Sample records for safety codes ipsc

  1. Nuclear Energy Advanced Modeling and Simulation (NEAMS) Waste Integrated Performance and Safety Codes (IPSC) : FY10 development and integration.

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

    Criscenti, Louise Jacqueline; Sassani, David Carl; Arguello, Jose Guadalupe, Jr.

    2011-02-01

    This report describes the progress in fiscal year 2010 in developing the Waste Integrated Performance and Safety Codes (IPSC) in support of the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The goal of the Waste IPSC is to develop an integrated suite of computational modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs,more » and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. Waste IPSC activities in fiscal year 2010 focused on specifying a challenge problem to demonstrate proof of concept, developing a verification and validation plan, and performing an initial gap analyses to identify candidate codes and tools to support the development and integration of the Waste IPSC. The current Waste IPSC strategy is to acquire and integrate the necessary Waste IPSC capabilities wherever feasible, and develop only those capabilities that cannot be acquired or suitably integrated, verified, or validated. This year-end progress report documents the FY10 status of acquisition, development, and integration of thermal-hydrologic-chemical-mechanical (THCM) code capabilities, frameworks, and enabling tools and infrastructure.« less

  2. Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC) : gap analysis for high fidelity and performance assessment code development.

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

    Lee, Joon H.; Siegel, Malcolm Dean; Arguello, Jose Guadalupe, Jr.

    2011-03-01

    This report describes a gap analysis performed in the process of developing the Waste Integrated Performance and Safety Codes (IPSC) in support of the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The goal of the Waste IPSC is to develop an integrated suite of computational modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repositorymore » designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with rigorous verification, validation, and software quality requirements. The gap analyses documented in this report were are performed during an initial gap analysis to identify candidate codes and tools to support the development and integration of the Waste IPSC, and during follow-on activities that delved into more detailed assessments of the various codes that were acquired, studied, and tested. The current Waste IPSC strategy is to acquire and integrate the necessary Waste IPSC capabilities wherever feasible, and develop only those capabilities that cannot be acquired or suitably integrated, verified, or validated. The gap analysis indicates that significant capabilities may already exist in the existing THC codes although there is no single code able to fully account for all physical and chemical processes involved in a waste disposal system. Large gaps exist in modeling chemical processes and their couplings with other processes. The coupling of chemical processes with flow transport and mechanical deformation remains challenging. The data for extreme environments (e.g., for elevated temperature and high ionic strength media) that

  3. Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC).

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

    Schultz, Peter Andrew

    The objective of the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC) is to provide an integrated suite of computational modeling and simulation (M&S) capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. Achieving the objective of modeling the performance of a disposal scenario requires describing processes involved in waste form degradation and radionuclide release at the subcontinuum scale, beginning with mechanistic descriptions of chemical reactions and chemical kinetics at the atomicmore » scale, and upscaling into effective, validated constitutive models for input to high-fidelity continuum scale codes for coupled multiphysics simulations of release and transport. Verification and validation (V&V) is required throughout the system to establish evidence-based metrics for the level of confidence in M&S codes and capabilities, including at the subcontiunuum scale and the constitutive models they inform or generate. This Report outlines the nature of the V&V challenge at the subcontinuum scale, an approach to incorporate V&V concepts into subcontinuum scale modeling and simulation (M&S), and a plan to incrementally incorporate effective V&V into subcontinuum scale M&S destined for use in the NEAMS Waste IPSC work flow to meet requirements of quantitative confidence in the constitutive models informed by subcontinuum scale phenomena.« less

  4. iPSCs, aging and age-related diseases.

