The CRISPR Conundrum: As Millions of Dollars Flow into Developing the Gene-Editing Tool, Scientists Continue to Discover the Technology's Potential and Pitfalls.

PubMed

Bates, Mary

2016-01-01

We are in the midst of a CRISPR craze. The last five years have seen the publication of over 1,000 scientific papers, the allocation of millions of research dollars, and the establishment of four start-up companies in the United States alone. Internationally, the genome-editing market, fueled by CRISPR technology, is expected to be worth more than US$3,000 million by 2019.

Artificial Organs 2017: A Year in Review.

PubMed

Malchesky, Paul S

2018-03-01

In this Editor's Review, articles published in 2017 are organized by category and summarized. We provide a brief reflection of the research and progress in artificial organs intended to advance and better human life while providing insight for continued application of these technologies and methods. Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level." Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. Peer-reviewed Special Issues this year included contributions from the 12th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion edited by Dr. Akif Undar, Artificial Oxygen Carriers edited by Drs. Akira Kawaguchi and Jan Simoni, the 24th Congress of the International Society for Mechanical Circulatory Support edited by Dr. Toru Masuzawa, Challenges in the Field of Biomedical Devices: A Multidisciplinary Perspective edited by Dr. Vincenzo Piemonte and colleagues and Functional Electrical Stimulation edited by Dr. Winfried Mayr and colleagues. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Administration of the Small Public Library. Fourth Edition.

ERIC Educational Resources Information Center

Weingand, Darlene E.

Since the publication of its first edition in 1965, this book has been a standard resource for setting up and managing cutting-edge small public library facilities. Completely revised and updated, this fourth edition continues that tradition with many more figures (28 in this edition), case studies and sample policies, and new content on grant…

Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe

PubMed Central

Spicer, Andrew

2018-01-01

It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe. PMID:29509719

Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe.

PubMed

Spicer, Andrew; Molnar, Attila

2018-03-06

It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe.

MapEdit: solution to continuous raster map creation

NASA Astrophysics Data System (ADS)

Rančić, Dejan; Djordjevi-Kajan, Slobodanka

2003-03-01

The paper describes MapEdit, MS Windows TM software for georeferencing and rectification of scanned paper maps. The software produces continuous raster maps which can be used as background in geographical information systems. Process of continuous raster map creation using MapEdit "mosaicking" function is also described as well as the georeferencing and rectification algorithms which are used in MapEdit. Our approach for georeferencing and rectification using four control points and two linear transformations for each scanned map part, together with nearest neighbor resampling method, represents low cost—high speed solution that produce continuous raster maps with satisfactory quality for many purposes (±1 pixel). Quality assessment of several continuous raster maps at different scales that have been created using our software and methodology, has been undertaken and results are presented in the paper. For the quality control of the produced raster maps we referred to three wide adopted standards: US Standard for Digital Cartographic Data, National Standard for Spatial Data Accuracy and US National Map Accuracy Standard. The results obtained during the quality assessment process are given in the paper and show that our maps meat all three standards.

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

Adult Education and Social Responsibility: Reconciling the Irreconcilable? 2nd Revised Edition. Studies in Pedagogy, Andragogy and Gerontagogy, Vol. 36.

ERIC Educational Resources Information Center

Wildemeersch, Danny, Ed.; Finger, Matthias, Ed.; Jansen, Theo, Ed.

In this book, 16 authors from Europe, Africa, and the United States reflect on the transformations that are currently taking place in the field of adult and continuing education. The 12 chapters are "Reconciling the Irreconcilable? Adult and Continuing Education Between Personal Development, Corporate Concerns, and Public Responsibility"…

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.

Is School Funding Fair? A National Report Card. Third Edition

ERIC Educational Resources Information Center

Baker, Bruce D.; Sciarra, David G.; Farrie, Danielle

2014-01-01

The third edition of the National Report Card examines the condition of states' finance systems as the country emerges from the Great Recession, but is still wrestling with its consequences. As in prior editions, this Third Edition of the National Report Card continues to make the case for states to take immediate and longer-term action to improve…

United States Port Development Expenditure Report

DOT National Transportation Integrated Search

1997-10-01

This report is the seventh edition in a series of reports that continues the capital expenditure survey first begun by the Port Authority of New York and New Jersey in 1956. Subsequent reports were published by the American Association of Port Author...

Le Francais Courant (Contemporary French), Part II.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

This course has been developed basically within the limits of Units 4-6 of "A-LM French: Level 1", second edition. The primary objectives are to develop French vocabulary relative to the family, home, transportation, and foods by continuing to work with short dialogues based on everyday, teenage experiences. While reviewing previously studied…

Particle Physics, 2nd Edition

NASA Astrophysics Data System (ADS)

Martin, B. R.; Shaw, G.

1998-01-01

Particle Physics, Second Edition is a concise and lucid account of the fundamental constituents of matter. The standard model of particle physics is developed carefully and systematically, without heavy mathematical formalism, to make this stimulating subject accessible to undergraduate students. Throughout, the emphasis is on the interpretation of experimental data in terms of the basic properties of quarks and leptons, and extensive use is made of symmetry principles and Feynman diagrams, which are introduced early in the book. The Second Edition brings the book fully up to date, including the discovery of the top quark and the search for the Higgs boson. A final short chapter is devoted to the continuing search for new physics beyond the standard model. Particle Physics, Second Edition features: * A carefully structured and written text to help students understand this exciting and demanding subject. * Many worked examples and problems to aid student learning. Hints for solving the problems are given in an Appendix. * Optional "starred" sections and appendices, containing more specialised and advanced material for the more ambitious reader.

Board Policies on Student Records. Educational Policies Development Kit.

ERIC Educational Resources Information Center

National School Boards Association, Waterford, CT. Educational Policies Service.

This report of policy samples is the 17th in a continuing series of kit-booklets issued to help school boards develop written policies in key subject areas. The intent in providing samples is to encourage thinking in policy terms; and to provide working papers to be edited, modified, or adapted to meet local requirements. Policy samples herein…

"Cuts in Action": A High-Density EEG Study Investigating the Neural Correlates of Different Editing Techniques in Film.

PubMed

Heimann, Katrin S; Uithol, Sebo; Calbi, Marta; Umiltà, Maria A; Guerra, Michele; Gallese, Vittorio

2017-08-01

In spite of their striking differences with real-life perception, films are perceived and understood without effort. Cognitive film theory attributes this to the system of continuity editing, a system of editing guidelines outlining the effect of different cuts and edits on spectators. A major principle in this framework is the 180° rule, a rule recommendation that, to avoid spectators' attention to the editing, two edited shots of the same event or action should not be filmed from angles differing in a way that expectations of spatial continuity are strongly violated. In the present study, we used high-density EEG to explore the neural underpinnings of this rule. In particular, our analysis shows that cuts and edits in general elicit early ERP component indicating the registration of syntactic violations as known from language, music, and action processing. However, continuity edits and cuts-across the line differ from each other regarding later components likely to be indicating the differences in spatial remapping as well as in the degree of conscious awareness of one's own perception. Interestingly, a time-frequency analysis of the occipital alpha rhythm did not support the hypothesis that such differences in processing routes are mainly linked to visual attention. On the contrary, our study found specific modulations of the central mu rhythm ERD as an indicator of sensorimotor activity, suggesting that sensorimotor networks might play an important role. We think that these findings shed new light on current discussions about the role of attention and embodied perception in film perception and should be considered when explaining spectators' different experience of different kinds of cuts. Copyright © 2016 Cognitive Science Society, Inc.

[Understanding new progress in prosthodontics from the perspective of updates in the glossary of prosthodontic terms].

PubMed

Jiang, T

2017-12-09

Glossary of Prosthodontic Terms is a standardized vocabulary with international influence. Its ninth edition was published in J Prosthet Dent in 2017, 12 years after the last edition. During this period, great development has taken place in the dental prosthetics due to dental implant and digital dentistry as well as application of new materials and technologies. The research results of dental adhesion, aesthetic dentistry, orofacial function, and tissue regeneration has been fully applied in dental clinic. This paper attempts to capture and accurately understand the changes of some important, especially controversial academic concepts through the comparison of the seventh, eighth and ninth edition of vocabulary. Four parts including new terms, obsolete terms, terms with updated concept, and terms with the continuity of concept are used to show the important progress of prosthodontics.

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…

Pre-evaluation and interactive editing of B-spline and GERBS curves and surfaces

NASA Astrophysics Data System (ADS)

Laksâ, Arne

2017-12-01

Interactive computer based geometry editing is very useful for designers and artists. Our goal has been to develop useful tools for geometry editing in a way that increases the ability for creative design. When we interactively editing geometry, we want to see the change happening gradually and smoothly on the screen. Pre-evaluation is a tool for increasing the speed of the graphics when doing interactive affine operation on control points and control surfaces. It is then possible to add details on surfaces, and change shape in a smooth and continuous way. We use pre-evaluation on basis functions, on blending functions and on local surfaces. Pre-evaluation can be made hierarchi-cally and is thus useful for local refinements. Sampling and plotting of curves, surfaces and volumes can today be handled by the GPU and it is therefore important to have a structured organization and updating system to be able to make interactive editing as smooth and user friendly as possible. In the following, we will show a structure for pre-evaluation and an optimal organisation of the computation and we will show the effect of implementing both of these techniques.

Developing and evaluating innovative items for the NCLEX: Part 2, item characteristics and cognitive processing.

PubMed

Wendt, Anne; Harmes, J Christine

2009-01-01

This article is a continuation of the research on the development and evaluation of innovative item formats for the NCLEX examinations that was published in the March/April 2009 edition of Nurse Educator. The authors discuss the innovative item templates and evaluate the statistical characteristics and level of cognitive processing required to answer the examination items.

Being Bright Is Not Enough: The Unwritten Rules of Doctoral Study. Third Edition

ERIC Educational Resources Information Center

Hawley, Peggy

2010-01-01

This third edition has been well revised and continues with the ideas expressed in the previous two editions. The details and reactions in light of experiences of the intervening years have been updated and expanded. This particularly interesting book is written from a student advocacy perspective, intended to speak to non-traditional students as…

Major Trends and Issues in Early Childhood Education: Challenges, Controversies, and Insights. (Second Edition).

ERIC Educational Resources Information Center

Isenberg, Joan Packer, Ed.; Jalongo, Mary Renck, Ed.

Noting that understanding the contexts, continuities, and controversies of early childhood education is especially challenging because of the diversity in the field, this book provides a critical examination of the issues and controversies surrounding early childhood practices, policies, and professional development. Following an introduction…

Management of Physical Education and Sport

ERIC Educational Resources Information Center

Krotee, March; Bucher, Charles

2006-01-01

This book offers a solid foundation of management concepts, skills, and techniques that enable students to develop and test the leadership, decision-making, and problem-solving required for their role in the profession of physical education and sport. The thirteenth edition continues to focus on the management and administration of physical…

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

PubMed Central

Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

2016-01-01

Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

Development of Biodegradable Implants for Use in Maxillofacial Surgery

DTIC Science & Technology

1988-09-23

Previous edit,ons are obsolete EC1_4 ’ Y C ,S ’iCAT ON OF 7±5S aGE I"L{..-. { ~; ABBREVIATIONS poly(DL-lactide) (DL-PLA) poly(L-lactide) (L-PLA...modulus of L-PLA plates ........... ......................... 53 13 Non-coated hydroxyapatite particles after drying .............. 59 14 Hydroxyapatite ...77 (continued) ix LIST OF FIGURES (continued) Fieure age 23 Drawing No. 1 scale: 1/2" - 1" iaterial:alumina (99.7% A1203

Global Issues: Activities and Resources for the High School Teacher. Second Edition.

ERIC Educational Resources Information Center

Switzer, Kenneth A.; And Others

Increasing student knowledge about other nations and interrelationships with them is the primary goal of this teaching guide. The activities and resources focus on six topics of continuing global importance: (1) trade and economic issues, (2) conflict and armaments, (3) modernization and development, (4) technology and the environment, (5) energy,…

The American Community College. Third Edition. The Jossey-Bass Higher and Adult Education Series.

ERIC Educational Resources Information Center

Cohen, Arthur M.; Brawer, Florence B.

This book provides a comprehensive overview of community college education in the United States, emphasizing trends affecting two-year colleges in the past decade. Chapter 1 identifies social forces contributing to the development and expansion of community colleges and the continuing changes in institutional purpose. Chapter 2 examines shifting…

Vocational Education and Training in Italy. Second Edition, 1999.

ERIC Educational Resources Information Center

Alluli, Giorgio

This monograph describes the Italian initial and continuing vocational education and training (VET) system and its qualitative and quantitative development. Chapter 1 outlines the general context of the VET system--both institutions and social and economic aspects. It provides facts and figures on such topics as demographic trends in Italy, the…

Bibliography of Assessment Alternatives: Mathematics. January 1998 Edition. Innovative Assessment.

ERIC Educational Resources Information Center

Northwest Regional Educational Lab., Portland, OR.

Mathematics alternative assessment continues to be a hot topic with much activity on development, standards setting, and relation to reform. This document defines alternative assessment as any assessment in which students construct a response to a question rather than choosing a response from a list. This annotated bibliography contains the…

Wm. Theodore de Bary: Asian Studies in the Core Curriculum.

ERIC Educational Resources Information Center

Turner, James S.

1991-01-01

Traces Asian studies' infusion into the curriculum at Columbia University. Attributes the program's development to Wm. Theodore de Bary's influence, including his translating and editing of primary sources. States his work continues to serve as basic texts in Japanese, Chinese, Indian, and Buddhist traditions. Discusses his views on scholarship,…

RNA editing makes mistakes in plant mitochondria: editing loses sense in transcripts of a rps19 pseudogene and in creating stop codons in coxI and rps3 mRNAs of Oenothera.

PubMed Central

Schuster, W; Brennicke, A

1991-01-01

An intact gene for the ribosomal protein S19 (rps19) is absent from Oenothera mitochondria. The conserved rps19 reading frame found in the mitochondrial genome is interrupted by a termination codon. This rps19 pseudogene is cotranscribed with the downstream rps3 gene and is edited on both sides of the translational stop. Editing, however, changes the amino acid sequence at positions that were well conserved before editing. Other strange editings create translational stops in open reading frames coding for functional proteins. In coxI and rps3 mRNAs CGA codons are edited to UGA stop codons only five and three codons, respectively, downstream to the initiation codon. These aberrant editings in essential open reading frames and in the rps19 pseudogene appear to have been shifted to these positions from other editing sites. These observations suggest a requirement for a continuous evolutionary constraint on the editing specificities in plant mitochondria. Images PMID:1762921

Aligning CASAS Competencies and Assessments to Basic Skills Content Standards. Second Edition

ERIC Educational Resources Information Center

CASAS - Comprehensive Adult Student Assessment Systems (NJ1), 2009

2009-01-01

Since its inception, the Comprehensive Adult Student Assessment System (CASAS) has focused on teaching and assessing basic skills in contexts that are relevant and important to adult learners. CASAS has developed and continues to refine a highly formalized hierarchy of competencies, the application of basic skills that adults need to be fully…

Early Paths and Trails to Conestoga Roads. Student Activity Book [And] Teacher's Edition.

ERIC Educational Resources Information Center

Pelow, Randall; And Others

This social studies unit traces the development of the American road system beginning with early Indian footpaths and continuing through horse trails, wagon roads, all-weather highways, and the first national road. The role played by the Conestoga wagon is emphasized as well as the physical, economic, and political factors involved in road…

47 CFR 24.202 - Service areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS... 1992 Commercial Atlas & Marketing Guide, 123rd Edition, at pages 38-39 (“BTA/MTA Map”). Rand McNally... Commercial Atlas & Marketing Guide, 123rd Edition, at pages 38-39, with the following exceptions and...

47 CFR 24.202 - Service areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS... 1992 Commercial Atlas & Marketing Guide, 123rd Edition, at pages 38-39 (“BTA/MTA Map”). Rand McNally... Commercial Atlas & Marketing Guide, 123rd Edition, at pages 38-39, with the following exceptions and...

DOSE RESPONSE MODELING FOR 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN

EPA Science Inventory

As science continues to appreciate the prevalence and power of dioxins, so it learns more about the harmful effects and effective preventive measures regarding these chemicals. Updating the acclaimed First Edition, Dioxins and Health, Second Edition covers the latest major scient...

Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database.

PubMed

Carver, Tim; Berriman, Matthew; Tivey, Adrian; Patel, Chinmay; Böhme, Ulrike; Barrell, Barclay G; Parkhill, Julian; Rajandream, Marie-Adèle

2008-12-01

Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences. Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text. Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/

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.

Genome Editing to Study Ca2+ Homeostasis in Zebrafish Cone Photoreceptors.

PubMed

Brockerhoff, Susan E

2017-01-01

Photoreceptors are specialized sensory neurons with unique biological features. Phototransduction is well understood due in part to the exclusive expression and function of the molecular components of this cascade. Many other processes are less well understood, but also extremely important for understanding photoreceptor function and for treating disease. One example is the role of Ca 2+ in the cell body and overall compartmentalization and regulation of Ca 2+ within the cell. The recent development of CRISPR/Cas9 genome editing techniques has made it possible to rapidly and cheaply alter specific genes. This will help to define the biological function of elusive processes that have been more challenging to study. CRISPR/Cas9 has been optimized in many systems including zebrafish, which already has some distinct advantages for studying photoreceptor biology and function. These new genome editing technologies and the continued use of the zebrafish model system will help advance our understanding of important understudied aspects of photoreceptor biology.

The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

PubMed

Amin, Mahul B; Greene, Frederick L; Edge, Stephen B; Compton, Carolyn C; Gershenwald, Jeffrey E; Brookland, Robert K; Meyer, Laura; Gress, Donna M; Byrd, David R; Winchester, David P

2017-03-01

The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society. © 2017 American Cancer Society.

The Horizon Report. 2007 Edition

ERIC Educational Resources Information Center

New Media Consortium, 2007

2007-01-01

This fourth edition of the New Media Consortium's (NMC) annual "Horizon Report" describes the continuing work of the Horizon Project, a research-oriented effort that seeks to identify and describe emerging technologies likely to have a large impact on teaching, learning, or creative expression within higher education. Drawing on ongoing…

School-to-Work Transition Is Now Law. AACC Letter, Special Issue #1.

ERIC Educational Resources Information Center

Pierce, Dave

This special edition of the "AACC Letter" is part of a continuing effort by the AACC to keep community colleges current with developments related to the School-To-Work (STW) Transition legislation, which President Clinton signed into law on May 4, 1994. The newsletter begins with a summary of the AACC's efforts to influence bill language…

The Horizon Report. 2006 Edition

ERIC Educational Resources Information Center

New Media Consortium, 2006

2006-01-01

This third edition of the New Media Consortium's (NMC) annual "Horizon Report" describes the continuing work of the Horizon Project, a research-oriented effort that seeks to identify and describe emerging technologies likely to have a large impact on teaching, learning, or creative expression within higher education. Drawing on ongoing discussions…

The Complete Learning Disabilities Directory. 2017 Edition

ERIC Educational Resources Information Center

Grey House Publishing, 2016

2016-01-01

Published for over a decade, this directory continues to be a successful, sought-after resource, providing valuable information to professionals, families, and individuals in the learning disabilities community. Supported by the National Center for Learning Disabilities, this 2017 edition brings together the most up-to-date information on LD…

The Horizon Report. 2005 Edition

ERIC Educational Resources Information Center

New Media Consortium, 2005

2005-01-01

This second edition of the New Media Consortium's (NMC) annual "Horizon Report" describes the continuing work of the Horizon Project, a research-oriented effort that seeks to identify and describe emerging technologies likely to have a large impact on teaching, learning, or creative expression within higher education. Drawing on an ongoing series…

The Complete Learning Disabilities Directory. 2011 Edition

ERIC Educational Resources Information Center

Grey House Publishing, 2010

2010-01-01

Published for over a decade, this directory continues to be a successful, sought-after resource, providing valuable information to professionals, families, and individuals in the learning disabilities community. Supported by the National Center for Learning Disabilities, this 2011 edition brings together the most up-to-date information on LD…

An Introduction to Computational Physics - 2nd Edition

NASA Astrophysics Data System (ADS)

Pang, Tao

2006-01-01

Preface to first edition; Preface; Acknowledgements; 1. Introduction; 2. Approximation of a function; 3. Numerical calculus; 4. Ordinary differential equations; 5. Numerical methods for matrices; 6. Spectral analysis; 7. Partial differential equations; 8. Molecular dynamics simulations; 9. Modeling continuous systems; 10. Monte Carlo simulations; 11. Genetic algorithm and programming; 12. Numerical renormalization; References; Index.

Textbook of Child and Adolescent Psychiatry. 3rd Edition.

ERIC Educational Resources Information Center

Wiener, Jerry M.; Dulcan, Mina K.

The third edition of this textbook continues its tradition of integrating clinical wisdom and scientific research to improve patient care and advocacy for children and families. Each of the 56 chapters presents a summary of a core topic, blending clinical experience with evidence-based practices in assessment and treatment. Divided into 10 parts,…

Theories of Educational Leadership and Management. Third Edition

ERIC Educational Resources Information Center

Bush, Tony

2003-01-01

In this established bestselling text, Tony Bush presents the major theories of educational management and links them to contemporary policy and practice. This fully revised Third Edition includes two important changes in content. First, the book takes account of the increasing interest in the concept of leadership. Leadership continues to be one…

China, A Country Study. Area Handbook Series. Third Edition.

ERIC Educational Resources Information Center

Bunge, Frederica M., Ed.; Shinn, Rinn-Sup, Ed.

Basic facts are given about the social, economic, political, and military institutions of China. The handbook, which is one of a continuing series designed for those interested in foreign affairs, is a revision of one published in 1972. The 1981 edition focuses on historical antecedents and China's new modernization strategies. Arranged into 14…

Kaleidoscope: A Multicultural Booklist for Grades K-8. Fourth Edition. NCTE Bibliography Series.

ERIC Educational Resources Information Center

Hansen-Krening, Nancy, Ed.; Aoki, Elaine M., Ed.; Mizokawa, Donald T., Ed.

The fourth edition of this annotated bibliography collection offers students, teachers, and librarians a helpful guide to the best multicultural literature (published from 1999 to 2001) for elementary and middle school readers. The book continues a tradition of promoting unity through diversity by highlighting fiction and nonfiction published by…

Basics and applications of genome editing technology.

PubMed

Yamamoto, Takashi; Sakamoto, Naoaki

2016-01-01

Genome editing with programmable site-specific nucleases is an emerging technology that enables the manipulation of targeted genes in many organisms and cell lines. Since the development of the CRISPR-Cas9 system in 2012, genome editing has rapidly become an indispensable technology for all life science researchers, applicable in various fields. In this seminar, we will introduce the basics of genome editing and focus on the recent development of genome editing tools and technologies for the modification of various organisms and discuss future directions of the genome editing research field, from basic to medical applications.

Virtual Doors to Brick and Mortar Learning

NASA Astrophysics Data System (ADS)

Shaw, M. S.; Gay, P. L.; Meyer, D. T.; Zamfirescu, J. D.; Smith, J. E.; MIT Educational Studies Program Team

2005-12-01

The MIT Educational Studies Program (ESP) has spent the past year developing an online gateway for outreach programs. The website has a five-fold purpose: to introduce the organization to potential students, teachers, volunteers and collaborators; to allow teachers to create, design and interact with classes and to allow students to register for and dialogue with these classes; to provide an online forum for continuing dialogue; and to provide organizers a wiki for documenting program administration. What makes our site unique is the free and flexible nature of our easily edited and expanded code. In its standard installation, teachers setup classes, and administrators can approve/edit classes and make classes visible in an online catalogues. Student registration is completely customizable - students can register for self-selected classes, or they can register for a program and later get placed into teacher-selected classes. Free wiki software allows users to interactively create and edit documentation and knowledgebases. This allows administrators to track online what has been done while at the same time creating instant documentation for future programs. The online forum is a place where students can go after our programs end to learn more, interact with their classmates, and continue dialogues started in our classrooms. We also use the forum to get feedback on past and future programs. The ease with which the software handles program creation, registration, communications and more allows programs for roughly 3000 students per year to be handled by about 20 volunteering undergraduates. By combining all these elements - promotion, class creation, program registration, an organizational wiki, and student forums - we create a one-stop virtual entryway into face-to-face learning that allows students to continue their experience after they leave the classroom. The code for this site is available for free upon request to other organizations.

Early language processing efficiency predicts later receptive vocabulary outcomes in children born preterm.

PubMed

Marchman, Virginia A; Adams, Katherine A; Loi, Elizabeth C; Fernald, Anne; Feldman, Heidi M

2016-01-01

As rates of prematurity continue to rise, identifying which preterm children are at increased risk for learning disabilities is a public health imperative. Identifying continuities between early and later skills in this vulnerable population can also illuminate fundamental neuropsychological processes that support learning in all children. At 18 months adjusted age, we used socioeconomic status (SES), medical variables, parent-reported vocabulary, scores on the Bayley Scales of Infant and Toddler Development (third edition) language composite, and children's lexical processing speed in the looking-while-listening (LWL) task as predictor variables in a sample of 30 preterm children. Receptive vocabulary as measured by the Peabody Picture Vocabulary Test (fourth edition) at 36 months was the outcome. Receptive vocabulary was correlated with SES, but uncorrelated with degree of prematurity or a composite of medical risk. Importantly, lexical processing speed was the strongest predictor of receptive vocabulary (r = -.81), accounting for 30% unique variance. Individual differences in lexical processing efficiency may be able to serve as a marker for information processing skills that are critical for language learning.

The Impact of Cognitive and Psychiatric Impairment of Psychotic Disorders on the Test of Memory Malingering (TOMM)

ERIC Educational Resources Information Center

Duncan, Alexander

2005-01-01

The author analyzes the scores of inpatient psychiatric patients with varying degrees of cognitive impairment who met criteria for a psychotic disorder on the following tests: the Test of Memory Malingering (TOMM), the California Verbal Learning Test-Second Edition, Conners Continuous Performance Test-Second Edition, and the Brief Psychiatric…

Articulated Instruction Objectives Guide for Typewriting (Module 1.0--Typewriting I) (Module 2.0--Typewriting II). Project Period, March 1981-February 1982 (Pilot Model). Edition I.

ERIC Educational Resources Information Center

Reid, Barbara; And Others

Developed during the course of a project designed to provide a continuous, competency-based line of vocational training in business and office education programs at the secondary and postsecondary levels, this package consists of an instructor's guide and learning modules for use in Typewriting I and Typewriting II. Various aspects of implementing…

La Palabra es Nuestra: Primaria para Adultos. Primera Parte, Volumen 1-2. Edicion Experimental. (The Language Is Ours: Primer for Adults. Part One, Volumes 1-2. Experimental Edition).

ERIC Educational Resources Information Center

Instituto Nacional para la Educacion de los Adultos, Mexico City (Mexico).

These workbooks are part of a Mexican series of instructional materials designed for Spanish speaking adults who are in the process of becoming literate or have recently become literate in their native language. These workbooks, designed to continue developing literacy skills, include pictures, dialogues, crossword puzzles, and fill-in-the blank…

RNA Editing During Sexual Development Occurs in Distantly Related Filamentous Ascomycetes

PubMed Central

Teichert, Ines; Dahlmann, Tim A.; Kück, Ulrich

2017-01-01

RNA editing is a post-transcriptional process that modifies RNA molecules leading to transcript sequences that differ from their template DNA. A-to-I editing was found to be widely distributed in nuclear transcripts of metazoa, but was detected in fungi only recently in a study of the filamentous ascomycete Fusarium graminearum that revealed extensive A-to-I editing of mRNAs in sexual structures (fruiting bodies). Here, we searched for putative RNA editing events in RNA-seq data from Sordaria macrospora and Pyronema confluens, two distantly related filamentous ascomycetes, and in data from the Taphrinomycete Schizosaccharomyces pombe. Like F. graminearum, S. macrospora is a member of the Sordariomycetes, whereas P. confluens belongs to the early-diverging group of Pezizomycetes. We found extensive A-to-I editing in RNA-seq data from sexual mycelium from both filamentous ascomycetes, but not in vegetative structures. A-to-I editing was not detected in different stages of meiosis of S. pombe. A comparison of A-to-I editing in S. macrospora with F. graminearum and P. confluens, respectively, revealed little conservation of individual editing sites. An analysis of RNA-seq data from two sterile developmental mutants of S. macrospora showed that A-to-I editing is strongly reduced in these strains. Sequencing of cDNA fragments containing more than one editing site from P. confluens showed that at the beginning of sexual development, transcripts were incompletely edited or unedited, whereas in later stages transcripts were more extensively edited. Taken together, these data suggest that A-to-I RNA editing is an evolutionary conserved feature during fruiting body development in filamentous ascomycetes. PMID:28338982

RNA Editing During Sexual Development Occurs in Distantly Related Filamentous Ascomycetes.

PubMed

Teichert, Ines; Dahlmann, Tim A; Kück, Ulrich; Nowrousian, Minou

2017-04-01

RNA editing is a post-transcriptional process that modifies RNA molecules leading to transcript sequences that differ from their template DNA. A-to-I editing was found to be widely distributed in nuclear transcripts of metazoa, but was detected in fungi only recently in a study of the filamentous ascomycete Fusarium graminearum that revealed extensive A-to-I editing of mRNAs in sexual structures (fruiting bodies). Here, we searched for putative RNA editing events in RNA-seq data from Sordaria macrospora and Pyronema confluens, two distantly related filamentous ascomycetes, and in data from the Taphrinomycete Schizosaccharomyces pombe. Like F. graminearum, S. macrospora is a member of the Sordariomycetes, whereas P. confluens belongs to the early-diverging group of Pezizomycetes. We found extensive A-to-I editing in RNA-seq data from sexual mycelium from both filamentous ascomycetes, but not in vegetative structures. A-to-I editing was not detected in different stages of meiosis of S. pombe. A comparison of A-to-I editing in S. macrospora with F. graminearum and P. confluens, respectively, revealed little conservation of individual editing sites. An analysis of RNA-seq data from two sterile developmental mutants of S. macrospora showed that A-to-I editing is strongly reduced in these strains. Sequencing of cDNA fragments containing more than one editing site from P. confluens showed that at the beginning of sexual development, transcripts were incompletely edited or unedited, whereas in later stages transcripts were more extensively edited. Taken together, these data suggest that A-to-I RNA editing is an evolutionary conserved feature during fruiting body development in filamentous ascomycetes. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Efficient genome engineering of a virulent Klebsiella bacteriophage using CRISPR-Cas9.

PubMed

Shen, Juntao; Zhou, Jinjie; Chen, Guo-Qiang; Xiu, Zhi-Long

2018-06-13

Klebsiella pneumoniae is one of the most common nosocomial opportunistic pathogens usually with multiple drug-resistance. Phage therapy, a potential new therapeutics to replace or supplement antibiotics, has attracted much attention. However, very few Klebsiella phages have been well-characterized as the lack of efficient genome editing tools. Here, Cas9 from Streptococcus pyogenes and a single guide RNA (sgRNA) were used to modify a virulent Klebsiella bacteriophage phiKpS2. We firstly evaluated the distribution of sgRNA activity in phages and proved that it's largely inconsistent with the predicted activity from current models trained on eukaryotic cell datasets. A simple CRISPR-based phage genome editing procedure was developed based on the discovery that homologous arms as short as 30-60 bp was sufficient to introduce point mutation, gene deletion and swap. We also demonstrated that weak sgRNAs could be used for precise phage genome editing but failed to select random recombinants, possibly because inefficient cleavage can be tolerated through continuous repair by homologous recombination with the uncut genomes. Small frameshift deletion was proved to be an efficient way to evaluate the essentiality of phage genes. By using the above strategies, a putative promoter and nine genes of phiKpS2 were successfully deleted. Interestingly, the holin gene can be deleted with little effect on phiKpS2 infection, but the reason is not yet clear. This study established an efficient, time-saving, and cost-effective procedure for phage genome editing, which is expected to significantly promote the development of bacteriophage therapy. IMPORTANCE In the present study, we have addressed an efficient, time-saving and cost-effective CRISPR-based phage genome editing of Klebsiella phage, which has the potential to significantly expand our knowledge of phage-host interactions and to promote the applications of phage therapy. The distribution of sgRNA activity was first evaluated in phages. Short homologous arms were proved enough to introduce point mutation, small frameshift deletion, gene deletion and swap into phages, and weak sgRNAs were proved useful for precise phage genome editing but failed to select random recombinants, which all make the CRISPR-based phage genome editing easier to use. Copyright © 2018 American Society for Microbiology.

Principles and Practices of Test Score Equating. Research Report. ETS RR-10-29

ERIC Educational Resources Information Center

Dorans, Neil J.; Moses, Tim P.; Eignor, Daniel R.

2010-01-01

Score equating is essential for any testing program that continually produces new editions of a test and for which the expectation is that scores from these editions have the same meaning over time. Particularly in testing programs that help make high-stakes decisions, it is extremely important that test equating be done carefully and accurately.…

Me and My Environment, Unit V: Air and Water in My Environment, Experimental Edition 1973-74.

ERIC Educational Resources Information Center

Biological Sciences Curriculum Study, Boulder, CO.

The experimental 1973-74 edition of Unit V consists of 35 life science curriculum activities intended for 13- to 16-year-old educable mentally handicapped adolescents. The role of the teacher in continuing field trials is noted and environmental themes and elements, inquiry skills, problem solving skills, and applicational behaviors and attitudes…

Me and My Environment, Unit IV: Transfer and Cycling of Materials in My Environment, Experimental Edition 1973-74.

ERIC Educational Resources Information Center

Biological Sciences Curriculum Study, Boulder, CO.

The experimental 1973-74 edition of Unit IV consists of 28 life science curriculum activities for 13- to 16-year-old educable mentally handicapped children. The role of the teacher in continuing field trials is noted and environmental themes and elements, inquiry skills, problem solving skills, and applicational behaviors and attitudes are…

100 Years of Mass Deworming Programmes: A Policy Perspective From the World Bank's Disease Control Priorities Analyses.

PubMed

Bundy, Donald A P; Appleby, Laura J; Bradley, Mark; Croke, Kevin; Hollingsworth, T Deirdre; Pullan, Rachel; Turner, Hugo C; de Silva, Nilanthi

2018-01-01

For more than 100 years, countries have used mass drug administration as a public health response to soil-transmitted helminth infection. The series of analyses published as Disease Control Priorities is the World Bank's vehicle for exploring the cost-effectiveness and value for money of public health interventions. The first edition was published in 1993 as a technical supplement to the World Bank's World Development Report Investing in Health where deworming was used as an illustrative example of value for money in treating diseases with relatively low morbidity but high prevalence. Over the second (2006) and now third (2017) editions deworming has been an increasingly persuasive example to use for this argument. The latest analyses recognize the negative impact of intestinal worm infection on human capital in poor communities and document a continuing decline in worm infection as a result of the combination of high levels of mass treatment and ongoing economic development trends in poor communities. © 2018 Elsevier Ltd All rights reserved.

Using Appendicitis to Improve Estimates of Childhood Medicaid Participation Rates.

PubMed

Silber, Jeffrey H; Zeigler, Ashley E; Reiter, Joseph G; Hochman, Lauren L; Ludwig, Justin M; Wang, Wei; Calhoun, Shawna R; Pati, Susmita

2018-03-23

Administrative data are often used to estimate state Medicaid/Children's Health Insurance Program duration of enrollment and insurance continuity, but they are generally not used to estimate participation (the fraction of eligible children enrolled) because administrative data do not include reasons for disenrollment and cannot observe eligible never-enrolled children, causing estimates of eligible unenrolled to be inaccurate. Analysts are therefore forced to either utilize survey information that is not generally linkable to administrative claims or rely on duration and continuity measures derived from administrative data and forgo estimating claims-based participation. We introduce appendectomy-based participation (ABP) to estimate statewide participation rates using claims by taking advantage of a natural experiment around statewide appendicitis admissions to improve the accuracy of participation rate estimates. We used Medicaid Analytic eXtract (MAX) for 2008-2010; and the American Community Survey for 2008-2010 from 43 states to calculate ABP, continuity ratio, duration, and participation based on the American Community Survey (ACS). In the validation study, median participation rate using ABP was 86% versus 87% for ACS-based participation estimates using logical edits and 84% without logical edits. Correlations between ABP and ACS with or without logical edits was 0.86 (P < .0001). Using regression analysis, ABP alone was a significant predictor of ACS (P < .0001) with or without logical edits, and adding duration and/or the continuity ratio did not significantly improve the model. Using the ABP rate derived from administrative claims (MAX) is a valid method to estimate statewide public insurance participation rates in children. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Giving Psychology Away: Implementation of Wikipedia Editing in an Introductory Human Development Course

ERIC Educational Resources Information Center

Shane-Simpson, Christina; Che, Elizabeth; Brooks, Patricia J.

2016-01-01

To test the feasibility of Wikipedia editing in large undergraduate psychology classrooms, we engaged groups of students in a large introductory-level Human Development course (N = 110) in editing Wikipedia articles to improve psychology-related content. Students attended in-class workshops and received online support to develop skills. They…

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

Editing in Technical Communication: Theory and Practice in Editing Processes at the Graduate Level.

ERIC Educational Resources Information Center

Masse, Roger E.

At New Mexico State University, technical communication teachers have developed a course to teach editing processes to graduate students who take the advanced workshop in technical and professional communication. In this seminar group, students work on writing processes; editing processes; written, edited, and tested products; and oral processes…

Genome Editing Tools in Plants

PubMed Central

Mohanta, Tapan Kumar; Bashir, Tufail; Hashem, Abeer; Bae, Hanhong

2017-01-01

Genome editing tools have the potential to change the genomic architecture of a genome at precise locations, with desired accuracy. These tools have been efficiently used for trait discovery and for the generation of plants with high crop yields and resistance to biotic and abiotic stresses. Due to complex genomic architecture, it is challenging to edit all of the genes/genomes using a particular genome editing tool. Therefore, to overcome this challenging task, several genome editing tools have been developed to facilitate efficient genome editing. Some of the major genome editing tools used to edit plant genomes are: Homologous recombination (HR), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), pentatricopeptide repeat proteins (PPRs), the CRISPR/Cas9 system, RNA interference (RNAi), cisgenesis, and intragenesis. In addition, site-directed sequence editing and oligonucleotide-directed mutagenesis have the potential to edit the genome at the single-nucleotide level. Recently, adenine base editors (ABEs) have been developed to mutate A-T base pairs to G-C base pairs. ABEs use deoxyadeninedeaminase (TadA) with catalytically impaired Cas9 nickase to mutate A-T base pairs to G-C base pairs. PMID:29257124

Factor Analysis of Computer-Based Multidimensional Aptitude Battery-Second Edition Intelligence Testing from Rated U.S. Air Force Pilots

DTIC Science & Technology

2012-09-01

intelligence continues to evolve as attention to cognitive processes and mechanisms, a deeper understanding of related issues, and new theories ...hierarchical models that describe specific abilities arranged according to increasing specificity and developmental complexity [6-8]. Theories have also...persistence) not tapped directly by existing measures of intellectual ability. Wechsler’s theory of intelligence is central to the development of the mostly

Lifelong Learning Trends: A Profile of Continuing Higher Education. Second Edition.

