017-05-01

In 2015, a flourish of "alarums and excursions" by the scientific community propelled CRISPR/Cas9 and other new gene-editing techniques into public attention. At issue were two kinds of potential gene-editing experiments in humans: those making inheritable germ-line modifications and those designed to enhance human traits beyond what is necessary for health and healing. The scientific consensus seemed to be that while research to develop safe and effective human gene editing should continue, society's moral uncertainties about these two kinds of experiments needed to be better resolved before clinical trials of either type should be attempted. In the United States, the National Academies of Science, Engineering and Medicine (NASEM) convened the Committee on Human Gene Editing: Scientific, Medical and Ethical Considerations to pursue that resolution. The committee's 2017 consensus report has been widely interpreted as "opening the door" to inheritable human genetic modification and holding a line against enhancement interventions. But on a close reading it does neither. There are two reasons for this eccentric conclusion, both of which depend upon the strength of the committee's commitment to engaging diverse public voices in the gene-editing policy-making process. © 2017 The Hastings Center.

Efficient CRISPR/Cas9-based gene knockout in watermelon.

PubMed

Tian, Shouwei; Jiang, Linjian; Gao, Qiang; Zhang, Jie; Zong, Mei; Zhang, Haiying; Ren, Yi; Guo, Shaogui; Gong, Guoyi; Liu, Fan; Xu, Yong

2017-03-01

CRISPR/Cas9 system can precisely edit genomic sequence and effectively create knockout mutations in T0 generation watermelon plants. Genome editing offers great advantage to reveal gene function and generate agronomically important mutations to crops. Recently, RNA-guided genome editing system using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) has been applied to several plant species, achieving successful targeted mutagenesis. Here, we report the genome of watermelon, an important fruit crop, can also be precisely edited by CRISPR/Cas9 system. ClPDS, phytoene desaturase in watermelon, was selected as the target gene because its mutant bears evident albino phenotype. CRISPR/Cas9 system performed genome editing, such as insertions or deletions at the expected position, in transfected watermelon protoplast cells. More importantly, all transgenic watermelon plants harbored ClPDS mutations and showed clear or mosaic albino phenotype, indicating that CRISPR/Cas9 system has technically 100% of genome editing efficiency in transgenic watermelon lines. Furthermore, there were very likely no off-target mutations, indicated by examining regions that were highly homologous to sgRNA sequences. Our results show that CRISPR/Cas9 system is a powerful tool to effectively create knockout mutations in watermelon.

Scalable and Versatile Genome Editing Using Linear DNAs with Microhomology to Cas9 Sites in Caenorhabditis elegans

PubMed Central

Paix, Alexandre; Wang, Yuemeng; Smith, Harold E.; Lee, Chih-Yung S.; Calidas, Deepika; Lu, Tu; Smith, Jarrett; Schmidt, Helen; Krause, Michael W.; Seydoux, Geraldine

2014-01-01

Homology-directed repair (HDR) of double-strand DNA breaks is a promising method for genome editing, but is thought to be less efficient than error-prone nonhomologous end joining in most cell types. We have investigated HDR of double-strand breaks induced by CRISPR-associated protein 9 (Cas9) in Caenorhabditis elegans. We find that HDR is very robust in the C. elegans germline. Linear repair templates with short (∼30–60 bases) homology arms support the integration of base and gene-sized edits with high efficiency, bypassing the need for selection. Based on these findings, we developed a systematic method to mutate, tag, or delete any gene in the C. elegans genome without the use of co-integrated markers or long homology arms. We generated 23 unique edits at 11 genes, including premature stops, whole-gene deletions, and protein fusions to antigenic peptides and GFP. Whole-genome sequencing of five edited strains revealed the presence of passenger variants, but no mutations at predicted off-target sites. The method is scalable for multi-gene editing projects and could be applied to other animals with an accessible germline. PMID:25249454

NASA thesaurus alphabetical update: Subject terms for indexing scientific and technical information

NASA Technical Reports Server (NTRS)

1971-01-01

The NASA THESAURUS - ALPHABETICAL UPDATE is an alphabetical listing of all subject terms (postable and nonpostable) that are currently approved for use in the NASA scientific and technical information system. Contained in the listing are the subject terms that were listed in the Preliminary Edition of the NASA THESAURUS and the additional subject terms that were approved during the period January 1, 1967 June 30, 1971. Complete Thesaurus structuring, including scope notes, category assignments, and cross-references, is provided for each term as appropriate.

Sodium Azide Associated Acute Hyperkalemia in a Swine Model of Sodium Azide Toxicity

DTIC Science & Technology

2017-06-16

FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 1. Your paper, entitled Sodium Azide Associated Acute Hvperkalemia in a Swine Model of... Sodium Azide Toxicity presented at/published to SURF, San Antonio, TX, 16 June 2017 in accordance with MDWI 41-108, has been approved and assigned local...34"FROYED On HIS I APPROVED Only] 40. aATE FOR’ n DISN"PRO’.EO TBEREACHED ~a. FRIHTED NA 50. DATE PRE\\ll0 EDIT10NSARE CBSO_ETE Sodium azide associated

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Cas9-based tools for targeted genome editing and transcriptional control.

PubMed

Xu, Tao; Li, Yongchao; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong

2014-03-01

Development of tools for targeted genome editing and regulation of gene expression has significantly expanded our ability to elucidate the mechanisms of interesting biological phenomena and to engineer desirable biological systems. Recent rapid progress in the study of a clustered, regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein system in bacteria has facilitated the development of newly facile and programmable platforms for genome editing and transcriptional control in a sequence-specific manner. The core RNA-guided Cas9 endonuclease in the type II CRISPR system has been harnessed to realize gene mutation and DNA deletion and insertion, as well as transcriptional activation and repression, with multiplex targeting ability, just by customizing 20-nucleotide RNA components. Here we describe the molecular basis of the type II CRISPR/Cas system and summarize applications and factors affecting its utilization in model organisms. We also discuss the advantages and disadvantages of Cas9-based tools in comparison with widely used customizable tools, such as Zinc finger nucleases and transcription activator-like effector nucleases.

LifeBridge new publication: Md.MD. Listing of 1,200 physicians a major part of consumer-type magazine.

PubMed

Botvin, Judith D

2004-01-01

LifeBridge Health, Baltimore, created a directory of its physicians, which developed into a 100-page consumer magazine titled Md.MD A Directory of the Region's Finest Physicians. Written and designed in-house, the premier edition paid for itself, thanks to publishing partner, Alter Communications. The premier edition was mailed to 50,000 Baltimore area homes last September.

Generation of Myostatin Gene-Edited Channel Catfish (Ictalurus punctatus) via Zygote Injection of CRISPR/Cas9 System.

PubMed

Khalil, Karim; Elayat, Medhat; Khalifa, Elsayed; Daghash, Samer; Elaswad, Ahmed; Miller, Michael; Abdelrahman, Hisham; Ye, Zhi; Odin, Ramjie; Drescher, David; Vo, Khoi; Gosh, Kamal; Bugg, William; Robinson, Dalton; Dunham, Rex

2017-08-04

The myostatin (MSTN) gene is important because of its role in regulation of skeletal muscle growth in all vertebrates. In this study, CRISPR/Cas9 was utilized to successfully target the channel catfish, Ictalurus punctatus, muscle suppressor gene MSTN. CRISPR/Cas9 induced high rates (88-100%) of mutagenesis in the target protein-encoding sites of MSTN. MSTN-edited fry had more muscle cells (p < 0.001) than controls, and the mean body weight of gene-edited fry increased by 29.7%. The nucleic acid alignment of the mutated sequences against the wild-type sequence revealed multiple insertions and deletions. These results demonstrate that CRISPR/Cas9 is a highly efficient tool for editing the channel catfish genome, and opens ways for facilitating channel catfish genetic enhancement and functional genomics. This approach may produce growth-enhanced channel catfish and increase productivity.

The principles of radio engineering and antennas. II Antennas (2nd revised and enlarged edition)

NASA Astrophysics Data System (ADS)

Belotserkovskii, G. B.

This book represents the second part of a textbook for technical schools. The characteristics and parameters of antennas are considered along with transmission lines, the theory of single dipoles and radiator systems, and the technological realization of elements and units of the antenna-feeder system, taking into account filters and multiport networks for microwave communications applications, and ferrite circulators and isolators. The first edition of this textbook was published in 1969. For the current edition, the material in the first edition has been revised, and new material has been introduced. Much attention is given to microwave antennas, including, in particular, arrays with electrical scanning characteristics. Other topics discussed are related to the general principles of antennas, the matching of the impedance of transmission lines, the elements of transmission lines, aperture-type antennas for microwaves, and the functional characteristics of antennas for ultrashort waves.

Quality Assurance of UMLS Semantic Type Assignments Using SNOMED CT Hierarchies.

PubMed

Gu, H; Chen, Y; He, Z; Halper, M; Chen, L

2016-01-01

The Unified Medical Language System (UMLS) is one of the largest biomedical terminological systems, with over 2.5 million concepts in its Metathesaurus repository. The UMLS's Semantic Network (SN) with its collection of 133 high-level semantic types serves as an abstraction layer on top of the Metathesaurus. In particular, the SN elaborates an aspect of the Metathesaurus's concepts via the assignment of one or more types to each concept. Due to the scope and complexity of the Metathesaurus, errors are all but inevitable in this semantic-type assignment process. To develop a semi-automated methodology to help assure the quality of semantic-type assignments within the UMLS. The methodology uses a cross-validation strategy involving SNOMED CT's hierarchies in combination with UMLS semantic types. Semantically uniform, disjoint concept groups are generated programmatically by partitioning the collection of all concepts in the same SNOMED CT hierarchy according to their respective semantic-type assignments in the UMLS. Domain experts are then called upon to review the concepts in any group having a small number of concepts. It is our hypothesis that a semantic-type assignment combination applicable only to a very small number of concepts in a SNOMED CT hierarchy is an indicator of potential problems. The methodology was applied to the UMLS 2013AA release along with the SNOMED CT from January 2013. An overall error rate of 33% was found for concepts proposed by the quality-assurance methodology. Supporting our hypothesis, that number was four times higher than the error rate found in control samples. The results show that the quality-assurance methodology can aid in effective and efficient identification of UMLS semantic-type assignment errors.

Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide.

PubMed

Wang, Hong-Xia; Song, Ziyuan; Lao, Yeh-Hsing; Xu, Xin; Gong, Jing; Cheng, Du; Chakraborty, Syandan; Park, Ji Sun; Li, Mingqiang; Huang, Dantong; Yin, Lichen; Cheng, Jianjun; Leong, Kam W

2018-05-08

Effective and safe delivery of the CRISPR/Cas9 gene-editing elements remains a challenge. Here we report the development of PEGylated nanoparticles (named P-HNPs) based on the cationic α-helical polypeptide poly(γ-4-((2-(piperidin-1-yl)ethyl)aminomethyl)benzyl-l-glutamate) for the delivery of Cas9 expression plasmid and sgRNA to various cell types and gene-editing scenarios. The cell-penetrating α-helical polypeptide enhanced cellular uptake and promoted escape of pCas9 and/or sgRNA from the endosome and transport into the nucleus. The colloidally stable P-HNPs achieved a Cas9 transfection efficiency up to 60% and sgRNA uptake efficiency of 67.4%, representing an improvement over existing polycation-based gene delivery systems. After performing single or multiplex gene editing with an efficiency up to 47.3% in vitro, we demonstrated that P-HNPs delivering Cas9 plasmid/sgRNA targeting the polo-like kinase 1 (Plk1) gene achieved 35% gene deletion in HeLa tumor tissue to reduce the Plk1 protein level by 66.7%, thereby suppressing the tumor growth by >71% and prolonging the animal survival rate to 60% within 60 days. Capable of delivering Cas9 plasmids to various cell types to achieve multiplex gene knock-out, gene knock-in, and gene activation in vitro and in vivo, the P-HNP system offers a versatile gene-editing platform for biological research and therapeutic applications. Copyright © 2018 the Author(s). Published by PNAS.

High-Efficiency Genome Editing of Streptomyces Species by an Engineered CRISPR/Cas System.

PubMed

Wang, Y; Cobb, R E; Zhao, H

2016-01-01

Next-generation sequencing technologies have rapidly expanded the genomic information of numerous organisms and revealed a rich reservoir of natural product gene clusters from microbial genomes, especially from Streptomyces, the largest genus of known actinobacteria at present. However, genetic engineering of these bacteria is often time consuming and labor intensive, if even possible. In this chapter, we describe the design and construction of pCRISPomyces, an engineered Type II CRISPR/Cas system, for targeted multiplex gene deletions in Streptomyces lividans, Streptomyces albus, and Streptomyces viridochromogenes with editing efficiency ranging from 70% to 100%. We demonstrate pCRISPomyces as a powerful tool for genome editing in Streptomyces. © 2016 Elsevier Inc. All rights reserved.

Discovering Astronomy: An Astro 101 e-book

NASA Astrophysics Data System (ADS)

Shawl, Stephen J.; Byrd, Gene; Deustua, Susana E.; LoPresto, Michael C.

2016-01-01

Discovering Astronomy, now available in its 6th edition as an eText, has many advantages and features for your students. We have partnered with etextink.com and WebAssign.net to produce an affordable set of cost-saving options for your students. Also available is the Discovering Astronomy Activity Manual, which provides students with an active-learning experience.Our etext is device independent and thus accessible through any web browser. Americans with Disabilities Act compatibility provides access for all students. Hotlinks to outside sites provide further information for interested students. Lecture demonstration videos of important concepts, made specifically for this new edition, are embedded within the text as appropriate. Students can highlight text, take notes, and bookmark locations within the text. Important terms are linked to the glossary. Search capabilities allow students to easily find what they want.Instructors can interact with their students directly through the etext once the class roster has been provided. For example, instructors can embed assignments into their students' etext and add their own notes and updates, which are immediately visible to their students.Updates can be quickly made by us as new findings become available. For example, updates from New Horizons were added at the time of the closest approach to Pluto, and an update on the recent announcement of current water on Mars was added the day of the announcement.We will present results of our own experience with college and high school students' use of Discovering Astronomy in online courses.Details of the book, a sample chapter, and other information are available at discoveringastronomy.weebly.com.

Chemoselective detection and discrimination of carbonyl-containing compounds in metabolite mixtures by 1H-detected 15N NMR

PubMed Central

Lane, Andrew N.; Arumugam, Sengodagounder; Lorkiewicz, Pawel K.; Higashi, Richard M.; Laulhé, Sébastien; Nantz, Michael H.; Moseley, Hunter N.B.; Fan, Teresa W.-M.

2015-01-01

NMR spectra of mixtures of metabolites extracted from cells or tissues are extremely complex, reflecting the large number of compounds that are present over a wide range of concentrations. Although multidimensional NMR can greatly improve resolution as well as improve reliability of compound assignments, lower abundance metabolites often remain hidden. We have developed a carbonyl selective aminooxy probe that specifically reacts with free keto and aldehyde functions, but not carboxylates. By incorporating 15N in the aminooxy functional group, 15N-edited NMR was used to select exclusively those metabolites that contain a free carbonyl function while all other metabolites are rejected. Here we demonstrate that the chemical shifts of the aminooxy adducts of ketones and aldehydes are very different, which can be used to discriminate between aldoses and ketoses for example. Utilizing the 2 or 3 bond 15N-1H couplings, the 15N-edited NMR analysis was optimized first with authentic standards and then applied to an extract of the lung adenocarcinoma cell line A549. More than 30 carbonyl containing compounds at NMR detectable levels, 6 of which we have assigned by reference to our database. As the aminooxy probe contains a permanently charged quaternary ammonium group, the adducts are also optimized for detection by mass spectrometry. Thus, this sample preparation technique provides a better link between the two structural determination tools, thereby paving the way to faster and more reliable identification of both known and unknown metabolites directly in crude biological extracts. PMID:25616249

Current status of genome editing in vector mosquitoes: A review.

PubMed

Reegan, Appadurai Daniel; Ceasar, Stanislaus Antony; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Al-Dhabi, Naif Abdullah

2017-01-16

Mosquitoes pose a major threat to human health as they spread many deadly diseases like malaria, dengue, chikungunya, filariasis, Japanese encephalitis and Zika. Identification and use of novel molecular tools are essential to combat the spread of vector borne diseases. Genome editing tools have been used for the precise alterations of the gene of interest for producing the desirable trait in mosquitoes. Deletion of functional genes or insertion of toxic genes in vector mosquitoes will produce either knock-out or knock-in mutants that will check the spread of vector-borne diseases. Presently, three types of genome editing tools viz., zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) are widely used for the editing of the genomes of diverse organisms. These tools are also applied in vector mosquitoes to control the spread of vector-borne diseases. A few studies have been carried out on genome editing to control the diseases spread by vector mosquitoes and more studies need to be performed with the utilization of more recently invented tools like CRISPR/Cas9 to combat the spread of deadly diseases by vector mosquitoes. The high specificity and flexibility of CRISPR/Cas9 system may offer possibilities for novel genome editing for the control of important diseases spread by vector mosquitoes. In this review, we present the current status of genome editing research on vector mosquitoes and also discuss the future applications of vector mosquito genome editing to control the spread of vectorborne diseases.

Nanoparticles for Site Specific Genome Editing

NASA Astrophysics Data System (ADS)

McNeer, Nicole Ali

Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to translate gene therapies for diseases of the blood and immune system to clinical practice. In addition, we have expanded the use of this technology to an additional nonhematopoietic model system: correction of the human cystic fibrosis transmembrane receptor gene in human bronchial epithelial cells. The work presented here represents (1) the first use of biodegradable nanoparticles for PNA delivery, (2) the first direct in vivo site-specific genome modification in human cells, and (3) the first use of triplex-PNA technology for site-specific genome editing in cystic fibrosis.

Book review: Extreme ocean waves

USGS Publications Warehouse

Geist, Eric L.

2017-01-01

“Extreme Ocean Waves”, edited by E. Pelinovsky and C. Kharif, second edition, Springer International Publishing, 2016; ISBN: 978-3-319-21574-7, ISBN (eBook): 978-3-319-21575-4The second edition of “Extreme Ocean Waves” published by Springer is an update of a collection of 12 papers edited by Efim Pelinovsky and Christian Kharif following the April 2007 meeting of the General Assembly of the European Geosciences Union. In this edition, three new papers have been added and three more have been substantially revised. Color figures are now included, which greatly aids in reading several of the papers, and is especially helpful in visualizing graphs as in the paper on symbolic computation of nonlinear wave resonance (Tobisch et al.). A note on terminology: extreme waves in this volume broadly encompass different types of waves, including deep-water and shallow-water rogue waves (which are alternatively termed freak waves), and internal waves. One new paper on tsunamis (Viroulet et al.) is now included in the second edition of this volume. Throughout the book, the reader will find a combination of laboratory, theoretical, and statistical/empirical treatment necessary for the complete examination of this subject. In the Introduction, the editors underscore the importance of studying extreme waves, documenting a dramatic instance of damaging extreme waves that recently occurred in 2014.

High content analysis platform for optimization of lipid mediated CRISPR-Cas9 delivery strategies in human cells.

PubMed

Steyer, Benjamin; Carlson-Stevermer, Jared; Angenent-Mari, Nicolas; Khalil, Andrew; Harkness, Ty; Saha, Krishanu

2016-04-01

Non-viral gene-editing of human cells using the CRISPR-Cas9 system requires optimized delivery of multiple components. Both the Cas9 endonuclease and a single guide RNA, that defines the genomic target, need to be present and co-localized within the nucleus for efficient gene-editing to occur. This work describes a new high-throughput screening platform for the optimization of CRISPR-Cas9 delivery strategies. By exploiting high content image analysis and microcontact printed plates, multi-parametric gene-editing outcome data from hundreds to thousands of isolated cell populations can be screened simultaneously. Employing this platform, we systematically screened four commercially available cationic lipid transfection materials with a range of RNAs encoding the CRISPR-Cas9 system. Analysis of Cas9 expression and editing of a fluorescent mCherry reporter transgene within human embryonic kidney cells was monitored over several days after transfection. Design of experiments analysis enabled rigorous evaluation of delivery materials and RNA concentration conditions. The results of this analysis indicated that the concentration and identity of transfection material have significantly greater effect on gene-editing than ratio or total amount of RNA. Cell subpopulation analysis on microcontact printed plates, further revealed that low cell number and high Cas9 expression, 24h after CRISPR-Cas9 delivery, were strong predictors of gene-editing outcomes. These results suggest design principles for the development of materials and transfection strategies with lipid-based materials. This platform could be applied to rapidly optimize materials for gene-editing in a variety of cell/tissue types in order to advance genomic medicine, regenerative biology and drug discovery. CRISPR-Cas9 is a new gene-editing technology for "genome surgery" that is anticipated to treat genetic diseases. This technology uses multiple components of the Cas9 system to cut out disease-causing mutations in the human genome and precisely suture in therapeutic sequences. Biomaterials based delivery strategies could help transition these technologies to the clinic. The design space for materials based delivery strategies is vast and optimization is essential to ensuring the safety and efficacy of these treatments. Therefore, new methods are required to rapidly and systematically screen gene-editing efficacy in human cells. This work utilizes an innovative platform to generate and screen many formulations of synthetic biomaterials and components of the CRISPR-Cas9 system in parallel. On this platform, we watch genome surgery in action using high content image analysis. These capabilities enabled us to identify formulation parameters for Cas9-material complexes that can optimize gene-editing in a specific human cell type. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Analysis of the Length of Braille Texts in English Braille American Edition, the Nemeth Code, and Computer Braille Code versus the Unified English Braille Code

ERIC Educational Resources Information Center

Knowlton, Marie; Wetzel, Robin

2006-01-01

This study compared the length of text in English Braille American Edition, the Nemeth code, and the computer braille code with the Unified English Braille Code (UEBC)--also known as Unified English Braille (UEB). The findings indicate that differences in the length of text are dependent on the type of material that is transcribed and the grade…

Genome-wide identification and analysis of A-to-I RNA editing events in bovine by transcriptome sequencing

PubMed Central

Salehi, Abdolreza; Rivera, Rocío Melissa

2018-01-01

RNA editing increases the diversity of the transcriptome and proteome. Adenosine-to-inosine (A-to-I) editing is the predominant type of RNA editing in mammals and it is catalyzed by the adenosine deaminases acting on RNA (ADARs) family. Here, we used a largescale computational analysis of transcriptomic data from brain, heart, colon, lung, spleen, kidney, testes, skeletal muscle and liver, from three adult animals in order to identify RNA editing sites in bovine. We developed a computational pipeline and used a rigorous strategy to identify novel editing sites from RNA-Seq data in the absence of corresponding DNA sequence information. Our methods take into account sequencing errors, mapping bias, as well as biological replication to reduce the probability of obtaining a false-positive result. We conducted a detailed characterization of sequence and structural features related to novel candidate sites and found 1,600 novel canonical A-to-I editing sites in the nine bovine tissues analyzed. Results show that these sites 1) occur frequently in clusters and short interspersed nuclear elements (SINE) repeats, 2) have a preference for guanines depletion/enrichment in the flanking 5′/3′ nucleotide, 3) occur less often in coding sequences than other regions of the genome, and 4) have low evolutionary conservation. Further, we found that a positive correlation exists between expression of ADAR family members and tissue-specific RNA editing. Most of the genes with predicted A-to-I editing in each tissue were significantly enriched in biological terms relevant to the function of the corresponding tissue. Lastly, the results highlight the importance of the RNA editome in nervous system regulation. The present study extends the list of RNA editing sites in bovine and provides pipelines that may be used to investigate the editome in other organisms. PMID:29470549

Anticipatory Speech Anxiety as a Function of Public Speaking Assignment Type

ERIC Educational Resources Information Center

Witt, Paul L.; Behnke, Ralph R.

2006-01-01

This investigation included two studies relating anticipatory public speaking anxiety to the nature of the speech assignment. Based on uncertainty reduction theory, which suggests that communicators are less comfortable in unfamiliar or unpredictable contexts, two hypotheses were advanced on the presumption that various types of assignments in a…

The Use of Mock NSF-type Grant Proposals and Blind Peer Review as the Capstone Assignment in Upper-Level Neurobiology and Cell Biology Courses

PubMed Central

Itagaki, Haruhiko

2013-01-01

Although the use of grant proposals and blind peer review are standard in the natural sciences, their use as a pedagogical tool is rarely mentioned in the literature. As a consequence of dissatisfaction with term papers and literature reviews as the capstone writing experience in 300-level undergraduate biology courses, I have been experimenting with mock NSF-type grant proposals followed by blind peer review as the major assignment in my junior/senior-level classes. The improvement in educational outcomes and competencies due to this assignment appears to be substantial and worth the additional effort on both the students’ and instructor’s parts. Here, I outline the mechanics of this assignment and its advantages and disadvantages as well as the type of curriculum that is required to support this type of capstone assignment. PMID:24319395

Vibrational Mode Assignment of α-Pinene by Isotope Editing: One Down, Seventy-One To Go

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

Upshur, Mary Alice; Chase, Hilary M.; Strick, Benjamin F.

This study aims to reliably assign the vibrational sum frequency generation (SFG) spectrum of α-pinene at the vapor/solid interface using a method involving deuteration of various methyl groups. The synthesis of five different deuterated isotopologues of α-pinene is presented in order to determine the impact that removing contributions from methyl group C$-$H oscillators has on its SFG response. 0.6 cm -1 Resolution SFG spectra of these isotopologues show varying degrees of differences in the C–H stretching region when compared to the SFG response of unlabeled α-pinene. The largest spectral changes were observed for the isotopologue containing a fully deuterated vinylmore » methyl group. Noticeable losses in signal intensities allow us to reliably assign the 2860 cm -1 peak to the vinyl methyl symmetric stretch. Furthermore, upon removing the vinyl methyl group entirely by synthesizing apopinene, the steric influence of the unlabeled C 9H 14 fragment on the SFG response of α-pinene SFG can be readily observed. The work presented here brings us one step closer to understanding the vibrational spectroscopy of α-pinene.« less

Dental responsibility loadings and the relative value of dental services.

PubMed

Teusner, D N; Ju, X; Brennan, D S

2017-09-01

To estimate responsibility loadings for a comprehensive list of dental services, providing a standardized unit of clinical work effort. Dentists (n = 2500) randomly sampled from the Australian Dental Association membership (2011) were randomly assigned to one of 25 panels. Panels were surveyed by questionnaires eliciting responsibility loadings for eight common dental services (core items) and approximately 12 other items unique to that questionnaire. In total, loadings were elicited for 299 items listed in the Australian Dental Schedule 9th Edition. Data were weighted to reflect the age and sex distribution of the workforce. To assess reliability, regression models assessed differences in core item loadings by panel assignment. Estimated loadings were described by reporting the median and mean. Response rate was 37%. Panel composition did not vary by practitioner characteristics. Core item loadings did not vary by panel assignment. Oral surgery and endodontic service areas had the highest proportion (91%) of services with median loadings ≥1.5, followed by prosthodontics (78%), periodontics (76%), orthodontics (63%), restorative (62%) and diagnostic services (31%). Preventive services had median loadings ≤1.25. Dental responsibility loadings estimated by this study can be applied in the development of relative value scales. © 2017 Australian Dental Association.

Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types

PubMed Central

McIntyre, Chloe L.; Knowles, Nick J.