    PubMed

    Isobe, Ken-Ichi; Cheng, Zhao; Nishio, Naomi; Suganya, Thanasegan; Tanaka, Yuriko; Ito, Sachiko

    2014-09-25

    Human histocompatibility antigens are quite heterogeneous and promote the rejection of transplanted tissue. Recent advances in stem cell research that enable the use of a patient's own stem cells for transplantation are very important because rejection could be avoided. In particular, Yamanaka's group in Japan gave new hope to patients with incurable diseases when they developed induced murine pluripotent stem cells (iPSCs) in 2006 and human iPSCs in 2007. Whereas embryonic stem cells (ESCs) are derived from the inner cell mass and are supported in culture by LIF, iPSCs are derived from fetal or adult somatic cells. Through the application of iPSC technology, adult somatic cells can develop a pluripotent state. One advantage of using iPSCs instead of ESCs in regenerative medicine is that (theoretically) immune rejection could be avoided, although there is some debate about immune rejection of a patient's own iPSCs. Many diseases occur in elderly patients. In order to use regenerative medicine with the elderly, it is important to demonstrate that iPSCs can indeed be generated from older patients. Recent findings have shown that iPSCs can be established from aged mice and aged humans. These iPSCs can differentiate to cells from all three germ layers. However, it is not known whether iPSCs from aged mice or humans show early senescence. Before clinical use of iPSCs, issues related to copy number variation, tumorigenicity and immunogenicity must be resolved. It is particularly important that researchers have succeeded in generating iPSCs that have differentiated to somatic cells related to specific diseases of the elderly, including atherosclerosis, diabetes, Alzheimer's disease and Parkinson's disease. These efforts will facilitate the use of personalized stem cell transplantation therapy for currently incurable diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Reprint of "iPSCs, aging and age-related diseases".

    PubMed

    Isobe, Ken-ichi; Cheng, Zhao; Nishio, Naomi; Suganya, Thanasegan; Tanaka, Yuriko; Ito, Sachiko

    2015-01-25

    Human histocompatibility antigens are quite heterogeneous and promote the rejection of transplanted tissue. Recent advances in stem cell research that enable the use of a patient's own stem cells for transplantation are very important because rejection could be avoided. In particular, Yamanaka’s group in Japan gave new hope to patients with incurable diseases when they developed induced murine pluripotent stem cells (iPSCs) in 2006 and human iPSCs in 2007. Whereas embryonic stem cells (ESCs) are derived from the inner cell mass and are supported in culture by LIF, iPSCs are derived from fetal or adult somatic cells. Through the application of iPSC technology, adult somatic cells can develop a pluripotent state. One advantage of using iPSCs instead of ESCs in regenerative medicine is that (theoretically) immune rejection could be avoided, although there is some debate about immune rejection of a patient's own iPSCs. Many diseases occur in elderly patients. In order to use regenerative medicine with the elderly, it is important to demonstrate that iPSCs can indeed be generated from older patients. Recent findings have shown that iPSCs can be established from aged mice and aged humans. These iPSCs can differentiate to cells from all three germ layers. However, it is not known whether iPSCs from aged mice or humans show early senescence. Before clinical use of iPSCs, issues related to copy number variation, tumorigenicity and immunogenicity must be resolved. It is particularly important that researchers have succeeded in generating iPSCs that have differentiated to somatic cells related to specific diseases of the elderly, including atherosclerosis, diabetes, Alzheimer's disease and Parkinson's disease. These efforts will facilitate the use of personalized stem cell transplantation therapy for currently incurable diseases.

  6. Global synchronization algorithms for the Intel iPSC/860

    NASA Technical Reports Server (NTRS)

    Seidel, Steven R.; Davis, Mark A.

    1992-01-01

    In a distributed memory multicomputer that has no global clock, global processor synchronization can only be achieved through software. Global synchronization algorithms are used in tridiagonal systems solvers, CFD codes, sequence comparison algorithms, and sorting algorithms. They are also useful for event simulation, debugging, and for solving mutual exclusion problems. For the Intel iPSC/860 in particular, global synchronization can be used to ensure the most effective use of the communication network for operations such as the shift, where each processor in a one-dimensional array or ring concurrently sends a message to its right (or left) neighbor. Three global synchronization algorithms are considered for the iPSC/860: the gysnc() primitive provided by Intel, the PICL primitive sync0(), and a new recursive doubling synchronization (RDS) algorithm. The performance of these algorithms is compared to the performance predicted by communication models of both the long and forced message protocols. Measurements of the cost of shift operations preceded by global synchronization show that the RDS algorithm always synchronizes the nodes more precisely and costs only slightly more than the other two algorithms.