ERIC Educational Resources Information Center

National Univ. Continuing Education Association, Washington, DC.

This publication provides national data on trends and participation in continuing higher education. The charts have been derived from data collected by the National University Continuing Education Association and governmental and private organizations. Narrative accompanies each chart. Section I highlights factors contributing to growth: part-time…

Continuity in Early Childhood: A Framework for Home, School, and Community Linkages. Revised Edition.

ERIC Educational Resources Information Center

Regional Educational Laboratories Early Childhood Collaboration Network.

This guide details a framework for supporting the efforts of home, school, and community partners to improve continuity and transition in early childhood. Following an introduction describing continuity in early childhood, the importance of a smooth transition, and the eight elements of early childhood continuity, the guide is presented in eight…

Nairobi Forward-looking Strategies for the Advancement of Women: Issues and the Canadian Situation. Fact Sheets--1992 Update.

ERIC Educational Resources Information Center

Status of Women Canada, Ottawa (Ontario).

The 1992 edition of the fact sheets provides information on new and revised Canadian government programs and policies about the implementation of the Nairobi Forward-looking Strategies for the Advancement of Women program that were adopted at the United Nations World Conference on Women in Kenya in 1985. This edition continues to address the…

Essential Study Skills: The Complete Guide to Success at University. Second Edition. Sage Study Skills Series

ERIC Educational Resources Information Center

Burns, Tom; Sinfield, Sandra

2008-01-01

The eagerly-awaited new edition of the successful "Essential Study Skills" continues to provide a truly practical guide to achieving success at university. Whether you are going to university straight from school, a mature student, or an overseas student studying in the UK for the first time, this is the book that will help you to better…

[Genome editing of industrial microorganism].

PubMed

Zhu, Linjiang; Li, Qi

2015-03-01

Genome editing is defined as highly-effective and precise modification of cellular genome in a large scale. In recent years, such genome-editing methods have been rapidly developed in the field of industrial strain improvement. The quickly-updating methods thoroughly change the old mode of inefficient genetic modification, which is "one modification, one selection marker, and one target site". Highly-effective modification mode in genome editing have been developed including simultaneous modification of multiplex genes, highly-effective insertion, replacement, and deletion of target genes in the genome scale, cut-paste of a large DNA fragment. These new tools for microbial genome editing will certainly be applied widely, and increase the efficiency of industrial strain improvement, and promote the revolution of traditional fermentation industry and rapid development of novel industrial biotechnology like production of biofuel and biomaterial. The technological principle of these genome-editing methods and their applications were summarized in this review, which can benefit engineering and construction of industrial microorganism.

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.

CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against the Right to Disability

PubMed Central

Benston, Shawna

2016-01-01

Reproductive genetic technologies (RGTs), including gene-editing technology, are being discovered and refined at an exponential pace. One gene-editing innovation that demands our swift attention is CRISPR/Cas9, a system of clustered regularly interspaced short palindromic repeats and a protein called Cas9. As CRISPR and other RGTs continue being developed, we must remain vigilant concerning the potential implications of genetic-engineering technology on our interpersonal and legal relationships. In the face of increasingly numerous and refined RGTs, we must maintain the rights of everyone: potential parents, prospective children, and individuals (both living and prospective) with disabilities. For those who wish to become parents, how should procreation be regulated in light of developing RGTs, especially gene-editing technology? What duties do parents owe their children, and when does such a duty attach? What role should RGTs play in parents’ fulfillment of their duties to their children? This article will contextualize the right to health and what I will term the “right to disability” in the CRISPR/Cas9 landscape. The article will then explore these rights in reference to the “subjunctive-threshold” interpretation of harm. Finally, I will argue that RGTs must be thoughtfully regulated, with such regulations taking into account the opinions of geneticists, bioethicists, and lay people concerning both the right to health and the right to disability. PMID:27688903

CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against the Right to Disability.

PubMed

Benston, Shawna

2016-03-01

Reproductive genetic technologies (RGTs), including gene-editing technology, are being discovered and refined at an exponential pace. One gene-editing innovation that demands our swift attention is CRISPR/Cas9, a system of clustered regularly interspaced short palindromic repeats and a protein called Cas9. As CRISPR and other RGTs continue being developed, we must remain vigilant concerning the potential implications of genetic-engineering technology on our interpersonal and legal relationships. In the face of increasingly numerous and refined RGTs, we must maintain the rights of everyone: potential parents, prospective children, and individuals (both living and prospective) with disabilities. For those who wish to become parents, how should procreation be regulated in light of developing RGTs, especially gene-editing technology? What duties do parents owe their children, and when does such a duty attach? What role should RGTs play in parents' fulfillment of their duties to their children? This article will contextualize the right to health and what I will term the "right to disability" in the CRISPR/Cas9 landscape. The article will then explore these rights in reference to the "subjunctive-threshold" interpretation of harm. Finally, I will argue that RGTs must be thoughtfully regulated, with such regulations taking into account the opinions of geneticists, bioethicists, and lay people concerning both the right to health and the right to disability.

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

PubMed

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

2017-07-01

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

Genome editing: progress and challenges for medical applications.

PubMed

Carroll, Dana

2016-11-15

The development of the CRISPR-Cas platform for genome editing has greatly simplified the process of making targeted genetic modifications. Applications of genome editing are expected to have a substantial impact on human therapies through the development of better animal models, new target discovery, and direct therapeutic intervention.

Handbook of Research on Teaching the English Language Arts. Second Edition.

ERIC Educational Resources Information Center

Flood, James, Ed.; Lapp, Diane, Ed.; Squire, James R., Ed.; Jensen, Julie M., Ed.

This updated second edition reflects developments in educational research and new information within the areas of language learning and instruction since the publication of the first edition in 1991. Its 75 essays assess the significance of research, evaluates new developments, and examines current conflicts, controversies, and issues, while…

A new user-assisted segmentation and tracking technique for an object-based video editing system

NASA Astrophysics Data System (ADS)

Yu, Hong Y.; Hong, Sung-Hoon; Lee, Mike M.; Choi, Jae-Gark

2004-03-01

This paper presents a semi-automatic segmentation method which can be used to generate video object plane (VOP) for object based coding scheme and multimedia authoring environment. Semi-automatic segmentation can be considered as a user-assisted segmentation technique. A user can initially mark objects of interest around the object boundaries and then the user-guided and selected objects are continuously separated from the unselected areas through time evolution in the image sequences. The proposed segmentation method consists of two processing steps: partially manual intra-frame segmentation and fully automatic inter-frame segmentation. The intra-frame segmentation incorporates user-assistance to define the meaningful complete visual object of interest to be segmentation and decides precise object boundary. The inter-frame segmentation involves boundary and region tracking to obtain temporal coherence of moving object based on the object boundary information of previous frame. The proposed method shows stable efficient results that could be suitable for many digital video applications such as multimedia contents authoring, content based coding and indexing. Based on these results, we have developed objects based video editing system with several convenient editing functions.

Towards a new era in medicine: therapeutic genome editing.

PubMed

Porteus, Matthew H

2015-12-22

Genome editing is the process of precisely modifying the nucleotide sequence of the genome. It has provided a powerful approach to research questions but, with the development of a new set of tools, it is now possible to achieve frequencies of genome editing that are high enough to be useful therapeutically. Genome editing is being developed to treat not only monogenic diseases but also infectious diseases and diseases that have both a genetic and an environmental component.

The commercialization of genome-editing technologies.

PubMed

Brinegar, Katelyn; K Yetisen, Ali; Choi, Sun; Vallillo, Emily; Ruiz-Esparza, Guillermo U; Prabhakar, Anand M; Khademhosseini, Ali; Yun, Seok-Hyun

2017-11-01

The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance. Although most of the gene-editing technologies originated from the industry, CRISPR has been pioneered by academic research institutions. The spinout of CRISPR biotechnology companies from academic institutions demonstrates a shift in entrepreneurship strategies that were previously led by the industry. These academic institutions, and their subsequent companies, are competing to generate comprehensive intellectual property portfolios to rapidly commercialize CRISPR products. Our analysis shows that the emergence of CRISPR has resulted in a fivefold increase in genome-editing bioenterprise investment over the last year. This entrepreneurial movement has spurred a global biotechnology revolution in the realization of novel gene-editing technologies. This global shift in bioenterprise will continue to grow as the demand for personalized medicine, genetically modified crops and environmentally sustainable biofuels increases. However, the monopolization of intellectual property, negative public perception of genetic engineering and ambiguous regulatory policies may limit the growth of these market segments.

Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

PubMed

Alapati, Deepthi; Morrisey, Edward E

2017-03-01

Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

A Fault Tolerant Self-Routing Computer Network Topology

DTIC Science & Technology

1987-01-01

Herr and Thomas J. Plevyak, *ISDN: The Opportunity Beginso, IEEECommunicationsMaqaz I t, pp. 6-10, November 1986. 5. Mario Gerla and Rodolfo A . Pazos ...WOLAVER a Dean for Research anProfessional Development Air Force Institute Bf Technology Wright-Patterson AFB OH 45433-6583 19. KEY WORDS (Continue...DD I 1473 EDITION OF I NOV 65 IS OBSOLETE UM!C[ASSIFIEy SECURITY CLASSIFICATION OF THIS PAGE (When Data Entered) 41 ,." 5.’ A Fault Tolerant Self

The use of self-modeling to improve the swimming performance of spina bifida children.

PubMed Central

Dowrick, P W; Dove, C

1980-01-01

The use of edited videotape replay (which showed only "positive" behaviors) to improve the water skills of three spina bifida children, aged 5 to 10 years was examined. A multiple baseline across subjects design was used, and behavioral changes were observed to occur in close association with intervention. One child was given successive reapplications of videotaped self-modeling with continuing improvements. It appears that a useful practical technique has been developed. PMID:6988381

RPMIS: The Roswell Park Management Information System

PubMed Central

Priore, R.L.; Lane, W.W.; Edgerton, F.T.; Naeher, C.H.; Reese, P.A.

1978-01-01

This paper presents a generalized approach to data entry and editing utilizing formatted video computer terminals. The purpose of the system developed is to facilitate the creation of many small data bases, with a minimum of implementation time, while maintaining extensive editing capability and preserving ease of use by data entry personnel. RPMIS has demonstrated its utility in shortening the time between research activities and clinical application of results. The system allows entry and retrieval of overlapping subsets of the patient's record in an order and format most appropriate to the individual application. It is used for production of synoptic presentations of information from the labs, the ward and the clinic. RPMIS was designed for the clinical trials setting and has been well received and implemented for numerous such studies. Additional uses have included several registries, screening clinics, retrospective studies, and epidemiologic investigations. The system has found fortuitous use in maintaining curriculum vitae, publications lists and continuing medical education credits.

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.

The clinical applications of genome editing in HIV.

PubMed

Wang, Cathy X; Cannon, Paula M

2016-05-26

HIV/AIDS has long been at the forefront of the development of gene- and cell-based therapies. Although conventional gene therapy approaches typically involve the addition of anti-HIV genes to cells using semirandomly integrating viral vectors, newer genome editing technologies based on engineered nucleases are now allowing more precise genetic manipulations. The possible outcomes of genome editing include gene disruption, which has been most notably applied to the CCR5 coreceptor gene, or the introduction of small mutations or larger whole gene cassette insertions at a targeted locus. Disruption of CCR5 using zinc finger nucleases was the first-in-human application of genome editing and remains the most clinically advanced platform, with 7 completed or ongoing clinical trials in T cells and hematopoietic stem/progenitor cells (HSPCs). Here we review the laboratory and clinical findings of CCR5 editing in T cells and HSPCs for HIV therapy and summarize other promising genome editing approaches for future clinical development. In particular, recent advances in the delivery of genome editing reagents and the demonstration of highly efficient homology-directed editing in both T cells and HSPCs are expected to spur the development of even more sophisticated applications of this technology for HIV therapy. © 2016 by The American Society of Hematology.

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.

Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening.

PubMed

O'Duibhir, Eoghan; Carragher, Neil O; Pollard, Steven M

2017-04-01

Patients diagnosed with glioblastoma (GBM) continue to face a bleak prognosis. It is critical that new effective therapeutic strategies are developed. GBM stem cells have molecular hallmarks of neural stem and progenitor cells and it is possible to propagate both non-transformed normal neural stem cells and GBM stem cells, in defined, feeder-free, adherent culture. These primary stem cell lines provide an experimental model that is ideally suited to cell-based drug discovery or genetic screens in order to identify tumour-specific vulnerabilities. For many solid tumours, including GBM, the genetic disruptions that drive tumour initiation and growth have now been catalogued. CRISPR/Cas-based genome editing technologies have recently emerged, transforming our ability to functionally annotate the human genome. Genome editing opens prospects for engineering precise genetic changes in normal and GBM-derived neural stem cells, which will provide more defined and reliable genetic models, with critical matched pairs of isogenic cell lines. Generation of more complex alleles such as knock in tags or fluorescent reporters is also now possible. These new cellular models can be deployed in cell-based phenotypic drug discovery (PDD). Here we discuss the convergence of these advanced technologies (iPS cells, neural stem cell culture, genome editing and high content phenotypic screening) and how they herald a new era in human cellular genetics that should have a major impact in accelerating glioblastoma drug discovery. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Standards of Good Practice for Education Abroad. Fourth Edition

ERIC Educational Resources Information Center

Forum on Education Abroad, 2011

2011-01-01

This fourth edition of the Forum on Education Abroad's "Standards of Good Practice for Education Abroad" augments previous editions of the "Standards." Since the last edition was published in 2008, Forum member institutions and organizations have implemented the Standards in program development and assessment, using the Standards in the Forum's…

Diesel Technology: Steering and Suspension. Second Edition. Teacher Edition [and] Student Edition.

ERIC Educational Resources Information Center

Miller, Roger; Scarberry, Terry; Tesch, Carl; Kellum, Mary

These teacher and student editions on steering and suspension are part of the diesel mechanics series of instructional materials. The series aligns with the medium/heavy duty truck task list developed by the National Automotive Technicians Education Foundation and used by the National Institute for Automotive Service Excellence in the…

Human Resources Administration: A School-Based Perspective. Fourth Edition

ERIC Educational Resources Information Center

Smith, Richard

2009-01-01

Enhanced and updated, this Fourth Edition of Richard E. Smith's highly successful text examines the growing role of the principal in planning, hiring, staff development, supervision, and other human resource functions. The Fourth Edition includes new sections on ethics, induction, and the role of the mentor teacher. This edition also introduces…

Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes.

PubMed

Hess, Gaelen T; Tycko, Josh; Yao, David; Bassik, Michael C

2017-10-05

The past several years have seen an explosion in development of applications for the CRISPR-Cas9 system, from efficient genome editing, to high-throughput screening, to recruitment of a range of DNA and chromatin-modifying enzymes. While homology-directed repair (HDR) coupled with Cas9 nuclease cleavage has been used with great success to repair and re-write genomes, recently developed base-editing systems present a useful orthogonal strategy to engineer nucleotide substitutions. Base editing relies on recruitment of cytidine deaminases to introduce changes (rather than double-stranded breaks and donor templates) and offers potential improvements in efficiency while limiting damage and simplifying the delivery of editing machinery. At the same time, these systems enable novel mutagenesis strategies to introduce sequence diversity for engineering and discovery. Here, we review the different base-editing platforms, including their deaminase recruitment strategies and editing outcomes, and compare them to other CRISPR genome-editing technologies. Additionally, we discuss how these systems have been applied in therapeutic, engineering, and research settings. Lastly, we explore future directions of this emerging technology. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of voice-automated transcription and human transcription in generating pathology reports.

PubMed

Al-Aynati, Maamoun M; Chorneyko, Katherine A

2003-06-01

Software that can convert spoken words into written text has been available since the early 1980s. Early continuous speech systems were developed in 1994, with the latest commercially available editions having a claimed accuracy of up to 98% of speech recognition at natural speech rates. To evaluate the efficacy of one commercially available voice-recognition software system with pathology vocabulary in generating pathology reports and to compare this with human transcription. To draw cost analysis conclusions regarding human versus computer-based transcription. Two hundred six routine pathology reports from the surgical pathology material handled at St Joseph's Healthcare, Hamilton, Ontario, were generated simultaneously using computer-based transcription and human transcription. The following hardware and software were used: a desktop 450-MHz Intel Pentium III processor with 192 MB of RAM, a speech-quality sound card (Sound Blaster), noise-canceling headset microphone, and IBM ViaVoice Pro version 8 with pathology vocabulary support (Voice Automated, Huntington Beach, Calif). The cost of the hardware and software used was approximately Can 2250 dollars. A total of 23 458 words were transcribed using both methods with a mean of 114 words per report. The mean accuracy rate was 93.6% (range, 87.4%-96%) using the computer software, compared to a mean accuracy of 99.6% (range, 99.4%-99.8%) for human transcription (P <.001). Time needed to edit documents by the primary evaluator (M.A.) using the computer was on average twice that needed for editing the documents produced by human transcriptionists (range, 1.4-3.5 times). The extra time needed to edit documents was 67 minutes per week (13 minutes per day). Computer-based continuous speech-recognition systems in pathology can be successfully used in pathology practice even during the handling of gross pathology specimens. The relatively low accuracy rate of this voice-recognition software with resultant increased editing burden on pathologists may not encourage its application on a wide scale in pathology departments with sufficient human transcription services, despite significant potential financial savings. However, computer-based transcription represents an attractive and relatively inexpensive alternative to human transcription in departments where there is a shortage of transcription services, and will no doubt become more commonly used in pathology departments in the future.

Coherence between Compulsory Education, Initial and Continuing Training and Adult Education in Norway. National Report. CEDEFOP Panorama. First Edition.

ERIC Educational Resources Information Center

Skinningsrud, Tone

This report discusses various aspects of continuity--internal, external, and complex--in education and training. Chapter 1 defines conditions for the three different types of continuity and describes the organization of the report, which distinguishes four different sectors of education and training: public education, private education, labor…

Lifelong Learning Trends. A Profile of Continuing Higher Education. Fourth Edition.

ERIC Educational Resources Information Center

National Univ. Continuing Education Association, Washington, DC.

This book reports national data on trends and participation in continuing higher education. Statistics in the book have been derived from data collected by the authors, as well as by governmental and private organizations. The book is organized in six sections that cover the following topics: factors contributing to the growth of continuing higher…

Twentieth Century Thinkers in Adult & Continuing Education. Second Edition.

ERIC Educational Resources Information Center

Jarvis, Peter, Ed.

This book contains 19 papers on 20th century thinkers in adult and continuing education. The book is arranged in four parts as follows: early 20th century English thinkers; early 20th century American thinkers; theorists of adult and continuing education; and theorists of adult education and social change. The following papers are included:…

General catalogue of variable stars: Version GCVS 5.1

NASA Astrophysics Data System (ADS)

Samus', N. N.; Kazarovets, E. V.; Durlevich, O. V.; Kireeva, N. N.; Pastukhova, E. N.

2017-01-01

Work aimed at compiling detailed catalogs of variable stars in the Galaxy, which has been carried out continuously by Moscow variable-star researchers since 1946 on behalf of the International Astronomical Union, has entered the stage of the publication of the 5th, completely electronic edition of the General Catalogue of Variable Stars (GCVS). This paper describes the requirements for the contents of the 5th edition and the current state of the catalog in its new version, GCVS 5.1. The complete revision of information for variable stars in the constellation Carina and the compilation of the 81st Name-list of Variable Stars are considered as examples of work on the 5th edition. The GCVS 5.1 is freely accessible on the Internet. We recommend the present paper as a unified reference to the 5th edition of the GCVS.

Optimizing sgRNA structure to improve CRISPR-Cas9 knockout efficiency.

PubMed

Dang, Ying; Jia, Gengxiang; Choi, Jennie; Ma, Hongming; Anaya, Edgar; Ye, Chunting; Shankar, Premlata; Wu, Haoquan

2015-12-15

Single-guide RNA (sgRNA) is one of the two key components of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing system. The current commonly used sgRNA structure has a shortened duplex compared with the native bacterial CRISPR RNA (crRNA)-transactivating crRNA (tracrRNA) duplex and contains a continuous sequence of thymines, which is the pause signal for RNA polymerase III and thus could potentially reduce transcription efficiency. Here, we systematically investigate the effect of these two elements on knockout efficiency and showed that modifying the sgRNA structure by extending the duplex length and mutating the fourth thymine of the continuous sequence of thymines to cytosine or guanine significantly, and sometimes dramatically, improves knockout efficiency in cells. In addition, the optimized sgRNA structure also significantly increases the efficiency of more challenging genome-editing procedures, such as gene deletion, which is important for inducing a loss of function in non-coding genes. By a systematic investigation of sgRNA structure we find that extending the duplex by approximately 5 bp combined with mutating the continuous sequence of thymines at position 4 to cytosine or guanine significantly increases gene knockout efficiency in CRISPR-Cas9-based genome editing experiments.

Twenty-five years of Social Science in Law.

PubMed

Monahan, John; Walker, Laurens

2011-02-01

In this essay, we take the publication of the seventh edition of the casebook Social Science in Law (2010) as an opportunity to reflect on continuities and changes that have occurred in the application of social science research to American law over the past quarter-century. We structure these reflections by comparing and contrasting the original edition of the book with the current one. When the first edition appeared, courts' reliance on social science was often confused and always contested. Now, courts' reliance on social science is so common as to be unremarkable. What has changed--sometimes radically--are the substantive legal questions on which social science has been brought to bear.

Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens

DTIC Science & Technology

1991-12-20

carciflogeflesis; bioassay; patholo 06 I 05 1 1,1,2,2-tetrachloroethane; cadmium; 2-acetylaminofluorene; 19. ABTRC (C1iu on1vrei eesr ethyl enedi bromide...vinylidene chloride; chlorodibromomethane; 19.ABSRAC (Cntiue n rvere i neessryand identify by block number) 1 Studies were conducted related to the...7325 1 SGRD-RMI-S OD Form 1473. JUN 86 P’re vious editions are obsolete. SECURITY CLASSIFICATION OF THIS PAGE I I 18. Subject Terms (Continued

A Guidance Document for Kentucky's Oil and Gas Operations

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

None, None

1998-11-10

This technical report is a summary of the progress made for "A Guidance Document for Kentucky's Oil and Gas Operators". During this quarter, the document received continued review and editing in an elec-tronic format to satisfy the United States Department of Energy (DOE). Comments received from oil and gas operators reviewing this document prompted contact to be made with the United States Environmental Protection Agency (USEPA) to develop an addendum section to provide better explanation of USEPA requirements for Class II injection wells in Kentucky.

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.

Fundamentals of Physics, 6th Edition Enhanced Problems Version

NASA Astrophysics Data System (ADS)

Halliday, David; Resnick, Robert; Walker, Jearl

2002-04-01

No other text on the market today can match the success of Halliday, Resnick and Walker's Fundamentals of Physics. This text continues to outperform the competition year after year, and the new edition will be no exception. Intended for Calculus-based Physics courses, the 6th edition of this extraordinary text is a major redesign of the best-selling 5th edition, which still maintains many of the elements that led to its enormous success. Jearl Walker adds his unique style to this edition with the addition of new problems designed to capture, and keep, students' attention. Nearly all changes are based on suggestions from instructors and students using the 5th edition, from reviewer comments, and from research done on the process of learning. The primary goal of this text is to provide students with a solid understanding of fundamental physics concepts, and to help them apply this conceptual understanding to quantitative problem solving. The principal goal of Halliday-Resnick-Walker is to provide instructors with a tool by which they can teach students how to effectively read scientific material and successfully reason through scientific questions. To sharpen this tool, the Enhanced Problems Version of the sixth edition of Fundamentals of Physics contains over 1000 new, high-quality problems that require thought and reasoning rather than simplistic plugging of data into formulas.

The Express-Lane Edit: Making Editing Useful for Young Adolescents

ERIC Educational Resources Information Center

Anderson, Jeff

2008-01-01

Editing is a powerful tool for writers, but are our methods of teaching it really demonstrating that power for young adolescents? The author, frustrated with students' inability to edit, blames his own approach and, beginning with a grocery store epiphany, works to develop a more effective system. Elements of his successful approach include time…

The Global Factors of the "16PF Fifth Edition": Contribution to Career Development and Guidance.

ERIC Educational Resources Information Center

Vansickle, Timothy R.; Conn, Steven R.

As part of an exploration of how best to use normal personality measures in career development and guidance, this study investigated the use of the Sixteen Personality Factor Questionnaire Fifth Edition (16PF Fifth Edition) assessment and its relationship to the widely used typology of J. L. Holland (1985) and the new Campbell Orientations (1992).…

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.

[Analysis of Musculoskeletal Systems and Their Diseases. The research for musculoskeletal disease using genome editing technology].

PubMed

Suzuki, Hidetsugu; Asahara, Hiroshi

2015-08-01

Genome editing is a genetic technology by which any DNA sequence is inserted, replaced or deleted. Genome editing has been making rapid progress recently, with the development of new techniques such as ZFN, TALEN and CRISPR/Cas9. Genome editing can be applied to various fields ranging from the production of knock out animals to gene therapy. This section summarizes these new genome editing technologies and its applications.

Steric antisense inhibition of AMPA receptor Q/R editing reveals tight coupling to intronic editing sites and splicing

PubMed Central

Penn, Andrew C.; Balik, Ales; Greger, Ingo H.

2013-01-01

Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional mechanism, evolved to diversify the transcriptome in metazoa. In addition to wide-spread editing in non-coding regions protein recoding by RNA editing allows for fine tuning of protein function. Functional consequences are only known for some editing sites and the combinatorial effect between multiple sites (functional epistasis) is currently unclear. Similarly, the interplay between RNA editing and splicing, which impacts on post-transcriptional gene regulation, has not been resolved. Here, we describe a versatile antisense approach, which will aid resolving these open questions. We have developed and characterized morpholino oligos targeting the most efficiently edited site—the AMPA receptor GluA2 Q/R site. We show that inhibition of editing closely correlates with intronic editing efficiency, which is linked to splicing efficiency. In addition to providing a versatile tool our data underscore the unique efficiency of a physiologically pivotal editing site. PMID:23172291

CRISPR Editing Technology in Biological and Biomedical Investigation.

PubMed

White, Martyn K; Kaminski, Rafal; Young, Won-Bin; Roehm, Pamela C; Khalili, Kamel

2017-11-01

The CRISPR or clustered regularly interspaced short palindromic repeats system is currently the most advanced approach to genome editing and is notable for providing an unprecedented degree of specificity, effectiveness, and versatility in genetic manipulation. CRISPR evolved as a prokaryotic immune system to provide an acquired immunity and resistance to foreign genetic elements such as bacteriophages. It has recently been developed into a tool for the specific targeting of nucleotide sequences within complex eukaryotic genomes for the purpose of genetic manipulation. The power of CRISPR lies in its simplicity and ease of use, its flexibility to be targeted to any given nucleotide sequence by the choice of an easily synthesized guide RNA, and its ready ability to continue to undergo technical improvements. Applications for CRISPR are numerous including creation of novel transgenic cell animals for research, high-throughput screening of gene function, potential clinical gene therapy, and nongene-editing approaches such as modulating gene activity and fluorescent tagging. In this prospect article, we will describe the salient features of the CRISPR system with an emphasis on important drawbacks and considerations with respect to eliminating off-target events and obtaining efficient CRISPR delivery. We will discuss recent technical developments to the system and we will illustrate some of the most recent applications with an emphasis on approaches to eliminate human viruses including HIV-1, JCV and HSV-1 and prospects for the future. J. Cell. Biochem. 118: 3586-3594, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Wound, Ostomy, and Continence Nursing: Scope and Standards of Practice, 2nd Edition: An Executive Summary.

PubMed

2018-04-25

Wound, ostomy, and continence (WOC) nursing was recognized as a nursing specialty by the American Nurses Association in February 2010, and the Society published the original scope and standards of WOC nursing practice in May 2010. The Wound, Ostomy, and Continence Nursing: Scope and Standards of Practice, 2nd Edition is the definitive resource promoting excellence in professional practice, quality care, and improved patient outcomes in WOC specialty practice. It can be used to articulate the value of WOC nurses to administrators, legislators, payers, patients, and others. The second edition also provides an overview of the scope of WOC nursing practice including a description of the specialty, the history and evolution of WOC nursing, characteristics of WOC nursing practice, and description of the trispecialty. The document describes various WOC nurse roles, populations served, practice settings, care coordination, and collaboration. Educational preparation, levels of practice within WOC specialty nursing, certification, mandate for continuous professional development, ethics, current trends, future considerations and challenges, and standards of WOC nursing practice and professional performance with competencies for each standard are provided. The purpose of this Executive Summary is to describe the process for developing the scope and standards document, provide an overview of the scope of WOC nursing practice, and list the standards of practice and professional performance along with the competencies for each level of WOC nurse provider. The original document is available from the WOCN Society's online book store (www.wocn.org).

Genome Editing Redefines Precision Medicine in the Cardiovascular Field

PubMed Central

Lahm, Harald; Dreßen, Martina; Lange, Rüdiger; Wu, Sean M.; Krane, Markus

2018-01-01

Genome editing is a powerful tool to study the function of specific genes and proteins important for development or disease. Recent technologies, especially CRISPR/Cas9 which is characterized by convenient handling and high precision, revolutionized the field of genome editing. Such tools have enormous potential for basic science as well as for regenerative medicine. Nevertheless, there are still several hurdles that have to be overcome, but patient-tailored therapies, termed precision medicine, seem to be within reach. In this review, we focus on the achievements and limitations of genome editing in the cardiovascular field. We explore different areas of cardiac research and highlight the most important developments: (1) the potential of genome editing in human pluripotent stem cells in basic research for disease modelling, drug screening, or reprogramming approaches and (2) the potential and remaining challenges of genome editing for regenerative therapies. Finally, we discuss social and ethical implications of these new technologies. PMID:29731778

Harnessing the Potential of Human Pluripotent Stem Cells and Gene Editing for the Treatment of Retinal Degeneration.

PubMed

Ovando-Roche, Patrick; Georgiadis, Anastasios; Smith, Alexander J; Pearson, Rachael A; Ali, Robin R

2017-01-01

A major cause of visual disorders is dysfunction and/or loss of the light-sensitive cells of the retina, the photoreceptors. To develop better treatments for patients, we need to understand how inherited retinal disease mutations result in the dysfunction of photoreceptors. New advances in the field of stem cell and gene editing research offer novel ways to model retinal dystrophies in vitro and present opportunities to translate basic biological insights into therapies. This brief review will discuss some of the issues that should be taken into account when carrying out disease modelling and gene editing of retinal cells. We will discuss (i) the use of human induced pluripotent stem cells (iPSCs) for disease modelling and cell therapy; (ii) the importance of using isogenic iPSC lines as controls; (iii) CRISPR/Cas9 gene editing of iPSCs; and (iv) in vivo gene editing using AAV vectors. Ground-breaking advances in differentiation of iPSCs into retinal organoids and methods to derive mature light sensitive photoreceptors from iPSCs. Furthermore, single AAV systems for in vivo gene editing have been developed which makes retinal in vivo gene editing therapy a real prospect. Genome editing is becoming a valuable tool for disease modelling and in vivo gene editing in the retina.

Generation of gene edited birds in one generation using sperm transfection assisted gene editing (STAGE).

PubMed

Cooper, Caitlin A; Challagulla, Arjun; Jenkins, Kristie A; Wise, Terry G; O'Neil, Terri E; Morris, Kirsten R; Tizard, Mark L; Doran, Timothy J

2017-06-01

Generating transgenic and gene edited mammals involves in vitro manipulation of oocytes or single cell embryos. Due to the comparative inaccessibility of avian oocytes and single cell embryos, novel protocols have been developed to produce transgenic and gene edited birds. While these protocols are relatively efficient, they involve two generation intervals before reaching complete somatic and germline expressing transgenic or gene edited birds. Most of this work has been done with chickens, and many protocols require in vitro culturing of primordial germ cells (PGCs). However, for many other bird species no methodology for long term culture of PGCs exists. Developing methodologies to produce germline transgenic or gene edited birds in the first generation would save significant amounts of time and resource. Furthermore, developing protocols that can be readily adapted to a wide variety of avian species would open up new research opportunities. Here we report a method using sperm as a delivery mechanism for gene editing vectors which we call sperm transfection assisted gene editing (STAGE). We have successfully used this method to generate GFP knockout embryos and chickens, as well as generate embryos with mutations in the doublesex and mab-3 related transcription factor 1 (DMRT1) gene using the CRISPR/Cas9 system. The efficiency of the method varies from as low as 0% to as high as 26% with multiple factors such as CRISPR guide efficiency and mRNA stability likely impacting the outcome. This straightforward methodology could simplify gene editing in many bird species including those for which no methodology currently exists.

Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage

PubMed Central

Cattenoz, Pierre B.; Taft, Ryan J.; Westhof, Eric; Mattick, John S.

2013-01-01

Adenosine to inosine (A > I) RNA editing, which is catalyzed by the ADAR family of proteins, is one of the fundamental mechanisms by which transcriptomic diversity is generated. Indeed, a number of genome-wide analyses have shown that A > I editing is not limited to a few mRNAs, as originally thought, but occurs widely across the transcriptome, especially in the brain. Importantly, there is increasing evidence that A > I editing is essential for animal development and nervous system function. To more efficiently characterize the complete catalog of ADAR events in the mammalian transcriptome we developed a high-throughput protocol to identify A > I editing sites, which exploits the capacity of glyoxal to protect guanosine, but not inosine, from RNAse T1 treatment, thus facilitating extraction of RNA fragments with inosine bases at their termini for high-throughput sequencing. Using this method we identified 665 editing sites in mouse brain RNA, including most known sites and suite of novel sites that include nonsynonymous changes to protein-coding genes, hyperediting of genes known to regulate p53, and alterations to non-protein-coding RNAs. This method is applicable to any biological system for the de novo discovery of A > I editing sites, and avoids the complicated informatic and practical issues associated with editing site identification using traditional RNA sequencing data. This approach has the potential to substantially increase our understanding of the extent and function of RNA editing, and thereby to shed light on the role of transcriptional plasticity in evolution, development, and cognition. PMID:23264566

[Genome editing ~Principle and possibility of a novel genetic engineering technology. Basic principles of genome editing.

PubMed

Yamamoto, Takashi

Programmable site-specific nuclease mediated-genome editing is an emerging biotechnology for precise manipulation of target genes. In genome editing, gene-knockout as well as gene-knockin are possible in various organisms and cultured cells. CRISPR-Cas9, which was developed in 2012, is a convenient and efficient programmable site-specific nuclease and the use spreads around the world rapidly. For this, it is important for the progress of life science research to introduce the genome editing technology.

Applications of CRISPR/Cas9 technology for targeted mutagenesis, gene replacement and stacking of genes in higher plants.

PubMed

Luo, Ming; Gilbert, Brian; Ayliffe, Michael

2016-07-01

Mutagenesis continues to play an essential role for understanding plant gene function and, in some instances, provides an opportunity for plant improvement. The development of gene editing technologies such as TALENs and zinc fingers has revolutionised the targeted mutation specificity that can now be achieved. The CRISPR/Cas9 system is the most recent addition to gene editing technologies and arguably the simplest requiring only two components; a small guide RNA molecule (sgRNA) and Cas9 endonuclease protein which complex to recognise and cleave a specific 20 bp target site present in a genome. Target specificity is determined by complementary base pairing between the sgRNA and target site sequence enabling highly specific, targeted mutation to be readily engineered. Upon target site cleavage, error-prone endogenous repair mechanisms produce small insertion/deletions at the target site usually resulting in loss of gene function. CRISPR/Cas9 gene editing has been rapidly adopted in plants and successfully undertaken in numerous species including major crop species. Its applications are not restricted to mutagenesis and target site cleavage can be exploited to promote sequence insertion or replacement by recombination. The multiple applications of this technology in plants are described.

Use of Genome Editing Tools to Treat Sickle Cell Disease

PubMed Central

Tasan, Ipek; Jain, Surbhi; Zhao, Huimin

2016-01-01

Recent advances in genome editing techniques have made it possible to modify any desired DNA sequence by employing programmable nucleases. These next generation genome-modifying tools are the ideal candidates for therapeutic applications, especially for the treatment of genetic disorders like sickle cell disease (SCD). SCD is an inheritable monogenic disorder which is caused by a point mutation in the β-globin gene. Substantial success has been achieved in the development of supportive therapeutic strategies for SCD but unfortunately there is still a lack of long-term universal cure. The only existing curative treatment is based on allogeneic stem cell transplantation from healthy donors; however, this treatment is applicable to a limited number of patients only. Hence, a universally applicable therapy is highly desirable. In this review we will discuss the three programmable nucleases that are commonly used for genome editing purposes: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). We will continue by exemplifying uses of these methods to correct the sickle cell mutation. Additionally, we will present induction of fetal globin expression as an alternative approach to cure sickle cell disease. We will conclude by comparing the three methods and explaining the concerns about their use in therapy. PMID:27250347

Genome Editing: A New Approach to Human Therapeutics.

PubMed

Porteus, Matthew

2016-01-01

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

Handbook of Adult and Continuing Education. New Edition.

ERIC Educational Resources Information Center

Wilson, Arthur L., Ed.; Hayes, Elisabeth R., Ed.

This handbook presents the perspectives of more than 60 leading authorities on the study and practice of adult and continuing education. The following are among the papers included: "A Selective History of Adult Education Handbooks" (A.L. Wilson, E.R. Hayes); "The Concept of Critically Reflective Practice" (Stephen D.…

Data-Base Software For Tracking Technological Developments

NASA Technical Reports Server (NTRS)

Aliberti, James A.; Wright, Simon; Monteith, Steve K.