2013-01-01

Human rhinoviruses (HRVs) frequently cause mild upper respiratory tract infections and more severe disease manifestations such as bronchiolitis and asthma exacerbations. HRV is classified into three species within the genus Enterovirus of the family Picornaviridae. HRV species A and B contain 75 and 25 serotypes identified by cross-neutralization assays, although the use of such assays for routine HRV typing is hampered by the large number of serotypes, replacement of virus isolation by molecular methods in HRV diagnosis and the poor or absent replication of HRV species C in cell culture. To address these problems, we propose an alternative, genotypic classification of HRV-based genetic relatedness analogous to that used for enteroviruses. Nucleotide distances between 384 complete VP1 sequences of currently assigned HRV (sero)types identified divergence thresholds of 13, 12 and 13 % for species A, B and C, respectively, that divided inter- and intra-type comparisons. These were paralleled by 10, 9.5 and 10 % thresholds in the larger dataset of >3800 VP4 region sequences. Assignments based on VP1 sequences led to minor revisions of existing type designations (such as the reclassification of serotype pairs, e.g. A8/A95 and A29/A44, as single serotypes) and the designation of new HRV types A101–106, B101–103 and C34–C51. A protocol for assignment and numbering of new HRV types using VP1 sequences and the restriction of VP4 sequence comparisons to type identification and provisional type assignments is proposed. Genotypic assignment and identification of HRV types will be of considerable value in the future investigation of type-associated differences in disease outcomes, transmission and epidemiology. PMID:23677786

Towards Automated Structure-Based NMR Resonance Assignment

NASA Astrophysics Data System (ADS)

Jang, Richard; Gao, Xin; Li, Ming

We propose a general framework for solving the structure-based NMR backbone resonance assignment problem. The core is a novel 0-1 integer programming model that can start from a complete or partial assignment, generate multiple assignments, and model not only the assignment of spins to residues, but also pairwise dependencies consisting of pairs of spins to pairs of residues. It is still a challenge for automated resonance assignment systems to perform the assignment directly from spectra without any manual intervention. To test the feasibility of this for structure-based assignment, we integrated our system with our automated peak picking and sequence-based resonance assignment system to obtain an assignment for the protein TM1112 with 91% recall and 99% precision without manual intervention. Since using a known structure has the potential to allow one to use only N-labeled NMR data and avoid the added expense of using C-labeled data, we work towards the goal of automated structure-based assignment using only such labeled data. Our system reduced the assignment error of Xiong-Pandurangan-Bailey-Kellogg's contact replacement (CR) method, which to our knowledge is the most error-tolerant method for this problem, by 5 folds on average. By using an iterative algorithm, our system has the added capability of using the NOESY data to correct assignment errors due to errors in predicting the amino acid and secondary structure type of each spin system. On a publicly available data set for Ubiquitin, where the type prediction accuracy is 83%, we achieved 91% assignment accuracy, compared to the 59% accuracy that was obtained without correcting for typing errors.

Graduate Writing Assignments across Faculties in a Canadian University

ERIC Educational Resources Information Center

Shi, Ling; Dong, Yanning

2015-01-01

This study examines 143 graduate assignments across 12 faculties or schools in a Canadian university in order to identify types of writing tasks. Based on the descriptions provided by the instructors, we identified nine types of assignments, with scholarly essay being the most common, followed by summary and response, literature review, project,…

Understanding Test-Type Assignment: Why Do Special Educators Make Unexpected Test-Type Assignments?

ERIC Educational Resources Information Center

Cho, Hyun-Jeong; Kingston, Neal

2014-01-01

We interviewed special educators (a) whose students with disabilities (SWDs) were proficient on the 2008 general education assessment but were assigned to the 2009 alternate assessment based on modified achievement standards (AA-MAS), and (b) whose students with mild disabilities took the 2008 alternate assessment based on alternate achievement…

Earth's Volcanoes and their Eruptions; the 3rd edition of the Smithsonian Institution's Volcanoes of the World

NASA Astrophysics Data System (ADS)

Siebert, L.; Simkin, T.; Kimberly, P.

2010-12-01

The 3rd edition of the Smithsonian Institution’s Volcanoes of the World incorporates data on the world’s volcanoes and their eruptions compiled since 1968 by the Institution’s Global Volcanism Program (GVP). Published this Fall jointly by the Smithsonian and the University of California Press, it supplements data from the 1994 2nd edition and includes new data on the number of people living in proximity to volcanoes, the dominant rock lithologies at each volcano, Holocene caldera-forming eruptions, and preliminary lists of Pleistocene volcanoes and large-volume Pleistocene eruptions. The 3rd edition contains data on nearly 1550 volcanoes of known or possible Holocene age, including chronologies, characteristics, and magnitudes for >10,400 Holocene eruptions. The standard 20 eruptive characteristics of the IAVCEI volcano catalog series have been modified to include dated vertical edifice collapse events due to magma chamber evacuation following large-volume explosive eruptions or mafic lava effusion, and lateral sector collapse. Data from previous editions of Volcanoes of the World are also supplemented by listings of up to the 5 most dominant lithologies at each volcano, along with data on population living within 5, 10, 30, and 100 km radii of each volcano or volcanic field. Population data indicate that the most populated regions also contain the most frequently active volcanoes. Eruption data document lava and tephra volumes and Volcanic Explosivity Index (VEI) assignments for >7800 eruptions. Interpretation of VRF data has led to documentation of global eruption rates and the power law relationship between magnitude and frequency of volcanic eruptions. Data with volcanic hazards implications include those on fatalities and evacuations and the rate at which eruptions reach their climax. In recognition of the hazards implications of potential resumption of activity at pre-Holocene volcanoes, the 3rd edition includes very preliminary lists of Pleistocene volcanoes and large-volume Pleistocene eruptions, the latter in collaboration with the VOGRIPA project of Steve Sparks and colleagues. The GVP volcano and eruption data derive both from the retrospective perspective of the volcanological and other literature and documentation of contemporary eruptions and volcanic unrest in the Smithsonian’s monthly bulletin and Weekly Volcanic Activity Reports compiled since 2000 in collaboration with the USGS.

Attention-Deficit/Hyperactivity Disorder. NICHCY Briefing Paper. Revised Edition.

ERIC Educational Resources Information Center

Fowler, Mary

This briefing paper is intended to improve understanding of attention/deficit hyperactivity disorder (Ad/HD)--what it is, what to look for, and what to do. Three subtypes are identified: (1) the predominantly combined type; (2) the predominantly inattentive type; and (3) the predominantly hyperactive/impulsive type. Causes and incidence of ADHD…

Federal Assistance for Programs Serving the Handicapped. Third Edition.

ERIC Educational Resources Information Center

Office of Human Development (DHEW), Washington, DC. Office for Handicapped Individuals.

The guide presents information on more than 200 federally assisted programs serving the handicapped. Information on uses and restrictions, types of assistance, eligibility requirements; application procedures, appropriations, program accomplishments, enabling legislation, and contact persons are listed for programs receiving four types of…

High-efficiency targeted editing of large viral genomes by RNA-guided nucleases.

PubMed

Bi, Yanwei; Sun, Le; Gao, Dandan; Ding, Chen; Li, Zhihua; Li, Yadong; Cun, Wei; Li, Qihan

2014-05-01

A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors. The type II prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)) RNA-guided nuclease system can be introduced into host cells during viral replication. The CRISPR-Cas9 system robustly stimulates targeted double-stranded breaks in the genomes of DNA viruses, where the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways can be exploited to introduce site-specific indels or insert heterologous genes with high frequency. Furthermore, CRISPR-Cas9 can specifically inhibit the replication of the original virus, thereby significantly increasing the abundance of the recombinant virus among progeny virus. As a result, purified recombinant virus can be obtained with only a single round of selection. In this study, we used recombinant adenovirus and type I herpes simplex virus as examples to demonstrate that the CRISPR-Cas9 system is a valuable tool for editing the genomes of large DNA viruses.

High-Efficiency Targeted Editing of Large Viral Genomes by RNA-Guided Nucleases

PubMed Central

Gao, Dandan; Ding, Chen; Li, Zhihua; Li, Yadong; Cun, Wei; Li, Qihan

2014-01-01

A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors. The type II prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)) RNA-guided nuclease system can be introduced into host cells during viral replication. The CRISPR-Cas9 system robustly stimulates targeted double-stranded breaks in the genomes of DNA viruses, where the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways can be exploited to introduce site-specific indels or insert heterologous genes with high frequency. Furthermore, CRISPR-Cas9 can specifically inhibit the replication of the original virus, thereby significantly increasing the abundance of the recombinant virus among progeny virus. As a result, purified recombinant virus can be obtained with only a single round of selection. In this study, we used recombinant adenovirus and type I herpes simplex virus as examples to demonstrate that the CRISPR-Cas9 system is a valuable tool for editing the genomes of large DNA viruses. PMID:24788700

CRISPR-engineered genome editing for the next generation neurological disease modeling.

PubMed

Feng, Weijun; Liu, Hai-Kun; Kawauchi, Daisuke

2018-02-02

Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate impact of mutated genes on these neurological diseases, a feasible but flexible genome editing tool had remained to be developed. An advance of genome editing technology using the clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR-associated protein (Cas) offers us a tremendous potential to create a variety of mutations in the cell, leading to "next generation" disease models carrying disease-associated mutations. We will here review recent progress of CRISPR-based brain disease modeling studies and discuss future requirement to tackle current difficulties in usage of these technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Breast Density Between Synthesized Versus Standard Digital Mammography.

PubMed

Haider, Irfanullah; Morgan, Matthew; McGow, Anna; Stein, Matthew; Rezvani, Maryam; Freer, Phoebe; Hu, Nan; Fajardo, Laurie; Winkler, Nicole

2018-06-12

To evaluate perceptual difference in breast density classification using synthesized mammography (SM) compared with standard or full-field digital mammography (FFDM) for screening. This institutional review board-approved, retrospective, multireader study evaluated breast density on 200 patients who underwent baseline screening mammogram during which both SM and FFDM were obtained contemporaneously from June 1, 2016, through November 30, 2016. Qualitative breast density was independently assigned by seven readers initially evaluating FFDM alone. Then, in a separate session, these same readers assigned breast density using synthetic views alone on the same 200 patients. The readers were again blinded to each other's assignment. Qualitative density assessment was based on BI-RADS fifth edition. Interreader agreement was evaluated with κ statistic using 95% confidence intervals. Testing for homogeneity in paired proportions was performed using McNemar's test with a level of significance of .05. For patients across the SM and standard 2-D data set, diagnostic testing with McNemar's test with P = 0.32 demonstrates that the minimal density transitions across FFDM and SM are not statistically significant density shifts. Taking clinical significance into account, only 8 of 200 (4%) patients had clinically significant transition (dense versus not dense). There was substantial interreader agreement with overall κ in FFDM of 0.71 (minimum 0.53, maximum 0.81) and overall SM κ average of 0.63 (minimum 0.56, maximum 0.87). Overall subjective breast density assignment by radiologists on SM is similar to density assignment on standard 2-D mammogram. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Interactive graphic editing tools in bioluminescent imaging simulation

NASA Astrophysics Data System (ADS)

Li, Hui; Tian, Jie; Luo, Jie; Wang, Ge; Cong, Wenxiang

2005-04-01

It is a challenging task to accurately describe complicated biological tissues and bioluminescent sources in bioluminescent imaging simulation. Several graphic editing tools have been developed to efficiently model each part of the bioluminescent simulation environment and to interactively correct or improve the initial models of anatomical structures or bioluminescent sources. There are two major types of graphic editing tools: non-interactive tools and interactive tools. Geometric building blocks (i.e. regular geometric graphics and superquadrics) are applied as non-interactive tools. To a certain extent, complicated anatomical structures and bioluminescent sources can be approximately modeled by combining a sufficient large number of geometric building blocks with Boolean operators. However, those models are too simple to describe the local features and fine changes in 2D/3D irregular contours. Therefore, interactive graphic editing tools have been developed to facilitate the local modifications of any initial surface model. With initial models composed of geometric building blocks, interactive spline mode is applied to conveniently perform dragging and compressing operations on 2D/3D local surface of biological tissues and bioluminescent sources inside the region/volume of interest. Several applications of the interactive graphic editing tools will be presented in this article.

NASTRAN data generation of helicopter fuselages using interactive graphics. [preprocessor system for finite element analysis using IBM computer

NASA Technical Reports Server (NTRS)

Sainsbury-Carter, J. B.; Conaway, J. H.

1973-01-01

The development and implementation of a preprocessor system for the finite element analysis of helicopter fuselages is described. The system utilizes interactive graphics for the generation, display, and editing of NASTRAN data for fuselage models. It is operated from an IBM 2250 cathode ray tube (CRT) console driven by an IBM 370/145 computer. Real time interaction plus automatic data generation reduces the nominal 6 to 10 week time for manual generation and checking of data to a few days. The interactive graphics system consists of a series of satellite programs operated from a central NASTRAN Systems Monitor. Fuselage structural models including the outer shell and internal structure may be rapidly generated. All numbering systems are automatically assigned. Hard copy plots of the model labeled with GRID or elements ID's are also available. General purpose programs for displaying and editing NASTRAN data are included in the system. Utilization of the NASTRAN interactive graphics system has made possible the multiple finite element analysis of complex helicopter fuselage structures within design schedules.

CRISPR/Cas9 Platforms for Genome Editing in Plants: Developments and Applications.

PubMed

Ma, Xingliang; Zhu, Qinlong; Chen, Yuanling; Liu, Yao-Guang

2016-07-06

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein9 (Cas9) genome editing system (CRISPR/Cas9) is adapted from the prokaryotic type II adaptive immunity system. The CRISPR/Cas9 tool surpasses other programmable nucleases, such as ZFNs and TALENs, for its simplicity and high efficiency. Various plant-specific CRISPR/Cas9 vector systems have been established for adaption of this technology to many plant species. In this review, we present an overview of current advances on applications of this technology in plants, emphasizing general considerations for establishment of CRISPR/Cas9 vector platforms, strategies for multiplex editing, methods for analyzing the induced mutations, factors affecting editing efficiency and specificity, and features of the induced mutations and applications of the CRISPR/Cas9 system in plants. In addition, we provide a perspective on the challenges of CRISPR/Cas9 technology and its significance for basic plant research and crop genetic improvement. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Therapeutic applications of CRISPR RNA-guided genome editing.

PubMed

Koo, Taeyoung; Kim, Jin-Soo

2017-01-01

The rapid development of programmable nuclease-based genome editing technologies has enabled targeted gene disruption and correction both in vitro and in vivo This revolution opens up the possibility of precise genome editing at target genomic sites to modulate gene function in animals and plants. Among several programmable nucleases, the type II clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated nuclease 9 (Cas9) system has progressed remarkably in recent years, leading to its widespread use in research, medicine and biotechnology. In particular, CRISPR-Cas9 shows highly efficient gene editing activity for therapeutic purposes in systems ranging from patient stem cells to animal models. However, the development of therapeutic approaches and delivery methods remains a great challenge for biomedical applications. Herein, we review therapeutic applications that use the CRISPR-Cas9 system and discuss the possibilities and challenges ahead. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

PubMed Central

Seah, Yu Fen Samantha; EL Farran, Chadi A.; Warrier, Tushar; Xu, Jian; Loh, Yuin-Han

2015-01-01

Embryonic stem cells (ESCs) are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs) via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases. PMID:26633382

Efficient Delivery and Nuclear Uptake Is Not Sufficient to Detect Gene Editing in CD34+ Cells Directed by a Ribonucleoprotein Complex.

PubMed

Modarai, Shirin R; Man, Dula; Bialk, Pawel; Rivera-Torres, Natalia; Bloh, Kevin; Kmiec, Eric B

2018-06-01

CD34+ cells are prime targets for therapeutic strategies for gene editing, because modified progenitor cells have the capacity to differentiate through an erythropoietic lineage. Although experimental advances have been reported, the associated experimental protocols have largely been less than clear or robust. As such, we evaluated the relationships among cellular delivery; nuclear uptake, often viewed as the benchmark metric of successful gene editing; and single base repair. We took a combinatorial approach using single-stranded oligonucleotide and a CRISPR/Cas9 ribonucleoprotein to convert wild-type HBB into the sickle cell genotype by evaluating conditions for two common delivery strategies of gene editing tools into CD34+ cells. Confocal microscopy data show that the CRISPR/Cas9 ribonucleoprotein tends to accumulate at the outer membrane of the CD34+ cell nucleus when the Neon Transfection System is employed, while the ribonucleoproteins do pass into the cell nucleus when nucleofection is used. Despite the high efficiency of cellular transformation, and the traditional view of success in efficient nuclear uptake, neither delivery methodology enabled gene editing activity. Our results indicate that more stringent criteria must be established to facilitate the clinical translation and scientific robustness of gene editing for sickle cell disease. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Gene editing for skin diseases: designer nucleases as tools for gene therapy of skin fragility disorders.

PubMed

March, Oliver P; Reichelt, Julia; Koller, Ulrich

2018-04-01

What is the topic of this review? This review concerns current gene editing strategies for blistering skin diseases with respect to individual genetic constellations and distinct conditions. What advances does it highlight? Specificity and safety dominate the discussion of gene editing applications for gene therapy, where a number of tools are implemented. Recent developments in this rapidly progressing field pose further questions regarding which tool is best suited for each particular use. The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB), is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required, and targeting the genetic basis of these severe diseases is now within reach. Here, we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques, transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), determining their preferential application for specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to target the mutation specifically. Both tools have traits beneficial in specific situations. Promising developments in the field engender gene editing as a potentially powerful therapeutic option for future clinical applications. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

CRYSTMET—The NRCC Metals Crystallographic Data File

PubMed Central

Wood, Gordon H.; Rodgers, John R.; Gough, S. Roger; Villars, Pierre

1996-01-01

CRYSTMET is a computer-readable database of critically evaluated crystallographic data for metals (including alloys, intermetallics and minerals) accompanied by pertinent chemical, physical and bibliographic information. It currently contains about 60 000 entries and covers the literature exhaustively from 1913. Scientific editing of the abstracted entries, consisting of numerous automated and manual checks, is done to ensure consistency with related, previously published studies, to assign structure types where necessary and to help guarantee the accuracy of the data and related information. Analyses of the entries and their distribution across key journals as a function of time show interesting trends in the complexity of the compounds studied as well as in the elements they contain. Two applications of CRYSTMET are the identification of unknowns and the prediction of properties of materials. CRYSTMET is available either online or via license of a private copy from the Canadian Scientific Numeric Database Service (CAN/SND). The indexed online search and analysis system is easy and economical to use yet fast and powerful. Development of a new system is under way combining the capabilities of ORACLE with the flexibility of a modern interface based on the Netscape browsing tool. PMID:27805157

Small kernel 1 encodes a pentatricopeptide repeat protein required for mitochondrial nad7 transcript editing and seed development in maize (Zea mays) and rice (Oryza sativa).

PubMed

Li, Xiao-Jie; Zhang, Ya-Feng; Hou, Mingming; Sun, Feng; Shen, Yun; Xiu, Zhi-Hui; Wang, Xiaomin; Chen, Zong-Liang; Sun, Samuel S M; Small, Ian; Tan, Bao-Cai

2014-09-01

RNA editing modifies cytidines (C) to uridines (U) at specific sites in the transcripts of mitochondria and plastids, altering the amino acid specified by the DNA sequence. Here we report the identification of a critical editing factor of mitochondrial nad7 transcript via molecular characterization of a small kernel 1 (smk1) mutant in Zea mays (maize). Mutations in Smk1 arrest both the embryo and endosperm development. Cloning of Smk1 indicates that it encodes an E-subclass pentatricopeptide repeat (PPR) protein that is targeted to mitochondria. Loss of SMK1 function abolishes the C → U editing at the nad7-836 site, leading to the retention of a proline codon that is edited to encode leucine in the wild type. The smk1 mutant showed dramatically reduced complex-I assembly and NADH dehydrogenase activity, and abnormal biogenesis of the mitochondria. Analysis of the ortholog in Oryza sativa (rice) reveals that rice SMK1 has a conserved function in C → U editing of the mitochondrial nad7-836 site. T-DNA knock-out mutants showed abnormal embryo and endosperm development, resulting in embryo or seedling lethality. The leucine at NAD7-279 is highly conserved from bacteria to flowering plants, and analysis of genome sequences from many plants revealed a molecular coevolution between the requirement for C → U editing at this site and the existence of an SMK1 homolog. These results demonstrate that Smk1 encodes a PPR-E protein that is required for nad7-836 editing, and this editing is critical to NAD7 function in complex-I assembly in mitochondria, and hence to embryo and endosperm development in maize and rice. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Analysis of Transmitter Produced Intermodulation Interference in Colocated VHF Sites using a Microcomputer.

DTIC Science & Technology

1986-06-01

intermodulation product type. The notation fl will be used to represent the first frequency in the frequency list , f2 to represent the second frequency, f3... frequency list . If you entered this function by mistake, just press <RETURN> without entering a frequency to return to the EDIT MENU. A-31 .9...frequency. At this point you may step through the frequency list , edit the data, or delete a frequency. To step through the frequency list use the

CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.

PubMed

Kang, HyunJun; Minder, Petra; Park, Mi Ae; Mesquitta, Walatta-Tseyon; Torbett, Bruce E; Slukvin, Igor I

2015-12-15

The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.

Evaluation of possible error sources in corneal endothelial morphometry with a semiautomated noncontact specular microscope.

PubMed

Doughty, Michael J

2013-09-01

To assess the corneal endothelium, particularly the polymegethism feature, using the Topcon SP-3000P specular microscope with newer center-dot software. Forty-eight healthy, normal weight, noncontact lens wearers of Asian ethnicity were assessed. Single endothelial images from each subject were processed with center-dot software, reevaluated after correction of obvious errors, and then by manual border marking and planimetry. Endothelial cell density based on average cell area and the coefficient of variation (COV) of cell area (polymegethism) were calculated. Error sources are associated with erroneous location of cell borders (usually creating larger or smaller "cells") or failure to assign cell borders to a marked cell. On the initial application of the center-dot software, the endothelial cell density values ranged from 1822 to 3244 cells per square millimeter (mean, 2644 cells/mm); this range was reduced (eg, 1955-3054 cells/mm; mean 2690 cells/mm on editing or in manual planimetry). The COV values ranged from 17% to 39% (mean, 27.5% ± 5.5%), with one third of the endothelia yielding COV values of greater than or equal to 30%. On editing or in manual planimetry, the COV values were reduced to between 17% and 29% (mean, 24.5% ± 3.2%; P < 0.001). In the use of a center-dot endothelial analysis program with cell border identification, it is likely that at least 1 set of editing steps is required to produce reasonable results.

The diagnostic utility of the Rarely Missed Index of the Wechsler Memory Scale-Third Edition in detecting response bias in an adult male incarcerated setting.

PubMed

D'Amato, Christopher P; Denney, Robert L

2008-09-01

The purpose of this study was to utilize a known-group research design to evaluate the diagnostic utility of the Rarely Missed Index (RMI) of the Wechsler Memory Scale-Third Edition [Wechsler, D. (1997). Wechsler Adult Intelligence Test-3rd Edition. San Antonio, TX: The Psychological Corporation] in assessing response bias in an adult male incarcerated setting. Archival data from a sample of 60 adult male inmates who presented for neuropsychological testing were reviewed. Evaluees were assigned to one of two groups; probable malingerers (PM; n=30) and a group of valid test responders (n=30) (1999). Using the recommended cut-off score of 136 or less, the sensitivity of the RMI was extremely low at 33%. Its specificity was 83%. The positive predictive power of the RMI with the published base rate of 22.8 was 38%; with a negative predictive power of 81%. The positive predictive power of the RMI with a published base rate of 70.5 was 82%. The negative predictive power using a base rate of 70.5% was 34%. Results of the receiver operating characteristics (ROC) analysis indicated that the RMI score with a cut-off 136 or less performed only slightly better than chance in delineating probable malingerers from valid responders in this setting. Overall, the findings suggest that the RMI may not be a reliable index for detecting response bias in this setting and perhaps in similar settings.

48 CFR 1552.211-74 - Work assignments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Work assignments. 1552.211... Work assignments. As prescribed in 1511.011-74, insert the following contract clause in cost-reimbursement type term form contracts when work assignments are to be used. Work Assignments (APR 1984) (a) The...

RNA Editing Responses to Oxidative Stress between a Wild Abortive Type Male-Sterile Line and Its Maintainer Line

PubMed Central

Xiong, Jie; Tao, Tao; Luo, Zhi; Yan, Shuaigang; Liu, Yi; Yu, Xinqiao; Liu, Guolan; Xia, Hui; Luo, Lijun

2017-01-01

RNA editing of mitochondrial gene transcripts plays a central role during plant development and evolutionary adaptation. RNA editing has previously been reported to differ between the rice cytoplasmic male sterile (CMS) line and its maintainer line, which has been suggested as a cause for their different performances under environmental stress. To specifically test this hypothesis, a wild abortive (WA) CMS line (Huhan-1A) and its maintainer line (Huhan-1B) were utilized to investigate performances in response to oxidative stress, as well as RNA editing efficiencies on transcripts of six selected mitochondrial genes. Compared to the maintainer line, Huhan-1A represented both lower plant height and total antioxidant capacity, possessed higher total soluble protein and chlorophyll contents, accumulated less H2O2 content on the 3rd day after treatment (DAT), and exhibited higher survival ratio after re-watering. Furthermore, a total of 90 editing sites were detected on transcripts of six mitochondrial genes (atp9, nad2, nad7, nad9, ccmB, and ccmC) in both Huhan-1A and Huhan-1B on the 0, 1st, and 3rd DAT. Forty-eight sites were furthermore determined as stress-responsive sites (SRS). Generally, in response to oxidative stress, SRS in Huhan-1A increased the resulting editing efficiencies, while SRS in Huhan-1B decreased the resulting editing efficiencies. In addition, 33 and 22 sites at ccmB and ccmC were differentially edited between Huhan-1A and Huhan-1B, respectively, on the 0, 1st, and 3rd DAT. Editing efficiencies of ccmB and ccmC were generally lower in Huhan-1A (ccmB, 37.3–47.8%; ccmC, 41.2–52.3%) than those in Huhan-1B (ccmB, 82.6–86.5%; ccmC, 81.0–82.9%). Deficiencies of RNA editing in Huhan-1A at ccmB and ccmC could lead to the loss of transmembrane domains in their protein structures. Consequently, differences in RNA editing at ccmB and ccmC between the WA-CMS line and its maintainer line partially explained their different performances under stress. Moreover, we detected differences in expressions of pentatricopeptide repeat (PPR) genes between both lines, as well as significant correlations with RNA editing. Our study indicated potential associations of RNA editing and PPR genes in rice tolerance to abiotic stresses. However, the underlying molecular mechanisms of stress-adaptation, which are attributed to RNA editing on transcripts of mitochondrial genes, require further investigation. PMID:29234339

Unexpected ethical dilemmas in sex assignment in 46,XY DSD due to 5-alpha reductase type 2 deficiency.

PubMed

Byers, Heather M; Mohnach, Lauren H; Fechner, Patricia Y; Chen, Ming; Thomas, Inas H; Ramsdell, Linda A; Shnorhavorian, Margarett; McCauley, Elizabeth A; Amies Oelschlager, Anne-Marie E; Park, John M; Sandberg, David E; Adam, Margaret P; Keegan, Catherine E

2017-06-01

Sex assignment at birth remains one of the most clinically challenging and controversial topics in 46,XY disorders of sexual development (DSD). This is particularly challenging in deficiency of 5-alpha reductase type 2 given that external genitalia are typically undervirilized at birth but typically virilize at puberty to a variable degree. Historically, most individuals with 5-alpha reductase deficiency were raised females. However, reports that over half of patients who underwent a virilizing puberty adopted an adult male gender identity have challenged this practice. Consensus guidelines on assignment of sex of rearing at birth are equivocal or favor male assignment in the most virilized cases. While a male sex of rearing assignment may avoid lifelong hormonal therapy and/or allow the potential for fertility, female sex assignment may be more consistent with external anatomy in the most severely undervirilized cases. Herein, we describe five patients with 46,XY DSD due 5-alpha-reductase type 2 deficiency, all with a severe phenotype. An inter-disciplinary DSD medical team at one of two academic centers evaluated each patient. This case series illustrates the complicated decision-making process of assignment of sex of rearing at birth in 5-alpha reductase type 2 deficiency and the challenges that arise when the interests of the child, parental wishes, recommendations of the medical team, and state law collide. © 2017 Wiley Periodicals, Inc.