  7. Common genetic variation drives molecular heterogeneity in human iPSCs

    PubMed Central

    Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard

    2017-01-01

    Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. PMID:28489815

  8. Alternative Fuels Data Center: Biodiesel Codes, Standards, and Safety

    Science.gov Websites

    Codes, Standards, and Safety to someone by E-mail Share Alternative Fuels Data Center: Biodiesel Codes, Standards, and Safety on Facebook Tweet about Alternative Fuels Data Center: Biodiesel Codes , Standards, and Safety on Twitter Bookmark Alternative Fuels Data Center: Biodiesel Codes, Standards, and

  9. Engineering-derived approaches for iPSC preparation, expansion, differentiation and applications.

    PubMed

    Li, Yang; Li, Ling; Chen, Zhi-Nan; Gao, Ge; Yao, Rui; Sun, Wei

    2017-07-31

    Remarkable achievements have been made since induced pluripotent stem cells (iPSCs) were first introduced in 2006. Compared with non-pluripotent stem cells, iPSC research faces several additional complexities, such as the choice of extracellular matrix proteins, growth and differentiation factors, as well as technical challenges related to self-renewal and directed differentiation. Overcoming these challenges requires the integration of knowledge and technologies from multiple fields including cell biology, biomaterial science, engineering, physics and medicine. Here, engineering-derived iPSC approaches are reviewed according to three aspects of iPSC studies: preparation, expansion, differentiation and applications. Engineering strategies, such as 3D systems establishment, cell-matrix mechanics and the regulation of biophysical and biochemical cues, together with engineering techniques, such as 3D scaffolds, cell microspheres and bioreactors, have been applied to iPSC studies and have generated insightful results and even mini-organs such as retinas, livers and intestines. Specific results are given to demonstrate how these approaches impact iPSC behavior, and related mechanisms are discussed. In addition, cell printing technologies are presented as an advanced engineering-derived approach since they have been applied in both iPSC studies and the construction of diverse tissues and organs. Further development and possible innovations of cell printing technologies are presented in terms of creating complex and functional iPSC-derived living tissues and organs.

  10. 38 CFR 61.20 - Life Safety Code capital grants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Life Safety Code capital... (CONTINUED) VA HOMELESS PROVIDERS GRANT AND PER DIEM PROGRAM § 61.20 Life Safety Code capital grants. (a) This section sets forth provisions for obtaining a Life Safety Code capital grant under 38 U.S.C. 2012...

  11. 38 CFR 61.20 - Life Safety Code capital grants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Life Safety Code capital... (CONTINUED) VA HOMELESS PROVIDERS GRANT AND PER DIEM PROGRAM § 61.20 Life Safety Code capital grants. (a) This section sets forth provisions for obtaining a Life Safety Code capital grant under 38 U.S.C. 2012...

  12. 38 CFR 61.20 - Life Safety Code capital grants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Life Safety Code capital... (CONTINUED) VA HOMELESS PROVIDERS GRANT AND PER DIEM PROGRAM § 61.20 Life Safety Code capital grants. (a) This section sets forth provisions for obtaining a Life Safety Code capital grant under 38 U.S.C. 2012...

  13. Synthesizing Safety Conditions for Code Certification Using Meta-Level Programming

    NASA Technical Reports Server (NTRS)