1996-01-01

Technology Tracking System (TechTracS) computer program developed for use in storing and retrieving information on technology and related patent information developed under auspices of NASA Headquarters and NASA's field centers. Contents of data base include multiple scanned still images and quick-time movies as well as text. TechTracS includes word-processing, report-editing, chart-and-graph-editing, and search-editing subprograms. Extensive keyword searching capabilities enable rapid location of technologies, innovators, and companies. System performs routine functions automatically and serves multiple users.

Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme.

PubMed

Vallecillo-Viejo, Isabel C; Liscovitch-Brauer, Noa; Montiel-Gonzalez, Maria Fernanda; Eisenberg, Eli; Rosenthal, Joshua J C

2018-01-02

Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.

REDO: RNA Editing Detection in Plant Organelles Based on Variant Calling Results.

PubMed

Wu, Shuangyang; Liu, Wanfei; Aljohi, Hasan Awad; Alromaih, Sarah A; Alanazi, Ibrahim O; Lin, Qiang; Yu, Jun; Hu, Songnian

2018-05-01

RNA editing is a post-transcriptional or cotranscriptional process that changes the sequence of the precursor transcript by substitutions, insertions, or deletions. Almost all of the land plants undergo RNA editing in organelles (plastids and mitochondria). Although several software tools have been developed to identify RNA editing events, there has been a great challenge to distinguish true RNA editing events from genome variation, sequencing errors, and other factors. Here we introduce REDO, a comprehensive application tool for identifying RNA editing events in plant organelles based on variant call format files from RNA-sequencing data. REDO is a suite of Perl scripts that illustrate a bunch of attributes of RNA editing events in figures and tables. REDO can also detect RNA editing events in multiple samples simultaneously and identify the significant differential proportion of RNA editing loci. Comparing with similar tools, such as REDItools, REDO runs faster with higher accuracy, and more specificity at the cost of slightly lower sensitivity. Moreover, REDO annotates each RNA editing site in RNAs, whereas REDItools reports only possible RNA editing sites in genome, which need additional steps to obtain RNA editing profiles for RNAs. Overall, REDO can identify potential RNA editing sites easily and provide several functions such as detailed annotations, statistics, figures, and significantly differential proportion of RNA editing sites among different samples.

Sequence editing by Apolipoprotein B RNA-editing catalytic component-B and epidemiological surveillance of transmitted HIV-1 drug resistance

PubMed Central

Gifford, Robert J.; Rhee, Soo-Yon; Eriksson, Nicolas; Liu, Tommy F.; Kiuchi, Mark; Das, Amar K.; Shafer, Robert W.

2008-01-01

Design Promiscuous guanine (G) to adenine (A) substitutions catalysed by apolipoprotein B RNA-editing catalytic component (APOBEC) enzymes are observed in a proportion of HIV-1 sequences in vivo and can introduce artifacts into some genetic analyses. The potential impact of undetected lethal editing on genotypic estimation of transmitted drug resistance was assessed. Methods Classifiers of lethal, APOBEC-mediated editing were developed by analysis of lentiviral pol gene sequence variation and evaluated using control sets of HIV-1 sequences. The potential impact of sequence editing on genotypic estimation of drug resistance was assessed in sets of sequences obtained from 77 studies of 25 or more therapy-naive individuals, using mixture modelling approaches to determine the maximum likelihood classification of sequences as lethally edited as opposed to viable. Results Analysis of 6437 protease and reverse transcriptase sequences from therapy-naive individuals using a novel classifier of lethal, APOBEC3G-mediated sequence editing, the polypeptide-like 3G (APOBEC3G)-mediated defectives (A3GD) index’, detected lethal editing in association with spurious ‘transmitted drug resistance’ in nearly 3% of proviral sequences obtained from whole blood and 0.2% of samples obtained from plasma. Conclusion Screening for lethally edited sequences in datasets containing a proportion of proviral DNA, such as those likely to be obtained for epidemiological surveillance of transmitted drug resistance in the developing world, can eliminate rare but potentially significant errors in genotypic estimation of transmitted drug resistance. PMID:18356601

Gene Editing: A View Through the Prism of Inherited Metabolic Disorders.

PubMed

Davison, James

2018-04-01

Novel technological developments mean that gene editing - making deliberately targeted alterations in specific genes - is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development of mitochondrial donation techniques is considered. Ultimately, decisions about what we should do with gene editing must be determined by reference to other non-genomic texts that determine what it is to be human - rather than simply to undertake gene editing because it can be done.

An interactive editor for definition of touch-sensitive zones for a graphic display

NASA Technical Reports Server (NTRS)

Monroe, Burt L., III; Jones, Denise R.

1987-01-01

In the continuing effort to develop more efficient man-machine communications methods, touch displays have shown potential as straightforward input systems. The development of software necessary to handle such systems, however, can become tedious. In order to reduce the need for redundant programming, a touch editor has been developed which allows a programmer to interactively define touch-sensitive areas for a graphic display. The information produced during the editing process is written to a data file, which can be accessed easily when needed by an application program. This paper outlines the structure, logic, and use of the editor, as well as the hardware with which it is presently compatible.

Applications of genome editing in insects

USDA-ARS?s Scientific Manuscript database

Insect genome editing was first reported 1991 in Drosophila melanogaster but the technology used was not portable to other species. Not until the recent development of facile, engineered DNA endonuclease systems has gene editing become widely available to insect scientists. Most applications in inse...

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.

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Holubkov, Richard; Clark, Amy E; Moler, Frank W; Slomine, Beth S; Christensen, James R; Silverstein, Faye S; Meert, Kathleen L; Pollack, Murray M; Dean, J Michael

2015-01-01

The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. Consensus assessment of potential outcomes and evaluation timepoints. None. We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.

GHEP-ISFG collaborative exercise on mixture profiles (GHEP-MIX06). Reporting conclusions: Results and evaluation.

PubMed

Barrio, P A; Crespillo, M; Luque, J A; Aler, M; Baeza-Richer, C; Baldassarri, L; Carnevali, E; Coufalova, P; Flores, I; García, O; García, M A; González, R; Hernández, A; Inglés, V; Luque, G M; Mosquera-Miguel, A; Pedrosa, S; Pontes, M L; Porto, M J; Posada, Y; Ramella, M I; Ribeiro, T; Riego, E; Sala, A; Saragoni, V G; Serrano, A; Vannelli, S

2018-07-01

One of the main goals of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the field of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, six exercises have been organized. At the present edition (GHEP-MIX06), with 25 participant laboratories, the exercise main aim was to assess mixture profiles results by issuing a report, from the proposal of a complex mock case. One of the conclusions obtained from this exercise is the increasing tendency of participating laboratories to validate DNA mixture profiles analysis following international recommendations. However, the results have shown some differences among them regarding the edition and also the interpretation of mixture profiles. Besides, although the last revision of ISO/IEC 17025:2017 gives indications of how results should be reported, not all laboratories strictly follow their recommendations. Regarding the statistical aspect, all those laboratories that have performed statistical evaluation of the data have employed the likelihood ratio (LR) as a parameter to evaluate the statistical compatibility. However, LR values obtained show a wide range of variation. This fact could not be attributed to the software employed, since the vast majority of laboratories that performed LR calculation employed the same software (LRmixStudio). Thus, the final allelic composition of the edited mixture profile and the parameters employed in the software could explain this data dispersion. This highlights the need, for each laboratory, to define through internal validations its criteria for editing and interpreting mixtures, and to continuous train in software handling. Copyright © 2018 Elsevier B.V. All rights reserved.

Exposure Factors Handbook 2011 Edition (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Exposure Factors Handbook: 2011 Edition (EPA/600/R-09/052F), prepared by the Office of Research and Development's National Center for Environmental Assessments (NCEA). This updated edition of the handbook provides the most up...

Cloud Properties of CERES-MODIS Edition 4 and CERES-VIIRS Edition 1

NASA Technical Reports Server (NTRS)

Sun-Mack, Sunny; Minnis, Patrick; Chang, Fu-Lung; Hong, Gang; Arduini, Robert; Chen, Yan; Trepte, Qing; Yost, Chris; Smith, Rita; Brown, Ricky;

May I Cut in? Gene Editing Approaches in Human Induced Pluripotent Stem Cells.

PubMed

Brookhouser, Nicholas; Raman, Sreedevi; Potts, Christopher; Brafman, David A

2017-02-06

In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs. Specifically, we describe the emergence of technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 that can be used to edit the genome at precise locations, and discuss the strengths and weaknesses of each of these technologies. In addition, we present the current applications of these technologies in elucidating the mechanisms of human development and disease, developing novel and effective therapeutic molecules, and engineering cell-based therapies. Finally, we discuss the emerging technological advances in targeted gene editing methods.

May I Cut in? Gene Editing Approaches in Human Induced Pluripotent Stem Cells

PubMed Central

Brookhouser, Nicholas; Raman, Sreedevi; Potts, Christopher; Brafman, David. A.

2017-01-01

In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs. Specifically, we describe the emergence of technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 that can be used to edit the genome at precise locations, and discuss the strengths and weaknesses of each of these technologies. In addition, we present the current applications of these technologies in elucidating the mechanisms of human development and disease, developing novel and effective therapeutic molecules, and engineering cell-based therapies. Finally, we discuss the emerging technological advances in targeted gene editing methods. PMID:28178187

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.

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.

Genome editing in pluripotent stem cells: research and therapeutic applications

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

Deleidi, Michela, E-mail: michela.deleidi@dzne.de; Hertie Institute for Clinical Brain Research, University of Tübingen; Yu, Cong

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases formore » ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. - Highlights: • Programmable nucleases have proven efficient and specific for genome editing in human pluripotent stem cells (hPSCs). • Genome edited hPSCs can be employed to study gene function in health and disease as well as drug and chemical screens. • Genome edited hPSCs hold great promise for ex vivo gene therapy approaches. • Technical and safety issues should be first addressed to advance the clinical use of gene-edited hPSCs.« less

Positive correlation between ADAR expression and its targets suggests a complex regulation mediated by RNA editing in the human brain

PubMed Central

Liscovitch, Noa; Bazak, Lily; Levanon, Erez Y; Chechik, Gal

2014-01-01

A-to-I RNA editing by adenosine deaminases acting on RNA is a post-transcriptional modification that is crucial for normal life and development in vertebrates. RNA editing has been shown to be very abundant in the human transcriptome, specifically at the primate-specific Alu elements. The functional role of this wide-spread effect is still not clear; it is believed that editing of transcripts is a mechanism for their down-regulation via processes such as nuclear retention or RNA degradation. Here we combine 2 neural gene expression datasets with genome-level editing information to examine the relation between the expression of ADAR genes with the expression of their target genes. Specifically, we computed the spatial correlation across structures of post-mortem human brains between ADAR and a large set of targets that were found to be edited in their Alu repeats. Surprisingly, we found that a large fraction of the edited genes are positively correlated with ADAR, opposing the assumption that editing would reduce expression. When considering the correlations between ADAR and its targets over development, 2 gene subsets emerge, positively correlated and negatively correlated with ADAR expression. Specifically, in embryonic time points, ADAR is positively correlated with many genes related to RNA processing and regulation of gene expression. These findings imply that the suggested mechanism of regulation of expression by editing is probably not a global one; ADAR expression does not have a genome wide effect reducing the expression of editing targets. It is possible, however, that RNA editing by ADAR in non-coding regions of the gene might be a part of a more complex expression regulation mechanism. PMID:25692240

Positive correlation between ADAR expression and its targets suggests a complex regulation mediated by RNA editing in the human brain.

PubMed

Liscovitch, Noa; Bazak, Lily; Levanon, Erez Y; Chechik, Gal

2014-01-01

A-to-I RNA editing by adenosine deaminases acting on RNA is a post-transcriptional modification that is crucial for normal life and development in vertebrates. RNA editing has been shown to be very abundant in the human transcriptome, specifically at the primate-specific Alu elements. The functional role of this wide-spread effect is still not clear; it is believed that editing of transcripts is a mechanism for their down-regulation via processes such as nuclear retention or RNA degradation. Here we combine 2 neural gene expression datasets with genome-level editing information to examine the relation between the expression of ADAR genes with the expression of their target genes. Specifically, we computed the spatial correlation across structures of post-mortem human brains between ADAR and a large set of targets that were found to be edited in their Alu repeats. Surprisingly, we found that a large fraction of the edited genes are positively correlated with ADAR, opposing the assumption that editing would reduce expression. When considering the correlations between ADAR and its targets over development, 2 gene subsets emerge, positively correlated and negatively correlated with ADAR expression. Specifically, in embryonic time points, ADAR is positively correlated with many genes related to RNA processing and regulation of gene expression. These findings imply that the suggested mechanism of regulation of expression by editing is probably not a global one; ADAR expression does not have a genome wide effect reducing the expression of editing targets. It is possible, however, that RNA editing by ADAR in non-coding regions of the gene might be a part of a more complex expression regulation mechanism.

[Progress of gene editing technologies and prospect in traditional Chinese medicine].

PubMed

Ma, Yan-Yan; Li, Jing-Zhe; Gao, Er-Ning; Qian, Dan; Zhong, Ju-Ying; Liu, Chang-Zhen

2017-01-01

Gene editing is a kind of technologies that makes precise modification to the genome. It can be used to knock out/in and replace the specific DNA fragment, and make accurate gene editing on the genome level. The essence of the technique is the DNA sequence change with use of non homologous end link repair and homologous recombination repair, combined with specific DNA target recognition and endonuclease.This technology has wide range of development prospects and high application value in terms of scientific research, agriculture, medical treatment and other fields. In the field of gene therapy, gene editing technology has achieved cross-time success in cancers such as leukemia, genetic disorders such as hemophilia, thalassemia, multiple muscle nutritional disorders and retrovirus associated infectious diseases such as AIDS and other diseases. The preparation work for new experimental methods and animal models combined with gene editing technology is under rapid development and improvement. Laboratories around the world have also applied gene editing technique in prevention of malaria, organ transplantation, biological pharmaceuticals, agricultural breeding improvement, resurrection of extinct species, and other research areas. This paper summarizes the application and development status of gene editing technique in the above fields, and also preliminarily explores the potential application prospect of the technology in the field of traditional Chinese medicine, and discusses the present controversy and thoughts. Copyright© by the Chinese Pharmaceutical Association.

The CRISPR/Cas Genome-Editing Tool: Application in Improvement of Crops

PubMed Central

Khatodia, Surender; Bhatotia, Kirti; Passricha, Nishat; Khurana, S. M. P.; Tuteja, Narendra

2016-01-01

The Clustered Regularly Interspaced Short Palindromic Repeats associated Cas9/sgRNA system is a novel targeted genome-editing technique derived from bacterial immune system. It is an inexpensive, easy, most user friendly and rapidly adopted genome editing tool transforming to revolutionary paradigm. This technique enables precise genomic modifications in many different organisms and tissues. Cas9 protein is an RNA guided endonuclease utilized for creating targeted double-stranded breaks with only a short RNA sequence to confer recognition of the target in animals and plants. Development of genetically edited (GE) crops similar to those developed by conventional or mutation breeding using this potential technique makes it a promising and extremely versatile tool for providing sustainable productive agriculture for better feeding of rapidly growing population in a changing climate. The emerging areas of research for the genome editing in plants include interrogating gene function, rewiring the regulatory signaling networks and sgRNA library for high-throughput loss-of-function screening. In this review, we have described the broad applicability of the Cas9 nuclease mediated targeted plant genome editing for development of designer crops. The regulatory uncertainty and social acceptance of plant breeding by Cas9 genome editing have also been described. With this powerful and innovative technique the designer GE non-GM plants could further advance climate resilient and sustainable agriculture in the future and maximizing yield by combating abiotic and biotic stresses. PMID:27148329

International Dictionary of Adult and Continuing Education. Revised Edition.

ERIC Educational Resources Information Center

Jarvis, Peter

This dictionary defines approximately 3,500 terms related to adult, continuing, higher, and lifelong learning. It provides detailed references to the main historical and contemporary figures, organizations, and concepts involved in adult and further education around the world with a distinct focus on the core issues in this rapidly changing field.…

The Keys to Effective Schools: Educational Reform as Continuous Improvement

ERIC Educational Resources Information Center

Hawley, Willis D., Ed.

2006-01-01

Working in tandem with the powerful National Education Association's KEYS initiative (Keys to Excellence in Your Schools), this second edition focuses on how to change a school's organizational structure and culture to improve the quality of teaching and learning. Each chapter, revised and updated to address continuous improvement and narrowing…

BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity.

PubMed

Jiang, Wen; Feng, Songjie; Huang, Shisheng; Yu, Wenxia; Li, Guanglei; Yang, Guang; Liu, Yajing; Zhang, Yu; Zhang, Lei; Hou, Yu; Chen, Jia; Chen, Jieping; Huang, Xingxu

2018-06-06

Base editor (BE), containing a cytidine deaminase and catalytically defective Cas9, has been widely used to perform base editing. However, the narrow editing window of BE limits its utility. Here, we developed a new editing technology named as base editor for programming larger C to U (T) scope (BE-PLUS) by fusing 10 copies of GCN4 peptide to nCas9(D10A) for recruiting scFv-APOBEC-UGI-GB1 to the target sites. The new system achieves base editing with a broadened window, resulting in an increased genome-targeting scope. Interestingly, the new system yielded much fewer unwanted indels and non-C-to-T conversions. We also demonstrated its potential use in gene disruption across the whole genome through induction of stop codons (iSTOP). Taken together, the BE-PLUS system offers a new editing tool with increased editing window and enhanced fidelity.

Development of a CRISPR/Cas9 genome editing toolbox for Corynebacterium glutamicum.

PubMed

Liu, Jiao; Wang, Yu; Lu, Yujiao; Zheng, Ping; Sun, Jibin; Ma, Yanhe

2017-11-16

Corynebacterium glutamicum is an important industrial workhorse and advanced genetic engineering tools are urgently demanded. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) have revolutionized the field of genome engineering. The CRISPR/Cas9 system that utilizes NGG as protospacer adjacent motif (PAM) and has good targeting specificity can be developed into a powerful tool for efficient and precise genome editing of C. glutamicum. Herein, we developed a versatile CRISPR/Cas9 genome editing toolbox for C. glutamicum. Cas9 and gRNA expression cassettes were reconstituted to combat Cas9 toxicity and facilitate effective termination of gRNA transcription. Co-transformation of Cas9 and gRNA expression plasmids was exploited to overcome high-frequency mutation of cas9, allowing not only highly efficient gene deletion and insertion with plasmid-borne editing templates (efficiencies up to 60.0 and 62.5%, respectively) but also simple and time-saving operation. Furthermore, CRISPR/Cas9-mediated ssDNA recombineering was developed to precisely introduce small modifications and single-nucleotide changes into the genome of C. glutamicum with efficiencies over 80.0%. Notably, double-locus editing was also achieved in C. glutamicum. This toolbox works well in several C. glutamicum strains including the widely-used strains ATCC 13032 and ATCC 13869. In this study, we developed a CRISPR/Cas9 toolbox that could facilitate markerless gene deletion, gene insertion, precise base editing, and double-locus editing in C. glutamicum. The CRISPR/Cas9 toolbox holds promise for accelerating the engineering of C. glutamicum and advancing its application in the production of biochemicals and biofuels.

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

Genome editing: a robust technology for human stem cells.

PubMed

Chandrasekaran, Arun Pandian; Song, Minjung; Ramakrishna, Suresh

2017-09-01

Human pluripotent stem cells comprise induced pluripotent and embryonic stem cells, which have tremendous potential for biological and therapeutic applications. The development of efficient technologies for the targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. Genome editing of stem cells is possible with the help of synthetic nucleases that facilitate site-specific modification of a gene of interest. Recent advances in genome editing techniques have improved the efficiency and speed of the development of stem cells for human disease models. Zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system are powerful tools for editing DNA at specific loci. Here, we discuss recent technological advances in genome editing with site-specific nucleases in human stem cells.

International Community Development Statistical Bulletin. Spring 1968 General Edition.

ERIC Educational Resources Information Center

Community Development Foundation, New York, NY.

The Spring 1968 general edition of the International Community Development Statistical Bulletin describes its reporting system based on the International Standard Classification of Community Development Activities and a special project registration and progress form; briefly summarizes overall international data; and presents statistics on…

A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression

PubMed Central

Goldstein, Boaz; Agranat-Tamir, Lily; Light, Dean; Ben-Naim Zgayer, Orna; Fishman, Alla; Lamm, Ayelet T.

2017-01-01

A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions, mainly noncoding. Mutations in ADAR enzymes in Caenorhabditis elegans cause defects in normal development but are not lethal as in human and mouse. Previous studies in C. elegans indicated competition between RNA interference (RNAi) and RNA editing mechanisms, based on the observation that worms that lack both mechanisms do not exhibit defects, in contrast to the developmental defects observed when only RNA editing is absent. To study the effects of RNA editing on gene expression and function, we established a novel screen that enabled us to identify thousands of RNA editing sites in nonrepetitive regions in the genome. These include dozens of genes that are edited at their 3′ UTR region. We found that these genes are mainly germline and neuronal genes, and that they are down-regulated in the absence of ADAR enzymes. Moreover, we discovered that almost half of these genes are edited in a developmental-specific manner, indicating that RNA editing is a highly regulated process. We found that many pseudogenes and other lncRNAs are also extensively down-regulated in the absence of ADARs in the embryo but not in the fourth larval (L4) stage. This down-regulation is not observed upon additional knockout of RNAi. Furthermore, levels of siRNAs aligned to pseudogenes in ADAR mutants are enhanced. Taken together, our results suggest a role for RNA editing in normal growth and development by regulating silencing via RNAi. PMID:28031250

Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

PubMed Central

Tang, Weixin; Hu, Johnny H.; Liu, David R.

2017-01-01

Programmable sequence-specific genome editing agents such as CRISPR-Cas9 have greatly advanced our ability to manipulate the human genome. Although canonical forms of genome-editing agents and programmable transcriptional regulators are constitutively active, precise temporal and spatial control over genome editing and transcriptional regulation activities would enable the more selective and potentially safer use of these powerful technologies. Here, by incorporating ligand-responsive self-cleaving catalytic RNAs (aptazymes) into guide RNAs, we developed a set of aptazyme-embedded guide RNAs that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells. PMID:28656978

Responsible innovation in human germline gene editing: Background document to the recommendations of ESHG and ESHRE.

PubMed

De Wert, Guido; Heindryckx, Björn; Pennings, Guido; Clarke, Angus; Eichenlaub-Ritter, Ursula; van El, Carla G; Forzano, Francesca; Goddijn, Mariëtte; Howard, Heidi C; Radojkovic, Dragica; Rial-Sebbag, Emmanuelle; Dondorp, Wybo; Tarlatzis, Basil C; Cornel, Martina C

2018-04-01

Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, preclinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g., gene editing goes against nature) do not seem convincing while consequentialist objections (e.g., safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.

CRISPR-Cas9: Tool for Qualitative and Quantitative Plant Genome Editing

PubMed Central

Noman, Ali; Aqeel, Muhammad; He, Shuilin

2016-01-01

Recent developments in genome editing techniques have aroused substantial excitement among agricultural scientists. These techniques offer new opportunities for developing improved plant lines with addition of important traits or removal of undesirable traits. Increased adoption of genome editing has been geared by swiftly developing Clustered regularly interspaced short palindromic repeats (CRISPR). This is appearing as driving force for innovative utilization in diverse branches of plant biology. CRISPR-Cas9 mediated genome editing is being used for rapid, easy and efficient alteration of genes among diverse plant species. With approximate completion of conceptual work about CRISPR-Cas9, plant scientists are applying this genome editing tool for crop attributes enhancement. The capability of this system for performing targeted and efficient modifications in genome sequence as well as gene expression will certainly spur novel developments not only in model plants but in crop and ornamental plants as well. Additionally, due to non-involvement of foreign DNA, this technique may help alleviating regulatory issues associated with genetically modified plants. We expect that prevailing challenges in plant science like genomic region manipulation, crop specific vectors etc. will be addressed along with sustained growth of this genome editing tool. In this review, recent progress of CRISPR-Cas9 technology in plants has been summarized and discussed. We reviewed significance of CRISPR-Cas9 for specific and non-traditional aspects of plant life. It also covers strengths of this technique in comparison with other genome editing techniques, e.g., Zinc finger nucleases, Transcription activator-like effector nucleases and potential challenges in coming decades have been described. PMID:27917188

Development of a genome editing technique using the CRISPR/Cas9 system in the industrial filamentous fungus Aspergillus oryzae.

PubMed

Katayama, Takuya; Tanaka, Yuki; Okabe, Tomoya; Nakamura, Hidetoshi; Fujii, Wataru; Kitamoto, Katsuhiko; Maruyama, Jun-Ichi

2016-04-01

To develop a genome editing method using the CRISPR/Cas9 system in Aspergillus oryzae, the industrial filamentous fungus used in Japanese traditional fermentation and for the production of enzymes and heterologous proteins. To develop the CRISPR/Cas9 system as a genome editing technique for A. oryzae, we constructed plasmids expressing the gene encoding Cas9 nuclease and single guide RNAs for the mutagenesis of target genes. We introduced these into an A. oryzae strain and obtained transformants containing mutations within each target gene that exhibited expected phenotypes. The mutational rates ranged from 10 to 20 %, and 1 bp deletions or insertions were the most commonly induced mutations. We developed a functional and versatile genome editing method using the CRISPR/Cas9 system in A. oryzae. This technique will contribute to the use of efficient targeted mutagenesis in many A. oryzae industrial strains.

Therapeutic gene editing: delivery and regulatory perspectives.

PubMed

Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

2017-06-01

Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues.

Therapeutic gene editing: delivery and regulatory perspectives

PubMed Central

Shim, Gayong; Kim, Dongyoon; Park, Gyu Thae; Jin, Hyerim; Suh, Soo-Kyung; Oh, Yu-Kyoung

2017-01-01

Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequence-specific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues. PMID:28392568

New daily persistent headache: An evolving entity.

PubMed

Uniyal, Ravi; Paliwal, Vimal Kumar; Anand, Sucharita; Ambesh, Paurush

2018-01-01

New daily persistent headache (NDPH) is characterized by an abrupt onset of headache that becomes a daily entity, is unremitting and continuous from the onset, and lasts for more than 3 months. Dr Walter Vanast first described NDPH in the year 1986. Originally, it was proposed as a chronic daily headache but it was placed under "other primary headaches" in the International Classification of Headache Disorder Second Edition (ICHD 2nd edition). However, with evolving literature and better understanding of its clinical characteristics, it was classified as a "chronic daily headache" in the ICHD 3 rd edition beta. There are still many knowledge-gaps regarding the underlying cause, pathophysiology, natural history and treatment of NDPH. This review tries to revisit the entity and discusses the current status of understanding regarding NDPH.

GROWTH OF THE INTERNATIONAL CRITICALITY SAFETY AND REACTOR PHYSICS EXPERIMENT EVALUATION PROJECTS

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

J. Blair Briggs; John D. Bess; Jim Gulliford

2011-09-01

Since the International Conference on Nuclear Criticality Safety (ICNC) 2007, the International Criticality Safety Benchmark Evaluation Project (ICSBEP) and the International Reactor Physics Experiment Evaluation Project (IRPhEP) have continued to expand their efforts and broaden their scope. Eighteen countries participated on the ICSBEP in 2007. Now, there are 20, with recent contributions from Sweden and Argentina. The IRPhEP has also expanded from eight contributing countries in 2007 to 16 in 2011. Since ICNC 2007, the contents of the 'International Handbook of Evaluated Criticality Safety Benchmark Experiments1' have increased from 442 evaluations (38000 pages), containing benchmark specifications for 3955 critical ormore » subcritical configurations to 516 evaluations (nearly 55000 pages), containing benchmark specifications for 4405 critical or subcritical configurations in the 2010 Edition of the ICSBEP Handbook. The contents of the Handbook have also increased from 21 to 24 criticality-alarm-placement/shielding configurations with multiple dose points for each, and from 20 to 200 configurations categorized as fundamental physics measurements relevant to criticality safety applications. Approximately 25 new evaluations and 150 additional configurations are expected to be added to the 2011 edition of the Handbook. Since ICNC 2007, the contents of the 'International Handbook of Evaluated Reactor Physics Benchmark Experiments2' have increased from 16 different experimental series that were performed at 12 different reactor facilities to 53 experimental series that were performed at 30 different reactor facilities in the 2011 edition of the Handbook. Considerable effort has also been made to improve the functionality of the searchable database, DICE (Database for the International Criticality Benchmark Evaluation Project) and verify the accuracy of the data contained therein. DICE will be discussed in separate papers at ICNC 2011. The status of the ICSBEP and the IRPhEP will be discussed in the full paper, selected benchmarks that have been added to the ICSBEP Handbook will be highlighted, and a preview of the new benchmarks that will appear in the September 2011 edition of the Handbook will be provided. Accomplishments of the IRPhEP will also be highlighted and the future of both projects will be discussed. REFERENCES (1) International Handbook of Evaluated Criticality Safety Benchmark Experiments, NEA/NSC/DOC(95)03/I-IX, Organisation for Economic Co-operation and Development-Nuclear Energy Agency (OECD-NEA), September 2010 Edition, ISBN 978-92-64-99140-8. (2) International Handbook of Evaluated Reactor Physics Benchmark Experiments, NEA/NSC/DOC(2006)1, Organisation for Economic Co-operation and Development-Nuclear Energy Agency (OECD-NEA), March 2011 Edition, ISBN 978-92-64-99141-5.« less

Diesel Technology: Engines. Second Edition. Teacher Edition [and] Student Edition.

ERIC Educational Resources Information Center

Barbieri, Dave; Miller, Roger; Kellum, Mary

This diesel technology series offers secondary and postsecondary students an opportunity for learning required skills in the diesel industry. It aligns with the medium/heavy duty truck task list developed by the National Automotive Technicians Education Foundation and used by the National Institute for Automotive Service Excellence in…

Vertical Hegelianism and Beyond: Digital Cinema Editing.

ERIC Educational Resources Information Center

Wyatt, Roger B.

Cinema as an art and communication form is entering its second century of development. Sergei Eisenstein conceived of editing in horizontal and vertical terms. He saw vertical editing patterns primarily as the synchronization of simultaneous image and sound elements, particularly music, no create cinematic meaning by means of the relationship…

Genome-Independent Identification of RNA Editing by Mutual Information (GIREMI) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Identification of single-nucleotide variants in RNA-seq data. Current version focuses on detection of RNA editing sites without requiring genome sequence data. New version is under development to separately identify RNA editing sites and genetic variants using RNA-seq data alone.

Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure.

PubMed

Mehedi, Masfique; Hoenen, Thomas; Robertson, Shelly; Ricklefs, Stacy; Dolan, Michael A; Taylor, Travis; Falzarano, Darryl; Ebihara, Hideki; Porcella, Stephen F; Feldmann, Heinz

2013-01-01

Ebolavirus (EBOV), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which non-template adenosine residues are incorporated into the EBOV mRNAs at an editing site encoding for 7 adenosine residues. However, the mechanism of EBOV RNA editing is currently not understood. In this study, we report for the first time that minigenomes containing the glycoprotein gene editing site can undergo RNA editing, thereby eliminating the requirement for a biosafety level 4 laboratory to study EBOV RNA editing. Using a newly developed dual-reporter minigenome, we have characterized the mechanism of EBOV RNA editing, and have identified cis-acting sequences that are required for editing, located between 9 nt upstream and 9 nt downstream of the editing site. Moreover, we show that a secondary structure in the upstream cis-acting sequence plays an important role in RNA editing. EBOV RNA editing is glycoprotein gene-specific, as a stretch encoding for 7 adenosine residues located in the viral polymerase gene did not serve as an editing site, most likely due to an absence of the necessary cis-acting sequences. Finally, the EBOV protein VP30 was identified as a trans-acting factor for RNA editing, constituting a novel function for this protein. Overall, our results provide novel insights into the RNA editing mechanism of EBOV, further understanding of which might result in novel intervention strategies against this viral pathogen.

Rat Genome and Model Resources.

PubMed

Shimoyama, Mary; Smith, Jennifer R; Bryda, Elizabeth; Kuramoto, Takashi; Saba, Laura; Dwinell, Melinda

2017-07-01

Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat's value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan. © The Author 2017. Published by Oxford University Press.

Therapeutic Gene Editing Safety and Specificity.

PubMed

Lux, Christopher T; Scharenberg, Andrew M

2017-10-01

Therapeutic gene editing is significant for medical advancement. Safety is intricately linked to the specificity of the editing tools used to cut at precise genomic targets. Improvements can be achieved by thoughtful design of nucleases and repair templates, analysis of off-target editing, and careful utilization of viral vectors. Advancements in DNA repair mechanisms and development of new generations of tools improve targeting of specific sequences while minimizing risks. It is important to plot a safe course for future clinical trials. This article reviews safety and specificity for therapeutic gene editing to spur dialogue and advancement. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuous-Time Random Walk with multi-step memory: an application to market dynamics

NASA Astrophysics Data System (ADS)

Gubiec, Tomasz; Kutner, Ryszard

2017-11-01

An extended version of the Continuous-Time Random Walk (CTRW) model with memory is herein developed. This memory involves the dependence between arbitrary number of successive jumps of the process while waiting times between jumps are considered as i.i.d. random variables. This dependence was established analyzing empirical histograms for the stochastic process of a single share price on a market within the high frequency time scale. Then, it was justified theoretically by considering bid-ask bounce mechanism containing some delay characteristic for any double-auction market. Our model appeared exactly analytically solvable. Therefore, it enables a direct comparison of its predictions with their empirical counterparts, for instance, with empirical velocity autocorrelation function. Thus, the present research significantly extends capabilities of the CTRW formalism. Contribution to the Topical Issue "Continuous Time Random Walk Still Trendy: Fifty-year History, Current State and Outlook", edited by Ryszard Kutner and Jaume Masoliver.

Integrated editing system for Japanese text and image information "Linernote"

NASA Astrophysics Data System (ADS)

Tanaka, Kazuto

Integrated Japanese text editing system "Linernote" developed by Toyo Industries Co. is explained. The system has been developed on the concept of electronic publishing. It is composed of personal computer NEC PC-9801 VX and other peripherals. Sentence, drawing and image data is inputted and edited under the integrated operating environment in the system and final text is printed out by laser printer. Handling efficiency of time consuming work such as pattern input or page make up has been improved by draft image data indication method on CRT. It is the latest DTP system equipped with three major functions, namly, typesetting for high quality text editing, easy drawing/tracing and high speed image processing.

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.

Career Choice and Development. Third Edition.

ERIC Educational Resources Information Center

Brown, Duane; And Others

This book contains 12 papers examining established and newly emerging theories of career choice and development. Following prefaces to the third, second, and first editions by Duane Brown and Linda Brooks, the following papers are included: "Introduction to Theories of Career Development and Choice: Origins, Evolution, and Current Efforts" (Duane…

Manpower Research and Development Projects; 1973 Edition.

ERIC Educational Resources Information Center

Manpower Administration (DOL), Washington, DC.

The third edition of Manpower Research and Development Projects presents descriptions of 455 projects which are grouped by subject matter to facilitate description of the research and development program and the use of the material. The 199 doctoral dissertation grants and the 12 manpower research institutional grants are classified by subject…

Developing Thinking and Understanding in Young Children: An Introduction for Students. Second Edition

ERIC Educational Resources Information Center

Robson, Sue

2012-01-01

Developing "Thinking and Understanding in Young Children" presents a comprehensive and accessible overview of contemporary theory and research about young children's developing thinking and understanding. Throughout this second edition, the ideas and theories presented are enlivened by transcripts of children's activities and conversations taken…

Home Study Course Development Handbook. Second Edition.

ERIC Educational Resources Information Center

Lambert, Michael P., Ed.; Welch, Sally R., Ed.

Intended to help developers of home study courses and their directors of education create good correspondence courses, this document updates the 1980 edition and was developed by members of the National Home Study Council's Research and Educational Standards Committee. The document begins with photographs and biographies of its authors. The…

[Genome-editing: focus on the off-target effects].

PubMed

He, Xiubin; Gu, Feng

2017-10-25

Breakthroughs of genome-editing in recent years have paved the way to develop new therapeutic strategies. These genome-editing tools mainly include Zinc-finger nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases. However, off-target effects are still the major issue in genome editing, and limit the application in gene therapy. Here, we summarized the cause and compared different detection methods of off-targets.

Efficient Resource Utilization in the Bayne-Jones Army Community Hospital Emergency Room

DTIC Science & Technology

1990-08-07

34 Previous editions are obsolete. SECURITY CLASSIFICATION OF THIS PAGE MI 9e9TEbc9$ff c6 Apxv~ k puUilt, -t 2A m BOCK #19 (continued) IT on ER patients...performed by nurses. American Journal of Public Health, 1989 Edition . (1989). Chicago: American Hospital Association. American College of Emergency Physicians... 6th Ed. New York: McGraw-Hill Book Company. Liptak, G.S., Super, D.M., Baker, N., & Roghmann, K.J. (1985). An analysis of waiting times in a pediatric

Presence and Accuracy of Drug Dosage Recommendations for Continuous Renal Replacement Therapy in Tertiary Drug Information References

PubMed Central

Gorman, Sean K; Slavik, Richard S; Lam, Stefanie

2012-01-01

Background: Clinicians commonly rely on tertiary drug information references to guide drug dosages for patients who are receiving continuous renal replacement therapy (CRRT). It is unknown whether the dosage recommendations in these frequently used references reflect the most current evidence. Objective: To determine the presence and accuracy of drug dosage recommendations for patients undergoing CRRT in 4 drug information references. Methods: Medications commonly prescribed during CRRT were identified from an institutional medication inventory database, and evidence-based dosage recommendations for this setting were developed from the primary and secondary literature. The American Hospital Formulary System—Drug Information (AHFS–DI), Micromedex 2.0 (specifically the DRUGDEX and Martindale databases), and the 5th edition of Drug Prescribing in Renal Failure (DPRF5) were assessed for the presence of drug dosage recommendations in the CRRT setting. The dosage recommendations in these tertiary references were compared with the recommendations derived from the primary and secondary literature to determine concordance. Results: Evidence-based drug dosage recommendations were developed for 33 medications administered in patients undergoing CRRT. The AHFS–DI provided no dosage recommendations specific to CRRT, whereas the DPRF5 provided recommendations for 27 (82%) of the medications and the Micromedex 2.0 application for 20 (61%) (13 [39%] in the DRUGDEX database and 16 [48%] in the Martindale database, with 9 medications covered by both). The dosage recommendations were in concordance with evidence-based recommendations for 12 (92%) of the 13 medications in the DRUGDEX database, 26 (96%) of the 27 in the DPRF5, and all 16 (100%) of those in the Martindale database. Conclusions: One prominent tertiary drug information resource provided no drug dosage recommendations for patients undergoing CRRT. However, 2 of the databases in an Internet-based medical information application and the latest edition of a renal specialty drug information resource provided recommendations for a majority of the medications investigated. Most dosage recommendations were similar to those derived from the primary and secondary literature. The most recent edition of the DPRF is the preferred source of information when prescribing dosage regimens for patients receiving CRRT. PMID:22783029

A-to-I RNA editing promotes developmental stage-specific gene and lncRNA expression.