Do therapeutic homework assignments address areas of need for individuals with severe mental illness?

PubMed

Kelly, Peter J; Deane, Frank P

2011-04-01

The current study explores the types of homework assignments used in a recovery orientated case management approach. It also examines the relationship between the types of homework used and the clients' area of need as rated on the CANSAS. There were 129 client and mental health case manager dyads that participated in the study. Written copies of all homework assignments administered during the 12-month research period were collected (N = 1,054). The homework assignments were categorised according to the 'type' and the 'need domain addressed by the task'. The majority of these tasks were behavioural in nature. On a group level homework tended to broadly address areas of need for clients in the study. Only 2 of the 1,054 homework assignments administered directly addressed areas of Intimate Relationships or Sexual Expression. The importance of addressing Intimate Relationship and Sexual Expression within mental health case management is discussed.

Integrated simultaneous analysis of different biomedical data types with exact weighted bi-cluster editing.

PubMed

Sun, Peng; Guo, Jiong; Baumbach, Jan

2012-07-17

The explosion of biological data has largely influenced the focus of today’s biology research. Integrating and analysing large quantity of data to provide meaningful insights has become the main challenge to biologists and bioinformaticians. One major problem is the combined data analysis of data from different types, such as phenotypes and genotypes. This data is modelled as bi-partite graphs where nodes correspond to the different data points, mutations and diseases for instance, and weighted edges relate to associations between them. Bi-clustering is a special case of clustering designed for partitioning two different types of data simultaneously. We present a bi-clustering approach that solves the NP-hard weighted bi-cluster editing problem by transforming a given bi-partite graph into a disjoint union of bi-cliques. Here we contribute with an exact algorithm that is based on fixed-parameter tractability. We evaluated its performance on artificial graphs first. Afterwards we exemplarily applied our Java implementation to data of genome-wide association studies (GWAS) data aiming for discovering new, previously unobserved geno-to-pheno associations. We believe that our results will serve as guidelines for further wet lab investigations. Generally our software can be applied to any kind of data that can be modelled as bi-partite graphs. To our knowledge it is the fastest exact method for weighted bi-cluster editing problem.

Integrated simultaneous analysis of different biomedical data types with exact weighted bi-cluster editing.

PubMed

Sun, Peng; Guo, Jiong; Baumbach, Jan

2012-06-01

The explosion of biological data has largely influenced the focus of today's biology research. Integrating and analysing large quantity of data to provide meaningful insights has become the main challenge to biologists and bioinformaticians. One major problem is the combined data analysis of data from different types, such as phenotypes and genotypes. This data is modelled as bi-partite graphs where nodes correspond to the different data points, mutations and diseases for instance, and weighted edges relate to associations between them. Bi-clustering is a special case of clustering designed for partitioning two different types of data simultaneously. We present a bi-clustering approach that solves the NP-hard weighted bi-cluster editing problem by transforming a given bi-partite graph into a disjoint union of bi-cliques. Here we contribute with an exact algorithm that is based on fixed-parameter tractability. We evaluated its performance on artificial graphs first. Afterwards we exemplarily applied our Java implementation to data of genome-wide association studies (GWAS) data aiming for discovering new, previously unobserved geno-to-pheno associations. We believe that our results will serve as guidelines for further wet lab investigations. Generally our software can be applied to any kind of data that can be modelled as bi-partite graphs. To our knowledge it is the fastest exact method for weighted bi-cluster editing problem.

People Types & Tiger Stripes. Third Edition.

ERIC Educational Resources Information Center

Lawrence, Gordon D.

This book presents one method for identifying mind-sets, learning styles, and motivation patterns, and using the patterns in planning instruction and other helping processes, with the objective of helping people find and use their strengths to ameliorate weaknesses. The approach presented is based on Carl Jung's ideas about psychological types, as…

High GC Content Cas9-Mediated Genome-Editing and Biosynthetic Gene Cluster Activation in Saccharopolyspora erythraea.

PubMed

Liu, Yong; Wei, Wen-Ping; Ye, Bang-Ce

2018-05-18

The overexpression of bacterial secondary metabolite biosynthetic enzymes is the basis for industrial overproducing strains. Genome editing tools can be used to further improve gene expression and yield. Saccharopolyspora erythraea produces erythromycin, which has extensive clinical applications. In this study, the CRISPR-Cas9 system was used to edit genes in the S. erythraea genome. A temperature-sensitive plasmid containing the PermE promoter, to drive Cas9 expression, and the Pj23119 and PkasO promoters, to drive sgRNAs, was designed. Erythromycin esterase, encoded by S. erythraea SACE_1765, inactivates erythromycin by hydrolyzing the macrolactone ring. Sequencing and qRT-PCR confirmed that reporter genes were successfully inserted into the SACE_1765 gene. Deletion of SACE_1765 in a high-producing strain resulted in a 12.7% increase in erythromycin levels. Subsequent PermE- egfp knock-in at the SACE_0712 locus resulted in an 80.3% increase in erythromycin production compared with that of wild type. Further investigation showed that PermE promoter knock-in activated the erythromycin biosynthetic gene clusters at the SACE_0712 locus. Additionally, deletion of indA (SACE_1229) using dual sgRNA targeting without markers increased the editing efficiency to 65%. In summary, we have successfully applied Cas9-based genome editing to a bacterial strain, S. erythraea, with a high GC content. This system has potential application for both genome-editing and biosynthetic gene cluster activation in Actinobacteria.

Gene editing of stem cells for kidney disease modelling and therapeutic intervention.

PubMed

Lau, Ricky W K; Wang, Bo; Ricardo, Sharon D

2018-05-30

Recent developments in targeted gene editing have paved the way for the wide adoption of cluster regular interspaced short palindromic repeats (CRISPR)-associated protein-9 nucleases (Cas9) as a RNA guide molecular tool to modify the genome of eukaryotic cells or animals. Theoretically, the translation of CRISPR-Cas9 can be applied to the treatment of inherited or acquired kidney disease, kidney transplantation and genetic corrections of somatic cells from kidneys with inherited mutations such as polycystic kidney disease. Human pluripotent stem cells have been used to generate an unlimited source of kidney progenitor cells or when spontaneously differentiated into three-dimensional kidney organoids to model kidney organogenesis or the pathogenesis of disease. Gene editing now allows for the tagging and selection of specific kidney cell types or disease specific gene knock in/out, which enables more precise understanding of kidney organogenesis and genetic diseases. This review discusses the mechanisms of action, in addition to the advantages and disadvantages, of the major three gene editing technologies, namely CRISPR-Cas9, zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). The implications of using gene editing to better understand kidney disease is reviewed in detail. In addition, the ethical issues of gene editing, which could be easily neglected in the modern fast paced research environment, are highlighted. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

CRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo-Brief Report.

PubMed

Wang, Xiao; Raghavan, Avanthi; Chen, Tao; Qiao, Lyon; Zhang, Yongxian; Ding, Qiurong; Musunuru, Kiran

2016-05-01

Although early proof-of-concept studies of somatic in vivo genome editing of the mouse ortholog of proprotein convertase subtilisin/kexin type 9 (Pcsk9) in mice have established its therapeutic potential for the prevention of cardiovascular disease, the unique nature of genome-editing technology-permanent alteration of genomic DNA sequences-mandates that it be tested in vivo against human genes in normal human cells with human genomes to give reliable preclinical insights into the efficacy (on-target mutagenesis) and safety (lack of off-target mutagenesis) of genome-editing therapy before it can be used in patients. We used a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) 9 genome-editing system to target the human PCSK9 gene in chimeric liver-humanized mice bearing human hepatocytes. We demonstrated high on-target mutagenesis (approaching 50%), greatly reduced blood levels of human PCSK9 protein, and minimal off-target mutagenesis. This work yields important information on the efficacy and safety of CRISPR-Cas9 therapy targeting the human PCSK9 gene in human hepatocytes in vivo, and it establishes humanized mice as a useful platform for the preclinical assessment of applications of somatic in vivo genome editing. © 2016 American Heart Association, Inc.

An Efficient, Rapid, and Recyclable System for CRISPR-Mediated Genome Editing in Candida albicans.

PubMed

Nguyen, Namkha; Quail, Morgan M F; Hernday, Aaron D

2017-01-01

Candida albicans is the most common fungal pathogen of humans. Historically, molecular genetic analysis of this important pathogen has been hampered by the lack of stable plasmids or meiotic cell division, limited selectable markers, and inefficient methods for generating gene knockouts. The recent development of clustered regularly interspaced short palindromic repeat(s) (CRISPR)-based tools for use with C. albicans has opened the door to more efficient genome editing; however, previously reported systems have specific limitations. We report the development of an optimized CRISPR-based genome editing system for use with C. albicans . Our system is highly efficient, does not require molecular cloning, does not leave permanent markers in the genome, and supports rapid, precise genome editing in C. albicans . We also demonstrate the utility of our system for generating two independent homozygous gene knockouts in a single transformation and present a method for generating homozygous wild-type gene addbacks at the native locus. Furthermore, each step of our protocol is compatible with high-throughput strain engineering approaches, thus opening the door to the generation of a complete C. albicans gene knockout library. IMPORTANCE Candida albicans is the major fungal pathogen of humans and is the subject of intense biomedical and discovery research. Until recently, the pace of research in this field has been hampered by the lack of efficient methods for genome editing. We report the development of a highly efficient and flexible genome editing system for use with C. albicans . This system improves upon previously published C. albicans CRISPR systems and enables rapid, precise genome editing without the use of permanent markers. This new tool kit promises to expedite the pace of research on this important fungal pathogen.

Efficient genome editing of wild strawberry genes, vector development and validation.

PubMed

Zhou, Junhui; Wang, Guoming; Liu, Zhongchi

2018-03-25

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system is an effective genome editing tool for plant and animal genomes. However, there are still few reports on the successful application of CRISPR-Cas9 to horticultural plants, especially with regard to germ-line transmission of targeted mutations. Here, we report high-efficiency genome editing in the wild strawberry Fragaria vesca and its successful application to mutate the auxin biosynthesis gene TAA1 and auxin response factor 8 (ARF8). In our CRISPR system, the Arabidopsis U6 promoter AtU6-26 and the wild strawberry U6 promoter FveU6-2 were each used to drive the expression of sgRNA, and both promoters were shown to lead to high-efficiency genome editing in strawberry. To test germ-line transmission of the edited mutations and new mutations induced in the next generation, the progeny of the primary (T0) transgenic plants carrying the CRISPR construct was analysed. New mutations were detected in the progeny plants at a high efficiency, including large deletions between the two PAM sites. Further, T1 plants harbouring arf8 homozygous knockout mutations grew considerably faster than wild-type plants. The results indicate that our CRISPR vectors can be used to edit the wild strawberry genome at a high efficiency and that both sgRNA design and appropriate U6 promoters contribute to the success of genomic editing. Our results open up exciting opportunities for engineering strawberry and related horticultural crops to improve traits of economic importance. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Dilemmas in Lung Cancer Staging.

PubMed

Vlahos, Ioannis

2018-05-01

The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

The USL NASA PC R and D interactive presentation development system

NASA Technical Reports Server (NTRS)

Dominick, Wayne D. (Editor); Moreau, Dennis R.

1984-01-01

The Interactive Presentation Development System (IPFS) is a highly interactive system for creating, editing, and displaying video presentation sequences, e.g., for developing and presenting displays of instructional material similiar to overhead transparency or slide presentations. However, since this system is PC-based, users (instructors) can step through sequences forward or backward, focusing attention to areas of the display with special cursor pointers. Additionally, screen displays may be dynamically modified during the presentation to show assignments or to answer questions, much like a traditional blackboard. This system is now implemented at the University of Southwestern Louisiana for use within the piloting phases of the NASA contract work.

Specdata: Automated Analysis Software for Broadband Spectra

NASA Astrophysics Data System (ADS)

Oliveira, Jasmine N.; Martin-Drumel, Marie-Aline; McCarthy, Michael C.

2017-06-01

With the advancement of chirped-pulse techniques, broadband rotational spectra with a few tens to several hundred GHz of spectral coverage are now routinely recorded. When studying multi-component mixtures that might result, for example, with the use of an electrical discharge, lines of new chemical species are often obscured by those of known compounds, and analysis can be laborious. To address this issue, we have developed SPECdata, an open source, interactive tool which is designed to simplify and greatly accelerate the spectral analysis and discovery. Our software tool combines both automated and manual components that free the user from computation, while giving him/her considerable flexibility to assign, manipulate, interpret and export their analysis. The automated - and key - component of the new software is a database query system that rapidly assigns transitions of known species in an experimental spectrum. For each experiment, the software identifies spectral features, and subsequently assigns them to known molecules within an in-house database (Pickett .cat files, list of frequencies...), or those catalogued in Splatalogue (using automatic on-line queries). With suggested assignments, the control is then handed over to the user who can choose to accept, decline or add additional species. Data visualization, statistical information, and interactive widgets assist the user in making decisions about their data. SPECdata has several other useful features intended to improve the user experience. Exporting a full report of the analysis, or a peak file in which assigned lines are removed are among several options. A user may also save their progress to continue at another time. Additional features of SPECdata help the user to maintain and expand their database for future use. A user-friendly interface allows one to search, upload, edit or update catalog or experiment entries.

The changing landscape of gene editing in hematopoietic stem cells: a step towards Cas9 clinical translation.

PubMed

Dever, Daniel P; Porteus, Matthew H

2017-11-01

Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system. With the discovery that the RNA-programmable (sgRNA) clustered regularly interspace short palindromic repeats (CRISPR)-Cas9 nuclease (Cas9/sgRNA) systems can be easily used to precisely modify the human genome in 2012, a genome-editing revolution of hematopoietic stem cells (HSC) has bloomed. We have observed that over the last 2 years, academic institutions and small biotech companies are developing HSC-based Cas9/sgRNA genome-editing curative strategies to treat monogenic disorders, including β-hemoglobinopathies and primary immunodeficiencies. We will focus on recent publications (within the past 2 years) that employ different genome-editing strategies to 'hijack' the cell's endogenous double-strand repair pathways to confer a disease-specific therapeutic advantage. The number of genome-editing strategies in HSCs that could offer therapeutic potential for diseases of the blood and immune system have dramatically risen over the past 2 years. The HSC-based genome-editing field is primed to enter clinical trials in the subsequent years. We will summarize the major advancements for the development of novel autologous GE-HSC cell and gene therapy strategies for hematopoietic diseases that are candidates for curative allogeneic bone marrow transplantation.

RNA Editing Modulates Human Hepatic Aryl Hydrocarbon Receptor Expression by Creating MicroRNA Recognition Sequence.

PubMed

Nakano, Masataka; Fukami, Tatsuki; Gotoh, Saki; Takamiya, Masataka; Aoki, Yasuhiro; Nakajima, Miki

2016-01-08

Adenosine to inosine (A-to-I) RNA editing is the most frequent type of post-transcriptional nucleotide conversion in humans, and it is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes. In this study we investigated the effect of RNA editing on human aryl hydrocarbon receptor (AhR) expression because the AhR transcript potentially forms double-stranded structures, which are targets of ADAR enzymes. In human hepatocellular carcinoma-derived Huh-7 cells, the ADAR1 knockdown reduced the RNA editing levels in the 3'-untranslated region (3'-UTR) of the AhR transcript and increased the AhR protein levels. The ADAR1 knockdown enhanced the ligand-mediated induction of CYP1A1, a gene downstream of AhR. We investigated the possibility that A-to-I RNA editing creates miRNA targeting sites in the AhR mRNA and found that the miR-378-dependent down-regulation of AhR was abolished by ADAR1 knockdown. These results indicated that the ADAR1-mediated down-regulation of AhR could be attributed to the creation of a miR-378 recognition site in the AhR 3'-UTR. The interindividual differences in the RNA editing levels within the AhR 3'-UTR in a panel of 32 human liver samples were relatively small, whereas the differences in ADAR1 expression were large (220-fold). In the human liver samples a significant inverse association was observed between the miR-378 and AhR protein levels, suggesting that the RNA-editing-dependent down-regulation of AhR by miR-378 contributes to the variability in the constitutive hepatic expression of AhR. In conclusion, this study uncovered for the first time that A-to-I RNA editing modulates the potency of xenobiotic metabolism in the human liver. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B.

PubMed

Whitley, Chester B; Cleary, Maureen; Eugen Mengel, Karl; Harmatz, Paul; Shapiro, Elsa; Nestrasil, Igor; Haslett, Patrick; Whiteman, David; Alexanderian, David

2018-06-01

To evaluate the natural course of disease progression in patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB), identify potential end points for future therapy trials, and characterize biomarkers related to the disease. A prospective, multicenter study was conducted. Baseline, 6-month, and 12-month assessments included neurodevelopmental status (Bayley Scales of Infant Development, Third edition), adaptive status (Vineland Adaptive Behavior Scales, Second Edition), volumetric brain magnetic resonance imaging, cerebrospinal fluid heparan sulfate, and urine glycosaminoglycan (GAG) measurements. Nineteen patients aged 1.6-31.7 years were enrolled. Over 12 months, cognition, adaptive behavior, and cortical gray matter volume (GMV) declined in most patients. For patients diagnosed at <6 years, although there was no overall mean change over 12 months, there were 10%-48%, 3%-66%, and 1%-14% decreases in cognitive development quotient score, Vineland Adaptive Behavior Scales, Second Edition development quotient score, and cortical GMV in 8/12, 9/11, and 10/11 patients, respectively. Mean urine GAG and cerebrospinal fluid heparan sulfate levels were stable, but patients diagnosed at <6 years (n = 14) had higher levels than those ≥6 years at diagnosis (n = 4), which was likely associated with age as they also were generally younger. Cognition, adaptive behavior, and cortical GMV measures sensitively tracked deterioration in patients with mucopolysaccharidosis type IIIB aged ≤8.6 years. Biomarkers may have prognostic value, but their sensitivity to disease progression requires further investigation. These findings should help evaluate enzyme replacement and gene therapy agents for this rare, devastating, neurodegenerative disease. ClinicalTrials.gov: NCT01509768. Copyright © 2018 Elsevier Inc. All rights reserved.

CRISPR-Cas9 technology: applications and human disease modelling.

PubMed

Torres-Ruiz, Raul; Rodriguez-Perales, Sandra

2017-01-01

Genome engineering is a powerful tool for a wide range of applications in biomedical research and medicine. The development of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has revolutionized the field of gene editing, thus facilitating efficient genome editing through the creation of targeted double-strand breaks of almost any organism and cell type. In addition, CRISPR-Cas9 technology has been used successfully for many other purposes, including regulation of endogenous gene expression, epigenome editing, live-cell labelling of chromosomal loci, edition of single-stranded RNA and high-throughput gene screening. The implementation of the CRISPR-Cas9 system has increased the number of available technological alternatives for studying gene function, thus enabling generation of CRISPR-based disease models. Although many mechanistic questions remain to be answered and several challenges have yet to be addressed, the use of CRISPR-Cas9-based genome engineering technologies will increase our knowledge of disease processes and their treatment in the near future. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

48 CFR 1511.011-74 - Work assignments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Work assignments. 1511.011... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS 1511.011-74 Work assignments. The Contracting Officer shall insert the contract clause at 1552.211-74, Work Assignments, in cost-reimbursement type term form...

The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models

PubMed Central

SHAO, Ming; XU, Tian-Rui; CHEN, Ce-Shi

2016-01-01

Targeted genome editing technology has been widely used in biomedical studies. The CRISPR-associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation. In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and biomedicine. PMID:27469250

The carboxypeptidase angiotensin converting enzyme (ACE) shapes the MHC class I peptide repertoire

PubMed Central

Shen, Xiao Z.; Billet, Sandrine; Lin, Chentao; Okwan-Duodu, Derick; Chen, Xu; Lukacher, Aron E.; Bernstein, Kenneth E.

2011-01-01

The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to CD8+ T cell mediated adaptive immune responses. Aminopeptidases are implicated in the editing of peptides for MHC class I loading, but C-terminal editing is thought due to proteasome cleavage. By comparing genetically deficient, wild-type and over-expressing mice, we now identify the dipeptidase angiotensin-converting enzyme (ACE) as playing a physiologic role in peptide processing for MHC class I. ACE edits the C-termini of proteasome-produced class I peptides. The lack of ACE exposes novel antigens but also abrogates some self-antigens. ACE has major effects on surface MHC class I expression in a haplotype-dependent manner. We propose a revised model of MHC class I peptide processing by introducing carboxypeptidase activity. PMID:21964607

150th Anniversary of the Astronomical Observatory Library of Sciences

NASA Astrophysics Data System (ADS)

Solntseva, T.

The scientific library of the Astronomical observatory of Kyiv Taras Shevchenko University is one of the oldest ones of such a type in Ukraine. Our Astronomical Observatory and its scientific library will celebrate 150th anniversary of their foundation. 900 volumes of duplicates of Olbers' private library underlay our library. These ones were acquired by Russian Academy of Sciences for Poulkovo observatory in 1841 but according to Struve's order were transmitted to Kyiv Saint Volodymyr University. These books are of great value. There are works edited during Copernicus', Kepler's, Galilei's, Newton's, Descartes' lifetime. Our library contains more than 100000 units of storage - monographs, periodical astronomical editions from the first (Astronomische Nachrichten, Astronomical journal, Monthly Notices etc.), editions of the majority of the astronomical observatories and institutions of the world, unique astronomical atlases and maps

The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models.

PubMed

Shao, Ming; Xu, Tian-Rui; Chen, Ce-Shi

2016-07-18

Targeted genome editing technology has been widely used in biomedical studies. The CRISPR-associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation. In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio-medicine.

Overcoming an obstacle in expanding a UMLS semantic type extent.

PubMed

Chen, Yan; Gu, Huanying; Perl, Yehoshua; Geller, James

2012-02-01

This paper strives to overcome a major problem encountered by a previous expansion methodology for discovering concepts highly likely to be missing a specific semantic type assignment in the UMLS. This methodology is the basis for an algorithm that presents the discovered concepts to a human auditor for review and possible correction. We analyzed the problem of the previous expansion methodology and discovered that it was due to an obstacle constituted by one or more concepts assigned the UMLS Semantic Network semantic type Classification. A new methodology was designed that bypasses such an obstacle without a combinatorial explosion in the number of concepts presented to the human auditor for review. The new expansion methodology with obstacle avoidance was tested with the semantic type Experimental Model of Disease and found over 500 concepts missed by the previous methodology that are in need of this semantic type assignment. Furthermore, other semantic types suffering from the same major problem were discovered, indicating that the methodology is of more general applicability. The algorithmic discovery of concepts that are likely missing a semantic type assignment is possible even in the face of obstacles, without an explosion in the number of processed concepts. Copyright © 2011 Elsevier Inc. All rights reserved.

Overcoming an Obstacle in Expanding a UMLS Semantic Type Extent

PubMed Central

Chen, Yan; Gu, Huanying; Perl, Yehoshua; Geller, James

2011-01-01

This paper strives to overcome a major problem encountered by a previous expansion methodology for discovering concepts highly likely to be missing a specific semantic type assignment in the UMLS. This methodology is the basis for an algorithm that presents the discovered concepts to a human auditor for review and possible correction. We analyzed the problem of the previous expansion methodology and discovered that it was due to an obstacle constituted by one or more concepts assigned the UMLS Semantic Network semantic type Classification. A new methodology was designed that bypasses such an obstacle without a combinatorial explosion in the number of concepts presented to the human auditor for review. The new expansion methodology with obstacle avoidance was tested with the semantic type Experimental Model of Disease and found over 500 concepts missed by the previous methodology that are in need of this semantic type assignment. Furthermore, other semantic types suffering from the same major problem were discovered, indicating that the methodology is of more general applicability. The algorithmic discovery of concepts that are likely missing a semantic type assignment is possible even in the face of obstacles, without an explosion in the number of processed concepts. PMID:21925287

48 CFR 1552.211-74 - Work assignments.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-reimbursement type term form contracts when work assignments are to be used. Work Assignments (APR 1984) (a) The... assignment or similar tasking document, the Contractor shall provide a conflict of interest certification... directly related to a site, the Contractor is only required to provide a conflict of interest certification...

Young Adult Reference Services in the Public Library.

ERIC Educational Resources Information Center

Boylan, Patricia

1984-01-01

Methods suggested for use by public libraries to stay on top of school assignments include a large, loose-leaf type binder entitled "School Assignments" to be kept at reference desk; assignment-related book lists; school assignment forms; and teacher notification forms to alert them if the library cannot fulfill their information…

Genetics Home Reference: pseudohypoaldosteronism type 1

MedlinePlus

... structural and functional considerations and new perspectives. Mol Cell Endocrinol. 2012 Mar 24;350(2):206-15. doi: ... are genome editing and CRISPR-Cas9? What is precision medicine? What is newborn ...

Food Buying Guide for Type A School Lunches.

ERIC Educational Resources Information Center

Moss, Mary Ann; And Others

This guide provides information for planning and calculating quantities of food to be purchased and used by schools serving Type A lunches in the National School Lunch Program. This edition includes changes resulting from new developments in food production and processing as well as changes in marketing procedures, packages, and quality of foods…

Yes, You Can Help! Information and Inspiration for French Immersion Parents. National Edition.

ERIC Educational Resources Information Center

Alberta Dept. of Education, Edmonton. Language Services Branch.

The guide for parents of French immersion students in Alberta (Canada) public schools is designed to answer frequently asked questions and encourage parent participation in the student's immersion experience. Chapters address these topics: terminology (program types, school types offering immersion programs, other terms); reasons for learning a…

Texas Boating Basics: A Course in Better Boating. Fifth Edition.

ERIC Educational Resources Information Center

Texas State Dept. of Parks and Wildlife, Austin.

This student manual and teacher's guide on boating provides basic information of boating laws, boat types, and boat operation. Part I includes information on types of boats, boat hulls, and motors. Part II covers what is legally required regarding registration of boats and equipment. Part III discusses basic safety regulations, navigation rules,…

Single-stranded DNA cleavage by divergent CRISPR-Cas9 enzymes

PubMed Central

Ma, Enbo; Harrington, Lucas B.; O’Connell, Mitchell R.; Zhou, Kaihong; Doudna, Jennifer A.