    Eusterbrock, Jutta

    2004-01-01

    In code certification the code consumer publishes a safety policy and the code producer generates a proof that the produced code is in compliance with the published safety policy. In this paper, a novel viewpoint approach towards an implementational re-use oriented framework for code certification is taken. It adopts ingredients from Necula's approach for proof-carrying code, but in this work safety properties can be analyzed on a higher code level than assembly language instructions. It consists of three parts: (1) The specification language is extended to include generic pre-conditions that shall ensure safety at all states that can be reached during program execution. Actual safety requirements can be expressed by providing domain-specific definitions for the generic predicates which act as interface to the environment. (2) The Floyd-Hoare inductive assertion method is refined to obtain proof rules that allow the derivation of the proof obligations in terms of the generic safety predicates. (3) A meta-interpreter is designed and experimentally implemented that enables automatic synthesis of proof obligations for submitted programs by applying the modified Floyd-Hoare rules. The proof obligations have two separate conjuncts, one for functional correctness and another for the generic safety obligations. Proof of the generic obligations, having provided the actual safety definitions as context, ensures domain-specific safety of program execution in a particular environment and is simpler than full program verification.

  14. An Overview of Direct Somatic Reprogramming: The Ins and Outs of iPSCs

    PubMed Central

    Menon, Siddharth; Shailendra, Siny; Renda, Andrea; Longaker, Michael; Quarto, Natalina

    2016-01-01

    Stem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine. The breakthrough of iPSCs has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. iPSCs are also relevant tools for modeling human diseases and drugs screening. However, there are still several hurdles to overcome before iPSCs can be used for translational purposes. Here, we review the recent advances in somatic reprogramming and the challenges that must be overcome to move this strategy closer to clinical application. PMID:26805822

  15. Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

    PubMed

    Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

    2016-12-08

    The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

  16. A performance study of sparse Cholesky factorization on INTEL iPSC/860

    NASA Technical Reports Server (NTRS)

    Zubair, M.; Ghose, M.

    1992-01-01

    The problem of Cholesky factorization of a sparse matrix has been very well investigated on sequential machines. A number of efficient codes exist for factorizing large unstructured sparse matrices. However, there is a lack of such efficient codes on parallel machines in general, and distributed machines in particular. Some of the issues that are critical to the implementation of sparse Cholesky factorization on a distributed memory parallel machine are ordering, partitioning and mapping, load balancing, and ordering of various tasks within a processor. Here, we focus on the effect of various partitioning schemes on the performance of sparse Cholesky factorization on the Intel iPSC/860. Also, a new partitioning heuristic for structured as well as unstructured sparse matrices is proposed, and its performance is compared with other schemes.

  17. Cellular trajectories and molecular mechanisms of iPSC reprogramming.

    PubMed

    Apostolou, Effie; Stadtfeld, Matthias

    2018-06-16

    The discovery of induced pluripotent stem cells (iPSCs) has solidified the concept of transcription factors as major players in controlling cell identity and provided a tractable tool to study how somatic cell identity can be dismantled and pluripotency established. A number of landmark studies have established hallmarks and roadmaps of iPSC formation by describing relative kinetics of transcriptional, protein and epigenetic changes, including alterations in DNA methylation and histone modifications. Recently, technological advancements such as single-cell analyses, high-resolution genome-wide chromatin assays and more efficient reprogramming systems have been used to challenge and refine our understanding of the reprogramming process. Here, we will outline novel insights into the molecular mechanisms underlying iPSC formation, focusing on how the core reprogramming factors OCT4, KLF4, SOX2 and MYC (OKSM) drive changes in gene expression, chromatin state and 3D genome topology. In addition, we will discuss unexpected consequences of reprogramming factor expression in in vitro and in vivo systems that may point towards new applications of iPSC technology. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Highway Safety Program Manual: Volume 6: Codes and Laws.

    ERIC Educational Resources Information Center

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    Volume 6 of the 19-volume Highway Safety Program Manual (which provides guidance to State and local governments on preferred safety practices) concentrates on codes and laws. The purpose and specific objectives of the Codes and Laws Program, Federal authority in the area of highway safety, and policies regarding traffic regulation are described.…

  19. 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

  20. Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation.