PubMed

Goldstein, Boaz; Agranat-Tamir, Lily; Light, Dean; Ben-Naim Zgayer, Orna; Fishman, Alla; Lamm, Ayelet T

2017-03-01

A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions, mainly noncoding. Mutations in ADAR enzymes in Caenorhabditis elegans cause defects in normal development but are not lethal as in human and mouse. Previous studies in C. elegans indicated competition between RNA interference (RNAi) and RNA editing mechanisms, based on the observation that worms that lack both mechanisms do not exhibit defects, in contrast to the developmental defects observed when only RNA editing is absent. To study the effects of RNA editing on gene expression and function, we established a novel screen that enabled us to identify thousands of RNA editing sites in nonrepetitive regions in the genome. These include dozens of genes that are edited at their 3' UTR region. We found that these genes are mainly germline and neuronal genes, and that they are down-regulated in the absence of ADAR enzymes. Moreover, we discovered that almost half of these genes are edited in a developmental-specific manner, indicating that RNA editing is a highly regulated process. We found that many pseudogenes and other lncRNAs are also extensively down-regulated in the absence of ADARs in the embryo but not in the fourth larval (L4) stage. This down-regulation is not observed upon additional knockout of RNAi. Furthermore, levels of siRNAs aligned to pseudogenes in ADAR mutants are enhanced. Taken together, our results suggest a role for RNA editing in normal growth and development by regulating silencing via RNAi. © 2017 Goldstein et al.; Published by Cold Spring Harbor Laboratory Press.

CRISPR editing in biological and biomedical investigation.

PubMed

Huang, Jiaojiao; Wang, Yanfang; Zhao, Jianguo

2018-05-01

Recently, clustered regularly interspaced short palindromic repeats (CRISPR) based genomic editing technologies have armed researchers with powerful new tools to biological and biomedical investigations. To further improve and expand its functionality, natural, and engineered CRISPR associated nine proteins (Cas9s) have been investigated, various CRISPR delivery strategies have been tested and optimized, and multiple schemes have been developed to ensure precise mammalian genome editing. Benefiting from those in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as accurate base editing, transcriptional regulation, and genome-wide screening. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders especially those large animals and non-human primates models, and gene therapy to combat virus infectious diseases, to correct monogenic disorders in vivo or in pluripotent cells. In this prospect article, after highlighting recent developments of CRISPR systems, we outline different applications and current limitations of CRISPR use in biological and biomedical investigation. Finally, we provide a perspective for future development and potential risks of this multifunctional technology. © 2017 Wiley Periodicals, Inc.

Data Management for a Climate Data Record in an Evolving Technical Landscape

NASA Astrophysics Data System (ADS)

Moore, K. D.; Walter, J.; Gleason, J. L.

2017-12-01

For nearly twenty years, NASA Langley Research Center's Clouds and the Earth's Radiant Energy System (CERES) Science Team has been producing a suite of data products that forms a persistent climate data record of the Earth's radiant energy budget. Many of the team's physical scientists and key research contributors have been with the team since the launch of the first CERES instrument in 1997. This institutional knowledge is irreplaceable and its longevity and continuity are among the reasons that the team has been so productive. Such legacy involvement, however, can also be a limiting factor. Some CERES scientists-cum-coders might possess skills that were state-of-the-field when they were emerging scientists but may now be outdated with respect to developments in software development best practices and supporting technologies. Both programming languages and processing frameworks have evolved significantly in the past twenty years, and updating one of these factors warrants consideration of updating the other. With the imminent launch of a final CERES instrument and the good health of those in flight, the CERES data record stands to continue far into the future. The CERES Science Team is, therefore, undergoing a re-architecture of its codebase to maintain compatibility with newer data processing platforms and technologies and to leverage modern software development best practices. This necessitates training our staff and consequently presents several challenges, including: Development continues immediately on the next "edition" of research algorithms upon release of the previous edition. How can code be rewritten at the same time that the science algorithms are being updated and integrated? With limited time to devote to training, how can we update the staff's existing skillset without slowing progress or introducing new errors? The CERES Science Team is large and complex, much like the current state of its codebase. How can we identify, in a breadth-wise manner, areas for code improvement across multiple research groups that maintain code with varying semantics but common concepts? In this work, we discuss the successes and pitfalls of this major re-architecture effort and share how we will sustain improvement into the future.

Flaws in Flynn Effect Research with the Wechsler Scales

ERIC Educational Resources Information Center

Weiss, Lawrence G.; Gregoire, Jacques; Zhu, Jianjun

2016-01-01

Many Flynn effect (FE) studies compare scores across different editions of Wechsler's IQ tests. When construct changes are introduced by the test developers in the new edition, however, the presumed generational effects are difficult to untangle from changes due to test content. To remove this confound, we use the same edition of Wechsler…

Financing Education in a Climate of Change. Eighth Edition.

ERIC Educational Resources Information Center

Brimley, Vern, Jr.; Garfield, Rulon R.

Since the publication of the seventh edition of this textbook in 1999, there have been many new developments in the education finance arena. Those changes are discussed in this eighth edition. Additional new material includes Internet resources, new exercises for further "laboratory" work, updated figures and tables, and fresh information on court…

Choice and Challenge for the American Woman. Revised Edition.

ERIC Educational Resources Information Center

Harbeson, Gladys Evans

The second edition, as the previous edition, deals with evolutionary processes contributing to changing life patterns of American women; however, new portions relate to the acceleration of the trend. The new self-image of women cannot be understood if viewed as an isolated development but must be interpreted with a perspective view. Two…

Developing Parallel Career and Occupational Development Objectives and Exercise (Test) Items in Spanish for Assessment and Evaluation.

ERIC Educational Resources Information Center

Muratti, Jose E.; And Others

A parallel Spanish edition was developed of released objectives and objective-referenced items used in the National Assessment of Educational Progress (NAEP) in the field of Career and Occupational Development (COD). The Spanish edition was designed to assess the identical skills, attitudes, concepts, and knowledge of Spanish-dominant students…

The prospects of transition metal dichalcogenides for ultimately scaled CMOS

NASA Astrophysics Data System (ADS)

Thiele, S.; Kinberger, W.; Granzner, R.; Fiori, G.; Schwierz, F.

2018-05-01

MOSFET gate length scaling has been a main source of progress in digital electronics for decades. Today, researchers still spend considerable efforts on reducing the gate length and on developing ultimately scaled MOSFETs, thereby exploring both new device architectures and alternative channel materials beyond Silicon such as two-dimensional TMDs (transition metal dichalcogenide). On the other hand, the envisaged scaling scenario for the next 15 years has undergone a significant change recently. While the 2013 ITRS edition required a continuation of aggressive gate length scaling for at least another 15 years, the 2015 edition of the ITRS suggests a deceleration and eventually a levelling off of gate length scaling and puts more emphasis on alternative options such as pitch scaling to keep Moore's Law alive. In the present paper, future CMOS scaling is discussed in the light of emerging two-dimensional MOSFET channel, in particular two-dimensional TMDs. To this end, the scaling scenarios of the 2013 and 2015 ITRS editions are considered and the scaling potential of TMD MOSFETs is investigated by means of quantum-mechanical device simulations. It is shown that for ultimately scaled MOSFETs as required in the 2013 ITRS, the heavy carrier effective masses of the Mo- and W-based TMDs are beneficial for the suppression of direct source-drain tunneling, while to meet the significantly relaxed scaling targets of the 2016 ITRS heavy-effective-mass channels are not needed.

Assessment and revision of clinical pharmacy practice internet web sites.

PubMed

Edwards, Krystal L; Salvo, Marissa C; Ward, Kristina E; Attridge, Russell T; Kiser, Katie; Pinner, Nathan A; Gallegos, Patrick J; Kesteloot, Lori Lynn; Hylton, Ann; Bookstaver, P Brandon

2014-02-01

Health care professionals, trainees, and patients use the Internet extensively. Editable Web sites may contain inaccurate, incomplete, and/or outdated information that may mislead the public's perception of the topic. To evaluate the editable, online descriptions of clinical pharmacy and pharmacist and attempt to improve their accuracy. The authors identified key areas within clinical pharmacy to evaluate for accuracy and appropriateness on the Internet. Current descriptions that were reviewed on public domain Web sites included: (1) clinical pharmacy and the clinical pharmacist, (2) pharmacy education, (3) clinical pharmacy and development and provision for reimbursement, (4) clinical pharmacists and advanced specialty certifications/training opportunities, (5) pharmacists and advocacy, and (6) clinical pharmacists and interdisciplinary/interprofessional content. The authors assessed each content area to determine accuracy and prioritized the need for updating, when applicable, to achieve consistency in descriptions and relevancy. The authors found that Wikipedia, a public domain that allows users to update, was consistently the most common Web site produced in search results. The authors' evaluation resulted in the creation or revision of 14 Wikipedia Web pages. However, rejection of 3 proposed newly created Web pages affected the authors' ability to address identified content areas with deficiencies and/or inaccuracies. Through assessing and updating editable Web sites, the authors strengthened the online representation of clinical pharmacy in a clear, cohesive, and accurate manner. However, ongoing assessments of the Internet are continually needed to ensure accuracy and appropriateness.

Substance use disorders: Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International Classification of Diseases, tenth edition (ICD-10).

PubMed

Hasin, Deborah; Hatzenbuehler, Mark L; Keyes, Katherine; Ogburn, Elizabeth

2006-09-01

Two major nomenclatures, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International Classification of Diseases, tenth edition (ICD-10), currently define substance use disorders for broad audiences of users with different training, experience and interests. A comparison of these definitions and their implications for DSM-V and ICD-11 has not been available. The background for the dependence concept and abuse, harmful use, withdrawal, substance-induced disorders and remission and other substance-related conditions is reviewed. Reliability evidence is presented, as is validity evidence from approaches including psychometric, genetic and animal studies. The relevance of the DSM-IV and ICD-10 compared to alternative systems (e.g. the Addiction Severity Index) is considered. Reliability and psychometric validity evidence for substance dependence is consistently strong, but more mixed for abuse and harmful use. Findings on the genetics of alcohol disorders support the validity of the dependence concept, while animal studies underscore the centrality of continued use despite negative consequences to the concept of dependence. While few studies on substance-induced disorders have been conducted, those published show good reliability and validity when elements of DSM-IV and ICD-10 are combined. Dependence in DSM-V and ICD-11 should be retained, standardizing both criteria sets and adding a severity measure. The consequences of heavy use should be measured independently of dependence; add cannabis withdrawal if further research supports existing evidence; conduct further studies of the substance-induced psychiatric categories; standardize their criteria across DSM-V and ICD-11; develop a theoretical basis for better remission criteria; consider changing substance 'abuse' to substance 'dysfunction disorder'; and conduct clinician education on the value of the diagnostic criteria.

Oligophrenin-1 (OPHN1), a Gene Involved in X-Linked Intellectual Disability, Undergoes RNA Editing and Alternative Splicing during Human Brain Development

PubMed Central

Athanasiadis, Alekos; Galeano, Federica; Locatelli, Franco; Bertini, Enrico; Zanni, Ginevra; Gallo, Angela

2014-01-01

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development. PMID:24637888

Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development.

PubMed

Barresi, Sabina; Tomaselli, Sara; Athanasiadis, Alekos; Galeano, Federica; Locatelli, Franco; Bertini, Enrico; Zanni, Ginevra; Gallo, Angela

2014-01-01

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development.

Therapeutic Genome Editing and its Potential Enhancement through CRISPR Guide RNA and Cas9 Modifications.

PubMed

Batzir, Nurit Assia; Tovin, Adi; Hendel, Ayal

2017-06-01

Genome editing with engineered nucleases is a rapidly growing field thanks to transformative technologies that allow researchers to precisely alter genomes for numerous applications including basic research, biotechnology, and human gene therapy. The genome editing process relies on creating a site-specific DNA double-strand break (DSB) by engineered nucleases and then allowing the cell's repair machinery to repair the break such that precise changes are made to the DNA sequence. The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing accelerates the progress towards using genome editing as a new approach to human therapeutics. Here we review how genome editing using engineered nucleases works and how using different genome editing outcomes can be used as a tool set for treating human diseases. We then review the major challenges of therapeutic genome editing and we discuss how its potential enhancement through CRISPR guide RNA and Cas9 protein modifications could resolve some of these challenges. Copyright© of YS Medical Media ltd.

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.

America's Children and the Environment (2003)

EPA Pesticide Factsheets

This 2nd edition report shows continued decline in the number of children with elevated blood lead levels; and reduced exposure to secondhand smoke, air pollution, and drinking water contaminants; but also increasing asthma rates.

Selected Reference Books of 1979-80.

ERIC Educational Resources Information Center

Sheehy, Eugene P.

1981-01-01

Presents book reviews of recently published scholarly and general works of interest to reference workers in university libraries. The listing includes a brief roundup of new editions of standard works, continuations, and supplements. (RAA)

Perspective: Challenges and Controversial Issues in the Dietary Guidelines for Americans, 1980-2015.

PubMed

Nestle, Marion

2018-03-01

Since 1980, every edition of the Dietary Guidelines for Americans (DGAs) has recommended increased consumption of fruits, vegetables, and whole grains, but reduced consumption of saturated fat, sugars, and sodium and, therefore, their primary food sources. Every edition has generated controversy, mainly from producers of foods affected by "eat less" recommendations, particularly meat. Objections to the 2015 DGAs focused on environmental as well as scientific issues, but also on purported conflicts of interest among members of the Dietary Guidelines Advisory Committee. On this basis, critics induced Congress to authorize the National Academy of Medicine (NAM) to review the process of drawing up the guidelines. The NAM's 2017 reports should strengthen the process, but as long as science continues to support advice to reduce consumption of targeted foods, the guidelines will continue to elicit political controversy.

Origins and applications of the Montroll-Weiss continuous time random walk

NASA Astrophysics Data System (ADS)

Shlesinger, Michael F.

2017-05-01

The Continuous Time Random Walk (CTRW) was introduced by Montroll and Weiss in 1965 in a purely mathematical paper. Its antecedents and later applications beginning in 1973 are discussed, especially for the case of fractal time where the mean waiting time between jumps is infinite. Contribution to the Topical Issue: "Continuous Time Random Walk Still Trendy: Fifty-year History, Current State and Outlook", edited by Ryszard Kutner and Jaume Masoliver.

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.

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

Precision genome editing using CRISPR-Cas9 and linear repair templates in C. elegans.

PubMed

Paix, Alexandre; Folkmann, Andrew; Seydoux, Geraldine

2017-05-15

The ability to introduce targeted edits in the genome of model organisms is revolutionizing the field of genetics. State-of-the-art methods for precision genome editing use RNA-guided endonucleases to create double-strand breaks (DSBs) and DNA templates containing the edits to repair the DSBs. Following this strategy, we have developed a protocol to create precise edits in the C. elegans genome. The protocol takes advantage of two innovations to improve editing efficiency: direct injection of CRISPR-Cas9 ribonucleoprotein complexes and use of linear DNAs with short homology arms as repair templates. The protocol requires no cloning or selection, and can be used to generate base and gene-size edits in just 4days. Point mutations, insertions, deletions and gene replacements can all be created using the same experimental pipeline. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Quantifying Genome Editing Outcomes at Endogenous Loci using SMRT Sequencing

PubMed Central

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

2014-01-01

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

Special Education: A Reference Book for Policy & Curriculum Development. Second Edition

ERIC Educational Resources Information Center

Grey House Publishing, 2009

2009-01-01

A reference work that presents a chronology focusing on special education, its development, and the important issues that both positively and negatively affect the field. Updated through current events, this second edition provides an excellent introduction to special education in all of its practical aspects--how it developed, its curriculum,…

Education: Politique Sectorielle. Troisieme Edition. (Education: Sector Policy Paper. Third Edition.)

ERIC Educational Resources Information Center

Haddad, Wadi D.; And Others

The present paper updates the World Bank's interpetation of education development and outlines a policy framework for lending for education. After chapters on the relationship between education and development and on the state of education development, the paper devotes a chapter to each of five issues: the expansion and equalization of…

Genome editing in pluripotent stem cells: research and therapeutic applications.

PubMed

Deleidi, Michela; Yu, Cong

2016-05-06

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. Copyright © 2016 Elsevier Inc. All rights reserved.

RNA editing of the GABAA receptor α3 subunit alters the functional properties of recombinant receptors

PubMed Central

Nimmich, Mitchell L.; Heidelberg, Laura S.; Fisher, Janet L.

2009-01-01

RNA editing provides a post-transcriptional mechanism to increase structural heterogeneity of gene products. Recently, the α3 subunit of the GABAA receptors has been shown to undergo RNA editing. As a result, a highly conserved isoleucine residue in the third transmembrane domain is replaced with a methionine. To determine the effect of this structural change on receptor function, we compared the GABA sensitivity, pharmacological properties and macroscopic kinetics of recombinant receptors containing either the edited or unedited forms of the α3 subunit along with β3 and γ2L. Editing substantially altered the GABA sensitivity and deactivation rate of the receptors, with the unedited form showing a lower GABA EC50 and slower decay. Comparable effects were observed with a mutation at the homologous location in the α1 subunit, suggesting a common role for this site in regulation of channel gating. Except for the response to GABA, the pharmacological properties of the receptor were unaffected by editing, with similar enhancement by a variety of modulators. Since RNA editing of the α3 subunit increases through development, our findings suggest that GABAergic neurotransmission may be more effective early in development, with greater GABA sensitivity and slower decay rates conferred by the unedited α3 subunit. PMID:19367790

An Evolutionary Landscape of A-to-I RNA Editome across Metazoan Species

PubMed Central

Hung, Li-Yuan; Chen, Yen-Ju; Mai, Te-Lun; Chen, Chia-Ying; Yang, Min-Yu; Chiang, Tai-Wei; Wang, Yi-Da

2018-01-01

Abstract Adenosine-to-inosine (A-to-I) editing is widespread across the kingdom Metazoa. However, for the lack of comprehensive analysis in nonmodel animals, the evolutionary history of A-to-I editing remains largely unexplored. Here, we detect high-confidence editing sites using clustering and conservation strategies based on RNA sequencing data alone, without using single-nucleotide polymorphism information or genome sequencing data from the same sample. We thereby unveil the first evolutionary landscape of A-to-I editing maps across 20 metazoan species (from worm to human), providing unprecedented evidence on how the editing mechanism gradually expands its territory and increases its influence along the history of evolution. Our result revealed that highly clustered and conserved editing sites tended to have a higher editing level and a higher magnitude of the ADAR motif. The ratio of the frequencies of nonsynonymous editing to that of synonymous editing remarkably increased with increasing the conservation level of A-to-I editing. These results thus suggest potentially functional benefit of highly clustered and conserved editing sites. In addition, spatiotemporal dynamics analyses reveal a conserved enrichment of editing and ADAR expression in the central nervous system throughout more than 300 Myr of divergent evolution in complex animals and the comparability of editing patterns between invertebrates and between vertebrates during development. This study provides evolutionary and dynamic aspects of A-to-I editome across metazoan species, expanding this important but understudied class of nongenomically encoded events for comprehensive characterization. PMID:29294013

Energy Efficiency and Renewable Energy Program. Bibliography, 1993 edition

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

Vaughan, K.H.

1993-06-01

The Bibliography contains listings of publicly available reports, journal articles, and published conference papers sponsored by the DOE Office of Energy Efficiency and Renewable Energy and published between 1987 and mid-1993. The topics of Bibliography include: analysis and evaluation; building equipment research; building thermal envelope systems and materials; district heating; residential and commercial conservation program; weatherization assistance program; existing buildings research program; ceramic technology project; alternative fuels and propulsion technology; microemulsion fuels; industrial chemical heat pumps; materials for advanced industrial heat exchangers; advanced industrial materials; tribology; energy-related inventions program; electric energy systems; superconducting technology program for electric energy systems; thermalmore » energy storage; biofuels feedstock development; biotechnology; continuous chromatography in multicomponent separations; sensors for electrolytic cells; hydropower environmental mitigation; environmental control technology; continuous fiber ceramic composite technology.« less

On the Shock-Response-Spectrum Recursive Algorithm of Kelly and Richman

NASA Technical Reports Server (NTRS)

Martin, Justin N.; Sinclair, Andrew J.; Foster, Winfred A.

2010-01-01

The monograph Principles and Techniques of Shock Data Analysis written by Kelly and Richman in 1969 has become a seminal reference on the shock response spectrum (SRS) [1]. Because of its clear physical descriptions and mathematical presentation of the SRS, it has been cited in multiple handbooks on the subject [2, 3] and research articles [4 10]. Because of continued interest, two additional versions of the monograph have been published: a second edition by Scavuzzo and Pusey in 1996 [11] and a reprint of the original edition in 2008 [12]. The main purpose of this note is to correct several typographical errors in the manuscript's presentation of a recursive algorithm for SRS calculations. These errors are consistent across all three editions of the monograph. The secondary purpose of this note is to present a Matlab implementation of the corrected algorithm.

Observaciones geomagnéticas de la Isla Livingston, Antártida 2000, 2001 y campaña 2001-2002 %t Livingston Island geomagnetic observations, Antarctica 2000, 2001, and 2001-2002 survey

NASA Astrophysics Data System (ADS)

Gaya-Piqué, L.; Torta, J. M.; Curto, J. J.; Sanclement, E.; Marsal, S.; Solé, J. G.; Altadill, D.; Ugalde, A.; de Santis, A.; Apostolov, E. M.; Alberca, L. F.; Garcí A.

This CD-ROM presents the Livingston Island Geomagnetic Observatory Bulletin, edited by Observatori de l'Ebre, containing the data obtained during the years 2000, 2001 and the first two months of the year 2002. For the first time this Bulletin is edited in digital format, being it the continuation of the paper-edited series as Misceláneas 41, 42 and 43 (ISSN 0211-4534). The structure of the CD-ROM consists of one file with the Bulletin contents in PDF and of a tree of directories and subdirectories with the data corresponding to the different years and months of the Bulletin. These data files and their names were built according to the IAGA-2000 data exchange format.

Comparison of the Vineland Adaptive Behavior Scales, Second Edition, and the Bayley Scales of Infant and Toddler Development, Third Edition.

PubMed

Scattone, Dorothy; Raggio, Donald J; May, Warren

2011-10-01

The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II), and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were administered to 65 children between the ages of 12 and 42 months referred for developmental delays. Standard scores and age equivalents were compared across instruments. Analyses showed no statistical difference between Vineland-II ABC standard scores and cognitive levels obtained from the Bayley-III. However, Vineland-II Communication and Motor domain standard scores were significantly higher than corresponding scores on the Bayley-III. In addition, age equivalent scores were significantly higher on the Vineland-II for the fine motor subdomain. Implications for early intervention are discussed.

Development of the Macro Command Editing Executive System for Factory Workers-Oriented Programless Visual Inspection System

NASA Astrophysics Data System (ADS)

Anezaki, Takashi; Wakitani, Kouichi; Nakamura, Masatoshi; Kubo, Hiroyasu

Because visual inspection systems are difficult to tune, they create many problems for the kaizen process. This results in increased development costs and time to assure that the inspection systems function properly. In order to improve inspection system development, we designed an easy-tuning system called a “Program-less” visual inspection system. The ROI macro command which consisted of eight kinds of shape recognition macro commands and decision, operation, control commands was built. Furthermore, the macro command editing executive system was developed by the operation of only the GUI without editing source program. The validity of the ROI macro command was proved by the application of 488 places.

Pleiades. The Journal of the University of Hawai'i Community Colleges. First Edition. February 1988.

ERIC Educational Resources Information Center

Pleiades: The Journal of the University of Hawai'i Community Colleges, 1988

1988-01-01

"Pleiades" is a new journal, intended to appear annually, with publication scheduled for February. This is the first edition; it is unnumbered. Designed as a staff development activity, "Pleiades" is intended to contain writings and art authored and edited by the faculty and staff of the University of Hawaii Community Colleges.…

Preventing Prejudice: A Guide for Counselors, Educators, and Parents, Second Edition

ERIC Educational Resources Information Center

Ponterotto, Joseph G.; Utsey, Shawn O.; Pedersen, Paul B.

2006-01-01

This second edition has been completely revised and expanded to provide the most up-to-date and extensive coverage of prejudice and racism available. The new edition of this bestselling text presents a comprehensive overview of these topics and also includes practical tools for combating prejudice development in children, adolescents, and adults.…

Recent Progress in Genome Editing Approaches for Inherited Cardiovascular Diseases.

PubMed

Kaur, Balpreet; Perea-Gil, Isaac; Karakikes, Ioannis

2018-06-02

This review describes the recent progress in nuclease-based therapeutic applications for inherited heart diseases in vitro, highlights the development of the most recent genome editing technologies and discusses the associated challenges for clinical translation. Inherited cardiovascular disorders are passed from generation to generation. Over the past decade, considerable progress has been made in understanding the genetic basis of inherited heart diseases. The timely emergence of genome editing technologies using engineered programmable nucleases has revolutionized the basic research of inherited cardiovascular diseases and holds great promise for the development of targeted therapies. The genome editing toolbox is rapidly expanding, and new tools have been recently added that significantly expand the capabilities of engineered nucleases. Newer classes of versatile engineered nucleases, such as the "base editors," have been recently developed, offering the potential for efficient and precise therapeutic manipulation of the human genome.

A Generic Approach for Pen-Based User Interface Development

NASA Astrophysics Data System (ADS)

Macé, Sébastien; Anquetil, Éric

Pen-based interaction is an intuitive way to realize hand drawn structured documents, but few applications take advantage of it. Indeed, the interpretation of the user hand drawn strokes in the context of document is a complex problem. In this paper, we propose a new generic approach to develop such systems based on three independent components. The first one is a set of graphical and editing functions adapted to pen interaction. The second one is a rule-based formalism that models structured document composition and the corresponding interpretation process. The last one is a hand drawn stroke analyzer that is able to interpret strokes progressively, directly while the user is drawing. We highlight in particular the human-computer interaction induced from this progressive interpretation process. Thanks to this generic approach, three pen-based system prototypes have already been developed, for musical score editing, for graph editing, and for UML class diagram editing

Financing Federal-Aid Highways. August 1999 Edition

DOT National Transportation Integrated Search

1999-08-01

Because of a continuing demand for information concerning the financing of Federal-aid highways, the Federal Highway Administration (FHWA) prepared a report, "Financing Federal-Aid Highways," in January 1974 to describe the basic process involved. Th...

Staff Development: A Practical Guide. Third Edition.

ERIC Educational Resources Information Center

Avery, Elizabeth Fuseler, Ed.; Dahlin, Terry, Ed.; Carver, Deborah A., Ed.

In this new, expanded edition step-by-step guidelines are provided for customizing a staff development program that is both proactive and goal-oriented. Drawing on the advice of 37 top experts with a variety of skill sets, this book presents information on how to assess a library's needs and set training goals, budget appropriately, develop a set…

Education and Identity. Second Edition. The Jossey-Bass Higher and Adult Education Series.

ERIC Educational Resources Information Center

Chickering, Arthur W.; Reisser, Linda

Developing policies and practices to create higher education environments that will foster broad-based development of human talent and potentials is the focus of this fully revised and updated edition, which adds findings from the last 25 years to a classic work. The volume begins with "A Current Theoretical Context for Student Development," which…

Recent advances and state-of-the-art strategies in strain and process engineering for biobutanol production by Clostridium acetobutylicum.

PubMed

Xue, Chuang; Zhao, Jingbo; Chen, Lijie; Yang, Shang-Tian; Bai, Fengwu

Butanol as an advanced biofuel has gained great attention due to its environmental benefits and superior properties compared to ethanol. However, the cost of biobutanol production via conventional acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum is not economically competitive, which has hampered its industrial application. The strain performance and downstream process greatly impact the economics of biobutanol production. Although various engineered strains with carefully orchestrated metabolic and sporulation-specific pathways have been developed, none of them is ideal for industrial biobutanol production. For further strain improvement, it is necessary to develop advanced genome editing tools and a deep understanding of cellular functioning of genes in metabolic and regulatory pathways. Processes with integrated product recovery can increase fermentation productivity by continuously removing inhibitory products while generating butanol (ABE) in a concentrated solution. In this review, we provide an overview of recent advances in C. acetobutylicum strain engineering and process development focusing on in situ product recovery. With deep understanding of systematic cellular bioinformatics, the exploration of state-of-the-art genome editing tools such as CRISPR-Cas for targeted gene knock-out and knock-in would play a vital role in Clostridium cell engineering for biobutanol production. Developing advanced hybrid separation processes for in situ butanol recovery, which will be discussed with a detailed comparison of advantages and disadvantages of various recovery techniques, is also imperative to the economical development of biobutanol. Copyright © 2017 Elsevier Inc. All rights reserved.

Consumer acceptance of food crops developed by genome editing.

PubMed

Ishii, Tetsuya; Araki, Motoko

2016-07-01

One of the major problems regarding consumer acceptance of genetically modified organisms (GMOs) is the possibility that their transgenes could have adverse effects on the environment and/or human health. Genome editing, represented by the CRISPR/Cas9 system, can efficiently achieve transgene-free gene modifications and is anticipated to generate a wide spectrum of plants. However, the public attitude against GMOs suggests that people will initially be unlikely to accept these plants. We herein explored the bottlenecks of consumer acceptance of transgene-free food crops developed by genome editing and made some recommendations. People should not pursue a zero-risk bias regarding such crops. Developers are encouraged to produce cultivars with a trait that would satisfy consumer needs. Moreover, they should carefully investigate off-target mutations in resultant plants and initially refrain from agricultural use of multiplex genome editing for better risk-benefit communication. The government must consider their regulatory status and establish appropriate regulations if necessary. The government also should foster communication between the public and developers. If people are informed of the benefits of genome editing-mediated plant breeding and trust in the relevant regulations, and if careful risk-benefit communication and sincere considerations for the right to know approach are guaranteed, then such transgene-free crops could gradually be integrated into society.

Liposomal Doxorubicin Plus Interleukin-12 for AIDS-Related Kaposi’s Sarcoma | Center for Cancer Research

Cancer.gov

Kaposi’s sarcoma (KS), a disease characterized by the development of malignant tumors usually in the lower extremities, is a major complication of HIV/AIDS. KS continues to be a problem even with the use of highly active antiretroviral therapy (HAART), today’s standard of care for patients with HIV/AIDS. CCR investigators recently investigated the effects of interleukin-12 (IL-12) on this malignancy in HIV/AIDS patients when combined with pegylated liposomal doxorubicin, an anthracycline. The findings appear in the September 10, 2007, online edition of Blood.

A rice dual-localized pentatricopeptide repeat protein is involved in organellar RNA editing together with OsMORFs.

PubMed

Xiao, Haijun; Xu, Yanghong; Ni, Chenzi; Zhang, Qiannan; Zhong, Feiya; Huang, Jishuai; Liu, Wei; Peng, Leilei; Zhu, Yingguo; Hu, Jun

2018-05-25

In flowering plants, various RNA editing events occur in the mitochondria and chloroplasts as part of post-transcriptional processes. Although several pentatricopeptide repeat (PPR) proteins and multiple organellar RNA editing factors (MORFs) have been identified as RNA editing factors, the underlying mechanism of PPRs and the cooperation among these proteins are still obscure. Here, we identified a rice dual-localized PPR protein, OsPGL1. The loss of function of OsPGL1 resulted in defects in both chloroplast RNA editing of ndhD-878 and mitochondrial RNA editing of ccmFc-543, both of which could be restored in transgenic complementation lines. Despite synonymous editing of ccmFc-543, the loss of editing of ndhD-878 caused a failed conversion of serine to leucine, leading to chloroplast dysfunction and defects in the photosynthetic complex; the results of additional experiments demonstrated that OsPGL1 directly binds to both transcripts. Interactions between three OsMORFs (OsMORF2/8/9) and OsPGL1 both in vitro and in vivo were confirmed, implying that OsPGL1 functions in RNA editing via an editosome. These findings also suggested that OsMORFs assist with and contribute to a flexible PPR-RNA recognition model during RNA editing. These results indicate that, in cooperation with PPRs, OsPGL1 is required for RNA editing. In addition, our study provides new insights into the relationship between RNA editing and plant development.

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.

Application of CRISPR/Cas9 system in breeding of new antiviral plant germplasm.

PubMed

Zhang, Dao-wei; Zhang, Chao-fan; Dong, Fang; Huang, Yan-lan; Zhang, Ya; Zhou, Hong

2016-09-01

With the development and improvement of CRISPR/Cas9 system in genomic editing technology, the system has been applied to the prevention and control of animal viral infectious diseases, which has made considerable achievements. It has also been applied to the study of highly efficient gene targeting editing in plant virus genomes. The CRISPR/Cas9-mediated targeted gene modification has not only achieved the genome editing of plant DNA virus, but also showed the genome editing potential of plant RNA virus. In addition, the CRISPR/Cas9 system functions at the gene transcriptional and post-transcriptional level, indicating that the system could regulate the replication of plant viruses through different ways. Compared with other plant viral disease control strategies, this system is more accurate in genome editing, more stable in gene expression regulation, and has broader spectrum of resistance to virus disease. In this review, we summarized the advantages, main problems and development tendency of CRISPR/cas9 system in breeding of new antiviral plant germplasms.

CRISPR-enabled tools for engineering microbial genomes and phenotypes.

PubMed

Tarasava, Katia; Oh, Eun Joong; Eckert, Carrie A; Gill, Ryan T

2018-06-19

In recent years CRISPR-Cas technologies have revolutionized microbial engineering approaches. Genome editing and non-editing applications of various CRISPR-Cas systems have expanded the throughput and scale of engineering efforts, as well as opened up new avenues for manipulating genomes of non-model organisms. As we expand the range of organisms used for biotechnological applications, we need to develop better, more versatile tools for manipulation of these systems. Here we summarize the current advances in microbial gene editing using CRISPR-Cas based tools, and highlight state-of-the-art methods for high-throughput, efficient genome-scale engineering in model organisms Escherichia coli and Saccharomyces cerevisiae. We also review non-editing CRISPR-Cas applications available for gene expression manipulation, epigenetic remodeling, RNA editing, labeling and synthetic gene circuit design. Finally, we point out the areas of research that need further development in order to expand the range of applications and increase the utility of these new methods. This article is protected by copyright. All rights reserved.

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.

Primordial germ cell-mediated transgenesis and genome editing in birds.

PubMed

Han, Jae Yong; Park, Young Hyun

2018-01-01

Transgenesis and genome editing in birds are based on a unique germline transmission system using primordial germ cells (PGCs), which is quite different from the mammalian transgenic and genome editing system. PGCs are progenitor cells of gametes that can deliver genetic information to the next generation. Since avian PGCs were first discovered in nineteenth century, there have been numerous efforts to reveal their origin, specification, and unique migration pattern, and to improve germline transmission efficiency. Recent advances in the isolation and in vitro culture of avian PGCs with genetic manipulation and genome editing tools enable the development of valuable avian models that were unavailable before. However, many challenges remain in the production of transgenic and genome-edited birds, including the precise control of germline transmission, introduction of exogenous genes, and genome editing in PGCs. Therefore, establishing reliable germline-competent PGCs and applying precise genome editing systems are critical current issues in the production of avian models. Here, we introduce a historical overview of avian PGCs and their application, including improved techniques and methodologies in the production of transgenic and genome-edited birds, and we discuss the future potential applications of transgenic and genome-edited birds to provide opportunities and benefits for humans.

Face to Face: A Sourcebook of Individual Consultation Techniques for Faculty/Instructional Developers. New Revised Edition.

ERIC Educational Resources Information Center

Lewis, Karron G., Ed.; Lunde, Joyce T. Povlacs, Ed.

Chapters in this edition contain many different approaches and strategies that can be used in individuals to improve teaching. The selections give the reader a variety of perspectives. The chapters from the first edition of this sourcebook have been updated or rewritten, and seven chapters have been added to provide additional information. The…

Prediction of constitutive A-to-I editing sites from human transcriptomes in the absence of genomic sequences

PubMed Central

2013-01-01

Background Adenosine-to-inosine (A-to-I) RNA editing is recognized as a cellular mechanism for generating both RNA and protein diversity. Inosine base pairs with cytidine during reverse transcription and therefore appears as guanosine during sequencing of cDNA. Current approaches of RNA editing identification largely depend on the comparison between transcriptomes and genomic DNA (gDNA) sequencing datasets from the same individuals, and it has been challenging to identify editing candidates from transcriptomes in the absence of gDNA information. Results We have developed a new strategy to accurately predict constitutive RNA editing sites from publicly available human RNA-seq datasets in the absence of relevant genomic sequences. Our approach establishes new parameters to increase the ability to map mismatches and to minimize sequencing/mapping errors and unreported genome variations. We identified 695 novel constitutive A-to-I editing sites that appear in clusters (named “editing boxes”) in multiple samples and which exhibit spatial and dynamic regulation across human tissues. Some of these editing boxes are enriched in non-repetitive regions lacking inverted repeat structures and contain an extremely high conversion frequency of As to Is. We validated a number of editing boxes in multiple human cell lines and confirmed that ADAR1 is responsible for the observed promiscuous editing events in non-repetitive regions, further expanding our knowledge of the catalytic substrate of A-to-I RNA editing by ADAR enzymes. Conclusions The approach we present here provides a novel way of identifying A-to-I RNA editing events by analyzing only RNA-seq datasets. This method has allowed us to gain new insights into RNA editing and should also aid in the identification of more constitutive A-to-I editing sites from additional transcriptomes. PMID:23537002

Gene editing in clinical isolates of Candida parapsilosis using CRISPR/Cas9.

PubMed

Lombardi, Lisa; Turner, Siobhán A; Zhao, Fang; Butler, Geraldine

2017-08-14

Candida parapsilosis is one of the most common causes of candidiasis, particularly in the very young and the very old. Studies of gene function are limited by the lack of a sexual cycle, the diploid genome, and a paucity of molecular tools. We describe here the development of a plasmid-based CRISPR-Cas9 system for gene editing in C. parapsilosis. A major advantage of the system is that it can be used in any genetic background, which we showed by editing genes in 20 different isolates. Gene editing is carried out in a single transformation step. The CAS9 gene is expressed only when the plasmid is present, and it can be removed easily from transformed strains. There is theoretically no limit to the number of genes that can be edited in any strain. Gene editing is increased by homology-directed repair in the presence of a repair template. Editing by non-homologous end joining (NHEJ) also occurs in some genetic backgrounds. Finally, we used the system to introduce unique tags at edited sites.