2015-01-01

Summary Double-stranded DNA (dsDNA) cleavage by Cas9 is a hallmark of type II CRISPR-Cas immune systems. Cas9–guide RNA complexes recognize 20-base-pair sequences in DNA and generate a site-specific double-strand break, a robust activity harnessed for genome editing. DNA recognition by all studied Cas9 enzymes requires a protospacer adjacent motif (PAM) next to the target site. We show that Cas9 enzymes from evolutionarily divergent bacteria can recognize and cleave single-stranded DNA (ssDNA) by an RNA-guided, PAM-independent recognition mechanism. Comparative analysis shows that in contrast to the type II-A S. pyogenes Cas9 that is widely used for genome engineering, the smaller type II-C Cas9 proteins have limited dsDNA binding and unwinding activity and promiscuous guide-RNA specificity. These results indicate that inefficiency of type II-C Cas9 enzymes for genome editing results from a limited ability to cleave dsDNA, and suggest that ssDNA cleavage was an ancestral function of the Cas9 enzyme family. PMID:26545076

Tree edit distance for leaf-labelled trees on free leafset and its comparison with frequent subsplit dissimilarity and popular distance measures

PubMed Central

2011-01-01

Background This paper is devoted to distance measures for leaf-labelled trees on free leafset. A leaf-labelled tree is a data structure which is a special type of a tree where only leaves (terminal) nodes are labelled. This data structure is used in bioinformatics for modelling of evolution history of genes and species and also in linguistics for modelling of languages evolution history. Many domain specific problems occur and need to be solved with help of tree postprocessing techniques such as distance measures. Results Here we introduce the tree edit distance designed for leaf labelled trees on free leafset, which occurs to be a metric. It is presented together with tree edit consensus tree notion. We provide statistical evaluation of provided measure with respect to R-F, MAST and frequent subsplit based dissimilarity measures as the reference measures. Conclusions The tree edit distance was proven to be a metric and has the advantage of using different costs for contraction and pruning, therefore their properties can be tuned depending on the needs of the user. Two of the presented methods carry the most interesting properties. E(3,1) is very discriminative (having a wide range of values) and has a very regular distance distribution which is similar to a normal distribution in its shape and is good both for similar and non-similar trees. NFC(2,1) on the other hand is proportional or nearly proportional to the number of mutation operations used, irrespective of their type. PMID:21612645

Ethics of using language editing services in an era of digital communication and heavily multi-authored papers.

PubMed

Lozano, George A

2014-06-01

Scientists of many countries in which English is not the primary language routinely use a variety of manuscript preparation, correction or editing services, a practice that is openly endorsed by many journals and scientific institutions. These services vary tremendously in their scope; at one end there is simple proof-reading, and at the other extreme there is in-depth and extensive peer-reviewing, proposal preparation, statistical analyses, re-writing and co-writing. In this paper, the various types of service are reviewed, along with authorship guidelines, and the question is raised of whether the high-end services surpass most guidelines' criteria for authorship. Three other factors are considered. First, the ease of collaboration possible in the internet era allows multiple iterations between the author(s) and the "editing service", so essentially, papers can be co-written. Second, "editing services" often offer subject-specific experts who comment not only on the language, but interpret and improve scientific content. Third, the trend towards heavily multi-authored papers implies that the threshold necessary to earn authorship is declining. The inevitable conclusion is that at some point the contributions by "editing services" should be deemed sufficient to warrant authorship. Trying to enforce any guidelines would likely be futile, but nevertheless, it might be time to revisit the ethics of using some of the high-end "editing services". In an increasingly international job market, awareness of this problem might prove increasingly important in authorship disputes, the allocation of research grants, and hiring decisions.

46 CFR 42.20-5 - Freeboard assignment: Type “B” vessels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Freeboard assignment: Type âBâ vessels. 42.20-5 Section 42.20-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES DOMESTIC AND...) and (d) as if it were a Type “A” vessel. [CGD 79-153, 48 FR 38647, Aug. 25, 1983, as amended by CGD 76...

46 CFR 42.20-5 - Freeboard assignment: Type “B” vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Freeboard assignment: Type âBâ vessels. 42.20-5 Section 42.20-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES DOMESTIC AND...) and (d) as if it were a Type “A” vessel. [CGD 79-153, 48 FR 38647, Aug. 25, 1983, as amended by CGD 76...

Genetics Home Reference: maternally inherited diabetes and deafness

MedlinePlus

... Maassen JA. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Class Notes for "Class-Y-News."

ERIC Educational Resources Information Center

Stuart, Judy L.

1991-01-01

A self-contained class of students with mild to moderate disabilities published a monthly newsletter which was distributed to students' families. Students became involved in writing, typing, drawing, folding, basic editing, and disseminating. (JDD)

Segmentation, dynamic storage, and variable loading on CDC equipment

NASA Technical Reports Server (NTRS)

Tiffany, S. H.

1980-01-01

Techniques for varying the segmented load structure of a program and for varying the dynamic storage allocation, depending upon whether a batch type or interactive type run is desired, are explained and demonstrated. All changes are based on a single data input to the program. The techniques involve: code within the program to suppress scratch pad input/output (I/O) for a batch run or translate the in-core data storage area from blank common to the end-of-code+1 address of a particular segment for an interactive run; automatic editing of the segload directives prior to loading, based upon data input to the program, to vary the structure of the load for interactive and batch runs; and automatic editing of the load map to determine the initial addresses for in core data storage for an interactive run.

A Phenotypic Screen for Functional Mutants of Human Adenosine Deaminase Acting on RNA 1.

PubMed

Wang, Yuru; Havel, Jocelyn; Beal, Peter A

2015-11-20

Adenosine deaminases acting on RNA (ADARs) are RNA-editing enzymes responsible for the conversion of adenosine to inosine at specific locations in cellular RNAs. ADAR1 and ADAR2 are two members of the family that have been shown to be catalytically active. Earlier, we reported a phenotypic screen for the study of human ADAR2 using budding yeast S. cerevisiae as the host system. While this screen has been successfully applied to the study of ADAR2, it failed with ADAR1. Here, we report a new reporter that uses a novel editing substrate and is suitable for the study of ADAR1. We screened plasmid libraries with randomized codons for two important residues in human ADAR1 (G1007 and E1008). The screening results combined with in vitro deamination assays led to the identification of mutants that are more active than the wild type protein. Furthermore, a screen of the ADAR1 E1008X library with a reporter construct bearing an A•G mismatch at the editing site suggests one role for the residue at position 1008 is to sense the identity of the base pairing partner for the editing site adenosine. This work has provided a starting point for future in vitro evolution studies of ADAR1 and led to new insight into ADAR's editing site selectivity.

Gene correction in patient-specific iPSCs for therapy development and disease modeling

PubMed Central

Jang, Yoon-Young

2018-01-01

The discovery that mature cells can be reprogrammed to become pluripotent and the development of engineered endonucleases for enhancing genome editing are two of the most exciting and impactful technology advances in modern medicine and science. Human pluripotent stem cells have the potential to establish new model systems for studying human developmental biology and disease mechanisms. Gene correction in patient-specific iPSCs can also provide a novel source for autologous cell therapy. Although historically challenging, precise genome editing in human iPSCs is becoming more feasible with the development of new genome-editing tools, including ZFNs, TALENs, and CRISPR. iPSCs derived from patients of a variety of diseases have been edited to correct disease-associated mutations and to generate isogenic cell lines. After directed differentiation, many of the corrected iPSCs showed restored functionality and demonstrated their potential in cell replacement therapy. Genome-wide analyses of gene-corrected iPSCs have collectively demonstrated a high fidelity of the engineered endonucleases. Remaining challenges in clinical translation of these technologies include maintaining genome integrity of the iPSC clones and the differentiated cells. Given the rapid advances in genome-editing technologies, gene correction is no longer the bottleneck in developing iPSC-based gene and cell therapies; generating functional and transplantable cell types from iPSCs remains the biggest challenge needing to be addressed by the research field. PMID:27256364

Digital detection of endonuclease mediated gene disruption in the HIV provirus

PubMed Central

Sedlak, Ruth Hall; Liang, Shu; Niyonzima, Nixon; De Silva Feelixge, Harshana S.; Roychoudhury, Pavitra; Greninger, Alexander L.; Weber, Nicholas D.; Boissel, Sandrine; Scharenberg, Andrew M.; Cheng, Anqi; Magaret, Amalia; Bumgarner, Roger; Stone, Daniel; Jerome, Keith R.

2016-01-01

Genome editing by designer nucleases is a rapidly evolving technology utilized in a highly diverse set of research fields. Among all fields, the T7 endonuclease mismatch cleavage assay, or Surveyor assay, is the most commonly used tool to assess genomic editing by designer nucleases. This assay, while relatively easy to perform, provides only a semi-quantitative measure of mutation efficiency that lacks sensitivity and accuracy. We demonstrate a simple droplet digital PCR assay that quickly quantitates a range of indel mutations with detection as low as 0.02% mutant in a wild type background and precision (≤6%CV) and accuracy superior to either mismatch cleavage assay or clonal sequencing when compared to next-generation sequencing. The precision and simplicity of this assay will facilitate comparison of gene editing approaches and their optimization, accelerating progress in this rapidly-moving field. PMID:26829887

TALEN- and CRISPR/Cas9-Mediated Gene Editing in Human Pluripotent Stem Cells Using Lipid-Based Transfection.

PubMed

Hendriks, William T; Jiang, Xin; Daheron, Laurence; Cowan, Chad A

2015-08-03

Using custom-engineered nuclease-mediated genome editing, such as Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 nucleases, human pluripotent stem cell (hPSC) lines with knockout or mutant alleles can be generated and differentiated into various cell types. This strategy of genome engineering in hPSCs will prove invaluable for studying human biology and disease. Here, we provide a detailed protocol for design and construction of TALEN and CRISPR vectors, testing of their nuclease activity, and delivery of TALEN or CRISPR vectors into hPSCs. In addition, we describe the use of single-stranded oligodeoxynucleotides (ssODNs) to introduce or repair point mutations. Next, we describe the identification of edited hPSC clones without antibiotic selection, including their clonal selection, genotyping, and expansion for downstream applications. Copyright © 2015 John Wiley & Sons, Inc.

A Student Authored Online Medical Education Textbook: Editing Patterns and Content Evaluation of a Medical Student Wiki

PubMed Central

Thompson, CL; Schulz1, Wade L.; Terrence, Adam

2011-01-01

The University of Minnesota medical student wiki (UMMedWiki) allows students to collaboratively edit classroom notes to support medical education. Since 2007, UMMedWiki has grown to include 1,591 articles that have collectively received 1.2 million pageviews. Although small-scale wikis have become increasingly important, little is known about their dynamics compared to large wikis, such as Wikipedia. To better understand UMMedWiki’s management and its potential reproducibility at other medical schools, we used an edit log with 28,000 entries to evaluate the behavior of its student editors. The development of tools to survey UMMedwiki allows for quality comparisons that improve both the wiki and the curriculum itself. We completed a content survey by comparing the UMMedWiki with two types of rubric data: TIME, a medical education taxonomy consisting of 1500 terms and national epidemiological data on 2,100 diseases. PMID:22195202

Amino acid selective unlabeling for sequence specific resonance assignments in proteins

PubMed Central

Krishnarjuna, B.; Jaipuria, Garima; Thakur, Anushikha

2010-01-01

Sequence specific resonance assignment constitutes an important step towards high-resolution structure determination of proteins by NMR and is aided by selective identification and assignment of amino acid types. The traditional approach to selective labeling yields only the chemical shifts of the particular amino acid being selected and does not help in establishing a link between adjacent residues along the polypeptide chain, which is important for sequential assignments. An alternative approach is the method of amino acid selective ‘unlabeling’ or reverse labeling, which involves selective unlabeling of specific amino acid types against a uniformly 13C/15N labeled background. Based on this method, we present a novel approach for sequential assignments in proteins. The method involves a new NMR experiment named, {12COi–15Ni+1}-filtered HSQC, which aids in linking the 1HN/15N resonances of the selectively unlabeled residue, i, and its C-terminal neighbor, i + 1, in HN-detected double and triple resonance spectra. This leads to the assignment of a tri-peptide segment from the knowledge of the amino acid types of residues: i − 1, i and i + 1, thereby speeding up the sequential assignment process. The method has the advantage of being relatively inexpensive, applicable to 2H labeled protein and can be coupled with cell-free synthesis and/or automated assignment approaches. A detailed survey involving unlabeling of different amino acid types individually or in pairs reveals that the proposed approach is also robust to misincorporation of 14N at undesired sites. Taken together, this study represents the first application of selective unlabeling for sequence specific resonance assignments and opens up new avenues to using this methodology in protein structural studies. Electronic supplementary material The online version of this article (doi:10.1007/s10858-010-9459-z) contains supplementary material, which is available to authorized users. PMID:21153044

antiSMASH 3.0—a comprehensive resource for the genome mining of biosynthetic gene clusters

PubMed Central

Blin, Kai; Duddela, Srikanth; Krug, Daniel; Kim, Hyun Uk; Bruccoleri, Robert; Lee, Sang Yup; Fischbach, Michael A; Müller, Rolf; Wohlleben, Wolfgang; Breitling, Rainer; Takano, Eriko

2015-01-01

Abstract Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software. PMID:25948579

Development of a web-based video management and application processing system

NASA Astrophysics Data System (ADS)

Chan, Shermann S.; Wu, Yi; Li, Qing; Zhuang, Yueting

2001-07-01

How to facilitate efficient video manipulation and access in a web-based environment is becoming a popular trend for video applications. In this paper, we present a web-oriented video management and application processing system, based on our previous work on multimedia database and content-based retrieval. In particular, we extend the VideoMAP architecture with specific web-oriented mechanisms, which include: (1) Concurrency control facilities for the editing of video data among different types of users, such as Video Administrator, Video Producer, Video Editor, and Video Query Client; different users are assigned various priority levels for different operations on the database. (2) Versatile video retrieval mechanism which employs a hybrid approach by integrating a query-based (database) mechanism with content- based retrieval (CBR) functions; its specific language (CAROL/ST with CBR) supports spatio-temporal semantics of video objects, and also offers an improved mechanism to describe visual content of videos by content-based analysis method. (3) Query profiling database which records the `histories' of various clients' query activities; such profiles can be used to provide the default query template when a similar query is encountered by the same kind of users. An experimental prototype system is being developed based on the existing VideoMAP prototype system, using Java and VC++ on the PC platform.

World commercial aircraft accidents: 1st edition, 1946--1991

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

Kimura, C.Y.

1992-02-01

This report is a compilation of all accidents world-wide involving aircraft in commercial service which resulted in the loss of the airframe or one or more fatality, or both. This information has been gathered in order to present a complete inventory of commercial aircraft accidents. Events involving military action, sabotage, terrorist bombings, hijackings, suicides, and industrial ground accidents are included within this list. This report is organized into six chapters. The first chapter is the introduction. The second chapter contains the compilation of accidents involving world commercial jet aircraft from 1952 to 1991. The third chapter presents a compilation ofmore » accidents involving world commercial turboprop aircraft from 1952 to 1991. The fourth chapter presents a compilation of accidents involving world commercial pistonprop aircraft with four or more engines from 1946 to 1991. Each accident compilation or database in chapters two, three and four is presented in chronological order. Each accident is presented with information the following categories: date of accident, airline or operator and its flight number (if known), type of flight, type of aircraft and model, aircraft registration number, construction number/manufacturers serial number, aircraft damage resulting from accident, accident flight phase, accident location, number of fatalities, number of occupants, references used to compile the information, and finally cause, remarks, or description (brief) of the accident. The fifth chapter presents a list of all commercial aircraft accidents for all aircraft types with 100 or more fatalities in order of decreasing number of fatalities. Chapter six presents the commercial aircraft accidents for all aircraft types by flight phase. Future editions of this report will have additional follow-on chapters which will present other studies still in preparation at the time this edition was being prepared.« less

Particle Detectors

NASA Astrophysics Data System (ADS)

Grupen, Claus; Shwartz, Boris

2011-09-01

Preface to the first edition; Preface to the second edition; Introduction; 1. Interactions of particles and radiation with matter; 2. Characteristic properties of detectors; 3. Units of radiation measurements and radiation sources; 4. Accelerators; 5. Main physical phenomena used for particle detection and basic counter types; 6. Historical track detectors; 7. Track detectors; 8. Calorimetry; 9. Particle identification; 10. Neutrino detectors; 11. Momentum measurement and muon detection; 12. Ageing and radiation effects; 13. Example of a general-purpose detector: Belle; 14. Electronics; 15. Data analysis; 16. Applications of particle detectors outside particle physics; 17. Glossary; 18. Solutions; 19. Resumé; Appendixes; Index.

Crowdsourcing The National Map

USGS Publications Warehouse

McCartney, Elizabeth; Craun, Kari J.; Korris, Erin M.; Brostuen, David A.; Moore, Laurence R.

2015-01-01

Using crowdsourcing techniques, the US Geological Survey’s (USGS) Volunteered Geographic Information (VGI) project known as “The National Map Corps (TNMCorps)” encourages citizen scientists to collect and edit data about man-made structures in an effort to provide accurate and authoritative map data for the USGS National Geospatial Program’s web-based The National Map. VGI is not new to the USGS, but past efforts have been hampered by available technologies. Building on lessons learned, TNMCorps volunteers are successfully editing 10 different structure types in all 50 states as well as Puerto Rico and the US Virgin Islands.

The Teacher's Role: Children and Epilepsy. A Guide for School Personnel. Revised Edition.

ERIC Educational Resources Information Center

Epilepsy Foundation of America, Landover, MD.

The brief guide offers information on epilepsy to teachers and other school personnel. Types of seizures are defined (e.g., simple and complex partial seizures, generalized tonic clonic seizures), and management practices in the classroom setting for each type of seizure are described. Signs indicating that a seizure requires immediate medical…

Audio Control Handbook For Radio and Television Broadcasting. Third Revised Edition.

ERIC Educational Resources Information Center

Oringel, Robert S.

Audio control is the operation of all the types of sound equipment found in the studios and control rooms of a radio or television station. Written in a nontechnical style for beginners, the book explains thoroughly the operation of all types of audio equipment. Diagrams and photographs of commercial consoles, microphones, turntables, and tape…

DNA Microarray Profiling of a Diverse Collection of Nosocomial Methicillin-Resistant Staphylococcus aureus Isolates Assigns the Majority to the Correct Sequence Type and Staphylococcal Cassette Chromosome mec (SCCmec) Type and Results in the Subsequent Identification and Characterization of Novel SCCmec-SCCM1 Composite Islands

PubMed Central

Brennan, Orla M.; Deasy, Emily C.; Rossney, Angela S.; Kinnevey, Peter M.; Ehricht, Ralf; Monecke, Stefan; Coleman, David C.

2012-01-01

One hundred seventy-five isolates representative of methicillin-resistant Staphylococcus aureus (MRSA) clones that predominated in Irish hospitals between 1971 and 2004 and that previously underwent multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing were characterized by spa typing (175 isolates) and DNA microarray profiling (107 isolates). The isolates belonged to 26 sequence type (ST)-SCCmec types and subtypes and 35 spa types. The array assigned all isolates to the correct MLST clonal complex (CC), and 94% (100/107) were assigned an ST, with 98% (98/100) correlating with MLST. The array assigned all isolates to the correct SCCmec type, but subtyping of only some SCCmec elements was possible. Additional SCCmec/SCC genes or DNA sequence variation not detected by SCCmec typing was detected by array profiling, including the SCC-fusidic acid resistance determinant Q6GD50/fusC. Novel SCCmec/SCC composite islands (CIs) were detected among CC8 isolates and comprised SCCmec IIA-IIE, IVE, IVF, or IVg and a ccrAB4-SCC element with 99% DNA sequence identity to SCCM1 from ST8/t024-MRSA, SCCmec VIII, and SCC-CI in Staphylococcus epidermidis. The array showed that the majority of isolates harbored one or more superantigen (94%; 100/107) and immune evasion cluster (91%; 97/107) genes. Apart from fusidic acid and trimethoprim resistance, the correlation between isolate antimicrobial resistance phenotype and the presence of specific resistance genes was ≥97%. Array profiling allowed high-throughput, accurate assignment of MRSA to CCs/STs and SCCmec types and provided further evidence of the diversity of SCCmec/SCC. In most cases, array profiling can accurately predict the resistance phenotype of an isolate. PMID:22869569

Low-energy-electron scattering by CH3CN

NASA Astrophysics Data System (ADS)

Maioli, Leticia S.; Bettega, Márcio H. F.

2017-12-01

We report integral and differential cross sections for the elastic scattering of low-energy electrons by methyl cyanide (CH3CN), also known as acetonitrile. The cross sections were computed using the Schwinger multichannel method implemented with pseudopotentials. The fixed-nuclei scattering calculations were performed in the static-exchange and static-exchange plus polarization approximations for energies up to 15 eV. In our calculations with polarization effects, we found a π* shape resonance at around 2.22 eV and a broad structure associated to a σ* shape resonance at around 7 eV. The low-lying resonance was assigned to the electron capture by the two-fold degenerate π* orbital of the E symmetry of C3v group; the second was assigned to a σ* shape resonance in the A1 symmetry. We compared our cross sections with theoretical results and experimental data available in the literature, and in general we found good agreement for the positions of the two resonances. Contribution to the Topical Issue: "Low Energy Positron and Electron Interactions", edited by James Sullivan, Ron White, Michael Bromley, Ilya Fabrikant, and David Cassidy.

Pasteurellosis

USDA-ARS?s Scientific Manuscript database

This book chapter for the 11th edition of Diseases of Swine describes the current state of knowledge regarding diseases of swine caused by Pasteurella multocida, including progressive atrophic rhinitis and pneumonic and septicemic pasteurellosis. Topics covered include traditional and novel typing ...

Potentially Reversible Social Deficits Among Transgender Youth.

PubMed

Turban, Jack L

2018-05-12

Recently, there has been increased attention to a putative relationship between Autism Spectrum Disorder (ASD) and gender dysphoria, the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis for those whose gender assigned at birth does not match their gender identity. Studies have shown an over-representation of ASD symptoms among transgender youth. These studies, however, have used scales that are non-specific for ASD. These ASD symptoms may represent social deficits that are secondary to social stress and deprivation, as transgender youth suffer high rates of peer and family rejection. These social deficits may not represent true ASD and may be reversible as patients are affirmed in their gender identities and social stress is reduced.

Modifying an Insect Cell N-Glycan Processing Pathway Using CRISPR-Cas Technology.

PubMed

Mabashi-Asazuma, Hideaki; Kuo, Chu-Wei; Khoo, Kay-Hooi; Jarvis, Donald L

2015-10-16

Fused lobes (FDL) is an enzyme that simultaneously catalyzes a key trimming reaction and antagonizes elongation reactions in the insect N-glycan processing pathway. Accordingly, FDL function accounts, at least in part, for major differences in the N-glycosylation patterns of glycoproteins produced by insect and mammalian cells. In this study, we used the CRISPR-Cas9 system to edit the fdl gene in Drosophila melanogaster S2 cells. CRISPR-Cas9 editing produced a high frequency of site-specific nucleotide insertions and deletions, reduced the production of insect-type, paucimannosidic products (Man3GlcNAc2), and led to the production of partially elongated, mammalian-type complex N-glycans (GlcNAc2Man3GlcNAc2) in S2 cells. As CRISPR-Cas9 has not been widely used to analyze or modify protein glycosylation pathways or edit insect cell genes, these results underscore its broad utility as a tool for these purposes. Our results also confirm the key role of FDL at the major branch point distinguishing insect and mammalian N-glycan processing pathways. Finally, the new FDL-deficient S2 cell derivative produced in this study will enable future bottom-up glycoengineering efforts designed to isolate insect cell lines that can efficiently produce recombinant glycoproteins with chemically predefined oligosaccharide side-chain structures.

Assembly line termination in cylindrocyclophane biosynthesis: discovery of an editing type II thioesterase domain in a type I polyketide synthase† †Electronic supplementary information (ESI) available: Fig. S1–S12; Tables S1–S8, full experimental details and procedures, 1H and 13C NMR spectral data and HRMS data of compounds 10 and 11 and the internal standards. See DOI: 10.1039/c4sc03132f Click here for additional data file.

PubMed Central

Nakamura, H.; Wang, J. X.

2015-01-01

The termination step is an important source of structural diversity in polyketide biosynthesis. Most type I polyketide synthase (PKS) assembly lines are terminated by a thioesterase (TE) domain located at the C-terminus of the final module, while other PKS assembly lines lack a terminal TE domain and are instead terminated by a separate enzyme in trans. In cylindrocyclophane biosynthesis, the type I modular PKS assembly line is terminated by a freestanding type III PKS (CylI). Unexpectedly, the final module of the type I PKS (CylH) also possesses a C-terminal TE domain. Unlike typical type I PKSs, the CylH TE domain does not influence assembly line termination by CylI in vitro. Instead, this domain phylogenetically resembles a type II TE and possesses activity consistent with an editing function. This finding may shed light on the evolution of unusual PKS termination logic. In addition, the presence of related type II TE domains in many cryptic type I PKS and nonribosomal peptide synthetase (NRPS) assembly lines has implications for pathway annotation, product prediction, and engineering. PMID:29218151

Optimized approach for Ion Proton RNA sequencing reveals details of RNA splicing and editing features of the transcriptome.

PubMed

Brown, Roger B; Madrid, Nathaniel J; Suzuki, Hideaki; Ness, Scott A

2017-01-01

RNA-sequencing (RNA-seq) has become the standard method for unbiased analysis of gene expression but also provides access to more complex transcriptome features, including alternative RNA splicing, RNA editing, and even detection of fusion transcripts formed through chromosomal translocations. However, differences in library methods can adversely affect the ability to recover these different types of transcriptome data. For example, some methods have bias for one end of transcripts or rely on low-efficiency steps that limit the complexity of the resulting library, making detection of rare transcripts less likely. We tested several commonly used methods of RNA-seq library preparation and found vast differences in the detection of advanced transcriptome features, such as alternatively spliced isoforms and RNA editing sites. By comparing several different protocols available for the Ion Proton sequencer and by utilizing detailed bioinformatics analysis tools, we were able to develop an optimized random primer based RNA-seq technique that is reliable at uncovering rare transcript isoforms and RNA editing features, as well as fusion reads from oncogenic chromosome rearrangements. The combination of optimized libraries and rapid Ion Proton sequencing provides a powerful platform for the transcriptome analysis of research and clinical samples.

Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model.

PubMed

Wu, Wenbo; Lu, Zhiwei; Li, Fei; Wang, Wenjie; Qian, Nannan; Duan, Jinzhi; Zhang, Yu; Wang, Fengchao; Chen, Ting

2017-02-14

The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that nonreplicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatal mice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mouse model, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues.

In vivo genome editing of the albumin locus as a platform for protein replacement therapy

PubMed Central

Sharma, Rajiv; Anguela, Xavier M.; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C.; Sproul, Scott; Paschon, David E.; Miller, Jeffrey C.; Davidson, Robert J.; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D.; Holmes, Michael C.; Rebar, Edward J.

2015-01-01

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) –mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. PMID:26297739

Comparisons of node-based and element-based approaches of assigning bone material properties onto subject-specific finite element models.

PubMed

Chen, G; Wu, F Y; Liu, Z C; Yang, K; Cui, F

2015-08-01

Subject-specific finite element (FE) models can be generated from computed tomography (CT) datasets of a bone. A key step is assigning material properties automatically onto finite element models, which remains a great challenge. This paper proposes a node-based assignment approach and also compares it with the element-based approach in the literature. Both approaches were implemented using ABAQUS. The assignment procedure is divided into two steps: generating the data file of the image intensity of a bone in a MATLAB program and reading the data file into ABAQUS via user subroutines. The node-based approach assigns the material properties to each node of the finite element mesh, while the element-based approach assigns the material properties directly to each integration point of an element. Both approaches are independent from the type of elements. A number of FE meshes are tested and both give accurate solutions; comparatively the node-based approach involves less programming effort. The node-based approach is also independent from the type of analyses; it has been tested on the nonlinear analysis of a Sawbone femur. The node-based approach substantially improves the level of automation of the assignment procedure of bone material properties. It is the simplest and most powerful approach that is applicable to many types of analyses and elements. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Personal, Expository, Critical, and Creative: Using Writing in Mathematics Courses

ERIC Educational Resources Information Center

Braun, Benjamin

2014-01-01

This article provides a framework for creating and using writing assignments based on four types of writing: personal, expository, critical, and creative. This framework includes specific areas of student growth affected by these writing styles. Illustrative sample assignments are given throughout for each type of writing and various combinations…

Optimization of non-denaturing protein extraction conditions for plant PPR proteins.