    PubMed

    Paes, Bárbara Cristina Martins Fernandes; Moço, Pablo Diego; Pereira, Cristiano Gonçalves; Porto, Geciane Silveira; de Sousa Russo, Elisa Maria; Reis, Luiza Cunha Junqueira; Covas, Dimas Tadeu; Picanço-Castro, Virginia

    2017-06-01

    Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation for cell therapy purpose and other clinical applications. This review provides a perspective on the iPSC potential for cell therapies, particularly for hematological applications. We discuss the advances in in vitro hematopoietic differentiation, the possibilities to employ iPSC in hematology studies, and their potential clinical application in hematologic diseases. The generation of red blood cells and functional T cells and the genome editing technology applied to mutation correction are also covered. We highlight some of the requirements and obstacles to be overcome before translating these cells from research to the clinic, for instance, iPSC variability, genotoxicity, the differentiation process, and engraftment. Also, we evaluate the patent landscape and compile the clinical trials in the field of pluripotent stem cells. Currently, we know much more about iPSC than in 2006, but there are still challenges that must be solved. A greater understanding of molecular mechanisms underlying the generation of hematopoietic stem cells is necessary to produce suitable and transplantable hematopoietic stem progenitor cells from iPSC.

  1. Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel.

    PubMed

    Chien, Yueh; Liao, Yi-Wen; Liu, Dean-Mo; Lin, Heng-Liang; Chen, Shih-Jen; Chen, Hen-Li; Peng, Chi-Hsien; Liang, Chang-Min; Mou, Chung-Yuan; Chiou, Shih-Hwa

    2012-11-01

    Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but whether iPSCs can promote corneal reconstruction remains undetermined. In this study, we successfully reprogrammed human corneal keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were cultured onto a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the availability of iPSCs as bioengineered substitutes in corneal repair, we developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel and found that such gel increased the viability and CD44+proportion of iPSCs, and maintained their stem-cell like gene expression, in the presence of culture media. Combined treatment of iPSC with CHC hydrogel (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced corneal reconstruction by downregulating oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Humanity in a Dish: Population Genetics with iPSCs.

    PubMed

    Warren, Curtis R; Cowan, Chad A

    2018-01-01

    Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype. Recent publications have described iPSC cohort studies of common genetic variants and their effects on gene expression and cellular phenotypes. These in vitro quantitative trait locus (QTL) studies are the first experiments in a new paradigm with great potential: iPSC-based functional population genetic studies. iPSC collections from large cohorts are currently under development to facilitate the next wave of these studies, which have the potential to discover the effects of common genetic variants on cellular phenotypes and to uncover the molecular basis of common genetic diseases. Here, we describe the recent advances in this developing field, and provide a road map for future in vitro functional population genetic studies and trial-in-a-dish experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. SAFETY IN THE DESIGN OF SCIENCE LABORATORIES AND BUILDING CODES.

    ERIC Educational Resources Information Center

    HOROWITZ, HAROLD

    THE DESIGN OF COLLEGE AND UNIVERSITY BUILDINGS USED FOR SCIENTIFIC RESEARCH AND EDUCATION IS DISCUSSED IN TERMS OF LABORATORY SAFETY AND BUILDING CODES AND REGULATIONS. MAJOR TOPIC AREAS ARE--(1) SAFETY RELATED DESIGN FEATURES OF SCIENCE LABORATORIES, (2) LABORATORY SAFETY AND BUILDING CODES, AND (3) EVIDENCE OF UNSAFE DESIGN. EXAMPLES EMPHASIZE…

  4. Modeling high-temperature superconductors and metallic alloys on the Intel IPSC/860

    NASA Astrophysics Data System (ADS)

    Geist, G. A.; Peyton, B. W.; Shelton, W. A.; Stocks, G. M.

    Oak Ridge National Laboratory has embarked on several computational Grand Challenges, which require the close cooperation of physicists, mathematicians, and computer scientists. One of these projects is the determination of the material properties of alloys from first principles and, in particular, the electronic structure of high-temperature superconductors. While the present focus of the project is on superconductivity, the approach is general enough to permit study of other properties of metallic alloys such as strength and magnetic properties. This paper describes the progress to date on this project. We include a description of a self-consistent KKR-CPA method, parallelization of the model, and the incorporation of a dynamic load balancing scheme into the algorithm. We also describe the development and performance of a consolidated KKR-CPA code capable of running on CRAYs, workstations, and several parallel computers without source code modification. Performance of this code on the Intel iPSC/860 is also compared to a CRAY 2, CRAY YMP, and several workstations. Finally, some density of state calculations of two perovskite superconductors are given.