Genome edited animals: Learning from GM crops?

PubMed

Bruce, Ann

2017-06-01

Genome editing of livestock is poised to become commercial reality, yet questions remain as to appropriate regulation, potential impact on the industry sector and public acceptability of products. This paper looks at how genome editing of livestock has attempted to learn some of the lessons from commercialisation of GM crops, and takes a systemic approach to explore some of the complexity and ambiguity in incorporating genome edited animals in a food production system. Current applications of genome editing are considered, viewed from the perspective of past technological applications. The question of what is genome editing, and can it be considered natural is examined. The implications of regulation on development of different sectors of livestock production systems are studied, with a particular focus on the veterinary sector. From an EU perspective, regulation of genome edited animals, although not necessarily the same as for GM crops, is advocated from a number of different perspectives. This paper aims to open up new avenues of research on genome edited animals, extending from the current primary focus on science and regulation, to engage with a wider-range of food system actors.

CRISPR Genome Engineering for Human Pluripotent Stem Cell Research

PubMed Central

Chaterji, Somali; Ahn, Eun Hyun; Kim, Deok-Ho

2017-01-01

The emergence of targeted and efficient genome editing technologies, such as repurposed bacterial programmable nucleases (e.g., CRISPR-Cas systems), has abetted the development of cell engineering approaches. Lessons learned from the development of RNA-interference (RNA-i) therapies can spur the translation of genome editing, such as those enabling the translation of human pluripotent stem cell engineering. In this review, we discuss the opportunities and the challenges of repurposing bacterial nucleases for genome editing, while appreciating their roles, primarily at the epigenomic granularity. First, we discuss the evolution of high-precision, genome editing technologies, highlighting CRISPR-Cas9. They exist in the form of programmable nucleases, engineered with sequence-specific localizing domains, and with the ability to revolutionize human stem cell technologies through precision targeting with greater on-target activities. Next, we highlight the major challenges that need to be met prior to bench-to-bedside translation, often learning from the path-to-clinic of complementary technologies, such as RNA-i. Finally, we suggest potential bioinformatics developments and CRISPR delivery vehicles that can be deployed to circumvent some of the challenges confronting genome editing technologies en route to the clinic. PMID:29158838

Teaching Career Development: A Primer for Instructors and Presenters, Second Edition

ERIC Educational Resources Information Center

Osbor, Debra S.

2016-01-01

This second edition not only provides strategies for delivering key components of career development in enthusiastic, innovative, and more meaningful ways, it covers updated standards and new technologies. An entire chapter offers 50+ active learning strategies useful for beginning and intermediate instructors of undergraduate and graduate career…

A-to-I RNA editing is developmentally regulated and generally adaptive for sexual reproduction in Neurospora crassa

PubMed Central

Li, Yang; Chen, Daipeng; Qi, Zhaomei; Wang, Qinhu; Wang, Jianhua; Jiang, Cong; Xu, Jin-Rong

2017-01-01

Although fungi lack adenosine deaminase acting on RNA (ADAR) enzymes, adenosine to inosine (A-to-I) RNA editing was reported recently in Fusarium graminearum during sexual reproduction. In this study, we profiled the A-to-I editing landscape and characterized its functional and adaptive properties in the model filamentous fungus Neurospora crassa. A total of 40,677 A-to-I editing sites were identified, and approximately half of them displayed stage-specific editing or editing levels at different sexual stages. RNA-sequencing analysis with the Δstc-1 and Δsad-1 mutants confirmed A-to-I editing occurred before ascus development but became more prevalent during ascosporogenesis. Besides fungal-specific sequence and secondary structure preference, 63.5% of A-to-I editing sites were in the coding regions and 81.3% of them resulted in nonsynonymous recoding, resulting in a significant increase in the proteome complexity. Many genes involved in RNA silencing, DNA methylation, and histone modifications had extensive recoding, including sad-1, sms-3, qde-1, and dim-2. Fifty pseudogenes harbor premature stop codons that require A-to-I editing to encode full-length proteins. Unlike in humans, nonsynonymous editing events in N. crassa are generally beneficial and favored by positive selection. Almost half of the nonsynonymous editing sites in N. crassa are conserved and edited in Neurospora tetrasperma. Furthermore, hundreds of them are conserved in F. graminearum and had higher editing levels. Two unknown genes with editing sites conserved between Neurospora and Fusarium were experimentally shown to be important for ascosporogenesis. This study comprehensively analyzed A-to-I editing in N. crassa and showed that RNA editing is stage-specific and generally adaptive, and may be functionally related to repeat induced point mutation and meiotic silencing by unpaired DNA. PMID:28847945

A comprehensive overview of computational resources to aid in precision genome editing with engineered nucleases.

PubMed

Periwal, Vinita

2017-07-01

Genome editing with engineered nucleases (zinc finger nucleases, TAL effector nucleases s and Clustered regularly inter-spaced short palindromic repeats/CRISPR-associated) has recently been shown to have great promise in a variety of therapeutic and biotechnological applications. However, their exploitation in genetic analysis and clinical settings largely depends on their specificity for the intended genomic target. Large and complex genomes often contain highly homologous/repetitive sequences, which limits the specificity of genome editing tools and could result in off-target activity. Over the past few years, various computational approaches have been developed to assist the design process and predict/reduce the off-target activity of these nucleases. These tools could be efficiently used to guide the design of constructs for engineered nucleases and evaluate results after genome editing. This review provides a comprehensive overview of various databases, tools, web servers and resources for genome editing and compares their features and functionalities. Additionally, it also describes tools that have been developed to analyse post-genome editing results. The article also discusses important design parameters that could be considered while designing these nucleases. This review is intended to be a quick reference guide for experimentalists as well as computational biologists working in the field of genome editing with engineered nucleases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Editable Supercapacitors with Customizable Stretchability Based on Mechanically Strengthened Ultralong MnO2 Nanowire Composite.

PubMed

Lv, Zhisheng; Luo, Yifei; Tang, Yuxin; Wei, Jiaqi; Zhu, Zhiqiang; Zhou, Xinran; Li, Wenlong; Zeng, Yi; Zhang, Wei; Zhang, Yanyan; Qi, Dianpeng; Pan, Shaowu; Loh, Xian Jun; Chen, Xiaodong

2018-01-01

Although some progress has been made on stretchable supercapacitors, traditional stretchable supercapacitors fabricated by predesigning structured electrodes for device assembling still lack the device-level editability and programmability. To adapt to wearable electronics with arbitrary configurations, it is highly desirable to develop editable supercapacitors that can be directly transferred into desirable shapes and stretchability. In this work, editable supercapacitors for customizable shapes and stretchability using electrodes based on mechanically strengthened ultralong MnO 2 nanowire composites are developed. A supercapacitor edited with honeycomb-like structure shows a specific capacitance of 227.2 mF cm -2 and can be stretched up to 500% without degradation of electrochemical performance, which is superior to most of the state-of-the-art stretchable supercapacitors. In addition, it maintains nearly 98% of the initial capacitance after 10 000 stretch-and-release cycles under 400% tensile strain. As a representative of concept for system integration, the editable supercapacitors are integrated with a strain sensor, and the system exhibits a stable sensing performance even under arm swing. Being highly stretchable, easily programmable, as well as connectable in series and parallel, an editable supercapacitor with customizable stretchability is promising to produce stylish energy storage devices to power various portable, stretchable, and wearable devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient, footprint-free human iPSC genome editing by consolidation of Cas9/CRISPR and piggyBac technologies.

PubMed

Wang, Gang; Yang, Luhan; Grishin, Dennis; Rios, Xavier; Ye, Lillian Y; Hu, Yong; Li, Kai; Zhang, Donghui; Church, George M; Pu, William T

2017-01-01

Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations. Treatment with doxycycline and transfection with guide RNA (gRNA), donor DNA and piggyBac transposase resulted in efficient, targeted genome editing and concurrent scarless transgene excision. Using this approach, in 7 weeks it is possible to efficiently obtain genome-edited clones with minimal off-target mutagenesis and with indel mutation frequencies of 40-50% and homology-directed repair (HDR) frequencies of 10-20%.

Has the Diagnostic and statistical manual of mental illnesses (fifth edition) jumped the shark and is it now time for Australia to reconsider reliance on it?

PubMed

Gaughwin, Peter

2014-10-01

The purpose of this article is to consider whether, in light of the significant controversy surrounding the Diagnostic and statistical manual of mental illnesses (fifth edition) (DSM-5), it may be time for Australia to reconsider the influence of, and its past reliance on, the DSM. Also considered is whether it is now time, with the imminent publication of the The international statistical classification of diseases and related health problems (eleventh edition) (ICD-11), to move to the ICD-11 as the primary instrument for diagnosis and research in Australia. That DSM-5 begins its life in an unprecedented plethora of criticism, not only from lay people but also from mental health professionals, which should sound a note of caution for continued reliance on it in Australia. © The Royal Australian and New Zealand College of Psychiatrists 2014.

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.

By Product Synergy Analysis

DTIC Science & Technology

2011-03-24

four phases represent an easy way to implement continuous improvement activities. Figure 3. PDCA Cycle ( Heizer and Render , 2006...Environment: a guide to sustainable product development”, McGraw-Hill, 2nd Edition, 2009. 78 Heizer , Jay and Barry Render (2006), “Principles of

ERBE S10N WFOV SF Edition 2

Atmospheric Science Data Center

2016-06-09

... warming caused by greenhouse gases. Absorption of Solar Radiation by Clouds The results of the study demonstrate the present ... spacecraft, as described below. WFOV Instruments: these two fixed detectors continuously view the earth disc (plus a small ring of ...

ERBE S10N WFOV NF Edition 3

Atmospheric Science Data Center

2016-06-09

... warming caused by greenhouse gases. Absorption of Solar Radiation by Clouds The results of the study demonstrate the present ... spacecraft, as described below. WFOV Instruments: these two fixed detectors continuously view the earth disc (plus a small ring of ...

ERBE S10N WFOV NF Edition 2

Atmospheric Science Data Center

2016-06-08

... warming caused by greenhouse gases. Absorption of Solar Radiation by Clouds The results of the study demonstrate the present ... spacecraft, as described below. WFOV Instruments: these two fixed detectors continuously view the earth disc (plus a small ring of ...

ERBE S10N WFOV SF Edition 3

Atmospheric Science Data Center

2016-06-09

... warming caused by greenhouse gases. Absorption of Solar Radiation by Clouds The results of the study demonstrate the present ... spacecraft, as described below. WFOV Instruments: these two fixed detectors continuously view the earth disc (plus a small ring of ...

Nevada National Security Site-Directed Research and Development FY 2011 Annual Report

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

Howard Bender, comp.

2012-04-25

This fiscal year 2011 annual report of the Site-Directed Research and Development program, the 10th anniversary edition, recognizes a full decade of innovative R&D accomplishments in support of the Nevada National Security Site (NNSS). Last year the NNSS itself was renamed to reflect a diversifying mission, and our R&D program has contributed significantly to shape emerging missions that will continue to evolve. New initiatives in stockpile stewardship science, nonproliferation, and treaty verification and monitoring have had substantial successes in FY 2011, and many more accomplishments are expected. SDRD is the cornerstone on which many of these initiatives rest. Historically supportingmore » our main focus areas, SDRD is also building a solid foundation for new, and non-traditional, emerging national security missions. The program continues its charter to advance science and technology for a broad base of agencies including the U.S. Department of Energy (DOE), U.S. Department of Defense (DoD), U.S. Department of Homeland Security (DHS), and many others.« less

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

Constituting objectivity: Transcendental perspectives on modern physics

NASA Astrophysics Data System (ADS)

Everett, Jonathan

2012-05-01

There is increasing interest in exploring Kantian approaches in the study of the history and philosophy of physics. The most well-known examples of this trend-Friedman's (2001), Ryckman's (2005) and DiSalle's (2006)-focus on Kantianism in the context of the development of the general theory of relativity. The edited collection Constituting Objectivity seeks to develop key Kantian insights-in the most part-in the context of later developments in physics: as well as discussing relativity the volume also provides Kantian interpretations of Bohr's development of quantum theory and continues to provide Kantian insight from later interpretations of quantum mechanics all the way through to considering noncommutative geometry and loop quantum gravity. The volume contains papers on a wide variety of subjects and offers an essential introduction to the breadth of Kantian trends in modern physics.

Linguistic Variability and Intellectual Development. Miami Linguistics Series No. 9.

ERIC Educational Resources Information Center

von Humboldt, Wilhelm

Although this edition of Wilhelm von Humboldt's "Linguistic Variability and Intellectual Development" is based entirely on the original German edition, the translators (George C. Buck and Frithjof A. Raven) and the publisher have attempted to clarify certain aspects of this work for the modern-day reader. These features include the addition of…

Phonological Skills and Learning to Read. Psychology Press & Routledge Classic Editions

ERIC Educational Resources Information Center

Goswami, Usha; Bryant, Peter

2016-01-01

In this classic edition of their ground-breaking work, Usha Goswami and Peter Bryant revisit their influential theory about how phonological skills support the development of literacy. The book describes three causal factors which can account for children's reading and spelling development: (1) pre­school phonological knowledge of rhyme and…

Multimedia Projects in Education: Designing, Producing, and Assessing, Third Edition

ERIC Educational Resources Information Center

Ivers, Karen S.; Barron, Ann E.

2005-01-01

Building on the materials in the two previous successful editions, this book features approximately 40% all new material and updates the previous information. The authors use the DDD-E model (Decide, Design, Develop--Evaluate) to show how to select and plan multimedia projects, use presentation and development tools, manage graphics, audio, and…

A Case Study Approach to Ethics in Career Development, Second Edition. Monograph Series

ERIC Educational Resources Information Center

Makela, Julia Panke; Perlus, Jessamyn G.

2017-01-01

This second edition tackles some of the most vexing questions that career development professionals encounter today. Using a case study design, it offers a hands-on experience with ethical terminology, resources, and issues. Each dilemma presented includes detailed, guided discussion of key issues and recommendations, with direct connections to…

Houston Cole Library Collection Management and Development Policy. Second Edition.

ERIC Educational Resources Information Center

McAbee, Sonja L., Comp.; Bevis, Mary D., Ed.; Poe, Jodi W., Ed.; Whitesel, George, Ed.

In 1991, the staff of the Houston Cole Library (Jacksonville State University, Alabama) published its first formal "Collection Management and Development Policy." This was used as a guide in conducting a complete assessment of the Library's collections. This second edition is a revision of the 1991 publication. The first section is an…

["Homesickness and crime"--a contribution of Karl Jaspers to criminal psychology].

PubMed

Bachhiesl, Sonja Maria

2009-01-01

Even a century after its first publication in "Archives of Criminology" (in German: Archiv für Kriminologie), the doctoral thesis of Karl Jaspers (1883-1969), which was newly edited in 1996, continues to be of interest. Although the crimes described by Jaspers, which took place in a rural area, do no longer occur in this form just as the rural culture itself has disappeared, this paper nevertheless contains reflections that may also be relevant for the interpretation of modern potentials of conflict and violence and crimes rooted therein. The former homesickness has developed into novel phenomena of uprooting. In both cases, problems of maladjustment are a contributing factor to crime motivation. Thus despite all terminological and methodological change, Jaspers' thesis is an example for the continuing relevance of certain subjects in criminological discourse.

Development and Potential Applications of CRISPR-Cas9 Genome Editing Technology in Sarcoma

PubMed Central

Liu, Tang; Shen, Jacson K.; Li, Zhihong; Choy, Edwin; Hornicek, Francis J.; Duan, Zhenfeng

2016-01-01

Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. PMID:26806808

Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma.

PubMed

Liu, Tang; Shen, Jacson K; Li, Zhihong; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

2016-04-01

Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Optimization of pyDock for the new CAPRI challenges: Docking of homology-based models, domain-domain assembly and protein-RNA binding.

PubMed

Pons, Carles; Solernou, Albert; Perez-Cano, Laura; Grosdidier, Solène; Fernandez-Recio, Juan

2010-11-15

We describe here our results in the last CAPRI edition. We have participated in all targets, both as predictors and as scorers, using our pyDock docking methodology. The new challenges (homology-based modeling of the interacting subunits, domain-domain assembling, and protein-RNA interactions) have pushed our computer tools to the limits and have encouraged us to devise new docking approaches. Overall, the results have been quite successful, in line with previous editions, especially considering the high difficulty of some of the targets. Our docking approaches succeeded in five targets as predictors or as scorers (T29, T34, T35, T41, and T42). Moreover, with the inclusion of available information on the residues expected to be involved in the interaction, our protocol would have also succeeded in two additional cases (T32 and T40). In the remaining targets (except T37), results were equally poor for most of the groups. We submitted the best model (in ligand RMSD) among scorers for the unbound-bound target T29, the second best model among scorers for the protein-RNA target T34, and the only correct model among predictors for the domain assembly target T35. In summary, our excellent results for the new proposed challenges in this CAPRI edition showed the limitations and applicability of our approaches and encouraged us to continue developing methodologies for automated biomolecular docking. © 2010 Wiley-Liss, Inc.

Advances in 4D Treatment Planning for Scanned Particle Beam Therapy — Report of Dedicated Workshops

PubMed Central

Bert, Christoph; Graeff, Christian; Riboldi, Marco; Nill, Simeon; Baroni, Guido; Knopf, Antje-Christin

2014-01-01

We report on recent progress in the field of mobile tumor treatment with scanned particle beams, as discussed in the latest editions of the 4D treatment planning workshop. The workshop series started in 2009, with about 20 people from 4 research institutes involved, all actively working on particle therapy delivery and development. The first workshop resulted in a summary of recommendations for the treatment of mobile targets, along with a list of requirements to apply these guidelines clinically. The increased interest in the treatment of mobile tumors led to a continuously growing number of attendees: the 2012 edition counted more than 60 participants from 20 institutions and commercial vendors. The focus of research discussions among workshop participants progressively moved from 4D treatment planning to complete 4D treatments, aiming at effective and safe treatment delivery. Current research perspectives on 4D treatments include all critical aspects of time resolved delivery, such as in-room imaging, motion detection, beam application, and quality assurance techniques. This was motivated by the start of first clinical treatments of hepato cellular tumors with a scanned particle beam, relying on gating or abdominal compression for motion mitigation. Up to date research activities emphasize significant efforts in investigating advanced motion mitigation techniques, with a specific interest in the development of dedicated tools for experimental validation. Potential improvements will be made possible in the near future through 4D optimized treatment plans that require upgrades of the currently established therapy control systems for time resolved delivery. But since also these novel optimization techniques rely on the validity of the 4DCT, research focusing on alternative 4D imaging technique, such as MRI based 4DCT generation will continue. PMID:24354749

On the road to DSM-V and ICD-11.

PubMed

Kupfer, David J; Regier, Darrel A; Kuhl, Emily A

2008-11-01

Development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) has been ongoing since 1994, though official release will not occur for another 4 years. Potential revisions are being derived from multiple sources, including building on perceived limitations of DSM-IV; broad-based literature reviews; secondary and primary data analyses; and discussions between global members of the mental health community. The current focus on aligning DSM with the International Classification of Diseases-11 (ICD-11) speaks to the importance of creating a unified text that embraces cross-cutting issues of diagnostics, such as developmental, age-related, and cultural phenomena. International discourse is vital to this process and has been fostered by a National Institutes of Health-sponsored conference series on diagnosis-specific topics. From this series, the DSM-V Task Force developed the following set of revision principals to guide the efforts of the DSM-V Work Groups: grounding recommendations in empirical evidence; maintaining continuity with previous editions of DSM; removing a priori limitations on the amount of changes DSM-V may incur; and maintaining DSM's status as a living document. With work group formation complete, members are currently carrying out the research and revision recommendations proposed during the conference series. Ongoing activities include adding specialized advisors to each work group; completing literature reviews and planning data analyses; and forming study groups to discuss integration of cross-cutting issues (e.g., developmental lifespan factors; formation of diagnostic spectra). The road to DSM-V and ICD-11 has been challenging, but members continue to work diligently in their goal of constructing the most harmonious, scientifically sound, and clinically relevant DSM to date.

Book Review: Astronomy: A Self-Teaching Guide, 6th Edition

NASA Astrophysics Data System (ADS)

Marigza, R. N., Jr.

2009-03-01

The sixth edition of Moche's book is up-to-date with the latest in astronomy. It contains accurate astronomical data on stars and constellations. The topics are incorporated with web site addresses for the reader to expand his/her knowledge and see high-resolution images of the celestial targets. This edition incorporates new discoveries and suggestions made prior to the first editions. Among the new developments is the twenty-first-century research into black holes, active galaxies and quasars, searches for life in space, origin and structure of our universe, and the latest in ground and space telescopes.

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

Education at a Glance. OECD Indicators. [Second Edition] = Regards sur l'education. Les indicateurs de l'OCDE. [Seconde edition.

ERIC Educational Resources Information Center

Bottani, Norberto; And Others

The educational indicators in this report show how education systems in the 24 member countries of the Organisation for Economic Co-Operation and Development (OECD) resemble each other and differ. This edition, the second, builds on the 1992 volume, with more up-to-date figures and coverage of a wider range of subjects and countries. The 38…

A simple and efficient method to visualize and quantify the efficiency of chromosomal mutations from genome editing

PubMed Central

Fu, Liezhen; Wen, Luan; Luu, Nga; Shi, Yun-Bo

2016-01-01

Genome editing with designer nucleases such as TALEN and CRISPR/Cas enzymes has broad applications. Delivery of these designer nucleases into organisms induces various genetic mutations including deletions, insertions and nucleotide substitutions. Characterizing those mutations is critical for evaluating the efficacy and specificity of targeted genome editing. While a number of methods have been developed to identify the mutations, none other than sequencing allows the identification of the most desired mutations, i.e., out-of-frame insertions/deletions that disrupt genes. Here we report a simple and efficient method to visualize and quantify the efficiency of genomic mutations induced by genome-editing. Our approach is based on the expression of a two-color fusion protein in a vector that allows the insertion of the edited region in the genome in between the two color moieties. We show that our approach not only easily identifies developing animals with desired mutations but also efficiently quantifies the mutation rate in vivo. Furthermore, by using LacZα and GFP as the color moieties, our approach can even eliminate the need for a fluorescent microscope, allowing the analysis with simple bright field visualization. Such an approach will greatly simplify the screen for effective genome-editing enzymes and identify the desired mutant cells/animals. PMID:27748423

Genome editing systems in novel therapies.

PubMed

Jang, Yoon-Young; Cai, Liuhong; Ye, Zhaohui

2016-01-01

Genome editing is the process in which DNA sequences at precise genomic locations are modified. In the past three decades, genome editing by homologous recombination has been successfully performed in mouse for generating genetic models. The low efficiency of this process in human cells, however, had prevented its clinical application until the recent advancements in designer endonuclease technologies. The significantly improved genome editing efficiencies aided by ZFN, TALEN, and CRISPR systems provide unprecedented opportunities not only for biomedical research, but also for developing novel therapies. Applications based on these genome editing tools to disrupt deleterious genes, correct genetic mutations, deliver functional transgenes more effectively or even modify the epigenetic landscape are being actively investigated for gene and cell therapy purposes. Encouraging results have been obtained in limited clinical trials in the past two years. While most of the applications are still in proof-of-principle or preclinical development stages, it is anticipated that the coming years will see increasing clinical success in novel therapies based on the modern genome editing technologies. It should be noted that critical issues still remain before the technologies can be translated into more reliable therapies. These key issues include off-target evaluation, establishing appropriate preclinical models and improving the currently low efficiency of homology-based precise gene replacement. In this review we discuss the preclinical and clinical studies aiming at translating the genome editing technologies as well as the issues that are important for more successful translation.

The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair.

PubMed

Jasin, Maria; Haber, James E

2016-08-01

DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occurs by homologous recombination, which relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution. Copyright © 2016. Published by Elsevier B.V.

Recent advance on genome editing for therapy of β-hemoglobinopathies.

PubMed

Liu, Jia-Wei; Hong, Tao; Qin, Xin; Liang, Ying-Min; Zhang, Ping

2018-02-20

β-hemoglobinopathies are one of six groups of common illnesses affecting human health. Although the genetic mechanisms have been elucidated for several decades, curable treatment options, other than allogeneic bone marrow transplantation, are still lacking. In recent years, rapid development in genome editing technologies and their clinical applications have opened up new directions for treatment of β-hemoglobinopathies. Genome editing technologies, as applied in autologous CD34 + hematopoietic stem and progenitor cells, represents a promising remedial means for the β-globin disorders. Hemoglobin gene mutations could be corrected with homologous recombination-mediated DNA repair pathway to repair the genetic defects, while the nonhomologous end-joining pathway may be used to silence the key repressor of fetal globin expression and reactivate fetal hemoglobin expression, thereby alleviating the clinical symptoms of β-hemoglobinopathies in patients. This review summarizes the recent advances on genome editing of β-hemoglobinopathies from the bench design to the establishment of clinical translational platforms, thereby providing critical insights and references on the application of genome editing technologies for the development of therapeutic strategies for β-hemoglobinopathies.

The Democratization of Gene Editing: Insights from site-specific cleavage and double-strand break repair

PubMed Central

Jasin, Maria; Haber, James E.

2017-01-01

DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occur by homologous recombination that relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution. PMID:27261202

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.

Vesalius Revised. His Annotations to the 1555 Fabrica1

PubMed Central

Nutton, Vivian

2012-01-01

The De humani corporis fabrica [The Fabric of the Human Body], Basle, 1543, of Andreas Vesalius is deservedly famous as the first modern book of anatomy. A second edition was published in Basle in 1555, but little is known of Vesalius’ activities after that date. This article discusses a recent find: Vesalius’ own copy of the 1555 edition, heavily annotated in preparation for a never published third edition. Vesalius made hundreds of changes to the second edition, the great majority being stylistic, altering the Latin words but not the overall meaning. There are also changes to the plates to give greater clarity or to correct mistakes by the original block-cutter. There is little new anatomical material, although Vesalius continued to meditate about what he had earlier discovered. He shows no sign of being acquainted with the findings of others, like Colombo or Falloppia, that were published after he had moved his residence from Brussels to Spain in summer 1559, perhaps leaving this volume behind. The number of annotations shows Vesalius’ passionate concern not only for accuracy but also for the most effective way of proclaiming his new anatomical message. PMID:23112379

Thirty years of the Paediatric Standard Treatment Book.

PubMed

Vince, John D; Mokela, David

2006-01-01

The publication of the 8th edition of the Paediatric Standard Treatment Book 30 years after the first edition was introduced in 1975 provided an opportunity to examine the changes in the book's content and composition that have occurred over time. A detailed analysis of all editions of the book was made. The 8th edition is bigger, contains more clinical and guidance topics, and is undoubtedly more complex than the first. Health workers of different levels of training undoubtedly value the book, but there is evidence that it is frequently not used appropriately. The books form an important historical record of the changes in treatment of various clinical conditions that have been driven by alterations in antimicrobial susceptibility and by the emergence of evidence for efficacy. The current book is intricately linked with the Integrated Management of Childhood Illness and the treatments it contains are based on best evidence and practicality. Whilst there are challenges in ensuring that the information in the standard treatment book is accessible, practical and up to date, the book will continue to provide the basis for treatment of the common conditions presenting in children in the future.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

The Extent of mRNA Editing Is Limited in Chicken Liver and Adipose, but Impacted by Tissular Context, Genotype, Age, and Feeding as Exemplified with a Conserved Edited Site in COG3.

PubMed

Roux, Pierre-François; Frésard, Laure; Boutin, Morgane; Leroux, Sophie; Klopp, Christophe; Djari, Anis; Esquerré, Diane; Martin, Pascal G P; Zerjal, Tatiana; Gourichon, David; Pitel, Frédérique; Lagarrigue, Sandrine

2015-12-04

RNA editing is a posttranscriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, yielding contradictory conclusions regarding the extent of this phenomenon. We show, by detailed description of the 25 studies focusing so far on mRNA editing at the whole-transcriptome scale, that systematic sequencing artifacts are considered in most studies whereas biological replication is often neglected and multi-alignment not properly evaluated, which ultimately impairs the legitimacy of results. We recently developed a rigorous strategy to identify mRNA editing using mRNA and genomic DNA sequencing, taking into account sequencing and mapping artifacts, and biological replicates. We applied this method to screen for mRNA editing in liver and white adipose tissue from eight chickens and confirm the small extent of mRNA recoding in this species. Among the 25 unique edited sites identified, three events were previously described in mammals, attesting that this phenomenon is conserved throughout evolution. Deeper investigations on five sites revealed the impact of tissular context, genotype, age, feeding conditions, and sex on mRNA editing levels. More specifically, this analysis highlighted that the editing level at the site located on COG3 was strongly regulated by four of these factors. By comprehensively characterizing the mRNA editing landscape in chickens, our results highlight how this phenomenon is limited and suggest regulation of editing levels by various genetic and environmental factors. Copyright © 2016 Roux et al.

The Extent of mRNA Editing Is Limited in Chicken Liver and Adipose, but Impacted by Tissular Context, Genotype, Age, and Feeding as Exemplified with a Conserved Edited Site in COG3

PubMed Central

Roux, Pierre-François; Frésard, Laure; Boutin, Morgane; Leroux, Sophie; Klopp, Christophe; Djari, Anis; Esquerré, Diane; Martin, Pascal GP; Zerjal, Tatiana; Gourichon, David; Pitel, Frédérique; Lagarrigue, Sandrine

2015-01-01

RNA editing is a posttranscriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, yielding contradictory conclusions regarding the extent of this phenomenon. We show, by detailed description of the 25 studies focusing so far on mRNA editing at the whole-transcriptome scale, that systematic sequencing artifacts are considered in most studies whereas biological replication is often neglected and multi-alignment not properly evaluated, which ultimately impairs the legitimacy of results. We recently developed a rigorous strategy to identify mRNA editing using mRNA and genomic DNA sequencing, taking into account sequencing and mapping artifacts, and biological replicates. We applied this method to screen for mRNA editing in liver and white adipose tissue from eight chickens and confirm the small extent of mRNA recoding in this species. Among the 25 unique edited sites identified, three events were previously described in mammals, attesting that this phenomenon is conserved throughout evolution. Deeper investigations on five sites revealed the impact of tissular context, genotype, age, feeding conditions, and sex on mRNA editing levels. More specifically, this analysis highlighted that the editing level at the site located on COG3 was strongly regulated by four of these factors. By comprehensively characterizing the mRNA editing landscape in chickens, our results highlight how this phenomenon is limited and suggest regulation of editing levels by various genetic and environmental factors. PMID:26637431

Master Curriculum Guide in Economics. A Framework for Teaching the Basic Concepts. Second Edition.

ERIC Educational Resources Information Center

Saunders, Phillip; And Others

Intended for curriculum developers, this revised Framework presents a set of basic concepts for teaching K-12 economics. The revision reflects the change and development which the field of economics has undergone and includes improvements suggested by users of the first edition. The purpose of teaching economics is to impart a general…

Using National Instruments LabVIEW[TM] Education Edition in Schools

ERIC Educational Resources Information Center

Butlin, Chris A.

2011-01-01

With the development of LabVIEW[TM] Education Edition schools can now provide experience of using this widely used software. Here, a few of the many applications that students aged around 11 years and over could develop are outlined in the resulting front panel screen displays and block diagrams showing the associated graphical programmes, plus a…

Exploring Leadership: For College Students Who Want to Make a Difference. 2nd Edition

ERIC Educational Resources Information Center

Komives, Susan R.; Lucas, Nance; McMahon, Timothy R.

2006-01-01

This is the thoroughly revised and updated second edition of the bestselling book Exploring Leadership. The book is designed to help college students understand that they are capable of being effective leaders and to guide them in developing their leadership potential. Exploring Leadership incorporates new insights and material developed in the…

The Lecturer's Toolkit: A Resource for Developing Learning, Teaching & Assessment. Second Edition.

ERIC Educational Resources Information Center

Race, Phil

This "toolkit" ring binder is designed to help teachers develop their professional practice in higher education and to enhance their instruction and assessment. A smaller bound version of this second edition is designed to be used by individual lecturers as their personal copy; it contains fewer tasks and activities. The chapters are: (1)…

One small edit for humans, one giant edit for humankind? Points and questions to consider for a responsible way forward for gene editing in humans.

PubMed

Howard, Heidi C; van El, Carla G; Forzano, Francesca; Radojkovic, Dragica; Rial-Sebbag, Emmanuelle; de Wert, Guido; Borry, Pascal; Cornel, Martina C

2018-01-01

Gene editing, which allows for specific location(s) in the genome to be targeted and altered by deleting, adding or substituting nucleotides, is currently the subject of important academic and policy discussions. With the advent of efficient tools, such as CRISPR-Cas9, the plausibility of using gene editing safely in humans for either somatic or germ line gene editing is being considered seriously. Beyond safety issues, somatic gene editing in humans does raise ethical, legal and social issues (ELSI), however, it is suggested to be less challenging to existing ethical and legal frameworks; indeed somatic gene editing is already applied in (pre-) clinical trials. In contrast, the notion of altering the germ line or embryo such that alterations could be heritable in humans raises a large number of ELSI; it is currently debated whether it should even be allowed in the context of basic research. Even greater ELSI debates address the potential use of germ line or embryo gene editing for clinical purposes, which, at the moment is not being conducted and is prohibited in several jurisdictions. In the context of these ongoing debates surrounding gene editing, we present herein guidance to further discussion and investigation by highlighting three crucial areas that merit the most attention, time and resources at this stage in the responsible development and use of gene editing technologies: (1) conducting careful scientific research and disseminating results to build a solid evidence base; (2) conducting ethical, legal and social issues research; and (3) conducting meaningful stakeholder engagement, education and dialogue.

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.

The Impact of Chromatin Dynamics on Cas9-Mediated Genome Editing in Human Cells.

PubMed

Daer, René M; Cutts, Josh P; Brafman, David A; Haynes, Karmella A

2017-03-17

In order to efficiently edit eukaryotic genomes, it is critical to test the impact of chromatin dynamics on CRISPR/Cas9 function and develop strategies to adapt the system to eukaryotic contexts. So far, research has extensively characterized the relationship between the CRISPR endonuclease Cas9 and the composition of the RNA-DNA duplex that mediates the system's precision. Evidence suggests that chromatin modifications and DNA packaging can block eukaryotic genome editing by custom-built DNA endonucleases like Cas9; however, the underlying mechanism of Cas9 inhibition is unclear. Here, we demonstrate that closed, gene-silencing-associated chromatin is a mechanism for the interference of Cas9-mediated DNA editing. Our assays use a transgenic cell line with a drug-inducible switch to control chromatin states (open and closed) at a single genomic locus. We show that closed chromatin inhibits binding and editing at specific target sites and that artificial reversal of the silenced state restores editing efficiency. These results provide new insights to improve Cas9-mediated editing in human and other mammalian cells.

REDIdb 3.0: A Comprehensive Collection of RNA Editing Events in Plant Organellar Genomes.

PubMed

Lo Giudice, Claudio; Pesole, Graziano; Picardi, Ernesto

2018-01-01

RNA editing is an important epigenetic mechanism by which genome-encoded transcripts are modified by substitutions, insertions and/or deletions. It was first discovered in kinetoplastid protozoa followed by its reporting in a wide range of organisms. In plants, RNA editing occurs mostly by cytidine (C) to uridine (U) conversion in translated regions of organelle mRNAs and tends to modify affected codons restoring evolutionary conserved aminoacid residues. RNA editing has also been described in non-protein coding regions such as group II introns and structural RNAs. Despite its impact on organellar transcriptome and proteome complexity, current primary databases still do not provide a specific field for RNA editing events. To overcome these limitations, we developed REDIdb a specialized database for RNA editing modifications in plant organelles. Hereafter we describe its third release containing more than 26,000 events in a completely novel web interface to accommodate RNA editing in its genomics, biological and evolutionary context through whole genome maps and multiple sequence alignments. REDIdb is freely available at http://srv00.recas.ba.infn.it/redidb/index.html.

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.

Translating human genetics into mouse: the impact of ultra-rapid in vivo genome editing.

PubMed

Aida, Tomomi; Imahashi, Risa; Tanaka, Kohichi

2014-01-01

Gene-targeted mutant animals, such as knockout or knockin mice, have dramatically improved our understanding of the functions of genes in vivo and the genetic diversity that characterizes health and disease. However, the generation of targeted mice relies on gene targeting in embryonic stem (ES) cells, which is a time-consuming, laborious, and expensive process. The recent groundbreaking development of several genome editing technologies has enabled the targeted alteration of almost any sequence in any cell or organism. These technologies have now been applied to mouse zygotes (in vivo genome editing), thereby providing new avenues for simple, convenient, and ultra-rapid production of knockout or knockin mice without the need for ES cells. Here, we review recent achievements in the production of gene-targeted mice by in vivo genome editing. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer.

PubMed

Singh, Nathan; Shi, Junwei; June, Carl H; Ruella, Marco

2017-12-01

In this review, we discuss the most recent developments in gene-editing technology and discuss their application to adoptive T cell immunotherapy. Engineered T cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations. Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH™ (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies. As CART19 enters routine clinical use, improving the efficacy of this exciting platform is the next step in broader application. Novel gene-editing technologies like CRISPR-Cas9 allow facile editing of specific genes within the genome, generating a powerful platform to further optimize the activity of engineered T cells.