PubMed

Andrés-Colás, Nuria; Van Der Straeten, Dominique

2017-01-01

Pentatricopeptide repeat proteins are one of the major protein families in flowering plants, containing around 450 members. They participate in RNA editing and are related to plant growth, development and reproduction, as well as to responses to ABA and abiotic stresses. Their characteristics have been described in silico; however, relatively little is known about their biochemical properties. Different types of PPR proteins, with different tasks in RNA editing, have been suggested to interact in an editosome to complete RNA editing. Other non-PPR editing factors, such as the multiple organellar RNA editing factors and the organelle RNA recognition motif-containing protein family, for example, have also been described in plants. However, while evidence on protein interactions between non-PPR RNA editing proteins is accumulating, very few PPR protein interactions have been reported; possibly due to their high instability. In this manuscript, we aimed to optimize the conditions for non-denaturing protein extraction of PPR proteins allowing in vivo protein analyses, such as interaction assays by co-immunoprecipitation. The unusually high protein degradation rate, the aggregation properties and the high pI, as well as the ATP-dependence of some PPR proteins, are key aspects to be considered when extracting PPR proteins in a non-denatured state. During extraction of PPR proteins, the use of proteasome and phosphatase inhibitors is critical. The use of the ATP-cofactor reduces considerably the degradation of PPR proteins. A short centrifugation step to discard cell debris is essential to avoid PPR precipitation; while in some cases, addition of a reductant is needed, probably caused by the pI/pH context. This work provides an easy and rapid optimized non-denaturing total protein extraction protocol from plant tissue, suitable for polypeptides of the PPR family.

Genetics of the connective tissue proteins: Assignment of the gene for human type I procollagen to chromosome 17 by analysis of cell hybrids and microcell hybrids*

PubMed Central

Raj, Cholappadi V. Sundar; Church, Robert L.; Klobutcher, Lawrence A.; Ruddle, Frank H.

1977-01-01

Somatic cell hybrids between mouse and human cell lines have been used to identify the specific chromosome that governs the synthesis of type I procollagen. Fourteen hybrid clones and subclones were derived independently from crosses between mouse parents [LM (thymidine kinase-negative) or A9 (hypoxanthine phosphoribosyltransferase-negative)] and human cells (human diploid lung fibroblasts WI-38 or diploid skin fibroblasts GM5, GM17, and GM9). The cultures were labeled with [3H]proline in modified Eagle's medium without serum. Radioactive procollagens were purified from the medium by the method of Church et al. [(1974) J. Mol. Biol. 86, 785-799]. DEAE-cellulose chromatography was used to separate collagen and type I and type III procollagen. Human type I procollagen was assayed by double immunodiffusion analysis with type I procollagen antibodies prepared by immunizing rabbits with purified human type I procollagen. These analyses combined with karyology and isozyme analyses of each hybrid line have produced evidence for the assignment of the gene for human type I procollagen to chromosome 17. A human microcell-mouse hybrid cell line containing only human chromosome 17 was positive for human type I procollagen, lending further support to the assignment of the human type I procollagen gene to chromosome 17. Finally, by using a hybrid line containing only the long arm of human chromosome 17 translocated onto a mouse chromosome, the type I procollagen gene can be assigned more specifically to the long arm of chromosome 17. Images PMID:412188

Statistical Optics

NASA Astrophysics Data System (ADS)

Goodman, Joseph W.

2000-07-01

The Wiley Classics Library consists of selected books that have become recognized classics in their respective fields. With these new unabridged and inexpensive editions, Wiley hopes to extend the life of these important works by making them available to future generations of mathematicians and scientists. Currently available in the Series: T. W. Anderson The Statistical Analysis of Time Series T. S. Arthanari & Yadolah Dodge Mathematical Programming in Statistics Emil Artin Geometric Algebra Norman T. J. Bailey The Elements of Stochastic Processes with Applications to the Natural Sciences Robert G. Bartle The Elements of Integration and Lebesgue Measure George E. P. Box & Norman R. Draper Evolutionary Operation: A Statistical Method for Process Improvement George E. P. Box & George C. Tiao Bayesian Inference in Statistical Analysis R. W. Carter Finite Groups of Lie Type: Conjugacy Classes and Complex Characters R. W. Carter Simple Groups of Lie Type William G. Cochran & Gertrude M. Cox Experimental Designs, Second Edition Richard Courant Differential and Integral Calculus, Volume I RIchard Courant Differential and Integral Calculus, Volume II Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume I Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume II D. R. Cox Planning of Experiments Harold S. M. Coxeter Introduction to Geometry, Second Edition Charles W. Curtis & Irving Reiner Representation Theory of Finite Groups and Associative Algebras Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume I Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume II Cuthbert Daniel Fitting Equations to Data: Computer Analysis of Multifactor Data, Second Edition Bruno de Finetti Theory of Probability, Volume I Bruno de Finetti Theory of Probability, Volume 2 W. Edwards Deming Sample Design in Business Research

Extended Edited Synoptic Cloud Reports from Ships and Land Stations Over the Globe, 1952-2009 (NDP-026C)

DOE Data Explorer

Hahn, C. J. [University of Arizona; Warren, S. G. [University of Washington; Eastman, R.

1999-08-01

This database contains surface synoptic weather reports for the entire globe, gathered from various available data sets. The reports were processed, edited, and rewritten to provide a single dataset of individual observations of clouds, spanning the 57 years 1952-2008 for ship data and the 39 years 1971-2009 for land station data. In addition to the cloud portion of the synoptic report, each edited report also includes the associated pressure, present weather, wind, air temperature, and dew point (and sea surface temperature over oceans). This data set is called the "Extended Edited Cloud Report Archive" (EECRA). The EECRA is based solely on visual cloud observations from weather stations, reported in the WMO synoptic code (WMO, 1974). Reports must contain cloud-type information to be included in the archive. Past data sources include those from the Fleet Numerical Oceanographic Center (FNOC, 1971-1976) and the National Centers for Environmental Prediction (NCEP, 1977-1996). This update uses data from a new source, the 'Integrated Surface Database' (ISD, 1997-2009; Smith et al., 2011). Our past analyses of the EECRA identified a subset of 5388 weather stations that were determined to produce reliable day and night observations of cloud amount and type. The update contains observations only from this subset of stations. Details concerning processing, previous problems, contents, and comments are available in the archive's original documentation . The EECRA contains about 81 million cloud observations from ships and 380 million from land stations. The data files have been compressed using unix. Unix/linux users can "uncompress" or "gunzip" the files after downloading. If you're interested in the NDP-026C database, then you'll also want to explore its related data products, NDP-026D and NDP-026E.

Training for healthy older drivers : traffic tech.

DOT National Transportation Integrated Search

2013-05-01

The research described in this edition of "Traffic Tech" examined the effectiveness of four types of : training techniques designed to improve the driving performance : of normally aging adults. Each technique is suitable : for a broad cross-section ...

Accessing the Microform Publication.

ERIC Educational Resources Information Center

Schindler, Stan

1985-01-01

Characterizes types of indexing programs used by Research Publications, Inc. and describes provision of access to four major projects: "The Official Washington Post Index" (provides access to newspaper and microfilm edition); "The Eighteenth Century"; "The Declassified Documents Reference System" (ongoing fiche…

Project Management and Systems Engineering Guide. Second Edition

DTIC Science & Technology

1989-09-30

depend on the type of requirement. In general, opera- tional requirements will fall into one of the following categories : 1. Replacement of an existing...Warranty service and maintenance contracts also fall into this support category . The planning for phase-in type support must be accomplished during the...fixed-price incentive (FPI). The second general category of contracts is cost reimbursement. Under a cost- type contract, the product is not paid for on

Cancer of the Esophagus and Esophagogastric Junction: An Eighth Edition Staging Primer

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Ferguson, Mark K.; Blackstone, Eugene H.; Goldstraw, Peter

2017-01-01

This primer for eighth edition staging of esophageal and esophagogastric epithelial cancers presents separate classifications for the clinical (cTNM), pathologic (pTNM), and postneoadjuvant pathologic (ypTNM) stage groups, which are no longer shared. For pTNM, pT1 has been subcategorized as pT1a and pT1b for the subgrouping pStage I adenocarcinoma and squamous cell carcinoma. A new, simplified esophagus-specific regional lymph node map has been introduced. Undifferentiated histologic grade (G4) has been eliminated; additional analysis is required to expose histopathologic cell type. Location has been removed as a category for pT2N0M0 squamous cell cancer. The definition of the esophagogastric junction has been revised. ypTNM stage groups are identical for both histopathologic cell types, unlike those for cTNM and pTNM. PMID:27810391

Are two spaces better than one? The effect of spacing following periods and commas during reading.

PubMed

Johnson, Rebecca L; Bui, Becky; Schmitt, Lindsay L

2018-04-24

The most recent edition of the American Psychological Association (APA) Manual states that two spaces should follow the punctuation at the end of a sentence. This is in contrast to the one-space requirement from previous editions. However, to date, there has been no empirical support for either convention. In the current study, participants performed (1) a typing task to assess spacing usage and (2) an eye-tracking experiment to assess the effect that punctuation spacing has on reading performance. Although comprehension was not affected by punctuation spacing, the eye movement record suggested that initial processing of the text was facilitated when periods were followed by two spaces, supporting the change made to the APA Manual. Individuals' typing usage also influenced these effects such that those who use two spaces following a period showed the greatest overall facilitation from reading with two spaces.

28 CFR 524.72 - CIM assignment categories.

Code of Federal Regulations, 2010 CFR

2010-07-01

... groups (e.g., prison gangs), which have a history of disrupting operations and security in either state... assignment categories. CIM cases are classified according to the following assignments: (a) Witness Security... safety of these individuals. There are two types of Witness Security cases: Department of Justice...

A graph edit dictionary for correcting errors in roof topology graphs reconstructed from point clouds

NASA Astrophysics Data System (ADS)

Xiong, B.; Oude Elberink, S.; Vosselman, G.

2014-07-01

In the task of 3D building model reconstruction from point clouds we face the problem of recovering a roof topology graph in the presence of noise, small roof faces and low point densities. Errors in roof topology graphs will seriously affect the final modelling results. The aim of this research is to automatically correct these errors. We define the graph correction as a graph-to-graph problem, similar to the spelling correction problem (also called the string-to-string problem). The graph correction is more complex than string correction, as the graphs are 2D while strings are only 1D. We design a strategy based on a dictionary of graph edit operations to automatically identify and correct the errors in the input graph. For each type of error the graph edit dictionary stores a representative erroneous subgraph as well as the corrected version. As an erroneous roof topology graph may contain several errors, a heuristic search is applied to find the optimum sequence of graph edits to correct the errors one by one. The graph edit dictionary can be expanded to include entries needed to cope with errors that were previously not encountered. Experiments show that the dictionary with only fifteen entries already properly corrects one quarter of erroneous graphs in about 4500 buildings, and even half of the erroneous graphs in one test area, achieving as high as a 95% acceptance rate of the reconstructed models.

Reading Aloud, Play, and Social-Emotional Development.

PubMed

Mendelsohn, Alan L; Cates, Carolyn Brockmeyer; Weisleder, Adriana; Berkule Johnson, Samantha; Seery, Anne M; Canfield, Caitlin F; Huberman, Harris S; Dreyer, Benard P

2018-05-01

To determine impacts on social-emotional development at school entry of a pediatric primary care intervention (Video Interaction Project [VIP]) promoting positive parenting through reading aloud and play, delivered in 2 phases: infant through toddler (VIP birth to 3 years [VIP 0-3]) and preschool-age (VIP 3 to 5 years [VIP 3-5]). Factorial randomized controlled trial with postpartum enrollment and random assignment to VIP 0-3, control 0 to 3 years, and a third group without school entry follow-up (Building Blocks) and 3-year second random assignment of VIP 0-3 and control 0 to 3 years to VIP 3-5 or control 3 to 5 years. In the VIP, a bilingual facilitator video recorded the parent and child reading and/or playing using provided learning materials and reviewed videos to reinforce positive interactions. Social-emotional development at 4.5 years was assessed by parent-report Behavior Assessment System for Children, Second Edition (Social Skills, Attention Problems, Hyperactivity, Aggression, Externalizing Problems). VIP 0-3 and VIP 3-5 were independently associated with improved 4.5-year Behavior Assessment System for Children, Second Edition T-scores, with effect sizes (Cohen's d) ∼-0.25 to -0.30. Receipt of combined VIP 0-3 and VIP 3-5 was associated with d = -0.63 reduction in Hyperactivity ( P = .001). VIP 0-3 resulted in reduced "Clinically Significant" Hyperactivity (relative risk reduction for overall sample: 69.2%; P = .03; relative risk reduction for increased psychosocial risk: 100%; P = .006). Multilevel models revealed significant VIP 0-3 linear effects and age × VIP 3-5 interactions. Phase VIP 0-3 resulted in sustained impacts on behavior problems 1.5 years after program completion. VIP 3-5 had additional, independent impacts. With our findings, we support the use of pediatric primary care to promote reading aloud and play from birth to 5 years, and the potential for such programs to enhance social-emotional development. Copyright © 2018 by the American Academy of Pediatrics.

Easing Your Pain: A Method for Evaluating Research Writing from Students

ERIC Educational Resources Information Center

Jensen, Barbara E.; Martin, Kathleen A.; Mann, Betty L.; Fogarty, Tracey

2004-01-01

Throughout their undergraduate and graduate careers, students are assigned various types of papers that require scientific writing style. The scope of these assignments include laboratory reports that require only graphing and statements of findings; abstract assignments with critical summaries included; abbreviated research papers, including…

Automated solar collector installation design

DOEpatents

Wayne, Gary; Frumkin, Alexander; Zaydman, Michael; Lehman, Scott; Brenner, Jules

2014-08-26

Embodiments may include systems and methods to create and edit a representation of a worksite, to create various data objects, to classify such objects as various types of pre-defined "features" with attendant properties and layout constraints. As part of or in addition to classification, an embodiment may include systems and methods to create, associate, and edit intrinsic and extrinsic properties to these objects. A design engine may apply of design rules to the features described above to generate one or more solar collectors installation design alternatives, including generation of on-screen and/or paper representations of the physical layout or arrangement of the one or more design alternatives.

Validity aspects of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, narcissistic personality disorder construct.

PubMed

Karterud, Sigmund; Øien, Maria; Pedersen, Geir

2011-01-01

The Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, narcissistic personality disorder (NPD) construct has been criticized for being too narrowly defined, for example, by focusing on overt grandiosity at the expense of exhibitionism and narcissistic vulnerability and thus covering only parts of the domain of narcissism. The purpose of this study was to elucidate several validity aspects of the NPD construct. The material consisted of data from 2277 patients (80% of whom had a personality disorder [PD]) who were admitted to units connected to The Norwegian Network of Psychotherapeutic Day Hospitals. The Axis II diagnoses were assessed by Structured Clinical Interview for DSM, Fourth Edition, Axis II Personality Disorders. The frequency of NPD was very low (0.8%). Male patients were overrepresented both on a diagnostic level and on criteria levels. The NPD category was positively associated with other cluster B disorders and negatively associated with avoidant PD. The criteria "demands excessive admiration" and "fantasies of unlimited success" correlated almost as highly with the histrionic PD category and loaded primarily on a histrionic factor. The dominant NPD factor also included the antisocial criterion of "showing no regret having injured others." The major part of the patients' personality pathology could be attributed to other PD criteria. The results challenge the notion of NPD as a distinct diagnostic category. Rather, narcissism should be conceived as personality dimensions pertinent to the whole range of PDs. The results support the views put forward by Russ et al (Refining the construct of narcissistic personality disorder: diagnostic criteria and subtypes. Am J Psychiatry 2008;11:1473-1481) that what clinicians conceive as narcissism consists of several subtypes (dimensions). Our data support the existence of a grandiose/malignant type and an exhibitionistic type. Unfortunately, there was no measure of hypersensitivity. The proposal to delete NPD as a prototype category in the DSM, Fifth Edition, seems well justified. However, the proposed trait domain of antagonism in the DSM, Fifth Edition, seems to account better for the grandiose/malignant dimension than the exhibitionistic/histrionic dimension. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Plagiarism-Proofing Assignments

ERIC Educational Resources Information Center

Johnson, Doug

2004-01-01

Mr. Johnson has discovered that the higher the level of student engagement and creativity, the lower the probability of plagiarism. For teachers who would like to see such desirable results, he describes the characteristics of assignments that are most likely to produce them. Two scenarios of types of assignments that avoid plagiarism are…

Learner Perspectives Regarding Device Type in Technology-Assisted Language Learning

ERIC Educational Resources Information Center

Ko, Myong-Hee

2017-01-01

This study compared learner perspectives regarding using PCs and smartphones as learning devices. A total of 167 Korean university students completed online assignments designed to maximize interaction with these devices. The assignments required students to submit their responses regarding assigned reading passages for a semester. Then they…

41 CFR 302-8.202 - Do provisions for the place, choice, or type of storage, allowable costs, or partial storage...

Code of Federal Regulations, 2010 CFR

2010-07-01

... place, choice, or type of storage, allowable costs, or partial storage during assignment OCONUS differ from those prescribed for storage during assignment to isolated locations in CONUS? 302-8.202 Section 302-8.202 Public Contracts and Property Management Federal Travel Regulation System RELOCATION...

41 CFR 302-3.208 - What relocation expenses will my agency pay for my overseas assignment and return?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 41 Public Contracts and Property Management 4 2011-07-01 2011-07-01 false What relocation expenses... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Overseas Assignment and Return § 302-3.208 What...

41 CFR 302-3.208 - What relocation expenses will my agency pay for my overseas assignment and return?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 41 Public Contracts and Property Management 4 2014-07-01 2014-07-01 false What relocation expenses... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Overseas Assignment and Return § 302-3.208 What...

41 CFR 302-3.208 - What relocation expenses will my agency pay for my overseas assignment and return?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 4 2013-07-01 2012-07-01 true What relocation expenses... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Overseas Assignment and Return § 302-3.208 What...

41 CFR 302-3.208 - What relocation expenses will my agency pay for my overseas assignment and return?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false What relocation expenses... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Overseas Assignment and Return § 302-3.208 What...

41 CFR 302-3.207 - Am I eligible to receive relocation allowances for overseas assignment and return travel?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 41 Public Contracts and Property Management 4 2014-07-01 2014-07-01 false Am I eligible to receive... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Overseas Assignment and Return § 302-3.207 Am I...

41 CFR 302-3.208 - What relocation expenses will my agency pay for my overseas assignment and return?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What relocation expenses... and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Overseas Assignment and Return § 302-3.208 What...

Rescuing discarded spectra: Full comprehensive analysis of a minimal proteome.

PubMed

Lluch-Senar, Maria; Mancuso, Francesco M; Climente-González, Héctor; Peña-Paz, Marcia I; Sabido, Eduard; Serrano, Luis

2016-02-01

A common problem encountered when performing large-scale MS proteome analysis is the loss of information due to the high percentage of unassigned spectra. To determine the causes behind this loss we have analyzed the proteome of one of the smallest living bacteria that can be grown axenically, Mycoplasma pneumoniae (729 ORFs). The proteome of M. pneumoniae cells, grown in defined media, was analyzed by MS. An initial search with both Mascot and a species-specific NCBInr database with common contaminants (NCBImpn), resulted in around 79% of the acquired spectra not having an assignment. The percentage of non-assigned spectra was reduced to 27% after re-analysis of the data with the PEAKS software, thereby increasing the proteome coverage of M. pneumoniae from the initial 60% to over 76%. Nonetheless, 33,413 spectra with assigned amino acid sequences could not be mapped to any NCBInr database protein sequence. Approximately, 1% of these unassigned peptides corresponded to PTMs and 4% to M. pneumoniae protein variants (deamidation and translation inaccuracies). The most abundant peptide sequence variants (Phe-Tyr and Ala-Ser) could be explained by alterations in the editing capacity of the corresponding tRNA synthases. About another 1% of the peptides not associated to any protein had repetitions of the same aromatic/hydrophobic amino acid at the N-terminus, or had Arg/Lys at the C-terminus. Thus, in a model system, we have maximized the number of assigned spectra to 73% (51,453 out of the 70,040 initial acquired spectra). All MS data have been deposited in the ProteomeXchange with identifier PXD002779 (http://proteomecentral.proteomexchange.org/dataset/PXD002779). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

PubMed

Coccaro, Emil F

2011-01-01

This study was designed to develop a revised diagnostic criteria set for intermittent explosive disorder (IED) for consideration for inclusion in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). This revised criteria set was developed by integrating previous research criteria with elements from the current DSM-IV set of diagnostic criteria. Evidence supporting the reliability and validity of IED-IR ("IED Integrated Criteria") in a new and well-characterized group of subjects with personality disorder is presented. Clinical, phenomenologic, and diagnostic data from 201 individuals with personality disorder were reviewed. All IED diagnoses were assigned using a best-estimate process (eg, kappa for IED-IR >0.85). In addition, subjects meeting IED-IR criteria had higher scores on dimensional measures of aggression and had lower global functioning scores than non-IED-IR subjects, even when related variables were controlled. The IED-IR criteria were more sensitive than the DSM-IV criteria only in identifying subjects with significant impulsive-aggressive behavior by a factor of 16. We conclude that the IED-IR criteria can be reliably applied and have sufficient validity to warrant consideration as DSM-V criteria for IED. Copyright © 2011 Elsevier Inc. All rights reserved.

The development of a computer assisted instruction and assessment system in pharmacology.

PubMed

Madsen, B W; Bell, R C

1977-01-01

We describe the construction of a computer based system for instruction and assessment in pharmacology, utilizing a large bank of multiple choice questions. Items were collected from many sources, edited and coded for student suitability, topic, taxonomy and difficulty and text references. Students reserve a time during the day, specify the type of test desired and questions are presented randomly from the subset satisfying their criteria. Answers are scored after each question and a summary given at the end of every test; details on item performance are recorded automatically. The biggest hurdle in implementation was the assembly, review, classification and editing of items, while the programming was relatively straight-forward. A number of modifications had to be made to the initial plans and changes will undoubtedly continue with further experience. When fully operational the system will possess a number of advantages including: elimination of test preparation, editing and marking; facilitated item review opportunities; increased objectivity, feedback, flexibility and descreased anxiety in students.

Molecular structure input on the web.

PubMed

Ertl, Peter

2010-02-02

A molecule editor, that is program for input and editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. This review focuses on a special type of molecule editors, namely those that are used for molecule structure input on the web. Scientific computing is now moving more and more in the direction of web services and cloud computing, with servers scattered all around the Internet. Thus a web browser has become the universal scientific user interface, and a tool to edit molecules directly within the web browser is essential.The review covers a history of web-based structure input, starting with simple text entry boxes and early molecule editors based on clickable maps, before moving to the current situation dominated by Java applets. One typical example - the popular JME Molecule Editor - will be described in more detail. Modern Ajax server-side molecule editors are also presented. And finally, the possible future direction of web-based molecule editing, based on technologies like JavaScript and Flash, is discussed.

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

PubMed

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

2015-02-05

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

CRISPR system for genome engineering: the application for autophagy study.

PubMed

Cui, Jianzhou; Chew, Shirley Jia Li; Shi, Yin; Gong, Zhiyuan; Shen, Han-Ming

2017-05-01

CRISPR/Cas9 is the latest tool introduced in the field of genome engineering and is so far the best genome-editing tool as compared to its precedents such as, meganucleases, zinc finger nucleases (ZFNs) and transcription activator-like effectors (TALENs). The simple design and assembly of the CRISPR/Cas9 system makes genome editing easy to perform as it uses small guide RNAs that correspond to their DNA targets for high efficiency editing. This has helped open the doors for multiplexible genome targeting in many species that were intractable using old genetic perturbation techniques. Currently, The CRISPR system is revolutionizing the way biological researches are conducted and paves a bright future not only in research but also in medicine and biotechnology. In this review, we evaluated the history, types and structure, the mechanism of action of CRISPR/Cas System. In particular, we focused on the application of this powerful tool in autophagy research. [BMB Reports 2017; 50(5): 247-256].

Genome Editing in Mouse Spermatogonial Stem/Progenitor Cells Using Engineered Nucleases

PubMed Central

Fanslow, Danielle A.; Wirt, Stacey E.; Barker, Jenny C.; Connelly, Jon P.; Porteus, Matthew H.; Dann, Christina Tenenhaus

2014-01-01

Editing the genome to create specific sequence modifications is a powerful way to study gene function and promises future applicability to gene therapy. Creation of precise modifications requires homologous recombination, a very rare event in most cell types that can be stimulated by introducing a double strand break near the target sequence. One method to create a double strand break in a particular sequence is with a custom designed nuclease. We used engineered nucleases to stimulate homologous recombination to correct a mutant gene in mouse “GS” (germline stem) cells, testicular derived cell cultures containing spermatogonial stem cells and progenitor cells. We demonstrated that gene-corrected cells maintained several properties of spermatogonial stem/progenitor cells including the ability to colonize following testicular transplantation. This proof of concept for genome editing in GS cells impacts both cell therapy and basic research given the potential for GS cells to be propagated in vitro, contribute to the germline in vivo following testicular transplantation or become reprogrammed to pluripotency in vitro. PMID:25409432

On the problem of resonance assignments in solid state NMR of uniformly 15N, 13C-labeled proteins

NASA Astrophysics Data System (ADS)

Tycko, Robert

2015-04-01

Determination of accurate resonance assignments from multidimensional chemical shift correlation spectra is one of the major problems in biomolecular solid state NMR, particularly for relative large proteins with less-than-ideal NMR linewidths. This article investigates the difficulty of resonance assignment, using a computational Monte Carlo/simulated annealing (MCSA) algorithm to search for assignments from artificial three-dimensional spectra that are constructed from the reported isotropic 15N and 13C chemical shifts of two proteins whose structures have been determined by solution NMR methods. The results demonstrate how assignment simulations can provide new insights into factors that affect the assignment process, which can then help guide the design of experimental strategies. Specifically, simulations are performed for the catalytic domain of SrtC (147 residues, primarily β-sheet secondary structure) and the N-terminal domain of MLKL (166 residues, primarily α-helical secondary structure). Assuming unambiguous residue-type assignments and four ideal three-dimensional data sets (NCACX, NCOCX, CONCA, and CANCA), uncertainties in chemical shifts must be less than 0.4 ppm for assignments for SrtC to be unique, and less than 0.2 ppm for MLKL. Eliminating CANCA data has no significant effect, but additionally eliminating CONCA data leads to more stringent requirements for chemical shift precision. Introducing moderate ambiguities in residue-type assignments does not have a significant effect.

Spoken Records. Third Edition.

ERIC Educational Resources Information Center

Roach, Helen

Surveying 75 years of accomplishment in the field of spoken recording, this reference work critically evaluates commercially available recordings selected for excellence of execution, literary or historical merit, interest, and entertainment value. Some types of spoken records included are early recording, documentaries, lectures, interviews,…

Next Generation Satellite Communications: Automated Doppler Shift Compensation of PSK-31 Via Software-Defined Radio

DTIC Science & Technology

2014-05-09

Interfaces Configuration – Wired Network Connections before Editing Move the cursor to the end of the line that ends with “eth0 inet dhcp ” and type...X”. This will delete text one character back from the cursor. Delete the word “ dhcp ”. Once this is done, type “a” to begin inserting text and add

Pubertal Development in
17Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency
.