  5. Police accident report forms: safety device coding and enacted laws.

    PubMed

    Brock, K; Lapidus, G

    2008-12-01

    Safety device coding on state police accident report (PAR) forms was compared with provisions in state traffic safety laws. PAR forms were obtained from all 50 states and the District of Columbia (states/DC). For seat belts, 22 states/DC had a primary seat belt enforcement law vs 50 with a PAR code. For car seats, all 51 states/DC had a law and a PAR code. For booster seats, 39 states/DC had a law vs nine with a PAR code. For motorcycle helmets, 21 states/DC had an all-age rider helmet law and another 26 a partial-age law vs 50 with a PAR code. For bicycle helmets, 21 states/DC had a partial-age rider helmet law vs 48 with a PAR code. Therefore gaps in the ability of states to fully record accident data reflective of existing state traffic safety laws are revealed. Revising the PAR forms in all states to include complete variables for safety devices should be an important priority, independent of the laws.

  6. In situ genetic correction of F8 intron 22 inversion in hemophilia A patient-specific iPSCs

    PubMed Central

    Wu, Yong; Hu, Zhiqing; Li, Zhuo; Pang, Jialun; Feng, Mai; Hu, Xuyun; Wang, Xiaolin; Lin-Peng, Siyuan; Liu, Bo; Chen, Fangping; Wu, Lingqian; Liang, Desheng

    2016-01-01

    Nearly half of severe Hemophilia A (HA) cases are caused by F8 intron 22 inversion (Inv22). This 0.6-Mb inversion splits the 186-kb F8 into two parts with opposite transcription directions. The inverted 5′ part (141 kb) preserves the first 22 exons that are driven by the intrinsic F8 promoter, leading to a truncated F8 transcript due to the lack of the last 627 bp coding sequence of exons 23–26. Here we describe an in situ genetic correction of Inv22 in patient-specific induced pluripotent stem cells (iPSCs). By using TALENs, the 627 bp sequence plus a polyA signal was precisely targeted at the junction of exon 22 and intron 22 via homologous recombination (HR) with high targeting efficiencies of 62.5% and 52.9%. The gene-corrected iPSCs retained a normal karyotype following removal of drug selection cassette using a Cre-LoxP system. Importantly, both F8 transcription and FVIII secretion were rescued in the candidate cell types for HA gene therapy including endothelial cells (ECs) and mesenchymal stem cells (MSCs) derived from the gene-corrected iPSCs. This is the first report of an efficient in situ genetic correction of the large inversion mutation using a strategy of targeted gene addition. PMID:26743572

  7. In situ genetic correction of F8 intron 22 inversion in hemophilia A patient-specific iPSCs.

    PubMed

    Wu, Yong; Hu, Zhiqing; Li, Zhuo; Pang, Jialun; Feng, Mai; Hu, Xuyun; Wang, Xiaolin; Lin-Peng, Siyuan; Liu, Bo; Chen, Fangping; Wu, Lingqian; Liang, Desheng

    2016-01-08

    Nearly half of severe Hemophilia A (HA) cases are caused by F8 intron 22 inversion (Inv22). This 0.6-Mb inversion splits the 186-kb F8 into two parts with opposite transcription directions. The inverted 5' part (141 kb) preserves the first 22 exons that are driven by the intrinsic F8 promoter, leading to a truncated F8 transcript due to the lack of the last 627 bp coding sequence of exons 23-26. Here we describe an in situ genetic correction of Inv22 in patient-specific induced pluripotent stem cells (iPSCs). By using TALENs, the 627 bp sequence plus a polyA signal was precisely targeted at the junction of exon 22 and intron 22 via homologous recombination (HR) with high targeting efficiencies of 62.5% and 52.9%. The gene-corrected iPSCs retained a normal karyotype following removal of drug selection cassette using a Cre-LoxP system. Importantly, both F8 transcription and FVIII secretion were rescued in the candidate cell types for HA gene therapy including endothelial cells (ECs) and mesenchymal stem cells (MSCs) derived from the gene-corrected iPSCs. This is the first report of an efficient in situ genetic correction of the large inversion mutation using a strategy of targeted gene addition.