Whole organism lineage tracing by combinatorial and cumulative genome editing

PubMed Central

McKenna, Aaron; Findlay, Gregory M.; Gagnon, James A.; Horwitz, Marshall S.; Schier, Alexander F.; Shendure, Jay

2016-01-01

Multicellular systems develop from single cells through distinct lineages. However, current lineage tracing approaches scale poorly to whole, complex organisms. Here we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of CRISPR/Cas9 target sites, marks cells and enables the elucidation of lineage relationships via the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable, and that thousands of lineage-informative barcode alleles can be generated. By sampling hundreds of thousands of cells from individual zebrafish, we find that most cells in adult organs derive from relatively few embryonic progenitors. In future analyses, genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate large-scale maps of cell lineage in multicellular systems for normal development and disease. PMID:27229144

Germline Modification and Engineering in Avian Species

PubMed Central

Lee, Hong Jo; Lee, Hyung Chul; Han, Jae Yong

2015-01-01

Production of genome-edited animals using germline-competent cells and genetic modification tools has provided opportunities for investigation of biological mechanisms in various organisms. The recently reported programmed genome editing technology that can induce gene modification at a target locus in an efficient and precise manner facilitates establishment of animal models. In this regard, the demand for genome-edited avian species, which are some of the most suitable model animals due to their unique embryonic development, has also increased. Furthermore, germline chimera production through long-term culture of chicken primordial germ cells (PGCs) has facilitated research on production of genome-edited chickens. Thus, use of avian germline modification is promising for development of novel avian models for research of disease control and various biological mechanisms. Here, we discuss recent progress in genome modification technology in avian species and its applications and future strategies. PMID:26333275

Therapeutic Genome Editing: Prospects and Challenges

PubMed Central

Cox, David Benjamin Turitz; Platt, Randall Jeffrey; Zhang, Feng

2015-01-01

Recent advances in the development of genome editing technologies based on programmable nucleases have significantly improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress towards developing programmable nuclease-based therapies as well as future prospects and challenges. PMID:25654603

Assumptions and Grand Strategy

DTIC Science & Technology

2011-01-01

Germany; The Continuity of Change,” in National Security Cultures: Patterns of Global Governance, ed. Emil Kirchner and James Sperling (London...Britain in an Age of Uncertainty: The National Security Strategy (October 2010), 10. 25. Carl von Clausewitz, On War, edited and translated by Michael E

Audiences and Providers of Distance Education

ERIC Educational Resources Information Center

Nazarinia Roy, R. Roudi; Schumm, Walter R.

2011-01-01

As noted by Moore (2007, xxiii), the fifth section of the second edition of the "Handbook of Distance Education" focused on "some of the main consumers and suppliers of distance education programs," including elementary and secondary education, community colleges, universities, the corporate sector, continuing professional…

Lifelong Learning in Higher Education. Third Edition.

ERIC Educational Resources Information Center

Knapper, Christopher K.; Cropley, Arthur J.

This book, which is intended for academics, educators, educational managers, and policymakers concerned with higher education, examines how universities and colleges can prepare their students for lifelong learning through continuing education, specialized courses for adults, and mainstream teaching programs geared toward traditional students. The…

[Current advances and future prospects of genome editing technology in the field of biomedicine.

PubMed

Sakuma, Tetsushi

Genome editing technology can alter the genomic sequence at will, contributing the creation of cellular and animal models of human diseases including hereditary disorders and cancers, and the generation of the mutation-corrected human induced pluripotent stem cells for ex vivo regenerative medicine. In addition, novel approaches such as drug development using genome-wide CRISPR screening and cancer suppression using epigenome editing technology, which can change the epigenetic modifications in a site-specific manner, have also been conducted. In this article, I summarize the current advances and future prospects of genome editing technology in the field of biomedicine.

[Interpretation of update on The AJCC Esophageal Cancer Staging System, Eighth Edition].

PubMed

Yuan, Y; Chen, L Q

2017-02-01

The recently published AJCC Esophageal Cancer Staging System, 8(th) Edition will be implemented on Januray 1, 2018, which was developed by Worldwide Esophageal Cancer Collaboration based on 22 654 esophageal cancer patients from 33 worldwide centers. The definition of T, N, M, G stage and regional lymph nodes were optimized in the 8(th) edition. And the new "2 cm" principle has simplified the definition for the cancer of esophagogastric junction. In addition to pathologic staging, the 8(th) edition also provided clinical staging and pathologic staging after neoadjuvant therapy, making the new esophageal cancer staging system more practicable and reasonable.

Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

PubMed Central

Lau, Cia-Hin; Suh, Yousin

2016-01-01

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to development novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide an insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell- and in vivo animal-models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial- and temporal- manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools, including chemically inducible expression system, optogenetics, logic gate genetic circuits, tissue-specific promoters, and serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending healthspan and lifespan, ultimately improving the quality of life in the elderly populations. PMID:27974723

Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease.

PubMed

Lau, Cia-Hin; Suh, Yousin

2017-01-01

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations. © 2016 S. Karger AG, Basel.

A beginner's guide to gene editing.

PubMed

Harrison, Patrick T; Hart, Stephen

2018-04-01

What is the topic of this review? This review summarizes the development of gene editing from early proof-of-concept studies in the 1980s to contemporary programmable and RNA-guided nucleases, which enable rapid and precise alteration of DNA sequences of almost any living cell. What advances does it highlight? With an average of one clustered regularly interspaced short palindromic repeat (CRISPR) Cas9 paper published every 4 h in 2017, this review cannot highlight all new developments, but a number of key improvements, including increases in efficiency, a range of new options to reduce off-target effects and plans for CRISPR to enter clinical trials in 2018, are discussed. Genome editing enables precise changes to be made in the genome of living cells. The technique was originally developed in the 1980s but largely limited to use in mice. The discovery that a targeted double-stranded break at a unique site in the genome, close to the site to be changed, could substantially increase the efficiency of editing raised the possibility of using the technique in a broader range of animal models and, potentially, human cells. But the challenge was to identify reagents that could create targeted breaks at a unique genomic location with minimal off-target effects. In 2005, the demonstration that programmable zinc finger nucleases (ZFNs) could perform this task led to a number of proof-of-concept studies, but a limitation was the ease with which effective ZFNs could be produced. In 2009, the development of TAL effector nucleases (TALENs) increased the specificity of gene editing and the ease of design and production. However, it was not until 2013 and the development of the clustered regularly interspaced short palindromic repeat (CRISPR) Cas9/guide RNA that gene editing became a research tool that any laboratory could use. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

California Fault Parameters for the National Seismic Hazard Maps and Working Group on California Earthquake Probabilities 2007

USGS Publications Warehouse

Wills, Chris J.; Weldon, Ray J.; Bryant, W.A.

2008-01-01

This report describes development of fault parameters for the 2007 update of the National Seismic Hazard Maps and the Working Group on California Earthquake Probabilities (WGCEP, 2007). These reference parameters are contained within a database intended to be a source of values for use by scientists interested in producing either seismic hazard or deformation models to better understand the current seismic hazards in California. These parameters include descriptions of the geometry and rates of movements of faults throughout the state. These values are intended to provide a starting point for development of more sophisticated deformation models which include known rates of movement on faults as well as geodetic measurements of crustal movement and the rates of movements of the tectonic plates. The values will be used in developing the next generation of the time-independent National Seismic Hazard Maps, and the time-dependant seismic hazard calculations being developed for the WGCEP. Due to the multiple uses of this information, development of these parameters has been coordinated between USGS, CGS and SCEC. SCEC provided the database development and editing tools, in consultation with USGS, Golden. This database has been implemented in Oracle and supports electronic access (e.g., for on-the-fly access). A GUI-based application has also been developed to aid in populating the database. Both the continually updated 'living' version of this database, as well as any locked-down official releases (e.g., used in a published model for calculating earthquake probabilities or seismic shaking hazards) are part of the USGS Quaternary Fault and Fold Database http://earthquake.usgs.gov/regional/qfaults/ . CGS has been primarily responsible for updating and editing of the fault parameters, with extensive input from USGS and SCEC scientists.

Cognitive Development and Down Syndrome: Age-Related Change on the Stanford-Binet Test (Fourth Edition)

ERIC Educational Resources Information Center

Couzens, Donna; Cuskelly, Monica; Haynes, Michele

2011-01-01

Growth models for subtests of the Stanford-Binet Intelligence Scale, 4th edition (R. L. Thorndike, E. P. Hagen, & J. M. Sattler, 1986a, 1986b) were developed for individuals with Down syndrome. Models were based on the assessments of 208 individuals who participated in longitudinal and cross-sectional research between 1987 and 2004. Variation…

Manual for the Bateria de Examenes de Aptitud General (BEAG). Section II. Development.

ERIC Educational Resources Information Center

Employment of Training Administration (DOL), Washington, DC. Office of Research and Development.

The development and norming of a Spanish language edition of the United States Employment Service (USES) General Aptitude Test Battery (GATB) is described. The new edition, called the Bateria de Examenes de Aptitud General (BEAG), was designed to replace an earlier translation, the BGPA, prepared for use in Puerto Rico. Forms A and B were…

Reflective Practice: The Scholarship of Teaching and Learning. The CEET Faculty Development Program on Teaching and Learning. Second Edition: 2009 College Portfolio. Volumes I-IV

ERIC Educational Resources Information Center

Scarborough, Jule Dee

2009-01-01

"2009 Portfolio: The Second Edition of the College of Engineering's Portfolio" presents the 2009 Faculty Development Program on Teaching & Learning (TL) new content, modified models, new process and procedures, especially the new Instructional Analysis and Design Process Map, new PowerPoint presentations, modified teaching and…

An efficient system for selectively altering genetic information within mRNAs

PubMed Central

Montiel-González, Maria Fernanda; Vallecillo-Viejo, Isabel C.; Rosenthal, Joshua J. C.

2016-01-01

Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encoded iteration of SDRE could target adenosines expressed in human cells, but not efficiently. Here we developed a reporter assay to quantify editing, and used it to improve our strategy. By enhancing the linkage between ADAR's catalytic domain and the guide RNA, and by introducing a mutation in the catalytic domain, the efficiency of converting a UAG premature termination codon (PTC) to tryptophan (UGG) was improved from ∼11 % to ∼70 %. Other PTCs were edited, but less efficiently. Numerous off-target edits were identified in the targeted mRNA, but not in randomly selected endogenous messages. Off-target edits could be eliminated by reducing the amount of guide RNA with a reduction in on-target editing. The catalytic rate of SDRE was compared with those for human ADARs on various substrates and found to be within an order of magnitude of most. These data underscore the promise of site-directed RNA editing as a therapeutic or experimental tool. PMID:27557710

Cross-cultural validity of standardized motor development screening and assessment tools: a systematic review.

PubMed

Mendonça, Bianca; Sargent, Barbara; Fetters, Linda

2016-12-01

To investigate whether standardized motor development screening and assessment tools that are used to evaluate motor abilities of children aged 0 to 2 years are valid in cultures other than those in which the normative sample was established. This was a systematic review in which six databases were searched. Studies were selected based on inclusion/exclusion criteria and appraised for evidence level and quality. Study variables were extracted. Twenty-three studies representing six motor development screening and assessment tools in 16 cultural contexts met the inclusion criteria: Alberta Infant Motor Scale (n=7), Ages and Stages Questionnaire, 3rd edition (n=2), Bayley Scales of Infant and Toddler Development, 3rd edition (n=8), Denver Developmental Screening Test, 2nd edition (n=4), Harris Infant Neuromotor Test (n=1), and Peabody Developmental Motor Scales, 2nd edition (n=1). Thirteen studies found significant differences between the cultural context and normative sample. Two studies established reliability and/or validity of standardized motor development assessments in high-risk infants from different cultural contexts. Five studies established new population norms. Eight studies described the cross-cultural adaptation of a standardized motor development assessment. Standardized motor development assessments have limited validity in cultures other than that in which the normative sample was established. Their use can result in under- or over-referral for services. © 2016 Mac Keith Press.

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.

Looking forward to genetically edited fruit crops.

PubMed

Nagamangala Kanchiswamy, Chidananda; Sargent, Daniel James; Velasco, Riccardo; Maffei, Massimo E; Malnoy, Mickael

2015-02-01

The availability of genome sequences for many fruit crops has redefined the boundaries of genetic engineering and genetically modified (GM) crop plants. However commercialization of GM crops is hindered by numerous regulatory and social hurdles. Here, we focus on recently developed genome-editing tools for fruit crop improvement and their importance from the consumer perspective. Challenges and opportunities for the deployment of new genome-editing tools for fruit plants are also discussed. Copyright © 2014 Elsevier Ltd. 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.

CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development.

PubMed

Okoli, Arinze; Okeke, Malachy I; Tryland, Morten; Moens, Ugo

2018-01-22

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them.

A Java-based enterprise system architecture for implementing a continuously supported and entirely Web-based exercise solution.

PubMed

Wang, Zhihui; Kiryu, Tohru

2006-04-01

Since machine-based exercise still uses local facilities, it is affected by time and place. We designed a web-based system architecture based on the Java 2 Enterprise Edition that can accomplish continuously supported machine-based exercise. In this system, exercise programs and machines are loosely coupled and dynamically integrated on the site of exercise via the Internet. We then extended the conventional health promotion model, which contains three types of players (users, exercise trainers, and manufacturers), by adding a new player: exercise program creators. Moreover, we developed a self-describing strategy to accommodate a variety of exercise programs and provide ease of use to users on the web. We illustrate our novel design with examples taken from our feasibility study on a web-based cycle ergometer exercise system. A biosignal-based workload control approach was introduced to ensure that users performed appropriate exercise alone.

Engineering Delivery Vehicles for Genome Editing.

PubMed

Nelson, Christopher E; Gersbach, Charles A

2016-06-07

The field of genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by genome editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for genome editing are reviewed, and promising advances in particular therapeutic applications are discussed.

Practical strategies for becoming a successful medical book author.

PubMed

Hales, Robert E; McDuffie, John J; Gabbard, Glen O; Phillips, Katharine; Oldham, John; Stewart, Donna E

2008-01-01

The authors, all senior editors in the Books Division of American Psychiatric Publishing, Inc., provide practical advice to authors who may be considering writing or editing a medical book. The authors summarize strategies for developing a book proposal and outline an approach to developing a focus for a book. They also list a number of common errors that authors frequently make when they develop a book proposal. The authors provide guidance on publishing research and discuss how authors can collaborate with a publisher's marketing department to publicize their book. By employing a systematic and well-considered approach to preparing a book proposal and writing or editing a book, authors may achieve professional success and personal satisfaction. Writing or editing a medical book requires a different series of steps than authoring a journal article.

7 CFR 4274.337 - Other regulatory requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

....337 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE... recipient on the basis of sex, marital status, race, color, religion, national origin, age, physical or... of one of the following model building codes or the latest edition of that code providing an...

Diagnostic Specificity and Nonspecificity in the Dimensions of Preschool Psychopathology

ERIC Educational Resources Information Center

Sterba, Sonya; Egger, Helen L.; Angold, Adrian

2007-01-01

Background: The appropriateness of the "Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition" (DSM-IV) nosology for classifying preschool mental health disturbances continues to be debated. To inform this debate, we investigate whether preschool psychopathology shows differentiation along diagnostically specific lines…

Guidelines for Health Services for Migrant Students. 1984 Edition.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Bureau of Community Services and Migrant Education.

To promote uniformity and continuity, standards have been established for planning, implementing, and evaluating student health programs provided by grade K-12 migrant education programs throughout California. State mandated health requirements, the rationale for supplemental services, methods of providing supplemental services, and community…

Sub-Saharan Africa Report

DTIC Science & Technology

1985-11-14

official foreign reserves, and the general recognition in the market that there has been a continu- ous shortage of dollars. Whatever entered the forex ...employer by misusing his privileged access to the ’payroll system and editing the personnel database on payday to increase his monthly salary by

Ninth Edition: Adventures with a Textbook

ERIC Educational Resources Information Center

Bragdon, Henry Wilkinson

1978-01-01

Nearly three decades ago, the author started writing an American history textbook. He recently finished the revisions on the ninth edition and here he describes the struggles he had with his publisher, The Macmillan Publishing Company, in developing his history text. (Author/RK)

Methods and Sources of Data Used to Develop Selected Water-Quality Indicators for Streams and Ground Water for the 2007 Edition of The State of the Nation's Ecosystems Report with Comparisons to the 2002 Edition

USGS Publications Warehouse

Wilson, John T.; Baker, Nancy T.; Moran, Michael J.; Crawford, Charles G.; Nowell, Lisa H.; Toccalino, Patricia L.; Wilber, William G.

2008-01-01

The U.S. Geological Survey (USGS) was one of numerous governmental, private, and academic entities that provided input to the report The State of the Nation?s Ecosystems published periodically by the Heinz Center. This report describes the sources of data and methods used by the USGS to develop selected water?quality indicators for the 2007 edition of the Heinz Center report and documents modifications in the data sources and interpretations between the 2002 and 2007 editions of the Heinz Center report. Stream and ground?water quality data collected nationally as part of the USGS National Water-Quality Assessment Program were used to develop the ecosystem indicators for the Heinz Center report, including Core National indicators for the Movement of Nitrogen and Chemical Contamination and for selected ecosystems classified as Farmlands, Forest, Grasslands and Shrublands, Freshwater, and Urban and Suburban. In addition, the USGS provided water?quality and streamflow data collected as part of the National Stream Water Quality Accounting Network and the Federal?State Cooperative Program. The documentation provided herein serves not only as a reference for current and future editions of The State of the Nation?s Ecosystems but also provides critical information for future assessments of changes in contaminant occurrence in streams and ground water of the United States.

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.

A System for Supporting Development and Update of the International Classification of Health Interventions (ICHI).

PubMed

Donada, Marc; Della Mea, Vincenzo; Cumerlato, Megan; Rankin, Nicole; Madden, Richard

2018-01-01

The International Classification of Health Interventions (ICHI) is a member of the WHO Family of International Classifications, being developed to provide a common tool for reporting and analysing health interventions for statistical purposes. A web-based platform for classification development and update has been specifically developed to support the initial development step and then, after final approval, the continuous revision and update of the classification. The platform provides features for classification editing, versioning, comment management and URI identifiers. During the last 12 months it has been used for developing the ICHI Beta version, replacing the previous process based on the exchange of Excel files. At November 2017, 90 users have provided input to the development of the classification, which has resulted in 2913 comments and 2971 changes in the classification, since June 2017. Further work includes the development of an URI API for machine to machine communication, following the model established for ICD-11.

On the evaluation of segmentation editing tools

PubMed Central

Heckel, Frank; Moltz, Jan H.; Meine, Hans; Geisler, Benjamin; Kießling, Andreas; D’Anastasi, Melvin; dos Santos, Daniel Pinto; Theruvath, Ashok Joseph; Hahn, Horst K.

2014-01-01

Abstract. Efficient segmentation editing tools are important components in the segmentation process, as no automatic methods exist that always generate sufficient results. Evaluating segmentation editing algorithms is challenging, because their quality depends on the user’s subjective impression. So far, no established methods for an objective, comprehensive evaluation of such tools exist and, particularly, intermediate segmentation results are not taken into account. We discuss the evaluation of editing algorithms in the context of tumor segmentation in computed tomography. We propose a rating scheme to qualitatively measure the accuracy and efficiency of editing tools in user studies. In order to objectively summarize the overall quality, we propose two scores based on the subjective rating and the quantified segmentation quality over time. Finally, a simulation-based evaluation approach is discussed, which allows a more reproducible evaluation without the need for human input. This automated evaluation complements user studies, allowing a more convincing evaluation, particularly during development, where frequent user studies are not possible. The proposed methods have been used to evaluate two dedicated editing algorithms on 131 representative tumor segmentations. We show how the comparison of editing algorithms benefits from the proposed methods. Our results also show the correlation of the suggested quality score with the qualitative ratings. PMID:26158063

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.

A robust TALENs system for highly efficient mammalian genome editing.

PubMed

Feng, Yuanxi; Zhang, Siliang; Huang, Xin

2014-01-10

Recently, transcription activator-like effector nucleases (TALENs) have emerged as a highly effective tool for genomic editing. A pair of TALENs binds to two DNA recognition sites separated by a spacer sequence, and the dimerized FokI nucleases at the C terminal then cleave DNA in the spacer. Because of its modular design and capacity to precisely target almost any desired genomic locus, TALEN is a technology that can revolutionize the entire biomedical research field. Currently, for genomic editing in cultured cells, two plasmids encoding a pair of TALENs are co-transfected, followed by limited dilution to isolate cell colonies with the intended genomic manipulation. However, uncertain transfection efficiency becomes a bottleneck, especially in hard-to-transfect cells, reducing the overall efficiency of genome editing. We have developed a robust TALENs system in which each TALEN plasmid also encodes a fluorescence protein. Thus, cells transfected with both TALEN plasmids, a prerequisite for genomic editing, can be isolated by fluorescence-activated cell sorting. Our improved TALENs system can be applied to all cultured cells to achieve highly efficient genomic editing. Furthermore, an optimized procedure for genomic editing using TALENs is also presented. We expect our system to be widely adopted by the scientific community.

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

Collaborating with human factors when designing an electronic textbook

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

Ratner, J.A.; Zadoks, R.I.; Attaway, S.W.

The development of on-line engineering textbooks presents new challenges to authors to effectively integrate text and tools in an electronic environment. By incorporating human factors principles of interface design and cognitive psychology early in the design process, a team at Sandia National Laboratories was able to make the end product more usable and shorten the prototyping and editing phases. A critical issue was simultaneous development of paper and on-line versions of the textbook. In addition, interface consistency presented difficulties with distinct goals and limitations for each media. Many of these problems were resolved swiftly with human factors input using templates,more » style guides and iterative usability testing of both paper and on-line versions. Writing style continuity was also problematic with numerous authors contributing to the text.« less

[Overview of patents on targeted genome editing technologies and their implications for innovation and entrepreneurship education in universities].

PubMed

Fan, Xiang-yu; Lin, Yan-ping; Liao, Guo-jian; Xie, Jian-ping

2015-12-01

Zinc finger nuclease, transcription activator-like effector nuclease, and clustered regularly interspaced short palindromic repeats/Cas9 nuclease are important targeted genome editing technologies. They have great significance in scientific research and applications on aspects of functional genomics research, species improvement, disease prevention and gene therapy. There are past or ongoing disputes over ownership of the intellectual property behind every technology. In this review, we summarize the patents on these three targeted genome editing technologies in order to provide some reference for developing genome editing technologies with self-owned intellectual property rights and some implications for current innovation and entrepreneurship education in universities.

A to I editing in disease is not fake news.

PubMed

Bajad, Prajakta; Jantsch, Michael F; Keegan, Liam; O'Connell, Mary

2017-09-02

Adenosine deaminases acting on RNA (ADARs) are zinc-containing enzymes that deaminate adenosine bases to inosines within dsRNA regions in transcripts. In short, structured dsRNA hairpins individual adenosine bases may be targeted specifically and edited with up to one hundred percent efficiency, leading to the production of alternative protein variants. However, the majority of editing events occur within longer stretches of dsRNA formed by pairing of repetitive sequences. Here, many different adenosine bases are potential targets but editing efficiency is usually much lower. Recent work shows that ADAR-mediated RNA editing is also required to prevent aberrant activation of antiviral innate immune sensors that detect viral dsRNA in the cytoplasm. Missense mutations in the ADAR1 RNA editing enzyme cause a fatal auto-inflammatory disease, Aicardi-Goutières syndrome (AGS) in affected children. In addition RNA editing by ADARs has been observed to increase in many cancers and also can contribute to vascular disease. Thus the role of RNA editing in the progression of various diseases can no longer be ignored. The ability of ADARs to alter the sequence of RNAs has also been used to artificially target model RNAs in vitro and in cells for RNA editing. Potentially this approach may be used to repair genetic defects and to alter genetic information at the RNA level. In this review we focus on the role of ADARs in disease development and progression and on their potential use to artificially modify RNAs in a targeted manner.

Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.

PubMed

Hiramoto, Takafumi; Li, Li B; Funk, Sarah E; Hirata, Roli K; Russell, David W

2018-05-02

X-linked severe combined immunodeficiency (X-SCID) has been successfully treated by hematopoietic stem cell (HSC) transduction with retroviral vectors expressing the interleukin-2 receptor subunit gamma gene (IL2RG), but several patients developed malignancies due to vector integration near cellular oncogenes. This adverse side effect could in principle be avoided by accurate IL2RG gene editing with a vector that does not contain a functional promoter or IL2RG gene. Here, we show that adeno-associated virus (AAV) gene editing vectors can insert a partial Il2rg cDNA at the endogenous Il2rg locus in X-SCID murine bone marrow cells and that these ex vivo-edited cells repopulate transplant recipients and produce CD4 + and CD8 + T cells. Circulating, edited lymphocytes increased over time and appeared in secondary transplant recipients, demonstrating successful editing in long-term repopulating cells. Random vector integration events were nearly undetectable, and malignant transformation of the transplanted cells was not observed. Similar editing frequencies were observed in human hematopoietic cells. Our results demonstrate that therapeutically relevant HSC gene editing can be achieved by AAV vectors in the absence of site-specific nucleases and suggest that this may be a safe and effective therapy for hematopoietic diseases where in vivo selection can increase edited cell numbers. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Enriching Student Teaching Relationships. Supervising Teacher Edition.

ERIC Educational Resources Information Center

Clothier, Grant; Kingsley, Elizabeth

This training series was developed to improve the working relationships between supervising teachers and their student teachers. This supervising teacher's edition contains suggestions for such teachers as regards various activities dealing with the supervising/teaching situation, behavior problems, change, conference sessions, communication,…

Children and Adolescents with Autism Spectrum Disorders Compared to Typically Developing Controls on the Behavioral Assessment System for Children, Second Edition (BASC-2)

ERIC Educational Resources Information Center

Mahan, Sara; Matson, Johnny L.

2011-01-01

As the "Behavioral Assessment System for Children, Second Edition" ("BASC-2") is often used to aid in diagnosis it is important to discern how children and adolescents with Autism Spectrum Disorder (ASD) score on the "BASC-2" compared to typically developing controls. This study compared scores of typically developing…

Design of an Integrated Division-Level Battle Simulation for Research, Development, and Training. Volume 2. Detailed Design Notes

DTIC Science & Technology

1979-08-01

frag orders for tactical considerations. Frag orders issued by simulated modules will be " edited " by the same procedure as that used with populated...record and distributed as required. Queries transmitted from any staff module will be reviewed and edited at event time for technical accuracy. If an...of this kind will have to be carefully edited and interpreted by the control- ler(s) and/or computer before the chanqe is instituted in the real world

Genome editing comes of age.

PubMed

Kim, Jin-Soo

2016-09-01

Genome editing harnesses programmable nucleases to cut and paste genetic information in a targeted manner in living cells and organisms. Here, I review the development of programmable nucleases, including zinc finger nucleases (ZFNs), TAL (transcription-activator-like) effector nucleases (TALENs) and CRISPR (cluster of regularly interspaced palindromic repeats)-Cas9 (CRISPR-associated protein 9) RNA-guided endonucleases (RGENs). I specifically highlight the key advances that set the foundation for the rapid and widespread implementation of CRISPR-Cas9 genome editing approaches that has revolutionized the field.

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

New Phase of Growth for Xenogeneic-Based Bioartificial Organs

PubMed Central

Pitkin, Zorina

2016-01-01

In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent shortage of organs available for allotransplantation. The widespread introduction and adoption of bioengineered organs, incorporating cells and tissues derived from either human or animal sources, would help address this shortage. Despite the decades of development, the variety of organs studied and bioengineered, and continuous progress in the field, only two bioengineered systems are currently commercially available: Apligraf® and Dermagraft® are both approved by the FDA to treat diabetic foot ulcers, and Apligraf® is approved to treat venous leg ulcers. Currently, no products based on xenotransplantation have been approved by the FDA. Risk factors include immunological barriers and the potential infectivity of porcine endogenous retrovirus (PERV), which is unique to xenotransplantation. Recent breakthroughs in gene editing may, however, mitigate risks related to PERV. Because of its primary role in interrupting progress in xenotransplantation, we present a risk assessment for PERV infection, and conclude that the formerly high risk has been reduced to a moderate level. Advances in gene editing, and more broadly in the field, may make it more likely than ever before that bioartificial organs will alleviate the suffering of patients with organ failure. PMID:27657057

ADAR RNA editing below the backbone.

PubMed

Keegan, Liam; Khan, Anzer; Vukic, Dragana; O'Connell, Mary

2017-09-01

ADAR RNA editing enzymes ( a denosine d e a minases acting on R NA) that convert adenosine bases to inosines were first identified biochemically 30 years ago. Since then, studies on ADARs in genetic model organisms, and evolutionary comparisons between them, continue to reveal a surprising range of pleiotropic biological effects of ADARs. This review focuses on Drosophila melanogaster , which has a single Adar gene encoding a homolog of vertebrate ADAR2 that site-specifically edits hundreds of transcripts to change individual codons in ion channel subunits and membrane and cytoskeletal proteins. Drosophila ADAR is involved in the control of neuronal excitability and neurodegeneration and, intriguingly, in the control of neuronal plasticity and sleep. Drosophila ADAR also interacts strongly with RNA interference, a key antiviral defense mechanism in invertebrates. Recent crystal structures of human ADAR2 deaminase domain-RNA complexes help to interpret available information on Drosophila ADAR isoforms and on the evolution of ADARs from tRNA deaminase ADAT proteins. ADAR RNA editing is a paradigm for the now rapidly expanding range of RNA modifications in mRNAs and ncRNAs. Even with recent progress, much remains to be understood about these groundbreaking ADAR RNA modification systems. © 2017 Keegan et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

A Classification of Institutions of Higher Education. 1987 Edition.

ERIC Educational Resources Information Center

Carnegie Foundation for the Advancement of Teaching, Princeton, NJ.

Statistics classifying American colleges and universities according to their educational functions and missions are included. Rather than creating a hierarchy, this information groups institutions by shared characteristics. Changes in higher education are portrayed, and a continued growth in institutions of higher education is noted. There are…

CERES EBAF Data available in the ArcGIS Portal

Atmospheric Science Data Center

2018-06-22

... 28 variables from the Clouds and the Earth’s Radiant Energy System (CERES) Energy Balanced and Filled (EBAF) Edition 4 Top-of-Atmosphere (TOA) data ... climate model evaluation, estimating the Earth's global mean energy budget, and to infer meridional heat transport.  The ASDC will continue ...

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing.

PubMed

Certo, Michael T; Morgan, Richard A

2016-03-01

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications.

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing

PubMed Central

Certo, Michael T; Morgan, Richard A

2016-01-01

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications. PMID:26796671

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

Continuity of care: some experiences and thoughts.

PubMed

Volpe, F J

1994-09-01

Continuity of health care is a goal to be achieved. Most are for it. Many claim to provide it. But how do we know we have it? What are the key features of continuity? While dictionaries do not define the phrase "continuity of health care," we do find definitions of "continuity." The Oxford English Dictionary, Second Edition, includes in its definitions: "the state or quality of being uninterrupted in sequence or succession, or in essence or idea; connectedness, coherence, unbroken..." Stedman's Medical Dictionary includes: "absence of interruption, a succession of parts intimately united..." These definitions stress an uninterrupted succession and include the concept that there needs to be a connection to the parts. Without that connection, continuity, in health care delivery or elsewhere, does not exist.

Mass Media and Communication. Second, Revised Edition.

ERIC Educational Resources Information Center

Steinberg, Charles S., Ed.

This revised and enlarged second edition contains sections focusing on a number of mass media: newspapers, the American magazine, motion pictures, broadcasting media, and book publishing. Other section topics include the structure and development of mass communication, public opinion, international communication, the motivation of assent, the…

Unlocking Mathematics Teaching. Second Edition

ERIC Educational Resources Information Center

Koshy, Valsa, Ed.; Murray, Jean, Ed.

2011-01-01

Now in a fully updated second edition, "Unlocking Mathematics Teaching" is a comprehensive guide to teaching mathematics in the primary school. Combining theory and practice, selected experts outline the current context of mathematics education. They suggest strategies, activities and examples to help develop readers understanding and confidence…

CRISPR-Cas9 and CRISPR-Cpf1 mediated targeting of a stomatal developmental gene EPFL9 in rice.

PubMed

Yin, Xiaojia; Biswal, Akshaya K; Dionora, Jacqueline; Perdigon, Kristel M; Balahadia, Christian P; Mazumdar, Shamik; Chater, Caspar; Lin, Hsiang-Chun; Coe, Robert A; Kretzschmar, Tobias; Gray, Julie E; Quick, Paul W; Bandyopadhyay, Anindya

2017-05-01

CRISPR-Cas9/Cpf1 system with its unique gene targeting efficiency, could be an important tool for functional study of early developmental genes through the generation of successful knockout plants. The introduction and utilization of systems biology approaches have identified several genes that are involved in early development of a plant and with such knowledge a robust tool is required for the functional validation of putative candidate genes thus obtained. The development of the CRISPR-Cas9/Cpf1 genome editing system has provided a convenient tool for creating loss of function mutants for genes of interest. The present study utilized CRISPR/Cas9 and CRISPR-Cpf1 technology to knock out an early developmental gene EPFL9 (Epidermal Patterning Factor like-9, a positive regulator of stomatal development in Arabidopsis) orthologue in rice. Germ-line mutants that were generated showed edits that were carried forward into the T2 generation when Cas9-free homozygous mutants were obtained. The homozygous mutant plants showed more than an eightfold reduction in stomatal density on the abaxial leaf surface of the edited rice plants. Potential off-target analysis showed no significant off-target effects. This study also utilized the CRISPR-LbCpf1 (Lachnospiracae bacterium Cpf1) to target the same OsEPFL9 gene to test the activity of this class-2 CRISPR system in rice and found that Cpf1 is also capable of genome editing and edits get transmitted through generations with similar phenotypic changes seen with CRISPR-Cas9. This study demonstrates the application of CRISPR-Cas9/Cpf1 to precisely target genomic locations and develop transgene-free homozygous heritable gene edits and confirms that the loss of function analysis of the candidate genes emerging from different systems biology based approaches, could be performed, and therefore, this system adds value in the validation of gene function studies.

[sgRNA design for the CRISPR/Cas9 system and evaluation of its off-target effects].

PubMed

Xie, Sheng-song; Zhang, Yi; Zhang, Li-sheng; Li, Guang-lei; Zhao, Chang-zhi; Ni, Pan; Zhao, Shu-hong

2015-11-01

The third generation of CRISPR/Cas9-mediated genome editing technology has been successfully applied to genome modification of various species including animals, plants and microorganisms. How to improve the efficiency of CRISPR/Cas9 genome editing and reduce its off-target effects has been extensively explored in this field. Using sgRNA (Small guide RNA) with high efficiency and specificity is one of the critical factors for successful genome editing. Several software have been developed for sgRNA design and/or off-target evaluation, which have advantages and disadvantages respectively. In this review, we summarize characters of 16 kinds online and standalone software for sgRNA design and/or off-target evaluation and conduct a comparative analysis of these different kinds of software through developing 38 evaluation indexes. We also summarize 11 experimental approaches for testing genome editing efficiency and off-target effects as well as how to screen highly efficient and specific sgRNA.

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.

A non-inheritable maternal Cas9-based multiple-gene editing system in mice.

PubMed

Sakurai, Takayuki; Kamiyoshi, Akiko; Kawate, Hisaka; Mori, Chie; Watanabe, Satoshi; Tanaka, Megumu; Uetake, Ryuichi; Sato, Masahiro; Shindo, Takayuki

2016-01-28

The CRISPR/Cas9 system is capable of editing multiple genes through one-step zygote injection. The preexisting method is largely based on the co-injection of Cas9 DNA (or mRNA) and guide RNAs (gRNAs); however, it is unclear how many genes can be simultaneously edited by this method, and a reliable means to generate transgenic (Tg) animals with multiple gene editing has yet to be developed. Here, we employed non-inheritable maternal Cas9 (maCas9) protein derived from Tg mice with systemic Cas9 overexpression (Cas9 mice). The maCas9 protein in zygotes derived from mating or in vitro fertilization of Tg/+ oocytes and +/+ sperm could successfully edit the target genome. The efficiency of such maCas9-based genome editing was comparable to that of zygote microinjection-based genome editing widely used at present. Furthermore, we demonstrated a novel approach to create "Cas9 transgene-free" gene-modified mice using non-Tg (+/+) zygotes carrying maCas9. The maCas9 protein in mouse zygotes edited nine target loci simultaneously after injection with nine different gRNAs alone. Cas9 mouse-derived zygotes have the potential to facilitate the creation of genetically modified animals carrying the Cas9 transgene, enabling repeatable genome engineering and the production of Cas9 transgene-free mice.

Accurate identification of RNA editing sites from primitive sequence with deep neural networks.

PubMed

Ouyang, Zhangyi; Liu, Feng; Zhao, Chenghui; Ren, Chao; An, Gaole; Mei, Chuan; Bo, Xiaochen; Shu, Wenjie

2018-04-16

RNA editing is a post-transcriptional RNA sequence alteration. Current methods have identified editing sites and facilitated research but require sufficient genomic annotations and prior-knowledge-based filtering steps, resulting in a cumbersome, time-consuming identification process. Moreover, these methods have limited generalizability and applicability in species with insufficient genomic annotations or in conditions of limited prior knowledge. We developed DeepRed, a deep learning-based method that identifies RNA editing from primitive RNA sequences without prior-knowledge-based filtering steps or genomic annotations. DeepRed achieved 98.1% and 97.9% area under the curve (AUC) in training and test sets, respectively. We further validated DeepRed using experimentally verified U87 cell RNA-seq data, achieving 97.9% positive predictive value (PPV). We demonstrated that DeepRed offers better prediction accuracy and computational efficiency than current methods with large-scale, mass RNA-seq data. We used DeepRed to assess the impact of multiple factors on editing identification with RNA-seq data from the Association of Biomolecular Resource Facilities and Sequencing Quality Control projects. We explored developmental RNA editing pattern changes during human early embryogenesis and evolutionary patterns in Drosophila species and the primate lineage using DeepRed. Our work illustrates DeepRed's state-of-the-art performance; it may decipher the hidden principles behind RNA editing, making editing detection convenient and effective.

Enhanced guide-RNA design and targeting analysis for precise CRISPR genome editing of single and consortia of industrially relevant and non-model organisms.

PubMed

Mendoza, Brian J; Trinh, Cong T

2018-01-01

Genetic diversity of non-model organisms offers a repertoire of unique phenotypic features for exploration and cultivation for synthetic biology and metabolic engineering applications. To realize this enormous potential, it is critical to have an efficient genome editing tool for rapid strain engineering of these organisms to perform novel programmed functions. To accommodate the use of CRISPR/Cas systems for genome editing across organisms, we have developed a novel method, named CRISPR Associated Software for Pathway Engineering and Research (CASPER), for identifying on- and off-targets with enhanced predictability coupled with an analysis of non-unique (repeated) targets to assist in editing any organism with various endonucleases. Utilizing CASPER, we demonstrated a modest 2.4% and significant 30.2% improvement (F-test, P < 0.05) over the conventional methods for predicting on- and off-target activities, respectively. Further we used CASPER to develop novel applications in genome editing: multitargeting analysis (i.e. simultaneous multiple-site modification on a target genome with a sole guide-RNA requirement) and multispecies population analysis (i.e. guide-RNA design for genome editing across a consortium of organisms). Our analysis on a selection of industrially relevant organisms revealed a number of non-unique target sites associated with genes and transposable elements that can be used as potential sites for multitargeting. The analysis also identified shared and unshared targets that enable genome editing of single or multiple genomes in a consortium of interest. We envision CASPER as a useful platform to enhance the precise CRISPR genome editing for metabolic engineering and synthetic biology applications. https://github.com/TrinhLab/CASPER. ctrinh@utk.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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.