PubMed

Hiort, Olaf; Marshall, Louise; Birnbaum, Wiebke; Wünsch, Lutz; Holterhus, Paul-Martin; Döhnert, Ulla; Werner, Ralf

2017-01-01

17β-hydroxysteroid dehydrogenase (17β-HSD) type 3 deficiency is an autosomal recessive disorder with diminished testosterone synthesis and consequently underandrogenisation. 46,XY patients with 17β-HSD type 3 deficiency are often assigned a female sex at birth but have a high virilisation potential at the time of puberty. We studied four 46,XY patients with 17β-HSD type 3 deficiency at puberty with regard to the underlying mutations, the hormone values, and the clinical findings. Three patients were initially assigned a female sex and 1 was assigned a male sex. All had relevant mutations in the HSD17B3 gene. The 2 patients with deleterious mutations had lower testosterone values at the time of puberty than the patients with possible residual activity of 17β-HSD type 3. One of the latter patients changed to male gender. All 4 patients with 17β-HSD type 3 deficiency synthesized relevant amounts (>0.7 µg/L) of testosterone at puberty, which lead to variable androgenisation. In patients with presumable residual activity of the mutated enzyme, testosterone values in the male reference range can be achieved, thereby inducing male pubertal development. These patients should possibly be assigned a male sex. Any surgical intervention should be avoided until the patients are old enough to consider their options of medical and surgical intervention.
. © 2016 S. Karger AG, Basel.

Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei

PubMed Central

McDermott, Suzanne M.; Carnes, Jason

2015-01-01

KREPB5 is an essential component of ∼20S editosomes in Trypanosoma brucei which contains a degenerate, noncatalytic RNase III domain. To explore the function of this protein, we used a novel approach to make and screen numerous conditional null T. brucei bloodstream form cell lines that express randomly mutagenized KREPB5 alleles. We identified nine single amino acid substitutions that could not complement the conditional loss of wild-type KREPB5. Seven of these were within the RNase III domain, and two were in the C-terminal region that has no homology to known motifs. Exclusive expression of these mutated KREPB5 alleles in the absence of wild-type allele expression resulted in growth inhibition, the loss of ∼20S editosomes, and inhibition of RNA editing in BF cells. Eight of these mutations were lethal in bloodstream form parasites but not in procyclic-form parasites, showing that multiple domains function in a life cycle-dependent manner. Amino acid changes at a substantial number of positions, including up to 7 per allele, allowed complementation and thus did not block KREPB5 function. Hence, the degenerate RNase III domain and a newly identified domain are critical for KREPB5 function and have differential effects between the life cycle stages of T. brucei that differentially edit mRNAs. PMID:26370513

A Novel Tool for Microbial Genome Editing Using the Restriction-Modification System.

PubMed

Bai, Hua; Deng, Aihua; Liu, Shuwen; Cui, Di; Qiu, Qidi; Wang, Laiyou; Yang, Zhao; Wu, Jie; Shang, Xiuling; Zhang, Yun; Wen, Tingyi

2018-01-19

Scarless genetic manipulation of genomes is an essential tool for biological research. The restriction-modification (R-M) system is a defense system in bacteria that protects against invading genomes on the basis of its ability to distinguish foreign DNA from self DNA. Here, we designed an R-M system-mediated genome editing (RMGE) technique for scarless genetic manipulation in different microorganisms. For bacteria with Type IV REase, an RMGE technique using the inducible DNA methyltransferase gene, bceSIIM (RMGE-bceSIIM), as the counter-selection cassette was developed to edit the genome of Escherichia coli. For bacteria without Type IV REase, an RMGE technique based on a restriction endonuclease (RMGE-mcrA) was established in Bacillus subtilis. These techniques were successfully used for gene deletion and replacement with nearly 100% counter-selection efficiencies, which were higher and more stable compared to conventional methods. Furthermore, precise point mutation without limiting sites was achieved in E. coli using RMGE-bceSIIM to introduce a single base mutation of A128C into the rpsL gene. In addition, the RMGE-mcrA technique was applied to delete the CAN1 gene in Saccharomyces cerevisiae DAY414 with 100% counter-selection efficiency. The effectiveness of the RMGE technique in E. coli, B. subtilis, and S. cerevisiae suggests the potential universal usefulness of this technique for microbial genome manipulation.

Genome editing for human gene therapy.

PubMed

Meissner, Torsten B; Mandal, Pankaj K; Ferreira, Leonardo M R; Rossi, Derrick J; Cowan, Chad A

2014-01-01

The rapid advancement of genome-editing techniques holds much promise for the field of human gene therapy. From bacteria to model organisms and human cells, genome editing tools such as zinc-finger nucleases (ZNFs), TALENs, and CRISPR/Cas9 have been successfully used to manipulate the respective genomes with unprecedented precision. With regard to human gene therapy, it is of great interest to test the feasibility of genome editing in primary human hematopoietic cells that could potentially be used to treat a variety of human genetic disorders such as hemoglobinopathies, primary immunodeficiencies, and cancer. In this chapter, we explore the use of the CRISPR/Cas9 system for the efficient ablation of genes in two clinically relevant primary human cell types, CD4+ T cells and CD34+ hematopoietic stem and progenitor cells. By using two guide RNAs directed at a single locus, we achieve highly efficient and predictable deletions that ablate gene function. The use of a Cas9-2A-GFP fusion protein allows FACS-based enrichment of the transfected cells. The ease of designing, constructing, and testing guide RNAs makes this dual guide strategy an attractive approach for the efficient deletion of clinically relevant genes in primary human hematopoietic stem and effector cells and enables the use of CRISPR/Cas9 for gene therapy.

CRISPR-Cas9-Mediated Genome Editing and Transcriptional Control in Yarrowia lipolytica.

PubMed

Schwartz, Cory; Wheeldon, Ian

2018-01-01

The discovery and adaptation of RNA-guided nucleases has resulted in the rapid development of efficient, scalable, and easily accessible synthetic biology tools for targeted genome editing and transcriptional control. In these systems, for example CRISPR-Cas9 from Streptococcus pyogenes, a protein with nuclease activity is targeted to a specific nucleotide sequence by a short RNA molecule, whereupon binding it cleaves the targeted nucleotide strand. To extend this genome-editing ability to the industrially important oleaginous yeast Yarrowia lipolytica, we developed a set of easily usable and effective CRISPR-Cas9 episomal vectors. In this protocols chapter, we first present a method by which arbitrary protein-coding genes can be disrupted via indel formation after CRISPR-Cas9 targeting. A second method demonstrates how the same CRISPR-Cas9 system can be used to induce markerless gene cassette integration into the genome by inducing homologous recombination after DNA cleavage by Cas9. Finally, we describe how a catalytically inactive form of Cas9 fused to a transcriptional repressor can be used to control transcription of native genes in Y. lipolytica. The CRISPR-Cas9 tools and strategies described here greatly increase the types of genome editing and transcriptional control that can be achieved in Y. lipolytica, and promise to facilitate more advanced engineering of this important oleaginous host.

CRISPR/Cas9 mediated targeted mutagenesis of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973.

PubMed

Wendt, Kristen E; Ungerer, Justin; Cobb, Ryan E; Zhao, Huimin; Pakrasi, Himadri B

2016-06-23

As autotrophic prokaryotes, cyanobacteria are ideal chassis organisms for sustainable production of various useful compounds. The newly characterized cyanobacterium Synechococcus elongatus UTEX 2973 is a promising candidate for serving as a microbial cell factory because of its unusually rapid growth rate. Here, we seek to develop a genetic toolkit that enables extensive genomic engineering of Synechococcus 2973 by implementing a CRISPR/Cas9 editing system. We targeted the nblA gene because of its important role in biological response to nitrogen deprivation conditions. First, we determined that the Streptococcus pyogenes Cas9 enzyme is toxic in cyanobacteria, and conjugational transfer of stable, replicating constructs containing the cas9 gene resulted in lethality. However, after switching to a vector that permitted transient expression of the cas9 gene, we achieved markerless editing in 100 % of cyanobacterial exconjugants after the first patch. Moreover, we could readily cure the organisms of antibiotic resistance, resulting in a markerless deletion strain. High expression levels of the Cas9 protein in Synechococcus 2973 appear to be toxic and result in cell death. However, introduction of a CRISPR/Cas9 genome editing system on a plasmid backbone that leads to transient cas9 expression allowed for efficient markerless genome editing in a wild type genetic background.

CRISPR/Cas9 mediated targeted mutagenesis of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973

DOE PAGES

Wendt, Kristen E.; Ungerer, Justin; Cobb, Ryan E.; ...

2016-06-23

As autotrophic prokaryotes, cyanobacteria are ideal chassis organisms for sustainable production of various useful compounds. The newly characterized cyanobacterium Synechococcus elongatus UTEX 2973 is a promising candidate for serving as a microbial cell factory because of its unusually rapid growth rate. Here, we seek to develop a genetic toolkit that enables extensive genomic engineering of Synechococcus 2973 by implementing a CRISPR/Cas9 editing system. We targeted the nblA gene because of its important role in biological response to nitrogen deprivation conditions. First, we determined that the Streptococcus pyogenes Cas9 enzyme is toxic in cyanobacteria, and conjugational transfer of stable, replicating constructsmore » containing the cas9 gene resulted in lethality. However, after switching to a vector that permitted transient expression of the cas9 gene, we achieved markerless editing in 100 % of cyanobacterial exconjugants after the first patch. Moreover, we could readily cure the organisms of antibiotic resistance, resulting in a markerless deletion strain. In conclusion, high expression levels of the Cas9 protein in Synechococcus 2973 appear to be toxic and result in cell death. However, introduction of a CRISPR/Cas9 genome editing system on a plasmid backbone that leads to transient cas9 expression allowed for efficient markerless genome editing in a wild type genetic background.« less

CRISPR/Cas9 mediated targeted mutagenesis of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973

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

Wendt, Kristen E.; Ungerer, Justin; Cobb, Ryan E.

As autotrophic prokaryotes, cyanobacteria are ideal chassis organisms for sustainable production of various useful compounds. The newly characterized cyanobacterium Synechococcus elongatus UTEX 2973 is a promising candidate for serving as a microbial cell factory because of its unusually rapid growth rate. Here, we seek to develop a genetic toolkit that enables extensive genomic engineering of Synechococcus 2973 by implementing a CRISPR/Cas9 editing system. We targeted the nblA gene because of its important role in biological response to nitrogen deprivation conditions. First, we determined that the Streptococcus pyogenes Cas9 enzyme is toxic in cyanobacteria, and conjugational transfer of stable, replicating constructsmore » containing the cas9 gene resulted in lethality. However, after switching to a vector that permitted transient expression of the cas9 gene, we achieved markerless editing in 100 % of cyanobacterial exconjugants after the first patch. Moreover, we could readily cure the organisms of antibiotic resistance, resulting in a markerless deletion strain. In conclusion, high expression levels of the Cas9 protein in Synechococcus 2973 appear to be toxic and result in cell death. However, introduction of a CRISPR/Cas9 genome editing system on a plasmid backbone that leads to transient cas9 expression allowed for efficient markerless genome editing in a wild type genetic background.« less

In vivo genome editing of the albumin locus as a platform for protein replacement therapy.

PubMed

Sharma, Rajiv; Anguela, Xavier M; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C; Sproul, Scott; Paschon, David E; Miller, Jeffrey C; Davidson, Robert J; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D; Holmes, Michael C; Rebar, Edward J; High, Katherine A

2015-10-08

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) -mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. © 2015 by The American Society of Hematology.

Investigation of cloud/water vapor motion winds from geostationary satellite

NASA Technical Reports Server (NTRS)

1993-01-01

This report summarizes the research work accomplished on the NASA grant contract NAG8-892 during 1992. Research goals of this contract are the following: to complete upgrades to the Cooperative Institute for Meteorological Satellite Studies (CIMSS) wind system procedures for assigning heights and incorporating first guess information; to evaluate these modifications using simulated tracer fields; to add an automated quality control system to minimize the need for manual editing, while maintaining product quality; and to benchmark the upgraded algorithm in tests with NMC and/or MSFC. Work progressed on all these tasks and is detailed. This work was done in collaboration with CIMSS NOAA/NESDIS scientists working on the operational winds software, so that NASA funded research can benefit NESDIS operational algorithms.

Inconsistent identification of pit bull-type dogs by shelter staff.

PubMed

Olson, K R; Levy, J K; Norby, B; Crandall, M M; Broadhurst, J E; Jacks, S; Barton, R C; Zimmerman, M S

2015-11-01

Shelter staff and veterinarians routinely make subjective dog breed identification based on appearance, but their accuracy regarding pit bull-type breeds is unknown. The purpose of this study was to measure agreement among shelter staff in assigning pit bull-type breed designations to shelter dogs and to compare breed assignments with DNA breed signatures. In this prospective cross-sectional study, four staff members at each of four different shelters recorded their suspected breed(s) for 30 dogs; there was a total of 16 breed assessors and 120 dogs. The terms American pit bull terrier, American Staffordshire terrier, Staffordshire bull terrier, pit bull, and their mixes were included in the study definition of 'pit bull-type breeds.' Using visual identification only, the median inter-observer agreements and kappa values in pair-wise comparisons of each of the staff breed assignments for pit bull-type breed vs. not pit bull-type breed ranged from 76% to 83% and from 0.44 to 0.52 (moderate agreement), respectively. Whole blood was submitted to a commercial DNA testing laboratory for breed identification. Whereas DNA breed signatures identified only 25 dogs (21%) as pit bull-type, shelter staff collectively identified 62 (52%) dogs as pit bull-type. Agreement between visual and DNA-based breed assignments varied among individuals, with sensitivity for pit bull-type identification ranging from 33% to 75% and specificity ranging from 52% to 100%. The median kappa value for inter-observer agreement with DNA results at each shelter ranged from 0.1 to 0.48 (poor to moderate). Lack of consistency among shelter staff indicated that visual identification of pit bull-type dogs was unreliable. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Psychology Students' Understanding of the Skill-Based Learning Fostered through University Assignments

ERIC Educational Resources Information Center

Martini, Tanya S.; Rail, Ashley; Norton, Cole

2015-01-01

We examined first-year psychology majors' (N = 195) beliefs about the relevance of two types of university assignments (individual essay and group wiki) and their connection to the development of career-related skills. Students reported that assignments were only somewhat relevant to their career goals, and relevance ratings were typically…

A Citation Analysis of Psychology Students' Use of Sources in Online Distance Learning

ERIC Educational Resources Information Center

Weaver, Nancy Evans; Barnard, Estelle

2015-01-01

Reference lists from two assignments of psychology students in university-level online distance learning (ODL) were analyzed for number and type of sources and mark achieved. Most referenced were resources relevant to the assignment and provided by instructors. Use changed across assignments: Instructor sources were used more on the first…

Thinking Statistically in Writing: Journals and Discussion Boards in an Introductory Statistics Course

ERIC Educational Resources Information Center

Theoret, Julie M.; Luna, Andrea

2009-01-01

This action research combined qualitative and quantitative techniques to investigate two different types of writing assignments in an introductory undergraduate statistics course. The assignments were written in response to the same set of prompts but in two different ways: homework journal assignments or initial posts to a computer discussion…

Spermatogonial stem cell autotransplantation and germline genomic editing: a future cure for spermatogenic failure and prevention of transmission of genomic diseases

PubMed Central

Mulder, Callista L.; Zheng, Yi; Jan, Sabrina Z.; Struijk, Robert B.; Repping, Sjoerd; Hamer, Geert; van Pelt, Ans M.M.

2016-01-01

BACKGROUND Subfertility affects approximately 15% of all couples, and a severe male factor is identified in 17% of these couples. While the etiology of a severe male factor remains largely unknown, prior gonadotoxic treatment and genomic aberrations have been associated with this type of subfertility. Couples with a severe male factor can resort to ICSI, with either ejaculated spermatozoa (in case of oligozoospermia) or surgically retrieved testicular spermatozoa (in case of azoospermia) to generate their own biological children. Currently there is no direct treatment for azoospermia or oligozoospermia. Spermatogonial stem cell (SSC) autotransplantation (SSCT) is a promising novel clinical application currently under development to restore fertility in sterile childhood cancer survivors. Meanwhile, recent advances in genomic editing, especially the clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) system, are likely to enable genomic rectification of human SSCs in the near future. OBJECTIVE AND RATIONALE The objective of this review is to provide insights into the prospects of the potential clinical application of SSCT with or without genomic editing to cure spermatogenic failure and to prevent transmission of genetic diseases. SEARCH METHODS We performed a narrative review using the literature available on PubMed not restricted to any publishing year on topics of subfertility, fertility treatments, (molecular regulation of) spermatogenesis and SSCT, inherited (genetic) disorders, prenatal screening methods, genomic editing and germline editing. For germline editing, we focussed on the novel CRISPR-Cas9 system. We included papers written in English only. OUTCOMES Current techniques allow propagation of human SSCs in vitro, which is indispensable to successful transplantation. This technique is currently being developed in a preclinical setting for childhood cancer survivors who have stored a testis biopsy prior to cancer treatment. Similarly, SSCT could be used to restore fertility in sterile adult cancer survivors. In vitro propagation of SSCs might also be employed to enhance spermatogenesis in oligozoospermic men and in azoospermic men who still have functional SSCs albeit in insufficient numbers. The combination of SSCT with genomic editing techniques could potentially rectify defects in spermatogenesis caused by genomic mutations or, more broadly, prevent transmission of genomic diseases to the offspring. In spite of the promising prospects, SSCT and germline genomic editing are not yet clinically applicable and both techniques require optimization at various levels. WIDER IMPLICATIONS SSCT with or without genomic editing could potentially be used to restore fertility in cancer survivors to treat couples with a severe male factor and to prevent the paternal transmission of diseases. This will potentially allow these couples to have their own biological children. Technical development is progressing rapidly, and ethical reflection and societal debate on the use of SSCT with or without genomic editing is pressing. PMID:27240817

Graphical User Interface Development for Representing Air Flow Patterns

NASA Technical Reports Server (NTRS)

Chaudhary, Nilika

2004-01-01

In the Turbine Branch, scientists carry out experimental and computational work to advance the efficiency and diminish the noise production of jet engine turbines. One way to do this is by decreasing the heat that the turbine blades receive. Most of the experimental work is carried out by taking a single turbine blade and analyzing the air flow patterns around it, because this data indicates the sections of the turbine blade that are getting too hot. Since the cost of doing turbine blade air flow experiments is very high, researchers try to do computational work that fits the experimental data. The goal of computational fluid dynamics is for scientists to find a numerical way to predict the complex flow patterns around different turbine blades without physically having to perform tests or costly experiments. When visualizing flow patterns, scientists need a way to represent the flow conditions around a turbine blade. A researcher will assign specific zones that surround the turbine blade. In a two-dimensional view, the zones are usually quadrilaterals. The next step is to assign boundary conditions which define how the flow enters or exits one side of a zone. way of setting up computational zones and grids, visualizing flow patterns, and storing all the flow conditions in a file on the computer for future computation. Such a program is necessary because the only method for creating flow pattern graphs is by hand, which is tedious and time-consuming. By using a computer program to create the zones and grids, the graph would be faster to make and easier to edit. Basically, the user would run a program that is an editable graph. The user could click and drag with the mouse to form various zones and grids, then edit the locations of these grids, add flow and boundary conditions, and finally save the graph for future use and analysis. My goal this summer is to create a graphical user interface (GUI) that incorporates all of these elements. I am writing the program in Java, a language that is portable among platforms, because it can run on different operating systems such as Windows and Unix without having to be rewritten. I had no prior experience of programming in Java at the start of my internship; I am continuously learning as I create the program. I have written the part of the program that enables a user to draw several zones, edit them, and store their locations. The next phase of my project is to allow the user to click on the side of a zone and create a boundary condition for it. A previous intern wrote a program that allows the user to input boundary conditions. I can integrate the two programs to create a larger, more usable program. After that, I will develop a way for the user to save the graph for future reference. Another eventual goal is to make the GUI capable of creating three-dimensional zones as well. Researchers such as my mentor, Dr. David Ashpis, need a quick, user-friendly

A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

PubMed

Xu, Ling; Li, Jiang-Hong; Ye, Jing-Ming; Duan, Xue-Ning; Cheng, Yuan-Jia; Xin, Ling; Liu, Qian; Zhou, Bin; Liu, Yin-Hua

2017-08-20

Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant differences in either 5-year DFS (χ2 = 0.440, P= 0.507) or 5-year OS (χ2 = 1.530, P= 0.216). The prognostic staging system proposed in the AJCC 8th edition refines the anatomic stage group in Luminal B HER2-negative breast cancer and will lead to a more personalized approach to breast cancer treatment.

Mediator Deathwork

ERIC Educational Resources Information Center

Walter, Tony

2005-01-01

The most discussed and analyzed form of deathwork is the dyadic "therapist" [double arrow] "client" relationship, but this far from exhausts the various types of professional work involving the dead. Mediator deathwork is where the professional gleans or constructs information about the dead, edits and polishes it, and publicly…

[Tale nucleases--new tool for genome editing].

PubMed

Glazkova, D V; Shipulin, G A

2014-01-01

The ability to introduce targeted changes in the genome of living cells or entire organisms enables researchers to meet the challenges of basic life sciences, biotechnology and medicine. Knockdown of target genes in the zygotes gives the opportunity to investigate the functions of these genes in different organisms. Replacement of single nucleotide in the DNA sequence allows to correct mutations in genes and thus to cure hereditary diseases. Adding transgene to specific genomic.loci can be used in biotechnology for generation of organisms with certain properties or cell lines for biopharmaceutical production. Such manipulations of gene sequences in their natural chromosomal context became possible after the emergence of the technology called "genome editing". This technology is based on the induction of a double-strand break in a specific genomic target DNA using endonucleases that recognize the unique sequences in the genome and on subsequent recovery of DNA integrity through the use of cellular repair mechanisms. A necessary tool for the genome editing is a custom-designed endonuclease which is able to recognize selected sequences. The emergence of a new type of programmable endonucleases, which were constructed on the basis of bacterial proteins--TAL-effectors (Transcription activators like effector), has become an important stage in the development of technology and promoted wide spread of the genome editing. This article reviews the history of the discovery of TAL effectors and creation of TALE nucleases, and describes their advantages over zinc finger endonucleases that appeared earlier. A large section is devoted to description of genetic modifications that can be performed using the genome editing.

The Development of a Viral Mediated CRISPR/Cas9 System with Doxycycline Dependent gRNA Expression for Inducible In vitro and In vivo Genome Editing

PubMed Central

de Solis, Christopher A.; Ho, Anthony; Holehonnur, Roopashri; Ploski, Jonathan E.

2016-01-01

The RNA-guided Cas9 nuclease, from the type II prokaryotic Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) adaptive immune system, has been adapted and utilized by scientists to edit the genomes of eukaryotic cells. Here, we report the development of a viral mediated CRISPR/Cas9 system that can be rendered inducible utilizing doxycycline (Dox) and can be delivered to cells in vitro and in vivo utilizing adeno-associated virus (AAV). Specifically, we developed an inducible gRNA (gRNAi) AAV vector that is designed to express the gRNA from a H1/TO promoter. This AAV vector is also designed to express the Tet repressor (TetR) to regulate the expression of the gRNAi in a Dox dependent manner. We show that H1/TO promoters of varying length and a U6/TO promoter can edit DNA with similar efficiency in vitro, in a Dox dependent manner. We also demonstrate that our inducible gRNAi vector can be used to edit the genomes of neurons in vivo within the mouse brain in a Dox dependent manner. Genome editing can be induced in vivo with this system by supplying animals Dox containing food for as little as 1 day. This system might be cross compatible with many existing S. pyogenes Cas9 systems (i.e., Cas9 mouse, CRISPRi, etc.), and therefore it likely can be used to render these systems inducible as well. PMID:27587996

48 CFR 1511.011-74 - Work assignments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... insert the contract clause at 1552.211-74, Work Assignments, in cost-reimbursement type term form... conflict of interest certificates (e.g., Site Specific contracts, the Contract Laboratory Program (CLP...

The 2014 International Pressure Ulcer Guideline: methods and development.

PubMed

Haesler, Emily; Kottner, Jan; Cuddigan, Janet

2017-06-01

A discussion of the methodology used to develop the Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline. (2014). International experts representing National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel and Pan Pacific Pressure Injury Alliance developed the second edition of this clinical guideline. Discussion paper - methodology. A comprehensive search for papers published up to July 2013 was conducted in 11 databases and identified 4286 studies. After critical appraisal, 356 studies were included and assigned a level of evidence. Guideline recommendations provide guidance on best practice in pressure ulcer prevention and treatment. Understanding the development process of a guideline increases the meaningfulness of recommendations to clinicians. Five hundred and seventy five recommendations arose from the research and its interpretation. The body of evidence supporting each recommendation was assigned a strength of evidence. A strength of recommendation was assigned to recommendation statements using the GRADE system. Recommendations are primarily supported by a body of evidence rated as C (87% of recommendations), representing low quality and/or indirect evidence (30%) and expert opinion (57%). Two hundred and forty seven recommendations (43%) received a strong recommendation ('Do it'). Recommendations were developed with consideration to research of the highest methodological quality evidence and studies that add to clinical insight and provide guidance for areas of care where minimal research has been conducted. Recommendations in the guideline reflect best practice and should be implemented with consideration to local context and resources and the individual's preferences and needs. © 2016 John Wiley & Sons Ltd.

Nursing leadership succession planning in Veterans Health Administration: creating a useful database.

PubMed

Weiss, Lizabeth M; Drake, Audrey

2007-01-01

An electronic database was developed for succession planning and placement of nursing leaders interested and ready, willing, and able to accept an assignment in a nursing leadership position. The tool is a 1-page form used to identify candidates for nursing leadership assignments. This tool has been deployed nationally, with access to the database restricted to nurse executives at every Veterans Health Administration facility for the purpose of entering the names of developed nurse leaders ready for a leadership assignment. The tool is easily accessed through the Veterans Health Administration Office of Nursing Service, and by limiting access to the nurse executive group, ensures candidates identified are qualified. Demographic information included on the survey tool includes the candidate's demographic information and other certifications/credentials. This completed information form is entered into a database from which a report can be generated, resulting in a listing of potential candidates to contact to supplement a local or Veterans Integrated Service Network wide position announcement. The data forms can be sorted by positions, areas of clinical or functional experience, training programs completed, and geographic preference. The forms can be edited or updated and/or added or deleted in the system as the need is identified. This tool allows facilities with limited internal candidates to have a resource with Department of Veterans Affairs prepared staff in which to seek additional candidates. It also provides a way for interested candidates to be considered for positions outside of their local geographic area.

Missing genes, multiple ORFs, and C-to-U type RNA editing in Acrasis kona (Heterolobosea, Excavata) mitochondrial DNA.