  8. Complete exchange on the iPSC-860

    NASA Technical Reports Server (NTRS)

    Bokhari, Shahid H.

    1991-01-01

    The implementation of complete exchange on the circuit switched Intel iPSC-860 hypercube is described. This pattern, also known as all-to-all personalized communication, is the densest requirement that can be imposed on a network. On the iPSC-860, care needs to be taken to avoid edge contention, which can have a disastrous impact on communication time. There are basically two classes of algorithms that achieve contention-free complete exchange. The first contains the classical standard exchange algorithm that is generally useful for small message sizes. The second includes a number of optimal or near-optimal algorithms that are best for large messages. Measurement of communication overhead on the iPSC-860 are given and a notation for analyzing communication link usage is developed. It is shown that for the two classes of algorithms, there is substantial variation in performance with synchronization technique and choice of message protocol. Timings of six implementations are given; each of these is useful over a particular range of message size and cube dimension. Since the complete exchange is a superset of communication patterns, these timings represent upper bounds on the time required by an arbitrary communication requirement. These results indicate that the programmer needs to evaluate several possibilities before finalizing an implementation - a careful choice can lead to very significant savings in time.

  9. Transgene-free iPSCs generated from small volume peripheral blood nonmobilized CD34+ cells

    PubMed Central

    Merling, Randall K.; Sweeney, Colin L.; Choi, Uimook; De Ravin, Suk See; Myers, Timothy G.; Otaizo-Carrasquero, Francisco; Pan, Jason; Linton, Gilda; Chen, Lifeng; Koontz, Sherry; Theobald, Narda L.; Malech, Harry L.

    2013-01-01

    A variety of somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs), but CD34+ hematopoietic stem cells (HSCs) present in nonmobilized peripheral blood (PB) would be a convenient target. We report a method for deriving iPSC from PB HSCs using immunobead purification and 2- to 4-day culture to enrich CD34+ HSCs to 80% ± 9%, followed by reprogramming with loxP-flanked polycistronic (human Oct4, Klf4, Sox2, and c-Myc) STEMCCA-loxP lentivector, or with Sendai vectors. Colonies arising with STEMCCA-loxP were invariably TRA-1-60+, yielding 5.3 ± 2.8 iPSC colonies per 20 mL PB (n = 17), where most colonies had single-copy STEMCCA-loxP easily excised by transient Cre expression. Colonies arising with Sendai were variably reprogrammed (10%-80% TRA-1-60+), with variable yield (6 to >500 TRA-1-60+ iPSC colonies per 10 mL blood; n = 6). Resultant iPSC clones expressed pluripotent cell markers and generated teratomas. Genomic methylation patterns of STEMCCA-loxP–reprogrammed clones closely matched embryonic stem cells. Furthermore, we showed that iPSCs are derived from the nonmobilized CD34+ HSCs enriched from PB rather than from any lymphocyte or monocyte contaminants because they lack somatic rearrangements typical of T or B lymphocytes and because purified CD14+ monocytes do not yield iPSC colonies under these reprogramming conditions. PMID:23386128