Genome editing of Ralstonia eutropha using an electroporation-based CRISPR-Cas9 technique.

PubMed

Xiong, Bin; Li, Zhongkang; Liu, Li; Zhao, Dongdong; Zhang, Xueli; Bi, Changhao

2018-01-01

Ralstonia eutropha is an important bacterium for the study of polyhydroxyalkanoates (PHAs) synthesis and CO 2 fixation, which makes it a potential strain for industrial PHA production and attractive host for CO 2 conversion. Although the bacterium is not recalcitrant to genetic manipulation, current methods for genome editing based on group II introns or single crossover integration of a suicide plasmid are inefficient and time-consuming, which limits the genetic engineering of this organism. Thus, developing an efficient and convenient method for R. eutropha genome editing is imperative. An efficient genome editing method for R. eutropha was developed using an electroporation-based CRISPR-Cas9 technique. In our study, the electroporation efficiency of R. eutropha was found to be limited by its restriction-modification (RM) systems. By searching the putative RM systems in R. eutropha H16 using REBASE database and comparing with that in E. coli MG1655, five putative restriction endonuclease genes which are related to the RM systems in R. eutropha were predicated and disrupted. It was found that deletion of H16_A0006 and H16_A0008 - 9 increased the electroporation efficiency 1658 and 4 times, respectively. Fructose was found to reduce the leaky expression of the arabinose-inducible pBAD promoter, which was used to optimize the expression of cas9 , enabling genome editing via homologous recombination based on CRISPR-Cas9 in R. eutropha . A total of five genes were edited with efficiencies ranging from 78.3 to 100%. The CRISPR-Cpf1 system and the non-homologous end joining mechanism were also investigated, but failed to yield edited strains. We present the first genome editing method for R. eutropha using an electroporation-based CRISPR-Cas9 approach, which significantly increased the efficiency and decreased time to manipulate this facultative chemolithoautotrophic microbe. The novel technique will facilitate more advanced researches and applications of R. eutropha for PHA production and CO 2 conversion.

Every Ninth American (1982 Edition). An Analysis for the Chairman of the Select Committee on Aging. House of Representatives. Ninety-Seventh Congress. Second Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Aging.

According to the 1980 census, one in every nine Americans is over the age of 65. The segment of the population made up of individuals over the age of 65 continues to grow faster than that comprised of individuals under the age of 65. While older people continue to have about half the income of their younger counterparts, the elderly tend to have…

Segmentation editing improves efficiency while reducing inter-expert variation and maintaining accuracy for normal brain tissues in the presence of space-occupying lesions

PubMed Central

Deeley, MA; Chen, A; Datteri, R; Noble, J; Cmelak, A; Donnelly, EF; Malcolm, A; Moretti, L; Jaboin, J; Niermann, K; Yang, Eddy S; Yu, David S; Dawant, BM

2013-01-01

Image segmentation has become a vital and often rate limiting step in modern radiotherapy treatment planning. In recent years the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumors in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: STAPLE and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers’ segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy. PMID:23685866

Targeted Gene Editing of Glia Maturation Factor in Microglia: a Novel Alzheimer's Disease Therapeutic Target.

PubMed

Raikwar, Sudhanshu P; Thangavel, Ramasamy; Dubova, Iuliia; Selvakumar, Govindhasamy Pushpavathi; Ahmed, Mohammad Ejaz; Kempuraj, Duraisamy; Zaheer, Smita A; Iyer, Shankar S; Zaheer, Asgar

2018-04-27

Alzheimer's disease (AD) is a devastating, progressive neurodegenerative disorder that leads to severe cognitive impairment in elderly patients. Chronic neuroinflammation plays an important role in the AD pathogenesis. Glia maturation factor (GMF), a proinflammatory molecule discovered in our laboratory, is significantly upregulated in various regions of AD brains. We have previously reported that GMF is predominantly expressed in the reactive glial cells surrounding the amyloid plaques (APs) in the mouse and human AD brain. Microglia are the major source of proinflammatory cytokines and chemokines including GMF. Recently clustered regularly interspaced short palindromic repeats (CRISPR) based genome editing has been recognized to study the functions of genes that are implicated in various diseases. Here, we investigated if CRISPR-Cas9-mediated GMF gene editing leads to inhibition of GMF expression and suppression of microglial activation. Confocal microscopy of murine BV2 microglial cell line transduced with an adeno-associated virus (AAV) coexpressing Staphylococcus aureus (Sa) Cas9 and a GMF-specific guide RNA (GMF-sgRNA) revealed few cells expressing SaCas9 while lacking GMF expression, thereby confirming successful GMF gene editing. To further improve GMF gene editing efficiency, we developed lentiviral vectors (LVs) expressing either Streptococcus pyogenes (Sp) Cas9 or GMF-sgRNAs. BV2 cells cotransduced with LVs expressing SpCas9 and GMF-sgRNAs revealed reduced GMF expression and the presence of indels in the exons 2 and 3 of the GMF coding sequence. Lipopolysaccharide (LPS) treatment of GMF-edited cells led to reduced microglial activation as shown by reduced p38 MAPK phosphorylation. We believe that targeted in vivo GMF gene editing has a significant potential for developing a unique and novel AD therapy.

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 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.

Gene-Editing: Interpretation of Current Law and Legal Policy.

PubMed

Kim, Na-Kyoung

2017-09-01

With the development of the third-generation gene scissors, CRISPR-Cas9, concerns are being raised about ethical and social repercussions of the new gene-editing technology. In this situation, this article explores the legislation and interpretation of the positive laws in South Korea. The BioAct does not specify and regulate 'gene editing' itself. However, assuming that genetic editing is used in the process of research and treatment, we can look to the specific details of the regulations for research on humans as well as gene therapy research in order to see how genetic editing is regulated under the BioAct. BioAct differentiates the regulation between (born) humans and embryos etc. and the regulation differ entirely in the manner and scope. Moreover, due to the fact that gene therapy products are regarded as drugs, they fall under different regulations. The Korean Pharmacopoeia Act put stringent sanctions on clinical trials for gene therapy products and the official Notification "Approval and Examination Regulations for Biological Products, etc." by Food and Drug Safety Administration may be applied to gene editing for gene therapy purposes.

A Scaled Framework for CRISPR Editing of Human Pluripotent Stem Cells to Study Psychiatric Disease.

PubMed

Hazelbaker, Dane Z; Beccard, Amanda; Bara, Anne M; Dabkowski, Nicole; Messana, Angelica; Mazzucato, Patrizia; Lam, Daisy; Manning, Danielle; Eggan, Kevin; Barrett, Lindy E

2017-10-10

Scaling of CRISPR-Cas9 technology in human pluripotent stem cells (hPSCs) represents an important step for modeling complex disease and developing drug screens in human cells. However, variables affecting the scaling efficiency of gene editing in hPSCs remain poorly understood. Here, we report a standardized CRISPR-Cas9 approach, with robust benchmarking at each step, to successfully target and genotype a set of psychiatric disease-implicated genes in hPSCs and provide a resource of edited hPSC lines for six of these genes. We found that transcriptional state and nucleosome positioning around targeted loci was not correlated with editing efficiency. However, editing frequencies varied between different hPSC lines and correlated with genomic stability, underscoring the need for careful cell line selection and unbiased assessments of genomic integrity. Together, our step-by-step quantification and in-depth analyses provide an experimental roadmap for scaling Cas9-mediated editing in hPSCs to study psychiatric disease, with broader applicability for other polygenic diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Gene editing for cell engineering: trends and applications.

PubMed

Gupta, Sanjeev K; Shukla, Pratyoosh

2017-08-01

Gene editing with all its own advantages in molecular biology applications has made easy manipulation of various production hosts with the discovery and implementation of modern gene editing tools such as Crispr (Clustered regularly interspaced short palindromic repeats), TALENs (Transcription activator-like effector nucleases) and ZFNs (Zinc finger nucleases). With the advent of these modern tools, it is now possible to manipulate the genome of industrial production hosts such as yeast and mammalian cells which allows developing a potential and cost effective recombinant therapeutic protein. These tools also allow single editing to multiple genes for knocking-in or knocking-out of a host genome quickly in an efficient manner. A recent study on "multiplexed" gene editing revolutionized the knock-out and knock-in events of yeast and CHO, mammalian cells genome for metabolic engineering as well as high, stable, and consistent expression of a transgene encoding complex therapeutic protein such as monoclonal antibody. The gene of interest can either be integrated or deleted at single or multiple loci depending on the strategy and production requirement. This review will give a gist of all the modern tools with a brief description and advances in genetic manipulation using three major tools being implemented for the modification of such hosts with the emphasis on the use of Crispr-Cas9 for the "multiplexing gene-editing approach" for genetic manipulation of yeast and CHO mammalian hosts that ultimately leads to a fast track product development with consistent, improved product yield, quality, and thus affordability for a population at large.

CRISPR/Cas9—Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development

PubMed Central

Okoli, Arinze; Okeke, Malachy I.; Tryland, Morten; Moens, Ugo

2018-01-01

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them. PMID:29361752

Therapeutics in pediatric diabetes: insulin and non-insulin approaches. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

PubMed

Kim, Jongoh; Kim, Se Min; Nguyen, Ha Cam Thuy; Redondo, Maria Jose

2012-01-01

Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analogues and delivery devices such as continuous subcutaneous insulin infusion (CSII, insulin pump) may reduce hypoglycemia and improve glycemic control. CSII combined with continuous glucose monitoring can achieve even better glycemic control. The closed-loop system is rapidly evolving and an artificial pancreas will be available in the near future. It is now recognized that several hormones other than insulin such as glucagon, amylin, and incretins contribute to glucose homeostasis. The role of co-adjuncts such as metformin, amylin analogues, and incretin based therapy is now emerging. Immunotherapy in a high risk population or patients in the early phase of type 1 diabetes may prevent further destruction of pancreatic β cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Methods for the Determination of Chemical Substances in Marine and Estuarine Environmental Matrices - 2nd Edition

EPA Science Inventory

This NERL-Cincinnati publication, “Methods for the Determination of Chemical Substances in Marine and Estuarine Environmental Matrices - 2nd Edition” was prepared as the continuation of an initiative to gather together under a single cover a compendium of standardized laborato...

Historical Topics for the Mathematics Classroom.

ERIC Educational Resources Information Center

National Council of Teachers of Mathematics, Inc., Reston, VA.

The National Council of Teachers of Mathematics (NCTM) has published this updated edition in response to a continuing demand for historical materials to be used in teaching mathematics. This publication was originally issued in 1969 as the "Thirty-first Yearbook." Its primary objective is to make available to mathematics classes important material…

46 CFR 107.259 - Crane inspection and testing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Crane inspection and testing. 107.259 Section 107.259 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS....I.) Recommended Practice for Operation and Maintenance of Offshore Cranes, API RP 2D, First Edition...

46 CFR 107.259 - Crane inspection and testing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Crane inspection and testing. 107.259 Section 107.259 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS....I.) Recommended Practice for Operation and Maintenance of Offshore Cranes, API RP 2D, First Edition...

46 CFR 107.259 - Crane inspection and testing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Crane inspection and testing. 107.259 Section 107.259 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS....I.) Recommended Practice for Operation and Maintenance of Offshore Cranes, API RP 2D, First Edition...

46 CFR 107.259 - Crane inspection and testing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Crane inspection and testing. 107.259 Section 107.259 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS....I.) Recommended Practice for Operation and Maintenance of Offshore Cranes, API RP 2D, First Edition...

46 CFR 107.259 - Crane inspection and testing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Crane inspection and testing. 107.259 Section 107.259 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS....I.) Recommended Practice for Operation and Maintenance of Offshore Cranes, API RP 2D, First Edition...

Private Pay Progression. Research Brief. Edition 6

ERIC Educational Resources Information Center

Anders, Jake

2015-01-01

While the issue of access to the professions is relatively well understood, there is limited understanding of the impact of entrants' backgrounds on success once in graduate employment. The research looks at the way social background continues to influence graduate pay and career progression once in professional employment. Key findings include:…

An Introduction to Computational Physics

NASA Astrophysics Data System (ADS)

Pang, Tao

2010-07-01

Preface to first edition; Preface; Acknowledgements; 1. Introduction; 2. Approximation of a function; 3. Numerical calculus; 4. Ordinary differential equations; 5. Numerical methods for matrices; 6. Spectral analysis; 7. Partial differential equations; 8. Molecular dynamics simulations; 9. Modeling continuous systems; 10. Monte Carlo simulations; 11. Genetic algorithm and programming; 12. Numerical renormalization; References; Index.

Calculus of Elementary Functions, Part IV. Teacher's Commentary. Preliminary Edition.

ERIC Educational Resources Information Center

Herriot, Sarah T.; And Others

This teacher's guide is designed for use with the SMSG textbook "Calculus of Elementary Functions." It contains solutions to exercises found in Chapter 9, Integration Theory and Technique; Chapter 10, Simple Differential Equations; Appendix 5, Area and Integral; Appendix 6; Appendix 7, Continuity Theory; and Appendix 8, More About…

Integrating Streaming Media to Web-based Learning: A Modular Approach.

ERIC Educational Resources Information Center

Miltenoff, Plamen

2000-01-01

Explains streaming technology and discusses how to integrate it into Web-based instruction based on experiences at St. Cloud State University (Minnesota). Topics include a modular approach, including editing, copyright concerns, digitizing, maintenance, and continuing education needs; the role of the library; and how streaming can enhance…

What's New with MS Office Suites

ERIC Educational Resources Information Center

Goldsborough, Reid

2012-01-01

If one buys a new PC, laptop, or netbook computer today, it probably comes preloaded with Microsoft Office 2010 Starter Edition. This is a significantly limited, advertising-laden version of Microsoft's suite of productivity programs, Microsoft Office. This continues the trend of PC makers providing ever more crippled versions of Microsoft's…

Changing a Field of Change

ERIC Educational Resources Information Center

Conoley, Collie W.; Conoley, Jane Close; Reese, Robert J.

2009-01-01

"School Psychology: A Blueprint for Training and Practice III" (Ysseldyke et al., 2006) continues an over 20-year tradition of reenvisioning school psychology. This latest edition focuses with great clarity on school psychology as, ideally, a profession devoted to the prevention of school-based difficulties for children and capacity building for…

The College Completion Agenda: State Policy Guide. Latino Edition

ERIC Educational Resources Information Center

College Board Advocacy & Policy Center, 2011

2011-01-01

State public policy has been an important tool for improving the educational preparation and opportunity for many communities. However, without concerted statewide efforts it will continue to be difficult to substantially expand opportunities to accelerate higher education attainment and workforce preparation. Over the next 15 years, the states…

Medical College of Georgia Fact Book 1978-79.

ERIC Educational Resources Information Center

Georgia Medical Coll., Augusta.

The third edition of the Medical College of Georgia (MCG) fact book provides a chronicle of the year 1978-1979, reflecting data and events important to the institution. Sections include: general information/Augusta; general information/MCG; administration; budget and physical plant; library/learning resources; faculty; continuing education;…

Culturally Responsive Teaching. Second Edition. Multicultural Education Series

ERIC Educational Resources Information Center

Gay, Geneva

2010-01-01

The achievement of students of color continues to be disproportionately low at all levels of education. More than ever, Geneva Gay's foundational book on culturally responsive teaching is essential reading in addressing the needs of today's diverse student population. Combining insights from multicultural education theory and research with…

29 CFR 1910.35 - Compliance with alternate exit-route codes.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 1910.35 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Exit Routes and Emergency Planning § 1910.35...-route provisions of NFPA 101, Life Safety Code, 2009 edition, or the exit-route provisions of the...

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…

47 CFR 101.1007 - Geographic service areas and number of licenses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Geographic service areas and number of licenses. 101.1007 Section 101.1007 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... in the Rand McNally 1992 Commercial Atlas & Marketing Guide, 123rd Edition, at pages 38-39, that...

Franchise Opportunities Handbook.

ERIC Educational Resources Information Center

Office of Minority Business Enterprise (DOC), Washington, DC.

Franchising continues to be one of the rapidly growing forms of business because it offers a means through which an individual with limited capital and experience can own or operate his own business. The publication, in its eighth edition, identifies franchisors who do not discriminate on the basis of race, color, or national origin in the…

World Education Report.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

This first edition of the World Education Report presents an analysis of major trends and policy issues in education in the world today. The report reviews the worldwide expansion of enrollment in formal education since 1970, focusing especially on primary and elementary education and on continuing challenges for educational policy in those areas.…

24 CFR 200.925c - Model codes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Minimum Property Standards § 200.925c Model codes. (a... Plumbing Code, 1993 Edition, and the BOCA National Mechanical Code, 1993 Edition, excluding Chapter I, Administration, for the Building, Plumbing and Mechanical Codes and the references to fire retardant treated wood...

24 CFR 200.925c - Model codes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Minimum Property Standards § 200.925c Model codes. (a... Plumbing Code, 1993 Edition, and the BOCA National Mechanical Code, 1993 Edition, excluding Chapter I, Administration, for the Building, Plumbing and Mechanical Codes and the references to fire retardant treated wood...

A Multigroup Investigation of Latent Cognitive Abilities and Reading Achievement Relations

ERIC Educational Resources Information Center

Hajovsky, Daniel; Reynolds, Matthew R.; Floyd, Randy G.; Turek, Joshua J.; Keith, Timothy Z.

2014-01-01

The structural relations between the Cattell-Horn-Carroll abilities and reading achievement outcome variables across child and adolescent development were examined in the "Kaufman Assessment Battery for Children, Second Edition", and the "Kaufman Test of Educational Achievement, Second Edition", co-normed sample. We estimated…

Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos.

PubMed

Plaza Reyes, Alvaro; Lanner, Fredrik

2017-01-01

Developmental biologists have become increasingly aware that the wealth of knowledge generated through genetic studies of pre-implantation mouse development might not easily be translated to the human embryo. Comparative studies have been fueled by recent technological advances in single-cell analysis, allowing in-depth analysis of the human embryo. This field could shortly gain more momentum as novel genome editing technologies might, for the first time, also allow functional genetic studies in the human embryo. In this Spotlight article, we summarize the CRISPR-Cas9 genome editing system and discuss its potential applications and limitations in human pre-implantation embryos, and the ethical considerations thereof. © 2017. Published by The Company of Biologists Ltd.

Genome-scale engineering for systems and synthetic biology

PubMed Central

Esvelt, Kevin M; Wang, Harris H

2013-01-01

Genome-modification technologies enable the rational engineering and perturbation of biological systems. Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome. The handful of methods capable of targeted gene editing suffered from low efficiencies, significant labor costs, or both. Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner. Here, we review current technologies and methodologies for genome-scale engineering, discuss the prospects for extending efficient genome modification to new hosts, and explore the implications of continued advances toward the development of flexibly programmable chasses, novel biochemistries, and safer organismal and ecological engineering. PMID:23340847

Structure, inhibition, and regulation of essential lipid A enzymes.

PubMed

Zhou, Pei; Zhao, Jinshi

2017-11-01

The Raetz pathway of lipid A biosynthesis plays a vital role in the survival and fitness of Gram-negative bacteria. Research efforts in the past three decades have identified individual enzymes of the pathway and have provided a mechanistic understanding of the action and regulation of these enzymes at the molecular level. This article reviews the discovery, biochemical and structural characterization, and regulation of the essential lipid A enzymes, as well as continued efforts to develop novel antibiotics against Gram-negative pathogens by targeting lipid A biosynthesis. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

Advances in Engineering the Fly Genome with the CRISPR-Cas System

PubMed Central

Bier, Ethan; Harrison, Melissa M.; O’Connor-Giles, Kate M.; Wildonger, Jill

2018-01-01

Drosophila has long been a premier model for the development and application of cutting-edge genetic approaches. The CRISPR-Cas system now adds the ability to manipulate the genome with ease and precision, providing a rich toolbox to interrogate relationships between genotype and phenotype, to delineate and visualize how the genome is organized, to illuminate and manipulate RNA, and to pioneer new gene drive technologies. Myriad transformative approaches have already originated from the CRISPR-Cas system, which will likely continue to spark the creation of tools with diverse applications. Here, we provide an overview of how CRISPR-Cas gene editing has revolutionized genetic analysis in Drosophila and highlight key areas for future advances. PMID:29301946

Application of the gene editing tool, CRISPR-Cas9, for treating neurodegenerative diseases.

PubMed

Kolli, Nivya; Lu, Ming; Maiti, Panchanan; Rossignol, Julien; Dunbar, Gary L

2018-01-01

Increased accumulation of transcribed protein from the damaged DNA and reduced DNA repair capability contributes to numerous neurological diseases for which effective treatments are lacking. Gene editing techniques provide new hope for replacing defective genes and DNA associated with neurological diseases. With advancements in using such editing tools as zinc finger nucleases (ZFNs), meganucleases, and transcription activator-like effector nucleases (TALENs), etc., scientists are able to design DNA-binding proteins, which can make precise double-strand breaks (DSBs) at the target DNA. Recent developments with the CRISPR-Cas9 gene-editing technology has proven to be more precise and efficient when compared to most other gene-editing techniques. Two methods, non-homologous end joining (NHEJ) and homology-direct repair (HDR), are used in CRISPR-Cas9 system to efficiently excise the defective genes and incorporate exogenous DNA at the target site. In this review article, we provide an overview of the CRISPR-Cas9 methodology, including its molecular mechanism, with a focus on how in this gene-editing tool can be used to counteract certain genetic defects associated with neurological diseases. Detailed understanding of this new tool could help researchers design specific gene editing strategies to repair genetic disorders in selective neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments.

PubMed

Canver, Matthew C; Haeussler, Maximilian; Bauer, Daniel E; Orkin, Stuart H; Sanjana, Neville E; Shalem, Ophir; Yuan, Guo-Cheng; Zhang, Feng; Concordet, Jean-Paul; Pinello, Luca

2018-05-01

CRISPR (clustered regularly interspaced short palindromic repeats) genome-editing experiments offer enormous potential for the evaluation of genomic loci using arrayed single guide RNAs (sgRNAs) or pooled sgRNA libraries. Numerous computational tools are available to help design sgRNAs with optimal on-target efficiency and minimal off-target potential. In addition, computational tools have been developed to analyze deep-sequencing data resulting from genome-editing experiments. However, these tools are typically developed in isolation and oftentimes are not readily translatable into laboratory-based experiments. Here, we present a protocol that describes in detail both the computational and benchtop implementation of an arrayed and/or pooled CRISPR genome-editing experiment. This protocol provides instructions for sgRNA design with CRISPOR (computational tool for the design, evaluation, and cloning of sgRNA sequences), experimental implementation, and analysis of the resulting high-throughput sequencing data with CRISPResso (computational tool for analysis of genome-editing outcomes from deep-sequencing data). This protocol allows for design and execution of arrayed and pooled CRISPR experiments in 4-5 weeks by non-experts, as well as computational data analysis that can be performed in 1-2 d by both computational and noncomputational biologists alike using web-based and/or command-line versions.

Collateral DNA damage produced by genome-editing drones: exception or rule?

PubMed

Canela, Andres; Stanlie, Andre; Nussenzweig, André

2015-05-21

In the recent issue of Nature Biotechnology, Frock et al. (2015) developed an elegant technique to capture translocation partners that can be utilized to determine off-target regions of genome-editing endonucleases as well as endogenous mutators at nucleotide resolution. Copyright © 2015 Elsevier Inc. All rights reserved.

The Law of Higher Education, 1997 Supplement. Third Edition.

ERIC Educational Resources Information Center

Kaplin, William A.; Lee, Barbara A.

This 1997 supplement to "The Law of Higher Education: A Comprehensive Guide to Lead Implications of Administrative Decision Making, Third Edition" (1995) (ED 383 256), includes discussions of court opinions, statutes, regulations, and related developments, and cites selected law journal articles, books, and other resources concerning the legal…

Compendium of fruit fly host information (CoFFHI), edition 3.0

USDA-ARS?s Scientific Manuscript database

The Compendium of Fruit Fly Host Information (CoFFHI), edition 3.0 (available at: https://coffhi.cphst.org/), developed through collaborative efforts of scientists in USDA-APHIS, USDA-ARS, and the Center for Integrated Pest Management (CIPM) of North Carolina State University (NCSU), provides centra...

Developing & Managing Your School Guidance & Counseling Program. Fifth Edition

ERIC Educational Resources Information Center

Gysbers, Norman C.; Henderson, Patricia

2012-01-01

Five phases for establishing and improving Pre-K-12 comprehensive guidance and counseling programs serve as the organizational framework for this enduring, influential textbook written for counselor educators and their students, school leaders, practicing school counselors, and state or district supervisors. The fifth edition of this bestseller…

77 FR 41172 - Trademark Board Manual of Procedure, Third Edition, Revision 1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-12

... DEPARTMENT OF COMMERCE Patent and Trademark Office [Docket No. PTO-T-2012-0028] Trademark Board Manual of Procedure, Third Edition, Revision 1 AGENCY: United States Patent and Trademark Office... not have the force and effect of law. Its guidelines have been developed as a matter of internal...

Compendium of fruit fly host information (CoFFHI), edition 2.0

USDA-ARS?s Scientific Manuscript database

The Compendium of Fruit Fly Host Information (CoFFHI), edition 2.0, developed through collaborative efforts of scientists in USDA-APHIS, USDA-ARS, and the Center for Integrated Pest Management (CIPM) of North Carolina State University (NCSU), provides centralized online documentation of what is know...

Learn, Grow, Become. TSA Edition. Second Edition.

ERIC Educational Resources Information Center

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

This curriculum guide contains seven Technology Student Association (TSA) units of study for secondary students. The units focus on helping students to develop and apply social, civic, and technology-related skills and achieve course competencies in applied technology courses. Each of the instructional units includes some or all of the basic…

Power Product Equipment Technician: Construction Equipment. Teacher Edition. Student Edition.

ERIC Educational Resources Information Center

Hilley, Robert

The instructor's guide in this package, which is one in a series of new publications developed to replace the Multistate Academic and Vocational Curriculum Consortium's previous small-engine curricula, contains the materials required to teach a competency-based course in repairing construction equipment. The guide begins with an introduction…

Invasion Ecology. Student Edition. Cornell Scientific Inquiry Series.

ERIC Educational Resources Information Center

Krasny, Marianne E.; Trautmann, Nancy; Carlsen, William; Cunningham, Christine

This book contains the student edition of the Environmental Inquiry curriculum series developed at Cornell University. It is designed to teach learning skills for investigating the behaviors of non-native and native species and demonstrate how to apply scientific knowledge to solve real-life problems. This book focuses on strange intruders…

A Counselor's Guide to Career Assessment Instruments, Sixth Edition

ERIC Educational Resources Information Center

Wood, Chris; Hays, Danica G.

2013-01-01

This book contains exemplary resources for counselors, career development facilitators, school counselors, and other career professionals working in a variety of settings. This edition is an essential guide to career assessment and contains a comprehensive list of career assessment instruments. It has over 70 reviews and includes…

The GLAS editing procedures for the FGGE level II-B data collected during SOP-1 and 2

NASA Technical Reports Server (NTRS)

Baker, W.; Edelmann, D.; Carus, H.

1981-01-01

The modifications made to the FGGE Level II-b data are discussed and the FORTRAN program developed to perform the modifications is described. It is suggested that the edited database is the most accurate one available for FGGE SOP-1 and 2.

America's Heritage: An Adventure in Liberty. Elementary Edition. First Edition.

ERIC Educational Resources Information Center

Houston Independent School District, TX.

These curriculum materials are intended to supplement school resources for elementary school teachers as they deliver instruction. They focus on developing an understanding about the nation's factual and philosophical heritage to promote freedom, unity, progress, and responsibility among students and citizens. The resource points out that the…

Read Them Now

ERIC Educational Resources Information Center

Tour, Rachel

2008-01-01

University presses have largely abdicated the job of substantive editing to outside readers, who write reports evaluating the quality of the work and offering both major and minor editing suggestions. Editors develop a cadre of readers they know they can trust, who will be fair, rigorous, and prompt with their reports. The author particularly…

Applying a Service-Oriented Architecture to Operational Flight Program Development

DTIC Science & Technology

2007-09-01

using two Java 2 Enterprise Edition (J2EE) Web servers. The weapon models were accessed using a SUN Microsystems Java Web Services Development Pack...Oriented Architectures 22 CROSSTALK The Journal of Defense Software Engineering September 2007 tion, and Spring/ Hibernate to provide the data access...tion since a major coding effort was avoided. The majority of the effort was tweaking pre-existing Java source code and editing of eXtensible Markup

Explanatory Supplement to the Astronomical Almanac, Third Edition

NASA Astrophysics Data System (ADS)

Seidelmann, P. Kenneth; Urban, S. E.

2010-01-01

"The Explanatory Supplement to the Astronomical Almanac" (hereafter "The Explanatory Supplement") is a comprehensive reference book on the topic of positional astronomy, covering the theories and algorithms used to produce "The Astronomical Almanac" (AsA), an annual publication produced jointly by the Nautical Almanac Office of the US Naval Observatory (USNO) and Her Majesty's Nautical Almanac Office (HMNAO) of the UK Hydrographic Office. The first edition of The Explanatory Supplement appeared in 1961 and was reprinted with amendments during the 1970s. The second edition was printed in 1992 and reprinted until 2006. Since the second edition, several changes have taken place in positional astronomy regarding reference systems and internationally accepted models, data sets, and computational methods; these have been incorporated into the AsA. Additionally, the data presented in the AsA have been modified over the years, with new tables being added and some being discontinued. Given these changes, a new edition of The Explanatory Supplement is appropriate. The third edition has been in development for the last few years and will be available in 2010. The book is organized similarly to the second (1991) edition, with each chapter written by subject matter experts. Authors from USNO and HMNAO contributed to the majority of the book, but there are authors from Jet Propulsion Laboratory, Technical University of Dresden, National Geospatial-Intelligence Agency, University of Texas Austin, and University of Virginia. This paper will discuss this latest edition of the Explanatory Supplement.

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.

[Assessment of learning activities using streaming video for laboratory practice education: aiming for development of E-learning system that promotes self-learning].

PubMed

Takeda, Naohito; Takeuchi, Isao; Haruna, Mitsumasa

2007-12-01

In order to develop an e-learning system that promotes self-learning, lectures and basic operations in laboratory practice of chemistry were recorded and edited on DVD media, consisting of 8 streaming videos as learning materials. Twenty-six students wanted to watch the DVD, and answered the following questions after they had watched it: "Do you think the video would serve to encourage you to study independently in the laboratory practice?" Almost all students (95%) approved of its usefulness, and more than 60% of them watched the videos repeatedly in order to acquire deeper knowledge and skill of the experimental operations. More than 60% answered that the demonstration-experiment should be continued in the laboratory practice, in spite of distribution of the DVD media.

Flu, Floods, and Fire: Ethical Public Health Preparedness.

PubMed

Phelan, Alexandra L; Gostin, Lawrence O

2017-05-01

Even as public health ethics was developing as a field, major incidents such as 9/11 and the SARS epidemic propelled discourse around public health emergency preparedness and response. Policy and practice shifted to a multidisciplinary approach, recognizing the broad range of potential threats to public health, including biological, physical, radiological, and chemical threats. This propelled the development of surveillance systems to detect incidents, laboratory capacities to rapidly test for potential threats, and therapeutic and social countermeasures to prepare for and respond to a range of hazards. In bringing public health ethics and emergency preparedness together, Emergency Ethics: Public Health Preparedness and Response adds depth and complexity to both fields. As global threats continue to emerge, the book, edited by Bruce Jennings, John D. Arras, Drue H. Barrett, and Barbara A. Ellis, will offer a vital compass. © 2017 The Hastings Center.

The dynamic nature of conflict in Wikipedia

NASA Astrophysics Data System (ADS)

Gandica, Y.; Sampaio dos Aidos, F.; Carvalho, J.

2014-10-01

The voluntary process of Wikipedia edition provides an environment in which the outcome is clearly a collective product of interactions involving a large number of people. We propose a simple agent-based model, developed from real data, to reproduce the collaborative process of Wikipedia edition. With a small number of simple ingredients, our model mimics several interesting features of real human behaviour, namely in the context of edit wars. We show that the level of conflict is determined by a tolerance parameter, which measures the editors' capability to accept different opinions and to change their own opinion. We propose to measure conflict with a parameter based on mutual reverts, which increases only in contentious situations. Using this parameter, we find a distribution for the inter-peace periods that is heavy tailed. The effects of wiki-robots in the conflict levels and in the edition patterns are also studied. Our findings are compared with previous parameters used to measure conflicts in edit wars.

Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy

PubMed Central

Bengtsson, Niclas E.; Hall, John K.; Odom, Guy L.; Phelps, Michael P.; Andrus, Colin R.; Hawkins, R. David; Hauschka, Stephen D.; Chamberlain, Joel R.; Chamberlain, Jeffrey S.

2017-01-01

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders. PMID:28195574

ADAR1-mediated 3' UTR editing and expression control of antiapoptosis genes fine-tunes cellular apoptosis response.

PubMed

Yang, Chang-Ching; Chen, Yi-Tung; Chang, Yi-Feng; Liu, Hsuan; Kuo, Yu-Ping; Shih, Chieh-Tien; Liao, Wei-Chao; Chen, Hui-Wen; Tsai, Wen-Sy; Tan, Bertrand Chin-Ming

2017-05-25

Adenosine-to-inosine RNA editing constitutes a crucial component of the cellular transcriptome and critically underpins organism survival and development. While recent high-throughput approaches have provided comprehensive documentation of the RNA editome, its functional output remains mostly unresolved, particularly for events in the non-coding regions. Gene ontology analysis of the known RNA editing targets unveiled a preponderance of genes related to apoptosis regulation, among which proto-oncogenes XIAP and MDM2 encode two the most abundantly edited transcripts. To further decode this potential functional connection, here we showed that the main RNA editor ADAR1 directly targets this 3' UTR editing of XIAP and MDM2, and further exerts a negative regulation on the expression of their protein products. This post-transcriptional silencing role was mediated via the inverted Alu elements in the 3' UTR but independent of alteration in transcript stability or miRNA targeting. Rather, we discovered that ADAR1 competes transcript occupancy with the RNA shuttling factor STAU1 to facilitate nuclear retention of the XIAP and MDM2 mRNAs. As a consequence, ADAR1 may acquire functionality in part by conferring spatial distribution and translation efficiency of the target transcripts. Finally, abrogation of ADAR1 expression or catalytic activity elicited a XIAP-dependent suppression of apoptotic response, whereas ectopic expression reversed this protective effect on cell death. Together, our results extended the known functions of ADAR1 and RNA editing to the critical fine-tuning of the intracellular apoptotic signaling and also provided mechanistic explanation for ADAR1's roles in development and tumorigenesis.

To CRISPR and beyond: the evolution of genome editing in stem cells

PubMed Central

Chen, Kuang-Yui; Knoepfler, Paul S

2016-01-01

The goal of editing the genomes of stem cells to generate model organisms and cell lines for genetic and biological studies has been pursued for decades. There is also exciting potential for future clinical impact in humans. While recent, rapid advances in targeted nuclease technologies have led to unprecedented accessibility and ease of gene editing, biology has benefited from past directed gene modification via homologous recombination, gene traps and other transgenic methodologies. Here we review the history of genome editing in stem cells (including via zinc finger nucleases, transcription activator-like effector nucleases and CRISPR–Cas9), discuss recent developments leading to the implementation of stem cell gene therapies in clinical trials and consider the prospects for future advances in this rapidly evolving field. PMID:27905217

To CRISPR and beyond: the evolution of genome editing in stem cells.

PubMed

Chen, Kuang-Yui; Knoepfler, Paul S

2016-12-01

The goal of editing the genomes of stem cells to generate model organisms and cell lines for genetic and biological studies has been pursued for decades. There is also exciting potential for future clinical impact in humans. While recent, rapid advances in targeted nuclease technologies have led to unprecedented accessibility and ease of gene editing, biology has benefited from past directed gene modification via homologous recombination, gene traps and other transgenic methodologies. Here we review the history of genome editing in stem cells (including via zinc finger nucleases, transcription activator-like effector nucleases and CRISPR-Cas9), discuss recent developments leading to the implementation of stem cell gene therapies in clinical trials and consider the prospects for future advances in this rapidly evolving field.

Advanced Digital Imaging Laboratory Using MATLAB® (Second edition)

NASA Astrophysics Data System (ADS)

Yaroslavsky, Leonid P.

2016-09-01

The first edition of this text book focussed on providing practical hands-on experience in digital imaging techniques for graduate students and practitioners keeping to a minimum any detailed discussion on the underlying theory. In this new extended edition, the author builds on the strength of the original edition by expanding the coverage to include formulation of the major theoretical results that underlie the exercises as well as introducing numerous modern concepts and new techniques. Whether you are studying or already using digital imaging techniques, developing proficiency in the subject is not possible without mastering practical skills. Including more than 100 MATLAB® exercises, this book delivers a complete applied course in digital imaging theory and practice. Part of IOP Series in Imaging Engineering Supplementary MATLAB codes and data files are available within Book Information.

From Precaution to Peril: Public Relations Across Forty Years of Genetic Engineering.

PubMed

Hogan, Andrew J

2016-12-01

The Asilomar conference on genetic engineering in 1975 has long been pointed to by scientists as a model for internal regulation and public engagement. In 2015, the organizers of the International Summit on Human Gene Editing in Washington, DC looked to Asilomar as they sought to address the implications of the new CRISPR gene editing technique. Like at Asilomar, the conveners chose to limit the discussion to a narrow set of potential CRISPR applications, involving inheritable human genome editing. The adoption by scientists in 2015 of an Asilomar-like script for discussing genetic engineering offers historians the opportunity to analyze the adjustments that have been made since 1975, and to identify the blind spots that remain in public engagement. Scientists did take important lessons from the fallout of their limited engagement with public concerns at Asilomar. Nonetheless, the scientific community has continued to overlook some of the longstanding public concerns about genetic engineering, in particular the broad and often covert genetic modification of food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-Wide Characterization of RNA Editing in Chicken Embryos Reveals Common Features among Vertebrates.