PubMed

Fu, Cheng-Jie; Sheikh, Sanea; Miao, Wei; Andersson, Siv G E; Baldauf, Sandra L

2014-08-21

Discoba (Excavata) is an ancient group of eukaryotes with great morphological and ecological diversity. Unlike the other major divisions of Discoba (Jakobida and Euglenozoa), little is known about the mitochondrial DNAs (mtDNAs) of Heterolobosea. We have assembled a complete mtDNA genome from the aggregating heterolobosean amoeba, Acrasis kona, which consists of a single circular highly AT-rich (83.3%) molecule of 51.5 kb. Unexpectedly, A. kona mtDNA is missing roughly 40% of the protein-coding genes and nearly half of the transfer RNAs found in the only other sequenced heterolobosean mtDNAs, those of Naegleria spp. Instead, over a quarter of A. kona mtDNA consists of novel open reading frames. Eleven of the 16 protein-coding genes missing from A. kona mtDNA were identified in its nuclear DNA and polyA RNA, and phylogenetic analyses indicate that at least 10 of these 11 putative nuclear-encoded mitochondrial (NcMt) proteins arose by direct transfer from the mitochondrion. Acrasis kona mtDNA also employs C-to-U type RNA editing, and 12 homologs of DYW-type pentatricopeptide repeat (PPR) proteins implicated in plant organellar RNA editing are found in A. kona nuclear DNA. A mapping of mitochondrial gene content onto a consensus phylogeny reveals a sporadic pattern of relative stasis and rampant gene loss in Discoba. Rampant loss occurred independently in the unique common lineage leading to Heterolobosea + Tsukubamonadida and later in the unique lineage leading to Acrasis. Meanwhile, mtDNA gene content appears to be remarkably stable in the Acrasis sister lineage leading to Naegleria and in their distant relatives Jakobida. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The art of scientific writing

NASA Astrophysics Data System (ADS)

Gad-El-Hak, Mohamed

2015-11-01

The humanities teach students how to learn and communicate. Science teaches why everything works. Engineering teaches how to make things work. But scientists and engineers need to communicate their ideas amongst themselves as well as to everyone else. A newly developed technical writing course is outlined. In the class, offered to senior undergraduate and beginning graduate students, we read numerous short novels, essays, and op-eds. Some of the reading materials are technical but many are not. The students also have weekly writing assignments. When the first assignment is returned to the students with a grade of 20-30%, their first reaction is, ``how come I did not receive my usual 80-90%?'' I retort, ``you reach that level only when your essay is ready to be published in The New York Times.'' What is emphasized in the class is the process of creating something to write about, researching that something, expressing ideas coherently and comprehensibly, then endlessly editing the essay. The elective class has been offered three times thus far, all of its available seats are always filled, the students' evaluations have been outstanding, and the improvements in the students' ability to write by the end of the semester is quite impressive.

Use of NMR-Based Metabolomics To Chemically Characterize the Roasting Process of Chicory Root.

PubMed

Wei, Feifei; Furihata, Kazuo; Zhang, Mimin; Miyakawa, Takuya; Tanokura, Masaru

2016-08-16

Roasted chicory root (Cichorium intybus) has been widely accepted as the most important coffee substitute. In this study, a nuclear magnetic resonance (NMR)-based comprehensive analysis was performed to monitor the substantial changes in the composition of chicory root during the roasting process. A detailed signal assignment of dried raw and roasted chicory roots was carried out using 1 H, 13 C, 1 H- 1 H DQF-COSY, 1 H- 13 C edited-HSQC, 1 H- 13 C CT-HMBC, and 1 H- 13 C HSQC-TOCSY NMR spectra. On the basis of the signal assignments, 36 NMR-visible components were monitored simultaneously during roasting. Inulins, sucrose, and most of the amino acids were largely degraded during the roasting process, whereas monosaccharides decreased at the beginning and then increased until the dark roasting stage. Acetamide, 5-hydroxymethylfurfural, di-d-fructose dianhydride, and norfuraneol were newly formed during roasting. Furthermore, a principal component analysis score plot indicated that similar chemical composition profiles could be achieved by roasting the chicory root either at a higher firepower for a shorter time or at a lower firepower for a longer time.

Distance Learning Courses and Master of Arts in Physics Education

NASA Astrophysics Data System (ADS)

Lindgren, Richard; Thornton, Stephen

2006-11-01

More than twenty distance learning courses in physics have been taken by hundreds of High School Physics Teachers over the past 7 years. The success of these courses helped initiate our 30 credit Master of Arts in Physics Education degree program. We have graduated 28 teachers over the last 6 years and expect 13 more to graduate in 2006. The candidates earn 14 credits in residence at the University of Virginia and 16 credits online. This allows teachers to matriculate, while earning more than half the credits at home. Presently, there are over 50 Master degree candidates. Three of the five online courses utilize CD-ROMS with edited lectures of live Physics courses taught at the University of Virginia by Physics Professors recognized for their teaching. Homework and examinations are submitted using WebAssign. Local high school teachers and administrators proctor the examinations. General communication and pedagogical feedback on homework assignments and exams are submitted through Blackboard as well as email. Screen captured video shots of physics demonstrations are widely used in the audio chat room to facilitate discussion and also used on examinations. We will discuss the changes of our distance-learning model based on what has worked (or not) and new technology.

Results From Nigeria's 2016 Report Card on Physical Activity for Children and Youth.

PubMed

Adeniyi, Ade F; Odukoya, Olukemi O; Oyeyemi, Adewale L; Adedoyin, Rufus A; Ojo, Olatunde S; Metseagharun, Edirin; Akinroye, Kingsley K

2016-11-01

The Nigerian Report card on Physical Activity (PA) in Children and Youth was first developed in 2013 to inform practice and policy on healthy living and prevention of noncommunicable diseases among Nigerian children and youth. This article summarizes the results of the 2016 report card and provides updated evidence on the current situation in Nigeria. A comprehensive review of literature was undertaken by the Report Card Working Group. Grades were assigned to 10 PA indicators based on the criteria used for the 2013 edition. Grades assigned to the indicators were Overall PA, D; Active Play and Leisure, C; Active Transportation, B; Sedentary Behaviors (screen-based, F and nonscreen-based, D); Overweight and Obesity, A; PA in Schools, C-; Government/Nongovernment Organizations/Private Sector/Policy, B. The following indicators were graded as Incomplete: Organized Sport and PA, Community and Built Environment, and Family and Peers. The overall PA levels of Nigerian children and youth seemed to be declining compared with the 2013 Report card but with slight improvement in active play and leisure, and PA in school settings. A substantial number of Nigerian children and youth still have high sedentary behaviors, overweight and obesity. Efforts are needed to promote PA among them.

Reliability of routinely collected hospital data for child maltreatment surveillance.

PubMed

McKenzie, Kirsten; Scott, Debbie A; Waller, Garry S; Campbell, Margaret

2011-01-05

Internationally, research on child maltreatment-related injuries has been hampered by a lack of available routinely collected health data to identify cases, examine causes, identify risk factors and explore health outcomes. Routinely collected hospital separation data coded using the International Classification of Diseases and Related Health Problems (ICD) system provide an internationally standardised data source for classifying and aggregating diseases, injuries, causes of injuries and related health conditions for statistical purposes. However, there has been limited research to examine the reliability of these data for child maltreatment surveillance purposes. This study examined the reliability of coding of child maltreatment in Queensland, Australia. A retrospective medical record review and recoding methodology was used to assess the reliability of coding of child maltreatment. A stratified sample of hospitals across Queensland was selected for this study, and a stratified random sample of cases was selected from within those hospitals. In 3.6% of cases the coders disagreed on whether any maltreatment code could be assigned (definite or possible) versus no maltreatment being assigned (unintentional injury), giving a sensitivity of 0.982 and specificity of 0.948. The review of these cases where discrepancies existed revealed that all cases had some indications of risk documented in the records. 15.5% of cases originally assigned a definite or possible maltreatment code, were recoded to a more or less definite strata. In terms of the number and type of maltreatment codes assigned, the auditor assigned a greater number of maltreatment types based on the medical documentation than the original coder assigned (22% of the auditor coded cases had more than one maltreatment type assigned compared to only 6% of the original coded data). The maltreatment types which were the most 'under-coded' by the original coder were psychological abuse and neglect. Cases coded with a sexual abuse code showed the highest level of reliability. Given the increasing international attention being given to improving the uniformity of reporting of child-maltreatment related injuries and the emphasis on the better utilisation of routinely collected health data, this study provides an estimate of the reliability of maltreatment-specific ICD-10-AM codes assigned in an inpatient setting.

Reliability of Routinely Collected Hospital Data for Child Maltreatment Surveillance

PubMed Central

2011-01-01

Background Internationally, research on child maltreatment-related injuries has been hampered by a lack of available routinely collected health data to identify cases, examine causes, identify risk factors and explore health outcomes. Routinely collected hospital separation data coded using the International Classification of Diseases and Related Health Problems (ICD) system provide an internationally standardised data source for classifying and aggregating diseases, injuries, causes of injuries and related health conditions for statistical purposes. However, there has been limited research to examine the reliability of these data for child maltreatment surveillance purposes. This study examined the reliability of coding of child maltreatment in Queensland, Australia. Methods A retrospective medical record review and recoding methodology was used to assess the reliability of coding of child maltreatment. A stratified sample of hospitals across Queensland was selected for this study, and a stratified random sample of cases was selected from within those hospitals. Results In 3.6% of cases the coders disagreed on whether any maltreatment code could be assigned (definite or possible) versus no maltreatment being assigned (unintentional injury), giving a sensitivity of 0.982 and specificity of 0.948. The review of these cases where discrepancies existed revealed that all cases had some indications of risk documented in the records. 15.5% of cases originally assigned a definite or possible maltreatment code, were recoded to a more or less definite strata. In terms of the number and type of maltreatment codes assigned, the auditor assigned a greater number of maltreatment types based on the medical documentation than the original coder assigned (22% of the auditor coded cases had more than one maltreatment type assigned compared to only 6% of the original coded data). The maltreatment types which were the most 'under-coded' by the original coder were psychological abuse and neglect. Cases coded with a sexual abuse code showed the highest level of reliability. Conclusion Given the increasing international attention being given to improving the uniformity of reporting of child-maltreatment related injuries and the emphasis on the better utilisation of routinely collected health data, this study provides an estimate of the reliability of maltreatment-specific ICD-10-AM codes assigned in an inpatient setting. PMID:21208411

The CRISPR-Cas system - from bacterial immunity to genome engineering.

PubMed

Czarnek, Maria; Bereta, Joanna

2016-09-01

Precise and efficient genome modifications present a great value in attempts to comprehend the roles of particular genes and other genetic elements in biological processes as well as in various pathologies. In recent years novel methods of genome modification known as genome editing, which utilize so called "programmable" nucleases, came into use. A true revolution in genome editing has been brought about by the introduction of the CRISP-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) system, in which one of such nucleases, i.e. Cas9, plays a major role. This system is based on the elements of the bacterial and archaeal mechanism responsible for acquired immunity against phage infections and transfer of foreign genetic material. Microorganisms incorporate fragments of foreign DNA into CRISPR loci present in their genomes, which enables fast recognition and elimination of future infections. There are several types of CRISPR-Cas systems among prokaryotes but only elements of CRISPR type II are employed in genome engineering. CRISPR-Cas type II utilizes small RNA molecules (crRNA and tracrRNA) to precisely direct the effector nuclease - Cas9 - to a specific site in the genome, i.e. to the sequence complementary to crRNA. Cas9 may be used to: (i) introduce stable changes into genomes e.g. in the process of generation of knock-out and knock-in animals and cell lines, (ii) activate or silence the expression of a gene of interest, and (iii) visualize specific sites in genomes of living cells. The CRISPR-Cas-based tools have been successfully employed for generation of animal and cell models of a number of diseases, e.g. specific types of cancer. In the future, the genome editing by programmable nucleases may find wide application in medicine e.g. in the therapies of certain diseases of genetic origin and in the therapy of HIV-infected patients.

Documentation for the machine-readable version of the Bright Star Catalogue

NASA Technical Reports Server (NTRS)

Warren, W. H., Jr.

1982-01-01

The machine-readable version of The Bright Star Catalogue, 4th edition, is described. In addition to the large number of newly determined fundamental data, such as photoelectric magnitudes, MK spectral types, parallaxes, and radial velocities, the new version contains data and information not included in the third edition such as the identification of IR sources, U-B and R-I colors, radial velocity comments (indication and identification of spectroscopic and occultation binaries), and projected rotational velocities. The equatorial coordinates for equinoxes 1900 and 2000 are recorded to greater precision details concerning variability, spectral characteristics, duplicity, and group membership are included. Data compiled through 1979, some information and variable-star designations found through 1981 are considered.

Responsiveness of the psychoeducational profile-third edition for children with autism spectrum disorders.

PubMed

Chen, Kuan-Lin; Chiang, Fu-Mei; Tseng, Mei-Hui; Fu, Chung-Pei; Hsieh, Ching-Lin

2011-12-01

The aim of this study was to examine the responsiveness of the Psychoeducational Profile-third edition (PEP-3) in children with Autism Spectrum Disorders (ASD). We investigated the responsiveness in terms of three types of scores (i.e., raw scores, developmental ages, and percentile ranks) of the subtests and composites of the PEP-3 and three methods of analysis were used: effect size, standardized response mean, and paired t test. The findings generally support the use of the PEP-3 as an outcome measure. We suggest using the raw scores and developmental ages of the PEP-3 when evaluating program effectiveness and developmental changes for children with ASD.

Types of Ownership. Unit 7. Level 3. Instructor Guide. PACE: Program for Acquiring Competence in Entrepreneurship. Third Edition. Research & Development Series No. 303-07.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center on Education and Training for Employment.

This instructor guide for a unit on types of ownership in the PACE (Program for Acquiring Competence in Entrepreneurship) curriculum includes the full text of the student module and lesson plans, instructional suggestions, and other teacher resources. The competencies that are incorporated into this module are at Level 3 of learning--starting and…

Types of Ownership. Unit 7. Level 1. Instructor Guide. PACE: Program for Acquiring Competence in Entrepreneurship. Third Edition. Research & Development Series No. 301-07.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center on Education and Training for Employment.

This instructor guide for a unit on types of ownership in the PACE (Program for Acquiring Competence in Entrepreneurship) curriculum includes the full text of the student module and lesson plans, instructional suggestions, and other teacher resources. The competencies that are incorporated into this module are at Level 1 of learning--understanding…

On the type series of Scinax perpusillus (Lutz & Lutz, 1939) (Anura: Hylidae).

PubMed

Colaço, Gustavo; Silva, Helio Ricardo Da

2016-08-19

The literature regarding the type series of Scinax perpusillus (Lutz & Lutz, 1939) presents two distinct numbers for the holotype. In 1973, thirty-four years after the description, Bertha Lutz associated numbers to the type series. This numbering has been followed by subsequent reviewers of Scinax ever since, with exception of Peixoto (1987) who assigned another number to the holotype. Our reevaluation of the literature and examination of the type series allowed us to access that, in both cases, the numbers were incorrectly assigned to the specimens and determine the proper museum numbers for this series.

antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters.

PubMed

Weber, Tilmann; Blin, Kai; Duddela, Srikanth; Krug, Daniel; Kim, Hyun Uk; Bruccoleri, Robert; Lee, Sang Yup; Fischbach, Michael A; Müller, Rolf; Wohlleben, Wolfgang; Breitling, Rainer; Takano, Eriko; Medema, Marnix H

2015-07-01

Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Audio-Visual Equipment Directory. Seventeenth Edition.

ERIC Educational Resources Information Center

Herickes, Sally, Ed.

The following types of audiovisual equipment are catalogued: 8 mm. and 16 mm. motion picture projectors, filmstrip and sound filmstrip projectors, slide projectors, random access projection equipment, opaque, overhead, and micro-projectors, record players, special purpose projection equipment, audio tape recorders and players, audio tape…

A Primer on Wastewater Treatment, July 1976 Edition.

ERIC Educational Resources Information Center

Environmental Protection Agency, Washington, DC. Office of Public Affairs.

This general information pamphlet is concerned with the types of wastewater treatment systems, the need for further treatment, and advanced methods of treating waste. Current methods are described, illustrated and evaluated. Pollution problems from oxygen-demanding wastes, disease-causing agents, plant nutrients, synthetic chemicals, inorganic…

A TALEN genome editing system to generate human stem cell-based disease models

PubMed Central

Ding, Qiurong; Lee, Youn-Kyoung; Schaefer, Esperance A. K.; Peters, Derek T.; Veres, Adrian; Kim, Kevin; Kuperwasser, Nicolas; Motola, Daniel L.; Meissner, Torsten B.; Hendriks, William T.; Trevisan, Marta; Gupta, Rajat M.; Moisan, Annie; Banks, Eric; Friesen, Max; Schinzel, Robert T.; Xia, Fang; Tang, Alexander; Xia, Yulei; Figueroa, Emmanuel; Wann, Amy; Ahfeldt, Tim; Daheron, Laurence; Zhang, Feng; Rubin, Lee L.; Peng, Lee F.; Chung, Raymond T.; Musunuru, Kiran; Cowan, Chad A.

2012-01-01

SUMMARY Transcription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter of which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease—dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor neuron death, and hepatitis C infection. We find little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease. PMID:23246482

Recent Advances in CRISPR-Cas9 Genome Editing Technology for Biological and Biomedical Investigations.

PubMed

Singh, Vijai; Gohil, Nisarg; Ramírez García, Robert; Braddick, Darren; Fofié, Christian Kuete

2018-01-01

The Type II CRISPR-Cas9 system is a simple, efficient, and versatile tool for targeted genome editing in a wide range of organisms and cell types. It continues to gain more scientific interest and has established itself as an extremely powerful technology within our synthetic biology toolkit. It works upon a targeted site and generates a double strand breaks that become repaired by either the NHEJ or the HDR pathway, modifying or permanently replacing the genomic target sequences of interest. These can include viral targets, single-mutation genetic diseases, and multiple-site corrections for wide scale disease states, offering the potential to manage and cure some of mankind's most persistent biomedical menaces. Here, we present the developing progress and future potential of CRISPR-Cas9 in biological and biomedical investigations, toward numerous therapeutic, biomedical, and biotechnological applications, as well as some of the challenges within. J. Cell. Biochem. 119: 81-94, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Interspecies Chimerism with Mammalian Pluripotent Stem Cells.

PubMed

Wu, Jun; Platero-Luengo, Aida; Sakurai, Masahiro; Sugawara, Atsushi; Gil, Maria Antonia; Yamauchi, Takayoshi; Suzuki, Keiichiro; Bogliotti, Yanina Soledad; Cuello, Cristina; Morales Valencia, Mariana; Okumura, Daiji; Luo, Jingping; Vilariño, Marcela; Parrilla, Inmaculada; Soto, Delia Alba; Martinez, Cristina A; Hishida, Tomoaki; Sánchez-Bautista, Sonia; Martinez-Martinez, M Llanos; Wang, Huili; Nohalez, Alicia; Aizawa, Emi; Martinez-Redondo, Paloma; Ocampo, Alejandro; Reddy, Pradeep; Roca, Jordi; Maga, Elizabeth A; Esteban, Concepcion Rodriguez; Berggren, W Travis; Nuñez Delicado, Estrella; Lajara, Jeronimo; Guillen, Isabel; Guillen, Pedro; Campistol, Josep M; Martinez, Emilio A; Ross, Pablo Juan; Izpisua Belmonte, Juan Carlos

2017-01-26

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos. Copyright © 2017 Elsevier Inc. All rights reserved.

CRISPR adaptive immune systems of Archaea

PubMed Central

Vestergaard, Gisle; Garrett, Roger A; Shah, Shiraz A

2014-01-01

CRISPR adaptive immune systems were analyzed for all available completed genomes of archaea, which included representatives of each of the main archaeal phyla. Initially, all proteins encoded within, and proximal to, CRISPR-cas loci were clustered and analyzed using a profile–profile approach. Then cas genes were assigned to gene cassettes and to functional modules for adaptation and interference. CRISPR systems were then classified primarily on the basis of their concatenated Cas protein sequences and gene synteny of the interference modules. With few exceptions, they could be assigned to the universal Type I or Type III systems. For Type I, subtypes I-A, I-B, and I-D dominate but the data support the division of subtype I-B into two subtypes, designated I-B and I-G. About 70% of the Type III systems fall into the universal subtypes III-A and III-B but the remainder, some of which are phyla-specific, diverge significantly in Cas protein sequences, and/or gene synteny, and they are classified separately. Furthermore, a few CRISPR systems that could not be assigned to Type I or Type III are categorized as variant systems. Criteria are presented for assigning newly sequenced archaeal CRISPR systems to the different subtypes. Several accessory proteins were identified that show a specific gene linkage, especially to Type III interference modules, and these may be cofunctional with the CRISPR systems. Evidence is presented for extensive exchange having occurred between adaptation and interference modules of different archaeal CRISPR systems, indicating the wide compatibility of the functionally diverse interference complexes with the relatively conserved adaptation modules. PMID:24531374

Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing.

PubMed

Zhang, Rui; Deng, Patricia; Jacobson, Dionna; Li, Jin Billy

2017-02-01

Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements. Furthermore, editing events that arose early in the species tree tend to be more highly edited in clusters and enriched in slowly-evolved neuronal genes, thus suggesting that the main role of RNA editing is for fine-tuning neurological functions. While nonsynonymous editing events have been long recognized as playing a functional role, in addition to nonsynonymous editing sites, a large fraction of 3'UTR editing sites is evolutionarily constrained, highly edited, and thus likely functional. We find that these 3'UTR editing events can alter mRNA stability and affect miRNA binding and thus highlight the functional roles of noncoding RNA editing. Our work, through evolutionary analyses of RNA editing in Drosophila, uncovers novel insights of RNA editing regulation as well as its functions in both coding and non-coding regions.

Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing

PubMed Central

Jacobson, Dionna

2017-01-01

Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements. Furthermore, editing events that arose early in the species tree tend to be more highly edited in clusters and enriched in slowly-evolved neuronal genes, thus suggesting that the main role of RNA editing is for fine-tuning neurological functions. While nonsynonymous editing events have been long recognized as playing a functional role, in addition to nonsynonymous editing sites, a large fraction of 3’UTR editing sites is evolutionarily constrained, highly edited, and thus likely functional. We find that these 3’UTR editing events can alter mRNA stability and affect miRNA binding and thus highlight the functional roles of noncoding RNA editing. Our work, through evolutionary analyses of RNA editing in Drosophila, uncovers novel insights of RNA editing regulation as well as its functions in both coding and non-coding regions. PMID:28166241

Occurrence of plastid RNA editing in all major lineages of land plants

PubMed Central

Freyer, Regina; Kiefer-Meyer, Marie-Christine; Kössel, Hans

1997-01-01

RNA editing changes posttranscriptionally single nucleotides in chloroplast-encoded transcripts. Although much work has been done on mechanistic and functional aspects of plastid editing, little is known about evolutionary aspects of this RNA processing step. To gain a better understanding of the evolution of RNA editing in plastids, we have investigated the editing patterns in ndhB and rbcL transcripts from various species comprising all major groups of land plants. Our results indicate that RNA editing occurs in plastids of bryophytes, fern allies, true ferns, gymnosperms, and angiosperms. Both editing frequencies and editing patterns show a remarkable degree of interspecies variation. Furthermore, we have found that neither plastid editing frequencies nor the editing pattern of a specific transcript correlate with the phylogenetic tree of the plant kingdom. The poor evolutionary conservation of editing sites among closely related species as well as the occurrence of single species-specific editing sites suggest that the differences in the editing patterns and editing frequencies are probably due both to independent loss and to gain of editing sites. In addition, our results indicate that RNA editing is a relatively ancient process that probably predates the evolution of land plants. This supposition is in good agreement with the phylogenetic data obtained for plant mitochondrial RNA editing, thus providing additional evidence for common evolutionary roots of the two plant organellar editing systems. PMID:9177209

[The research on the edition of Daquanbencao (Complete Collection of Materia Medica)].

PubMed

Li, Jian; Zhang, Wei; Zhang, Rui-xian

2009-07-01

Zhengleibencao (Classified Materia Medica) had been formed into several kinds of edition systems during its dissemination, among which there was the edition system of Daquanbencao (Complete Collection of Materia Medica). Daquanbencao was originally carved in the Jin dynasty, thereafter it was re-carved in the Yuan, Ming and Qing dynasties so as to form a series of editions such as the edition of Zhenyou in the second year of the Jin dynasty; the edition of the Zongwenshuyuan college in Dade renyan year of the Yuan dynasty; the WANG Qiu's carved edition of Shangyitang hall in the Ming dynasty; the carved edition of Jishanshuyuan, the Jishang mountain college in the Ming dynasty, the reprinted edition of PENG Duan-wu in the Ming dynasty, the supplementary edition of YANG Bi-da in the Qing dynasty;, and the carved edition of KE Feng-shi in the Qing dynasty. Among all the editions, Chongkanjingshizhengleidaquanbencao (Reprinted Classified Daquan Materia Medica from Historical Classics) was the representative one. As a representative of the above editions, the carved edition of WANG took the edition of the Zongwenshuyuan college of the Yuan dynasty as the original edition, but the images picture of materia medica adopted from the edition of Zhenghebencao (Materia Medica of the Zhenghe era).

Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa

PubMed Central

Sebastiano, Vittorio; Zhen, Hanson Hui; Haddad, Bahareh; Bashkirova, Elizaveta; Melo, Sandra P.; Wang, Pei; Leung, Thomas L.; Siprashvili, Zurab; Tichy, Andrea; Li, Jiang; Ameen, Mohammed; Hawkins, John; Lee, Susie; Li, Lingjie; Schwertschkow, Aaron; Bauer, Gerhard; Lisowski, Leszek; Kay, Mark A.; Kim, Seung K.; Lane, Alfred T.; Wernig, Marius; Oro, Anthony E.

2015-01-01

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB. PMID:25429056

CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish.

PubMed

González, Federico

2016-07-01

Because of their extraordinary differentiation potential, human pluripotent stem cells (hPSCs) can differentiate into virtually any cell type of the human body, providing a powerful platform not only for generating relevant cell types useful for cell replacement therapies, but also for modeling human development and disease. Expanding this potential, structures resembling human organs, termed organoids, have been recently obtained from hPSCs through tissue engineering. Organoids exhibit multiple cell types self-organizing into structures recapitulating in part the physiology and the cellular interactions observed in the organ in vivo, offering unprecedented opportunities for human disease modeling. To fulfill this promise, tissue engineering in hPSCs needs to be supported by robust and scalable genome editing technologies. With the advent of the CRISPR/Cas9 technology, manipulating the genome of hPSCs has now become an easy task, allowing modifying their genome with superior precision, speed, and throughput. Here we review current and potential applications of the CRISPR/Cas9 technology in hPSCs and how they contribute to establish hPSCs as a model of choice for studying human genetics. Developmental Dynamics 245:788-806, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Human coding RNA editing is generally nonadaptive

PubMed Central

Xu, Guixia; Zhang, Jianzhi

2014-01-01

Impairment of RNA editing at a handful of coding sites causes severe disorders, prompting the view that coding RNA editing is highly advantageous. Recent genomic studies have expanded the list of human coding RNA editing sites by more than 100 times, raising the question of how common advantageous RNA editing is. Analyzing 1,783 human coding A-to-G editing sites, we show that both the frequency and level of RNA editing decrease as the importance of a site or gene increases; that during evolution, edited As are more likely than unedited As to be replaced with Gs but not with Ts or Cs; and that among nonsynonymously edited As, those that are evolutionarily least conserved exhibit the highest editing levels. These and other observations reveal the overall nonadaptive nature of coding RNA editing, despite the presence of a few sites in which editing is clearly beneficial. We propose that most observed coding RNA editing results from tolerable promiscuous targeting by RNA editing enzymes, the original physiological functions of which remain elusive. PMID:24567376

AC-DCFS: a toolchain implementation to Automatically Compute Coulomb Failure Stress changes after relevant earthquakes.

NASA Astrophysics Data System (ADS)

Alvarez-Gómez, José A.; García-Mayordomo, Julián

2017-04-01

We present an automated free software-based toolchain to obtain Coulomb Failure Stress change maps on fault planes of interest following the occurrence of a relevant earthquake. The system uses as input the focal mechanism data of the event occurred and an active fault database for the region. From the focal mechanism the orientations of the possible rupture planes, the location of the event and the size of the earthquake are obtained. From the size of the earthquake, the dimensions of the rupture plane are obtained by means of an algorithm based on empirical relations. Using the active fault database in the area, the stress-receiving planes are obtained and a verisimilitude index is assigned to the source plane from the two nodal planes of the focal mechanism. The obtained product is a series of layers in a format compatible with any type of GIS (or map completely edited in PDF format) showing the possible stress change maps on the different families of fault planes present in the epicentral zone. These type of products are presented generally in technical reports developed in the weeks following the occurrence of the event, or in scientific publications; however they have been proven useful for emergency management in the hours and days after a major event being these stress changes responsible of aftershocks, in addition to the mid-term earthquake forecasting. The automation of the calculation allows its incorporation within the products generated by the alert and surveillance agencies shortly after the earthquake occurred. It is now being implemented in the Spanish Geological Survey as one of the products that this agency would provides after the occurrence of relevant seismic series in Spain.

Keypunching Manual. Third Edition.

ERIC Educational Resources Information Center

Oldsen, Carl F.; Spagnuolo, Lenore

Presented in the manual are keypunching procedures with associated representative forms and keypunching cards for bibliographies and five basic types of abstracts which are used with the Control Data 3600 computer by the Michigan State University Materials Center for Handicapped Children and Youth (IMC HCY). Emphasis is given to keypunching all…

Data Input for Libraries: State-of-the-Art Report.

ERIC Educational Resources Information Center

Buckland, Lawrence F.

This brief overview of new manuscript preparation methods which allow authors and editors to set their own type discusses the advantages and disadvantages of optical character recognition (OCR), microcomputers and personal computers, minicomputers, and word processors for editing and database entry. Potential library applications are also…

Test and Evaluation Management Guide, Fifth Edition

DTIC Science & Technology

2005-01-01

determine if a weapon will be useful in combat), chemical weapons testing involves two types of chemical tests—chemical mixing and biotoxicity . Chemical...mixing tests are conducted to obtain in- formation on the binary chemical reaction. Biotoxicity tests are performed to assess the potency of the agent

Voluntary Support of Education 1987-1988.

ERIC Educational Resources Information Center

Council for Aid to Education, New York, NY.

The 29th edition of a publication featuring statistics on voluntary support of education is presented. Three sections have the following titles: (1) "Colleges and Universities" (including national estimates of expenditures and voluntary support, and survey results noting voluntary support by type of institution, voluntary support by source,…

PROGRAMMES IN PRINT 1966.

ERIC Educational Resources Information Center

CAVANAGH, PETER, COMP., ED.; JONES, CLIVE, COMP., ED.

APPROXIMATELY 1200 PROGRAMS ARE LISTED WITH TITLE, AUTHOR, DATE OF PUBLICATION, PUBLISHER, PRICE, COUNTRY OF ORIGIN, DATE OF LATEST EDITION IF REVISED, MONTHLY RENTAL PRICE, TYPE OF PROGRAM, NUMBER OF FRAMES, NUMBER OF PAGES IF A BOOK PROGRAM, TARGET POPULATION, STUDY TIME, AVAILABILITY FOR MACHINE USE, AND SUPPLEMENTARY MATERIALS WITH THEIR…

Human Factors in Library Administration. Revised Edition.

ERIC Educational Resources Information Center

Barnhard, Neil

Intended for the beginning or inexperienced supervisor, this continuing education course syllabus presents basic information on the development of human relations skills, particularly in the areas of leadership, communication, conflict, and motivation. Role playing situations set in various types of medical libraries are also outlined to provide…

The Job Market for Business Librarians: 1983-1992.

ERIC Educational Resources Information Center

Rakevich, Doris

This paper analyzes a total of 235 job advertisements for business librarians from 1983 through 1992 listed in "Library Journal,""American Libraries,""C & RL News,""SpeciaList," and the Eastern edition of "The Wall Street Journal." Each advertisement was examined for level of job; type of…

Bibliocable. Revised Edition.

ERIC Educational Resources Information Center

Cable Television Information Center, Washington, DC.

This selective, annotated bibliography is a revision of the original published in 1972 (ED 071 402). Some 104 books, articles, and reports included here deal with access, applications, franchising, regulation, technology, and other aspects of cable television. The listings are of two types in each category. First are revisions of the original…

Tenure, Discrimination, and the Courts. Second Edition.

ERIC Educational Resources Information Center

Leap, Terry L.

This book examines issues related to faculty tenure, discrimination, and court litigation at American colleges and universities. It also analyzes legal cases, court rulings, personnel practices, and specific types of discrimination germane to reappointment, promotion, or denial of tenure in higher education. Individual chapters concentrate on the…

Reference Manual for Machine-Readable Bibliographic Descriptions. Second Revised Edition.

ERIC Educational Resources Information Center

Dierickx, H., Ed.; Hopkinson, A., Ed.

A product of the UNISIST International Centre for Bibliographic Descriptions (UNIBIB), this reference manual presents a standardized communication format for the exchange of machine-readable bibliographic information between bibliographic databases or other types of bibliographic information services, including libraries. The manual is produced in…

34 CFR 682.409 - Mandatory assignment by guaranty agencies of defaulted loans to the Secretary.

Code of Federal Regulations, 2014 CFR

2014-07-01

... loans to the Secretary. 682.409 Section 682.409 Education Regulations of the Offices of the Department... loans must be assigned to the Secretary, an agency must assign any loan that meets all of the following... standard under paragraph (a)(2)(ii) of this section for a loan type, and the Secretary determines that...

Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits.

PubMed

Smith, Andrew J P; Deloukas, Panos; Munroe, Patricia B

2018-04-13

Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, type 2 diabetes, cancer, obesity and autoimmune disease. We focus on analysis of variants occurring within non-coding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants, and how these may relate to the pathology of the trait, and look towards future directions for these technologies in post-GWAS analysis, such as base-editing.

Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei.

PubMed

McDermott, Suzanne M; Carnes, Jason; Stuart, Kenneth

2015-12-01

KREPB5 is an essential component of ∼ 20S editosomes in Trypanosoma brucei which contains a degenerate, noncatalytic RNase III domain. To explore the function of this protein, we used a novel approach to make and screen numerous conditional null T. brucei bloodstream form cell lines that express randomly mutagenized KREPB5 alleles. We identified nine single amino acid substitutions that could not complement the conditional loss of wild-type KREPB5. Seven of these were within the RNase III domain, and two were in the C-terminal region that has no homology to known motifs. Exclusive expression of these mutated KREPB5 alleles in the absence of wild-type allele expression resulted in growth inhibition, the loss of ∼ 20S editosomes, and inhibition of RNA editing in BF cells. Eight of these mutations were lethal in bloodstream form parasites but not in procyclic-form parasites, showing that multiple domains function in a life cycle-dependent manner. Amino acid changes at a substantial number of positions, including up to 7 per allele, allowed complementation and thus did not block KREPB5 function. Hence, the degenerate RNase III domain and a newly identified domain are critical for KREPB5 function and have differential effects between the life cycle stages of T. brucei that differentially edit mRNAs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats.

PubMed

Shao, Yanjiao; Wang, Liren; Guo, Nana; Wang, Shengfei; Yang, Lei; Li, Yajing; Wang, Mingsong; Yin, Shuming; Han, Honghui; Zeng, Li; Zhang, Ludi; Hui, Lijian; Ding, Qiurong; Zhang, Jiqin; Geng, Hongquan; Liu, Mingyao; Li, Dali

2018-05-04

Hereditary tyrosinemia type I (HTI) is a metabolic genetic disorder caused by mutation of fumarylacetoacetate hydrolase (FAH). Because of the accumulation of toxic metabolites, HTI causes severe liver cirrhosis, liver failure, and even hepatocellular carcinoma. HTI is an ideal model for gene therapy, and several strategies have been shown to ameliorate HTI symptoms in animal models. Although CRISPR/Cas9-mediated genome editing is able to correct the Fah mutation in mouse models, WT Cas9 induces numerous undesired mutations that have raised safety concerns for clinical applications. To develop a new method for gene correction with high fidelity, we generated a Fah mutant rat model to investigate whether Cas9 nickase (Cas9n)-mediated genome editing can efficiently correct the Fah First, we confirmed that Cas9n rarely induces indels in both on-target and off-target sites in cell lines. Using WT Cas9 as a positive control, we delivered Cas9n and the repair donor template/single guide (sg)RNA through adenoviral vectors into HTI rats. Analyses of the initial genome editing efficiency indicated that only WT Cas9 but not Cas9n causes indels at the on-target site in the liver tissue. After receiving either Cas9n or WT Cas9-mediated gene correction therapy, HTI rats gained weight steadily and survived. Fah-expressing hepatocytes occupied over 95% of the liver tissue 9 months after the treatment. Moreover, CRISPR/Cas9-mediated gene therapy prevented the progression of liver cirrhosis, a phenotype that could not be recapitulated in the HTI mouse model. These results strongly suggest that Cas9n-mediated genome editing is a valuable and safe gene therapy strategy for this genetic disease. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Gene Editing With CRISPR/Cas9 RNA-Directed Nuclease.

PubMed

Doetschman, Thomas; Georgieva, Teodora

2017-03-03

Genetic engineering of model organisms and cultured cells has for decades provided important insights into the mechanisms underlying cardiovascular development and disease. In the past few years the development of several nuclease systems has broadened the range of model/cell systems that can be engineered. Of these, the CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9) system has become the favorite for its ease of application. Here we will review this RNA-guided nuclease system for gene editing with respect to its usefulness for cardiovascular studies and with an eye toward potential therapy. Studies on its off-target activity, along with approaches to minimize this activity will be given. The advantages of gene editing versus gene targeting in embryonic stem cells, including the breadth of species and cell types to which it is applicable, will be discussed. We will also cover its use in iPSC for research and possible therapeutic purposes; and we will review its use in muscular dystrophy studies where considerable progress has been made toward dystrophin correction in mice. The CRISPR/Ca9s system is also being used for high-throughput screening of genes, gene regulatory regions, and long noncoding RNAs. In addition, the CRISPR system is being used for nongene-editing purposes such as activation and inhibition of gene expression, as well as for fluorescence tagging of chromosomal regions and individual mRNAs to track their cellular location. Finally, an approach to circumvent the inability of post-mitotic cells to support homologous recombination-based gene editing will be presented. In conclusion, applications of the CRISPR/Cas system are expanding at a breath-taking pace and are revolutionizing approaches to gain a better understanding of human diseases. © 2017 American Heart Association, Inc.

The gene-editing of super-ego.

PubMed

Hofmann, Bjørn

2018-04-17

New emerging biotechnologies, such as gene editing, vastly extend our ability to alter the human being. This comes together with strong aspirations to improve humans not only physically, but also mentally, morally, and socially. These conjoined ambitions aggregate to what can be labelled "the gene editing of super-ego." This article investigates a general way used to argue for new biotechnologies, such as gene-editing: if it is safe and efficacious to implement technology X for the purpose of a common good Y, why should we not do so? This is a rhetorical question with a conditional, and may be dismissed as such. Moreover, investigating the question transformed into a formal argument reveals that the argument does not hold either. Nonetheless, the compelling force of the question calls for closer scrutiny, revealing that this way of arguing for biotechnology is based on five assumptions. Analysis of these assumptions shows their significant axiological, empirical, and philosophical challenges. This makes it reasonable to claim that these kinds of question based promotions of specific biotechnologies fail. Hence, the aspirations to make a super-man with a super-ego appear fundamentally flawed. As these types of moral bioenhancement arguments become more prevalent, a revealing hype test is suggested: What is special with this technology (e.g., gene editing), compared to existing methods, that makes it successful in improving human social characteristics in order to make the world a better place for all? Valid answers to this question will provide good reasons to pursue such technologies. Hence, the aim is not to bar the development of modern biotechnology, but rather to ensure good developments and applications of highly potent technologies. So far, we still have a long way to go to make persons with goodness gene(s).

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.

Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9

PubMed Central

Mandal, Pankaj K.; Ferreira, Leonardo M. R.; Collins, Ryan; Meissner, Torsten B.; Boutwell, Christian L.; Friesen, Max; Vrbanac, Vladimir; Garrison, Brian S.; Stortchevoi, Alexei; Bryder, David; Musunuru, Kiran; Brand, Harrison; Tager, Andrew M.; Allen, Todd M.; Talkowski, Michael E.; Rossi, Derrick J.; Cowan, Chad A.

2014-01-01

SUMMARY Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9 mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4+ T cells and CD34+ hematopoietic stem and progenitor cells (HSPCs). Use of single RNA guides led to highly efficient mutagenesis in HSPCs but not in T cells. A dual guide approach improved gene deletion efficacy in both cell types. HSPCs that had undergone genome editing with CRISPR/Cas9 retained multi-lineage potential. We examined predicted on- and off-target mutations via target capture sequencing in HSPCs and observed low levels of off-target mutagenesis at only one site. These results demonstrate that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy. PMID:25517468

Genome-wide identification of RNA editing in hepatocellular carcinoma.

PubMed

Kang, Lin; Liu, Xiaoqiao; Gong, Zhoulin; Zheng, Hancheng; Wang, Jun; Li, Yingrui; Yang, Huanming; Hardwick, James; Dai, Hongyue; Poon, Ronnie T P; Lee, Nikki P; Mao, Mao; Peng, Zhiyu; Chen, Ronghua

2015-02-01

We did whole-transcriptome sequencing and whole-genome sequencing on nine pairs of Hepatocellular carcinoma (HCC) tumors and matched adjacent tissues to identify RNA editing events. We identified mean 26,982 editing sites with mean 89.5% canonical A→G edits in each sample using an improved bioinformatics pipeline. The editing rate was significantly higher in tumors than adjacent normal tissues. Comparing the difference between tumor and normal tissues of each patient, we found 7 non-synonymous tissue specific editing events including 4 tumor-specific edits and 3 normal-specific edits in the coding region, as well as 292 edits varying in editing degree. The significant expression changes of 150 genes associated with RNA editing were found in tumors, with 3 of the 4 most significant genes being cancer related. Our results show that editing might be related to higher gene expression. These findings indicate that RNA editing modification may play an important role in the development of HCC. Copyright © 2014 Elsevier Inc. All rights reserved.

General Chemistry Collection for Students (CD-ROM), Abstract of Special Issue 16, 4th Edition

NASA Astrophysics Data System (ADS)

2000-07-01

The General Chemistry Collection contains both new and previously published JCE Software programs that are intended for use by introductory-level chemistry students. These peer-reviewed programs for Macintosh and for Windows are available on a single CD-ROM for convenient distribution to and access by students, and the CD may be adopted for students to purchase as they would a textbook. General Chemistry Collection covers a broad range of topics providing students with interesting information, tutorials, and simulations that will be useful to them as they study chemistry for the first time. There are 22 programs included in the General Chemistry Collection 4th Edition. Their titles and the general chemistry topics they cover are listed in Table 1. Features in This Edition General Chemistry Collection, 4th edition includes:

• Lessons for Introductory Chemistry and INQUAL-S, two new programs not previously published by JCE Software (abstracts appear below)
• Writing Electron Dot Structures (1) and Viscosity Measurement: A Virtual Experiment for Windows (2), two programs published individually by JCE Software
• Periodic Table Live! LE, a limited edition of Periodic Table Live!, 2nd Edition (3) (this replaces Chemistry Navigator (4) and Illustrated Periodic Table (5))
• Many of the programs from previous editions (6)1

Alu elements shape the primate transcriptome by cis-regulation of RNA editing

PubMed Central

2014-01-01

Background RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly frequent in the human transcriptome, largely due to the presence of inverted Alu repeats and their ability to form double-stranded structures – a requisite for ADAR editing. While several hundred thousand editing sites have been identified within these primate-specific repeats, the function of Alu-editing has yet to be elucidated. Results We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective editing in cis on sites located several hundred nucleotides from the Alu elements. Furthermore, a computational analysis, based on available RNA-seq data, finds that site-selective editing occurs significantly closer to edited Alu elements than expected. These targets are poorly edited upon deletion of the editing inducers, as well as in homologous transcripts from organisms lacking Alus. Sequences surrounding sites near edited Alus in UTRs, have been subjected to a lesser extent of evolutionary selection than those far from edited Alus, indicating that their editing generally depends on cis-acting Alus. Interestingly, we find an enrichment of primate-specific editing within encoded sequence or the UTRs of zinc finger-containing transcription factors. Conclusions We propose a model whereby primate-specific editing is induced by adjacent Alu elements that function as recruitment elements for the ADAR editing enzymes. The enrichment of site-selective editing with potentially functional consequences on the expression of transcription factors indicates that editing contributes more profoundly to the transcriptomic regulation and repertoire in primates than previously thought. PMID:24485196

Contributions au probleme d'affectation des types d'avion

NASA Astrophysics Data System (ADS)

Belanger, Nicolas

In this thesis, we approach the problem of assigning aircraft types to flights (what is called aircraft fleet assignment) in a strategic planning context. The literature mentions many studies considering this problem on a daily flight schedule basis, but the proposed models do no allow to consider many elements that are either necessary to assure the practical feasibility of the solutions, or relevant to get more beneficial solutions. After describing the practical context of the problem (Chapter 1) and presenting the literature on the subject (Chapter 2), we propose new models and solution approaches to improve the quality of' the solutions obtained. The general scheme of the thesis is presented in Chapter 3. We summarize here the models and solution approaches that we propose; and present the main elements of our conclusions. First, in Chapter 4, we consider the problem of aircraft fleet Assignment over a weekly flight schedule, integrating into the objective an homogeneity factor for driving the choice of the aircraft types for the flights with the same flight number over the week. We present an integer linear model based on a time-space multicommodity network. This model includes, among others, decision variables relative to the aircraft type assigned to each flight and to the dominant aircraft type assigned to each flight number. We present in Chapter 5 the results of a research project made in collaboration with Air Canada within a consulting contract. The project aimed at analyzing the relevance for the planners of using an optimization software to help them to first identify non profitable flight legs in the network, and second to efficiently establish the aircraft fleet assignment. In this chapter, we propose an iterative approach to take into account the fact that the passenger demand is not known on a leg basis, but rather on an origin-destination and departure time basis. Finally, in Chapter 6, we propose a model and a solution approach that aim at solving the fleet assignment problem over a periodic schedule in the case where there is a flexibility on the flight departure times and the fleet size must be minimized. Moreover, the objective of this model includes the impact on the passenger demand for each flight of the variation of the flight departure times and the closing of the departure times of consecutive flights connecting the same pairs of stations. (Abstract shortened by UMI.)

Writing Assignments in Disguise: Lessons Learned Using Video Projects in the Classroom

NASA Astrophysics Data System (ADS)

Wade, P.; Courtney, A.

2012-12-01

This study describes the instructional approach of using student-created video documentaries as projects in an undergraduate non-science majors' Energy Perspectives science course. Four years of teaching this course provided many reflective teaching moments from which we have enhanced our instructional approach to teaching students how to construct a quality Ken Burn's style science video. Fundamental to a good video documentary is the story told via a narrative which involves significant writing, editing and rewriting. Many students primarily associate a video documentary with visual imagery and do not realize the importance of writing in the production of the video. Required components of the student-created video include: 1) select a topic, 2) conduct research, 3) write an outline, 4) write a narrative, 5) construct a project storyboard, 6) shoot or acquire video and photos (from legal sources), 7) record the narrative, 8) construct the video documentary, 9) edit and 10) finalize the project. Two knowledge survey instruments (administered pre- and post) were used for assessment purposes. One survey focused on the skills necessary to research and produce video documentaries and the second survey assessed students' content knowledge acquired from each documentary. This talk will focus on the components necessary for video documentaries and the instructional lessons learned over the years. Additionally, results from both surveys and student reflections of the video project will be shared.

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.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

PubMed

Seethala, Raja R; Stenman, Göran

2017-03-01

The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

Deferred Gifts: How to Get Them. Fourth Edition.

ERIC Educational Resources Information Center

King, George V.

A nontechnical guide on practical promotional and managerial aspects of deferred giving is presented to aid nonprofit organization executives. Contents include the following topics: types of deferred gifts; organizing the deferred giving program; staffing the program; recognizing the deferred gift prospect (age, past interest in your program,…

Designing Environments for Handicapped Children: A Design Guide and Case Study. First Edition.

ERIC Educational Resources Information Center

Moore, Gary T.; And Others

This guide addresses the planning and architectural design of play/learning environments for special needs children. The exceptional children discussed include those with most types of mild to severe handicaps and developmental disabilities. Specifically excluded from consideration are health impairments, severe psycho-emotional difficulties such…

Guidance Manual: Asbestos Operations & Maintenance Work Practices. Second Edition.

ERIC Educational Resources Information Center

National Inst. of Building Sciences, Washington, DC.

This technical manual provides detailed guidance to building owners, asbestos program managers, and operations and maintenance (O&M) workers for managing asbestos-containing materials (ACM) in buildings. The manual addresses four different types of ACM found in buildings and three different levels of precaution which may be warranted by…

A Guide to the Identification of Training Needs. Second Edition.

ERIC Educational Resources Information Center

Boydell, T. H.

This guide is intended to help planners and trainers assess the training needs of industrial organizations. Addressed in the individual chapters are the following topics: types of training needs (three levels of needs--organizational, occupational, individual, organizational training needs and objectives, and present and future needs); present…

Oregon School Bond Manual. Seventh Edition.

ERIC Educational Resources Information Center

Oregon State Dept. of Education, Salem.

To help school districts comply with Oregon's school bond laws, this manual provides guidelines for school district attorneys and personnel in the issuance and sale of school district bonds. The manual deals with the three primary types of Oregon school district borrowings: (1) general obligation bonds; (2) tax and revenue anticipation notes; and…

Software for Aerospace Education. A Bibliography (Second Edition).

ERIC Educational Resources Information Center

Vogt, Gregory L.; And Others

The software described in this bibliography represents programs made available to the National Aeronautics and Space Administration (NASA) Educational Technology Branch by software producers and vendors. More than 200 computer software programs and 12 laser videodisk programs are reviewed in terms of title, copyright, subject, application, type,…

Bending the Rules: When Deaf Writers Leave College

ERIC Educational Resources Information Center

Biser, Eileen; Rubel, Linda; Toscano, Rose Marie

2007-01-01

On-the-job writing of deaf college graduates at all degree levels was investigated. Institutional databases and questionnaires to alumni and employers were the sources for information. Respondents were asked about editing assistance, sources and types of assistance, and perceptions of such assistance by employers and employees. Results of the…

Women & Men in Management. Second Edition.

ERIC Educational Resources Information Center

Powell, Gary N.

This book chronicles and examines the transition that is taking place in female/male relationships in American organizations. The book offers two types of useful information to people who currently work or anticipate working in organizations--insight into themselves in relation to the managerial role, and insight into how other people in…

Arms Control and National Security: An Introduction. Advance Edition.

ERIC Educational Resources Information Center

Arms Control Association, Washington, DC.

Suitable for use with high school students, this booklet on arms control and national security provides background information, describes basic concepts, reviews recent history, and offers suggestions for further reading. The first section, on American attitudes toward national security and arms control, defines five types of limits on weapons…

Automatic Association of News Items.

ERIC Educational Resources Information Center

Carrick, Christina; Watters, Carolyn

1997-01-01

Discussion of electronic news delivery systems and the automatic generation of electronic editions focuses on the association of related items of different media type, specifically photos and stories. The goal is to be able to determine to what degree any two news items refer to the same news event. (Author/LRW)

Case Studies on Educational Administration. Third Edition.

ERIC Educational Resources Information Center

Kowalski, Theodore J.

This book contains 24 case studies selected to demonstrate the different types of challenges in contemporary educational leadership. It is intended to help prospective administrators develop decision-making skills. The cases are quite complex with multiple viewpoints and aspects. They represent a range of problems encountered by practitioners in…

Diesel Fuel Systems. Teacher Edition (Revised).

ERIC Educational Resources Information Center

Clark, Elton; Huston, Jane, Ed.

This module is one of a series of teaching guides that cover diesel mechanics. The module contains six instructional units that cover the following topics: (1) introduction to fuel injection systems and components; (2) injection nozzles; (3) distributor type injection pumps; (4) unit injectors; (5) in-line injection pumps; and (6) pressure timed…

Trustee Handbook. Fourth Edition.

ERIC Educational Resources Information Center

Johnson, Eric W.

The principles of sound governance and administration of independent schools are discussed in this handbook for private school trustees. The nature and responsibilities of school boards are presented, along with a description of the functions of various types of board committees. A chapter on the duties of school board members provides orientation…

The Expansive Executive. Report Number 147. Second Edition.

ERIC Educational Resources Information Center

Kaplan, Robert E.

This report seeks to understand executive leadership by focusing on a character type called "expansive." Expansive character revolves around mastery of tasks and a continual desire to accomplish. In the report, several goals are featured: to define what expansive character is; to discuss its origins; to show how moderate versus extreme…

Educating the Educator: Teaching Airway Adjunct Techniques in Athletic Training

ERIC Educational Resources Information Center

Berry, David C.; Seitz, S. Robert

2011-01-01

The 5th edition of the "Athletic Training Education Competencies" ("Competencies") now requires athletic training educators (ATEs) to introduce into the curriculum various types of airway adjuncts including: (1) oropharyngeal airways (OPA), (2) nasopharyngeal airways (NPA), (3) supraglottic airways (SGA), and (4) suction. The addition of these…

Education, Inequality, and National Policy.

ERIC Educational Resources Information Center

Ashline, Nelson F., Ed.; And Others

This book, based on an invitational conference held in Newport, Rhode Island, in June 1975, includes an edited record of that conference as well as additional papers which were developed by participants as a result of their conference experience. Twelve papers are included: "Public Education as the Great Equalizer", Fred M. Hechinger; "Types of…

CHARACTERIZATION OF HAZARDOUS WASTE SITES, A METHODS MANUAL. VOLUME 2. AVAILABLE SAMPLING METHODS (SECOND EDITION)

EPA Science Inventory

Investigations at hazardous waste sites and sites of chemical spills often require on-site measurements and sampling activities to assess the type and extent of contamination. This document is a compilation of sampling methods and materials suitable to address most needs that ari...

APPLIED AUDIOLOGY FOR CHILDREN. SECOND EDITION.

ERIC Educational Resources Information Center

DALE, D.M.C.

THE PURPOSE OF THE BOOK IS TO HELP TEACHERS, PARENTS, DOCTORS, AND WORKERS IN AUDIOLOGY CLINICS MAKE THE MOST OF SOUND IN THE EDUCATIONAL AND SOCIAL TREATMENT OF DEAFNESS. ASPECTS OF SOUND AMPLIFICATION CONSIDERED ARE THE NATURE OF SOUND, ELECTRICAL AMPLIFICATION, AND VARIOUS TYPES OF HEARING AIDS (INDIVIDUAL, GROUP, INDUCTION LOOP, SPEECH…

Accreditation Standards: Policies, Procedures, and Criteria. Revised Edition.

ERIC Educational Resources Information Center

Association of Independent Colleges and Schools, Washington, DC.

Statements of policies and procedures and evaluation criteria used by the Accrediting Commission of the Association of Independent Colleges and Schools are presented. The organization and function of the Accrediting Commission, the bases of eligibility for evaluation and accreditation of all types of institutions, and the general classification of…

Blackfoot Dictionary of Stems, Roots, and Affixes. Second Edition.

ERIC Educational Resources Information Center

Frantz, Donald G.; Russell, Norma Jean

The dictionary of stems, roots, and affixes for the Blackfoot language provides, for each entry, information on the item's morphological type (e.g., noun stem, verb stem, root), subclassification if relevant, English index, and certain diagnostic inflectional forms (full words or sentences), each with an English translation. In addition, entries…

Birth Order Bibliography and Index: 1976-1993.

ERIC Educational Resources Information Center

Stewart, Alan E.; Stewart, Elizabeth A.

This listing of journal articles, doctoral dissertations, several masters' theses, chapters in edited books, and authored books chronicles birth order research from 1976 to the end of 1993. The bibliography in this paper, arranged by publication types, consists of 685 papers published in journals, 326 dissertations and theses, 24 chapters from…