PubMed

Frésard, Laure; Leroux, Sophie; Roux, Pierre-François; Klopp, Christophe; Fabre, Stéphane; Esquerré, Diane; Dehais, Patrice; Djari, Anis; Gourichon, David; Lagarrigue, Sandrine; Pitel, Frédérique

2015-01-01

RNA editing results in a post-transcriptional nucleotide change in the RNA sequence that creates an alternative nucleotide not present in the DNA sequence. This leads to a diversification of transcription products with potential functional consequences. Two nucleotide substitutions are mainly described in animals, from adenosine to inosine (A-to-I) and from cytidine to uridine (C-to-U). This phenomenon is described in more details in mammals, notably since the availability of next generation sequencing technologies allowing whole genome screening of RNA-DNA differences. The number of studies recording RNA editing in other vertebrates like chicken is still limited. We chose to use high throughput sequencing technologies to search for RNA editing in chicken, and to extend the knowledge of its conservation among vertebrates. We performed sequencing of RNA and DNA from 8 embryos. Being aware of common pitfalls inherent to sequence analyses that lead to false positive discovery, we stringently filtered our datasets and found fewer than 40 reliable candidates. Conservation of particular sites of RNA editing was attested by the presence of 3 edited sites previously detected in mammals. We then characterized editing levels for selected candidates in several tissues and at different time points, from 4.5 days of embryonic development to adults, and observed a clear tissue-specificity and a gradual increase of editing level with time. By characterizing the RNA editing landscape in chicken, our results highlight the extent of evolutionary conservation of this phenomenon within vertebrates, attest to its tissue and stage specificity and provide support of the absence of non A-to-I events from the chicken transcriptome.

Genome-Wide Characterization of RNA Editing in Chicken Embryos Reveals Common Features among Vertebrates

PubMed Central

Frésard, Laure; Leroux, Sophie; Roux, Pierre-François; Klopp, Christophe; Fabre, Stéphane; Esquerré, Diane; Dehais, Patrice; Djari, Anis; Gourichon, David

2015-01-01

RNA editing results in a post-transcriptional nucleotide change in the RNA sequence that creates an alternative nucleotide not present in the DNA sequence. This leads to a diversification of transcription products with potential functional consequences. Two nucleotide substitutions are mainly described in animals, from adenosine to inosine (A-to-I) and from cytidine to uridine (C-to-U). This phenomenon is described in more details in mammals, notably since the availability of next generation sequencing technologies allowing whole genome screening of RNA-DNA differences. The number of studies recording RNA editing in other vertebrates like chicken is still limited. We chose to use high throughput sequencing technologies to search for RNA editing in chicken, and to extend the knowledge of its conservation among vertebrates. We performed sequencing of RNA and DNA from 8 embryos. Being aware of common pitfalls inherent to sequence analyses that lead to false positive discovery, we stringently filtered our datasets and found fewer than 40 reliable candidates. Conservation of particular sites of RNA editing was attested by the presence of 3 edited sites previously detected in mammals. We then characterized editing levels for selected candidates in several tissues and at different time points, from 4.5 days of embryonic development to adults, and observed a clear tissue-specificity and a gradual increase of editing level with time. By characterizing the RNA editing landscape in chicken, our results highlight the extent of evolutionary conservation of this phenomenon within vertebrates, attest to its tissue and stage specificity and provide support of the absence of non A-to-I events from the chicken transcriptome. PMID:26024316

Genome Editing and Its Applications in Model Organisms.

PubMed

Ma, Dongyuan; Liu, Feng

2015-12-01

Technological advances are important for innovative biological research. Development of molecular tools for DNA manipulation, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas), has revolutionized genome editing. These approaches can be used to develop potential therapeutic strategies to effectively treat heritable diseases. In the last few years, substantial progress has been made in CRISPR/Cas technology, including technical improvements and wide application in many model systems. This review describes recent advancements in genome editing with a particular focus on CRISPR/Cas, covering the underlying principles, technological optimization, and its application in zebrafish and other model organisms, disease modeling, and gene therapy used for personalized medicine. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Directrices de los Servicios de Salud para Estudiantes Migratorios (Guidelines for Health Services for Migrant Students).

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Bureau of Community Services and Migrant Education.

To promote uniformity and continuity, standards have been established for planning, implementing, and evaluating student health programs provided by grade K-12 migrant education programs throughout California. In this Spanish language edition, state-mandated health requirements, the rationale for supplemental services, methods of providing…

Educating for Leisure-Centered Living. Second Edition.

ERIC Educational Resources Information Center

Brightbill, Charles K.; Mobley, Tony A.

This handbook examines in depth the problems facing the increasing amount of leisure time available to individuals. It stresses the fact that creative use of leisure time involves more than play, entertainment, or recreation, but rather, it offers an opportunity for continued growth. The leisure philosophy of the authors is set out in the…

Privilege, Poverty, and Power: Remembering Paulo Freire's Work.

ERIC Educational Resources Information Center

Democracy & Education, 1999

1999-01-01

This special edition honors the life and work of Paulo Freire by recalling the impact he had and continues to have on educators and students. Articles in this issue are: (1) "Editor's Introduction" (Tom Wilson); (2) "Nita's Elegy to Paulo Freire (in Portuguese) 'Privilegio, Pobreza e Poder'" (Ana Maria Araujo "Nita"…

Library Law Handbook: State Laws Relating to Michigan Libraries. 1993 Edition.

ERIC Educational Resources Information Center

Michigan Library, Lansing.

This document is a compilation of state laws relating to Michigan libraries, intended as a tool for library managers and as an expression of continued commitment to strengthening library services throughout the state. It reprints legislation directly related to libraries of all levels, including: library networks; regional libraries: district…

Rethinking Our Classrooms: Teaching for Equity and Justice. Volume 2. Revised Edition

ERIC Educational Resources Information Center

Bigelow, Bill, Ed.

2004-01-01

With more than 180,000 copies in print, the first volume of "Rethinking Our Classrooms" broke new ground, providing teachers with hands-on ways to promote values of community, justice, and equality--and build students' academic skills. This companion volume continues in that tradition, presenting a rich new collection of…

America's Country Schools. Second Edition.

ERIC Educational Resources Information Center

Gulliford, Andrew

At the turn of the century, over 200,000 one-room schools existed in the United States. These simple, vernacular buildings represented the nation's commitment to education and were also the center of community life. The country school continues to be a powerful cultural symbol. This book consists of three parts. The first section describes country…

Christmas Tree Pest Manual, Third Edition

Treesearch

Steven Katovich; Deborah McCullough; Michael Ostry; Jill O’Donnell; Isabel Munck; Cliff Sadof

2014-01-01

Continuing mortality of red pine from an unknown cause has been observed in 30 to 40 year old plantations in southern and west central Wisconsin. A single tree or small group of trees die, followed by mortality of adjacent trees. These circular pockets of dead trees expand up to 0.3 acre per year.

"Queer Provocations"! Exploring Queerly Informed Disruptive Pedagogies within Feminist Community-Higher-Education Landscapes

ERIC Educational Resources Information Center

Quilty, Aideen

2017-01-01

Deborah Britzman, over 15 years ago in her insightful essay "Is There a Queer Pedagogy? Or Stop Thinking Straight", posed questions that continue to resonate (Britzman, Deborah P. 1998. "Curriculum: Toward New Identities", edited by William Pinar, 211. New York: Routledge). What if lesbian and gay theories were understood as…

OCLC Utilization in Health Sciences Libraries. CE 35, Revised Edition.

ERIC Educational Resources Information Center

Armes, Patti

This syllabus for a continuing education course describes the OCLC system and considers how it can be used by health science libraries. The general governance and administrative structure of OCLC and its network affiliates are detailed, and the OCLC subsystems--online union catalog, serials, interlibrary loan, and acquisitions--and their major…

Large Enhancement of the Sagnac Effect Based on Nonlinearly Induced Nonreciprocity.

DTIC Science & Technology

1983-05-30

Og4 ,, % 20. ABSTRACT (Continue on reverse side It ne c,&aty and Identify by block number) LL On Back -°. La . -k. DD 1JAN73 1473 EDITION OF ’NOV6S...be published. 8. L. A. Hackel, R. P. Hackel, and S. Ezekiel, Metrologia 13, 141 (1977). Ř. .4

Electrical Systems Specialist. Teacher Edition. Automotive Service Series.

ERIC Educational Resources Information Center

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

This curriculum guide is one of a series of automotive service specialty publications that continues students' training in the automotive service trade by providing instruction in the electrical systems speciality. It is based on the National Institute of Automotive Service Excellence tasks lists. It contains nine units. Each unit includes some or…

Full-Depth Asphalt Pavements for Parking Lots and Driveways.

ERIC Educational Resources Information Center

Asphalt Inst., College Park, MD.

The latest information for designing full-depth asphalt pavements for parking lots and driveways is covered in relationship to the continued increase in vehicle registration. It is based on The Asphalt Institute's Thickness Design Manual, Series No. 1 (MS-1), Seventh Edition, which covers all aspects of asphalt pavement thickness design in detail,…

Teacher Learning that Matters: International Perspectives. Routledge Research in Education

ERIC Educational Resources Information Center

Kooy, Mary, Ed.; van Veen, Klaas, Ed.

2011-01-01

In the continuing global call for educational reforms and change, the contributors in this edited collection address the critical issue of teacher learning from diverse national contexts and perspectives. They define "teacher learning that matters" as it shapes and directs pedagogical practices with the goal of improving student learning. Student…

The Schooled Society: An Introduction to the Sociology of Education. Second Edition

ERIC Educational Resources Information Center

Davies, Scott; Guppy, Neil

2010-01-01

"The Schooled Society" examines how education has come to occupy a central place in society and how its function and form continue to evolve. Structured around the three core roles of modern schooling--selection, social organization, and socialization-the authors integrate classical and contemporary theoretical approaches to discuss…

Two Perspectives on the Continuing Debate over School Choice. Dialogue Series, Number 13.

ERIC Educational Resources Information Center

Pioneer Inst. for Public Policy Research, Boston, MA.

In Pioneer Institute's November 1995 "Dialogue," nine school-choice advocates critiqued a draft manuscript of "Who Chooses, Who Loses? Culture, Institutions, and the Unequal Effects of School Choice," edited by Harvard professors Richard Elmore, Gary Orfield, and Bruce Fuller. This publication contains the response of Professor Fuller to the…

SER-LARS, Volume 4. Learning Objective History III. 1975-76 Edition.

ERIC Educational Resources Information Center

Montgomery County Intermediate Unit 23, Blue Bell, PA.

The fourth volume in the SER-LARS (Special Education Resources Location Analysis and Retrieval System) series, a diagnostic-prescriptive instructional data bank for teachers of handicapped children, presents a continuation of learning objectives organized by content descriptions. Entrees give a history of the use of each objective along with…

Mars landing site catalog

NASA Technical Reports Server (NTRS)

Greeley, Ronald (Editor)

1990-01-01

The catalog was compiled from material provided by the planetary community for areas on Mars that are of potential interest for future exploration. The catalog has been edited for consistency insofar as practical; however, the proposed scientific objectives and characteristics have not been reviewed. This is a working catalog that is being revised, updated, and expanded continually.

CRISPR-based technologies for the manipulation of eukaryotic genomes

PubMed Central

Komor, Alexis C.; Badran, Ahmed H.; Liu, David R.

2016-01-01

The CRISPR-Cas9 RNA-guided DNA endonuclease has contributed to an explosion of advances in the life sciences that have grown from the ability to edit genomes within living cells. In this review we summarize CRISPR-based technologies that enable mammalian genome editing and their various applications. We describe recent developments that extend the generality, DNA specificity, product selectivity, and fundamental capabilities of natural CRISPR systems, and some of the remarkable advancements in basic research, biotechnology, and therapeutics development that these developments have facilitated. PMID:27866654

Newer Gene Editing Technologies toward HIV Gene Therapy

PubMed Central

Manjunath, N.; Yi, Guohua; Dang, Ying; Shankar, Premlata

2013-01-01

Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

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.

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

New insights and current tools for genetically engineered (GE) sheep and goats.

PubMed

Menchaca, A; Anegon, I; Whitelaw, C B A; Baldassarre, H; Crispo, M

2016-07-01

Genetically engineered sheep and goats represent useful models applied to proof of concepts, large-scale production of novel products or processes, and improvement of animal traits, which is of interest in biomedicine, biopharma, and livestock. This disruptive biotechnology arose in the 80s by injecting DNA fragments into the pronucleus of zygote-staged embryos. Pronuclear microinjection set the transgenic concept into people's mind but was characterized by inefficient and often frustrating results mostly because of uncontrolled and/or random integration and unpredictable transgene expression. Somatic cell nuclear transfer launched the second wave in the late 90s, solving several weaknesses of the previous technique by making feasible the transfer of a genetically modified and fully characterized cell into an enucleated oocyte, capable of cell reprogramming to generate genetically engineered animals. Important advances were also achieved during the 2000s with the arrival of new techniques like the lentivirus system, transposons, RNA interference, site-specific recombinases, and sperm-mediated transgenesis. We are now living the irruption of the third technological wave in which genome edition is possible by using endonucleases, particularly the CRISPR/Cas system. Sheep and goats were recently produced by CRISPR/Cas9, and for sure, cattle will be reported soon. We will see new genetically engineered farm animals produced by homologous recombination, multiple gene editing in one-step generation and conditional modifications, among other advancements. In the following decade, genome edition will continue expanding our technical possibilities, which will contribute to the advancement of science, the development of clinical or commercial applications, and the improvement of people's life quality around the world. Copyright © 2016 Elsevier Inc. All rights reserved.

The Excellence of Play. Second Edition

ERIC Educational Resources Information Center

Moyles, Janet, Ed.

2005-01-01

This second edition of "The Excellence of Play" encapsulates all of the many changes that have taken place in early childhood in the last decade. It examines the vital importance of play as a tool for learning and teaching for children and practitioners, supporting all those who work in early childhood education and care in developing and…

How to Conduct Surveys: A Step-by-Step Guide. Sixth Edition

ERIC Educational Resources Information Center

Fink, Arlene

2016-01-01

Packed with new topics that reflect today's challenges, the Sixth Edition of the bestselling "How to Conduct Surveys" guides readers through the process of developing their own rigorous surveys and evaluating the credibility and transparency of surveys created by others. Offering practical, step-by-step advice and written in the same…

How Good Is Our School? 4th Edition

ERIC Educational Resources Information Center

Education Scotland, 2015

2015-01-01

This new updated fourth edition of "How Good is Our School?" is the result of a wide-ranging consultation through which stakeholders have contributed to the development of a substantially new set of quality indicators and supporting toolkit. This publication is designed to promote effective self-evaluation as the first stage in a process…

Focused Observations: How to Observe Young Children for Assessment and Curriculum Planning, Second Edition

ERIC Educational Resources Information Center

Gronlund, Gaye; James, Marlyn

2013-01-01

Intentional teaching begins with focused observations and systematic documentation of children's learning and development. "Focused Observations, Second Edition," explains why observation is one of the best methods to get to know each child well, track progress, and plan individualized curriculum. It also provides tools and techniques to…

Directory of Human Sciences Research Organizations and Professional Associations in South Africa. Second Edition.

ERIC Educational Resources Information Center

van der Berg, Henda, Ed.; Prinsloo, Roelf, Ed.; Pienaar, Drienie, Ed.

This directory is intended to be a comprehensive reference source for identifying research organizations and institutions, and for promoting research cooperation and facilitating networking. This second edition provides a broad background to the development of the human sciences as well as an overview of existing and emerging science and…

Beyond Discipline: From Compliance to Community. 10th Anniversary Edition

ERIC Educational Resources Information Center

Kohn, Alfie

2006-01-01

In this 10th anniversary edition of an Association for Supervision and Curriculum Development (ASCD) best seller, the author reflects on his revolutionary ideas in the context of today's emphasis on school accountability and high-stakes testing. The author relates how his innovative approach--where teachers learn to work with students, rather than…

Rentz's Student Affairs Practice in Higher Education. Fourth Edition

ERIC Educational Resources Information Center

Zhang, Naijian

2011-01-01

The mission of this new fourth edition is to provide the reader with a solid foundation in the historical and philosophical perspectives of college student affairs development; assist the reader in understanding the major concepts and purpose of student affairs' practice, methods, and program models; enable the reader to conceptualize the theme,…

Restructuring Schools for Linguistic Diversity: Linking Decision Making to Effective Programs. Second Edition. Language & Literacy Series

ERIC Educational Resources Information Center

Miramontes, Ofelia B.; Nadeau, Adel; Commins, Nancy L.

2011-01-01

This bestselling book addresses a major instructional and policy concern in public education--how personnel and resources can best be utilized to develop strong instructional programs for a culturally and linguistically diverse (CLD) student population. This meticulously updated second edition incorporates the experience that the authors have…

Efficacy of an Electronic Editing Strategy with College Students with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Woods-Groves, Suzanne; Hua, Youjia; Ford, Jeremy W.; Neil, Katelyn M.

2017-01-01

In this study we investigated an editing strategy to develop effective proofreading skills (i.e., mechanics and substantive revisions) within electronic texts through an experimental pre- and posttest group design with random assignment. Fifteen college students with intellectual and developmental disabilities participated in this investigation.…

Brief Articles for Latino Parents, 1999 Edition.

ERIC Educational Resources Information Center

ERIC Clearinghouse on Rural Education and Small Schools, Charleston, WV.

This packet contains six briefs developed specifically for Spanish-speaking Latino parents, and English translations of the briefs. These briefs state what researchers and practitioners have learned about various ways parents can help their children do well in school. Earlier editions of brief articles for parents have been used in various ways by…

Introduction to Technical Services. Seventh Edition. Library and Information Science Text Series.

ERIC Educational Resources Information Center

Evans, G. Edward; Intner, Sheila S.; Weihs, Jean

This updated edition covers all aspects of library technical services--from acquisitions to managing the cataloging department--with new emphasis on automation as it affects technical services work and those skills that can be developed through work experience or classroom instruction. Part One, General Background, consists of four chapters that…

Sketches of Innovators in Education: A Collection of Articles on Teaching with Technology. Fourth Edition.

ERIC Educational Resources Information Center

Indiana State Univ., Terre Haute.

"Sketches of Innovators in Education" is a collection of articles in which Indiana State University faculty and staff members discuss their experiences developing courses and teaching with educational technologies. This edition features a special section written by graduate student employees of the University's Faculty Computing Resource…

Material Objects. Basic Edition. Science for Micronesia.

ERIC Educational Resources Information Center

Trust Territory of the Pacific Islands Dept. of Education, Saipan.

Presented is a teacher's guide for an elementary science unit designed for use with first grade students in the Trust Territory of Micronesia. Although there is a degree of similarity to the curriculum materials developed for the Science Curriculum Improvement Study, this Micronesian unit does not purport to be an adaptation or edition of the SCIS…

Environments. Basic Edition. Science for Micronesia.

ERIC Educational Resources Information Center

Trust Territory of the Pacific Islands Dept. of Education, Saipan.

Presented is a teacher's guide to an elementary science unit designed for use with fourth grade, or higher, students in the Trust Territory of Micronesia. Although there is a degree of similarity to curriculum materials developed for the Science Curriculum Improvement Study, this Micronesian unit does not purport to be an adaption or edition of…

Analysis of Investigational Drugs in Biological Fluids - Method Development and Routine Assay

DTIC Science & Technology

1994-08-14

Principles of Internal Medicine, Tenth edition. Edited by Petersdorf, R.G.; Adams , R.P.; Braunwald, E.; Isselbacher K.J.; Martin, J.B.; and Wilson, J.D...artelinic acid in blood plasma by high-performance liquid chromatography. 1. Chromatogr., 1989, 495, 167-77. 60Lin ET, Benet LZ, Upton RA, Levai F

Cognitive Proficiency Index for the Canadian Edition of the Wechsler Intelligence Scale for Children-Fourth Edition

ERIC Educational Resources Information Center

Saklofske, Donald H.; Zhu, Jianjun; Coalson, Diane L.; Raiford, Susan E.; Weiss, Lawrence G.

2010-01-01

The Cognitive Proficiency Index (CPI) developed for the most recent Wechsler intelligence scales comprises the working memory and processing speed subtests. It reflects the proficiency and efficiency of cognitive processing and provides another lens for analyzing children's abilities assessed by the Wechsler Intelligence Scale for Children--Fourth…

Populations. Basic Edition. Science for Micronesia.

ERIC Educational Resources Information Center

Trust Territory of the Pacific Islands Dept. of Education, Saipan.

This teacher's guide is for an elementary school science unit designed for use with third grade (or older) children in the Trust Territory of Micronesia. Although there is a degree of similarity to curriculum materials developed for the Science Curriculum Improvement Study, this Micronesian unit does not purport to be an adaptation or edition of…

Dialogue for Change. Options for Re-Structuring K-12 Education. 3rd Edition, 1988.

ERIC Educational Resources Information Center

Metropolitan Affairs Corp., Detroit, MI.

This Third Edition of the 1985 report, "Dialogue for Change," discusses options and examples of educational choice and teacher empowerment and summarizes developments between 1985 and 1987. The following key options are discussed in Chapter 1, "Proposed Options for Change": (1) magnet schools; (2) open enrollment; (3) purchase…

Designing Interactive Courseware: Creating an Electronic Edition of the Notes of Debates in the Philadelphia Convention of 1787.

ERIC Educational Resources Information Center

Schick, James B. M.

2002-01-01

Describes the educational philosophy and decisions that shaped development of an electronic reader's edition of James Madison's notes on the debates of the Philadelphia Convention of 1787. Discusses the role of hypermedia in history instruction. %Illustrates and explains the design of the resource. (PAL)

The preliminary analysis of the reliability and validity of the Chinese Edition of the CSBS DP.

PubMed

Lin, Chu-Sui; Chang, Shu-Hui; Cheng, Shu-Fen; Chao, Pen-Chiang; Chiu, Chun-Hao

2015-03-01

This study marked a preliminary attempt to standardize the Chinese Edition of the Communication and Symbolic Behavior Scales Developmental Profile (Wetherby & Prizant, 2002; CSBS DP) to assist in the early identification of young children with special needs in Taiwan. The study was conducted among 171 infants and toddlers aged 1-2. It also included a follow-up study one year after the initial test. Three domestically developed standardized child development inventories were used to measure the concurrent validity and predictive validity. The Chinese Edition of the CSBS DP demonstrated overall good test-retest and inter-rater reliability. It also showed good concurrent and predictive validity. The current study yields preliminary evidence that the Chinese Edition of the CSBS DP could be a valuable assessment tool worthy of wider distribution. Future research should employ random sampling to establish a true national norm. Additionally, the follow-up study needs to include atypical groups and to expand to children aged 6-12 months to strengthen the applicability of the instrument in Taiwan. Copyright © 2014 Elsevier Ltd. All rights reserved.

CRISPR-Cas9: from Genome Editing to Cancer Research

PubMed Central

Chen, Si; Sun, Heng; Miao, Kai; Deng, Chu-Xia

2016-01-01

Cancer development is a multistep process triggered by innate and acquired mutations, which cause the functional abnormality and determine the initiation and progression of tumorigenesis. Gene editing is a widely used engineering tool for generating mutations that enhance tumorigenesis. The recent developed clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) system renews the genome editing approach into a more convenient and efficient way. By rapidly introducing genetic modifications in cell lines, organs and animals, CRISPR-Cas9 system extends the gene editing into whole genome screening, both in loss-of-function and gain-of-function manners. Meanwhile, the system accelerates the establishment of animal cancer models, promoting in vivo studies for cancer research. Furthermore, CRISPR-Cas9 system is modified into diverse innovative tools for observing the dynamic bioprocesses in cancer studies, such as image tracing for targeted DNA, regulation of transcription activation or repression. Here, we view recent technical advances in the application of CRISPR-Cas9 system in cancer genetics, large-scale cancer driver gene hunting, animal cancer modeling and functional studies. PMID:27994508

OpenStreetMap Collaborative Prototype, Phase 1

USGS Publications Warehouse

Wolf, Eric B.; Matthews, Greg D.; McNinch, Kevin; Poore, Barbara S.

2011-01-01

Phase One of the OpenStreetMap Collaborative Prototype (OSMCP) attempts to determine if the open source software developed for the OpenStreetMap (OSM, http://www.openstreetmap.org) can be used for data contributions and improvements that meet or exceed the requirements for integration into The National Map (http://www.nationalmap.gov). OpenStreetMap Collaborative Prototype Phase One focused on road data aggregated at the state level by the Kansas Data Access and Support Center (DASC). Road data from the DASC were loaded into a system hosted by the U.S. Geological Survey (USGS) National Geospatial Technical Operations Center (NGTOC) in Rolla, Missouri. U.S. Geological Survey editing specifications were developed by NGTOC personnel (J. Walters and G. Matthews, USGS, unpub. report, 2010). Interstate and U.S. Highways in the dataset were edited to the specifications by NGTOC personnel while State roads were edited by DASC personnel. Resulting data were successfully improved to meet standards for The National Map once the system and specifications were in place. The OSM software proved effective in providing a usable platform for collaborative data editing

A Communications Guide for Sustainable Development: How Interested Parties Become Partners, 2nd Edition

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

Fowler, Kimberly M.; Hund, Gretchen; Engel-Cox, Jill A.

2016-03-06

The 2nd edition is an updated version plus an e-book. This book was developed to assist organizations in designing and managing their communication and stakeholder involvement programs. The guidebook describes a step-by-step approach, provides case studies, and presents tools to consider. The book uses a scenario approach to outline changes an organization may confront, and provides a menu of communication and engagement activities that support organizational decision making.

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

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.

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

The Capabilities of the Graphical Observation Scheduling System (GROSS) as Used by the Astro-2 Spacelab Mission

NASA Technical Reports Server (NTRS)

Phillips, Shaun

1996-01-01

The Graphical Observation Scheduling System (GROSS) and its functionality and editing capabilities are reported on. The GROSS system was developed as a replacement for a suite of existing programs and associated processes with the aim of: providing a software tool that combines the functionality of several of the existing programs, and provides a Graphical User Interface (GUI) that gives greater data visibility and editing capabilities. It is considered that the improved editing capability provided by this approach enhanced the efficiency of the second astronomical Spacelab mission's (ASTRO-2) mission planning.

Characterization of a germline Vk gene encoding cationic anti-DNA antibody and role of receptor editing for development of the autoantibody in patients with systemic lupus erythematosus.

PubMed

Suzuki, N; Harada, T; Mihara, S; Sakane, T

1996-10-15

We found previously that cationic anti-DNA autoantibodies (autoAbs) have nephritogenic potential and usage of a specific germline Vk gene, A30, has major influences on cationic charge of the autoAb in human lupus nephritis. In the present study, we have characterized A30 germline Vk gene using cosmid cloning technique in patients with SLE. A30 gene locus locates in less than 250 kb from the Ck region, and the cationic anti-DNA mRNA used the upstream Jk2 gene, indicating that cationic anti-DNA mRNA is a product of primary gene rearrangement. By using PCR technique, we found that A30 gene locus in the genome was defective in eight out of nine SLE patients without nephritis. In contrast, all nine patients with lupus nephritis had intact A30 gene. The presence and absence of A30 gene was associated with the development of lupus nephritis or not (P < 0.01, by Fisher's exact test, two-sided). It was thus suggested that absence of functional A30 gene may rescue from developing lupus nephritis in the patients. A30 is reported to be a potentially functional but rarely expressed Vk gene in humans. It is possible that normal B cells edit primarily rearranged A30 gene with autoreactive potentials by receptor editing mechanism for changing the affinity of the B cell Ag receptor to avoid self-reactivity, whereas SLE B cells may have a defect in this mechanism. Indeed, we found that normal B cells edit A30-Jk2 gene in their genome possibly by inversion mechanism, whereas SLE B cells contain rearranged A30-Jk2-Ck gene in the genome and express A30-associated mRNA, suggesting that receptor editing mechanism is also defective in patients with SLE. Our study suggests that polymorphism of Ig Vk locus, and failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.

A Proposed Resident's Operative Case Tracking and Evaluation System.

PubMed

Sehli, Deema N; Esene, Ignatius N; Baeesa, Saleh S

2016-03-01

Neurosurgery program trainers are continuously searching for new methods to evaluate trainees' competency besides number of cases and training duration. Recently, efforts are made on the development of reliable methods to teach competency and valid methods to measure teaching efficacy. Herein, we propose the "Resident's Operative Case Tracking and Evaluation System" (ROCTES) for the assessment and monitoring of the resident's performance quality during each procedure. We developed a data-based website and smartphone application for neurosurgical attending physicians, residents, and resident review committees in our accredited neurosurgical institutions. ROCTES runs through five steps: Login (Resident), Case Entry, Login (Attending Physician), Case Approval and Evaluation, and Report. The Resident enters each case record under "Case Entry" field and can "save," "edit," or "submit" the case data to the Attending Physician. The latter from the attending physician login profile will be able to "approve and evaluate" the resident's "knowledge," "skills," and "attitude" ranking from 1 to 15 for that particular case; add his comments and then "save," "edit," or "submit" the data, which can be viewed by users as a "report." Program Directors can also "login" to monitor the resident's progress. The implementation of this communication tool should enable the filtering and retrieval of information needed for the better assessment and monitoring of residents' exposure to variety of cases in each training center. This proposed evaluation system will provide a transparent assessment for residency training programs and should convert trainees into competent neurosurgeons. Copyright © 2016 Elsevier Inc. All rights reserved.

Semi-automated ontology generation within OBO-Edit.

PubMed

Wächter, Thomas; Schroeder, Michael

2010-06-15

Ontologies and taxonomies have proven highly beneficial for biocuration. The Open Biomedical Ontology (OBO) Foundry alone lists over 90 ontologies mainly built with OBO-Edit. Creating and maintaining such ontologies is a labour-intensive, difficult, manual process. Automating parts of it is of great importance for the further development of ontologies and for biocuration. We have developed the Dresden Ontology Generator for Directed Acyclic Graphs (DOG4DAG), a system which supports the creation and extension of OBO ontologies by semi-automatically generating terms, definitions and parent-child relations from text in PubMed, the web and PDF repositories. DOG4DAG is seamlessly integrated into OBO-Edit. It generates terms by identifying statistically significant noun phrases in text. For definitions and parent-child relations it employs pattern-based web searches. We systematically evaluate each generation step using manually validated benchmarks. The term generation leads to high-quality terms also found in manually created ontologies. Up to 78% of definitions are valid and up to 54% of child-ancestor relations can be retrieved. There is no other validated system that achieves comparable results. By combining the prediction of high-quality terms, definitions and parent-child relations with the ontology editor OBO-Edit we contribute a thoroughly validated tool for all OBO ontology engineers. DOG4DAG is available within OBO-Edit 2.1 at http://www.oboedit.org. Supplementary data are available at Bioinformatics online.

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer

PubMed Central

Fu, Li; Qin, Yan-Ru; Ming, Xiao-Yan; Zuo, Xian-Bo; Diao, Yu-Wen; Zhang, Li-Yi; Ai, Jiaoyu; Liu, Bei-Lei; Huang, Tu-Xiong; Cao, Ting-Ting; Tan, Bin-Bin; Xiang, Di; Zeng, Chui-Mian; Gong, Jing; Zhang, Qiangfeng; Dong, Sui-Sui; Chen, Juan; Liu, Haibo; Wu, Jian-Lin; Qi, Robert Z.; Xie, Dan; Wang, Li-Dong

2017-01-01

Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3. Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals. PMID:28533408

[The indications of acupuncture-moxibustion in China state-compiled textbooks].

PubMed

Gang, Weijuan; Wu, Xiaodong; Wang, Fang; Wang, Xin

2017-03-12

The Acupuncture-moxibustion and Acupuncture-moxibustion therapy have been the state-compiled textbooks of acupuncture-moxibustion in colleges and universities of TCM for nearly more than half a century, which play a regulating and guiding role for acupuncture education and to a certain extent represent the development status of this discipline. The indications included in Acupuncture-moxibustion from 1th edition to 7th edition and Acupuncture-moxibustion therapy from 1th edition to 3rd edition were analyzed in this study, which was aimed to basically reflect the current situation of acupuncture indications. As a result, it was found the inheritance and innovation of indications were both reflected in each edition of textbooks, 1/3 of which occurred repeatedly in more than half of the textbooks, and 1/3 of which occurred only once. The indications were classified by internal medicine, surgery, gynecology, dermatology, orthopedics, etc., which were not consistent with system classification of modern medicine such as digestive system, respiratory system, etc. The indications were mainly named after TCM disease names, involving only several names of western medicine diseases, which were contradicted to the names adopted from journals and literature. This inconformity of classification method and naming method between TCM and western medicine was not only a difficulty for modern acupuncture and moxibustion, but also an essential factor to hinder the development of acupuncture, therefore comparative study was needed in the future.

Advances in the application of genetic manipulation methods to apicomplexan parasites.

PubMed

Suarez, C E; Bishop, R P; Alzan, H F; Poole, W A; Cooke, B M

2017-10-01

Apicomplexan parasites such as Babesia, Theileria, Eimeria, Cryptosporidium and Toxoplasma greatly impact animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular stages. Major gaps in our understanding of the biology of these relatively poorly characterised parasites and the diseases they cause severely limit options for designing novel control methods. Here we review potentially important shared aspects of the biology of these parasites, such as cell invasion, host cell modification, and asexual and sexual reproduction, and explore the potential of the application of relatively well-established or newly emerging genetic manipulation methods, such as classical transfection or gene editing, respectively, for closing important gaps in our knowledge of the function of specific genes and proteins, and the biology of these parasites. In addition, genetic manipulation methods impact the development of novel methods of control of the diseases caused by these economically important parasites. Transient and stable transfection methods, in conjunction with whole and deep genome sequencing, were initially instrumental in improving our understanding of the molecular biology of apicomplexan parasites and paved the way for the application of the more recently developed gene editing methods. The increasingly efficient and more recently developed gene editing methods, in particular those based on the CRISPR/Cas9 system and previous conceptually similar techniques, are already contributing to additional gene function discovery using reverse genetics and related approaches. However, gene editing methods are only possible due to the increasing availability of in vitro culture, transfection, and genome sequencing and analysis techniques. We envisage that rapid progress in the development of novel gene editing techniques applied to apicomplexan parasites of veterinary interest will ultimately lead to the development of novel and more efficient methods for disease control. Published by Elsevier Ltd.

DNA Editing of LTR Retrotransposons Reveals the Impact of APOBECs on Vertebrate Genomes

PubMed Central

Knisbacher, Binyamin A.; Levanon, Erez Y.

2016-01-01

Long terminal repeat retrotransposons (LTR) are widespread in vertebrates and their dynamism facilitates genome evolution. However, these endogenous retroviruses (ERVs) must be restricted to maintain genomic stability. The APOBECs, a protein family that can edit C-to-U in DNA, do so by interfering with reverse transcription and hypermutating retrotransposon DNA. In some cases, a retrotransposon may integrate into the genome despite being hypermutated. Such an event introduces a unique sequence into the genome, increasing retrotransposon diversity and the probability of developing new function at the locus of insertion. The prevalence of this phenomenon and its effects on vertebrate genomes are still unclear. In this study, we screened ERV sequences in the genomes of 123 diverse species and identified hundreds of thousands of edited sites in multiple vertebrate lineages, including placental mammals, marsupials, and birds. Numerous edited ERVs carry high mutation loads, some with greater than 350 edited sites, profoundly damaging their open-reading frames. For many of the species studied, this is the first evidence that APOBECs are active players in their innate immune system. Unexpectedly, some birds and especially zebra finch and medium ground-finch (one of Darwin’s finches) are exceptionally enriched in DNA editing. We demonstrate that edited retrotransposons may be preferentially retained in active genomic regions, as reflected from their enrichment in genes, exons, promoters, and transcription start sites, thereby raising the probability of their exaptation for novel function. In conclusion, DNA editing of retrotransposons by APOBECs has a substantial role in vertebrate innate immunity and may boost genome evolution. PMID:26541172

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

CERN Winter School on Supergravity, Strings, and Gauge Theory 2010

ScienceCinema

McAllister, Liam

2018-05-14

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series of pedagogical lectures, complemented by tutorial discussion sessions in the afternoons. Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher

CERN Winter School on Supergravity, Strings, and Gauge Theory 2010

ScienceCinema

None

2018-05-22

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series of pedagogical lectures, complemented by tutorial discussion sessions in the afternoons.Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher

CERN Winter School on Supergravity, Strings, and Gauge Theory 2010

ScienceCinema

None

2018-06-28

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series of pedagogical lectures, complemented by tutorial discussion sessions in the afternoons. Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher

CERN Winter School on Supergravity, Strings, and Gauge Theory 2010

ScienceCinema

None

2018-05-23

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series of pedagogical lectures, complemented by tutorial discussion sessions in the afternoons. Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher

CERN Winter School on Supergravity, Strings, and Gauge Theory 2010

ScienceCinema

None

2017-12-09

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series of pedagogical lectures, complemented by tutorial discussion sessions in the afternoons. Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher

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

None

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series ofmore » pedagogical lectures, complemented by tutorial discussion sessions in the afternoons.Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher« less

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

McAllister, Liam

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe";. The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series ofmore » pedagogical lectures, complemented by tutorial discussion sessions in the afternoons. Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions".This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde. Local organizers: A. Uranga, J. Walcher« less

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

McAllister, Liam

The CERN Winter School on Supergravity, Strings, and Gauge Theory is the analytic continuation of the yearly training school of the former EC-RTN string network "Constituents, Fundamental Forces and Symmetries of the Universe". The 2010 edition of the school is supported and organized by the CERN Theory Divison, and will take place from Monday January 25 to Friday January 29, at CERN. As its predecessors, this school is meant primarily for training of doctoral students and young postdoctoral researchers in recent developments in theoretical high-energy physics and string theory. The programme of the school will consist of five series ofmore » pedagogical lectures, complemented by tutorial discussion sessions in the afternoons. Previous schools in this series were organized in 2005 at SISSA in Trieste, and in 2006, 2007, 2008, and 2009 at CERN, Geneva. Other similar schools have been organized in the past by the former related RTN network "The Quantum Structure of Spacetime and the Geometric Nature of Fundamental Interactions". This edition of the school is not funded by the European Union. The school is funded by the CERN Theory Division, and the Arnold Sommerfeld Center at Ludwig-Maximilians University of Munich. Scientific committee: M. Gaberdiel, D. Luest, A. Sevrin, J. Simon, K. Stelle, S. Theisen, A. Uranga, A. Van Proeyen, E. Verlinde Local organizers: A. Uranga, J. Walcher« less