  10. Disease modeling and cell based therapy with iPSC: future therapeutic option with fast and safe application.

    PubMed

    Kim, Changsung

    2014-03-01

    Induced pluripotent stem cell (iPSC) technology has shown us great hope to treat various human diseases which have been known as untreatable and further endows personalized medicine for future therapy without ethical issues and immunological rejection which embryonic stem cell (hES) treatment has faced. It has been agreed that iPSCs knowledge can be harnessed from disease modeling which mimics human pathological development rather than trials utilizing conventional rodent and cell lines. Now, we can routinely generate iPSC from patient specific cell sources, such as skin fibroblast, hair follicle cells, patient blood samples and even urine containing small amount of epithelial cells. iPSC has both similarity and dissimilarity to hES. iPSC is similar enough to regenerate tissue and even full organism as ES does, however what we want for therapeutic advantage is limited to regenerated tissue and lineage specific differentiation. Depending on the lineage and type of cells, both tissue memory containing (DNA rearrangement/epigenetics) and non-containing iPSC can be generated. This makes iPSC even better choice to perform disease modeling as well as cell based therapy. Tissue memory containing iPSC from mature leukocytes would be beneficial for curing cancer and infectious disease. In this review, the benefit of iPSC for translational approaches will be presented.

  11. 29 CFR 1915.90 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Safety color code for marking physical hazards. 1915.90 Section 1915.90 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... General Working Conditions § 1915.90 Safety color code for marking physical hazards. The requirements...

  12. 29 CFR 1915.90 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Safety color code for marking physical hazards. 1915.90 Section 1915.90 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... General Working Conditions § 1915.90 Safety color code for marking physical hazards. The requirements...

  13. 29 CFR 1915.90 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Safety color code for marking physical hazards. 1915.90 Section 1915.90 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... General Working Conditions § 1915.90 Safety color code for marking physical hazards. The requirements...

  14. Senescence-associated ultrastructural features of long-term cultures of induced pluripotent stem cells (iPSCs)

    PubMed Central

    Colasuonno, Fiorella; Borghi, Rossella; Niceforo, Alessia; Muzzi, Maurizio; Bertini, Enrico; Di Giulio, Andrea

    2017-01-01

    Induced pluripotent stem cells (iPSCs) hold great promise for developing personalized regenerative medicine, however characterization of their biological features is still incomplete. Moreover, changes occurring in long-term cultured iPSCs have been reported, suggesting these as a model of cellular aging. For this reason, we addressed the ultrastructural characterization of iPSCs, with a focus on possible time-dependent changes, involving specific cell compartments. To this aim, we comparatively analysed cultures at different timepoints, by an innovative electron microscopic technology (FIB/SEM). We observed progressive loss of cell-to-cell contacts, associated with increased occurrence of exosomes. Mitochondria gradually increased, while acquiring an elongated shape, with well-developed cristae. Such mitochondrial maturation was accompanied by their turnover, as assessed by the presence of autophagomes (undetectable in young iPSCs), some containing recognizable mitochondria. This finding was especially frequent in middle-aged iPSCs, while being occasional in aged cells, suggesting early autophagic activation followed by a decreased efficiency of the process with culturing time. Accordingly, confocal microscopy showed age-dependent alterations to the expression and distribution of autophagic markers. Interestingly, responsivity to rapamycin, highest in young iPSCs, was almost lost in aged cells. Overall, our results strongly support long-term cultured iPSCs as a model for studying relevant aspects of cellular senescence, involving intercellular communication, energy metabolism, and autophagy. PMID:29064821

  15. The European General Data Protection Regulation: challenges and considerations for iPSC researchers and biobanks

    PubMed Central

    Morrison, Michael; Bell, Jessica; George, Carol; Harmon, Shawn; Munsie, Megan; Kaye, Jane

    2017-01-01

    Increasingly, human induced pluripotent stem cells (iPSC) and their associated genetic and clinical information are being used in a wide range of applications, with large biobanks being established to support and increase their scientific use. The new European General Data Protection Regulations, which comes into effect in 2018, will have implications for biobanks that generate, store and allow research access to iPSC. This paper describes some of the challenges that iPSC biobanks face and suggests some points for the development of appropriate governance structures to address these new requirements. These suggestions also have implications for iPSC research in general. PMID:28976812

  16. The dynamics of synchronized neurotransmitter release determined from compound spontaneous IPSCs in rat dentate granule neurones in vitro

    PubMed Central

    Williams, Stephen R; Buhl, Eberhard H; Mody, Istvan

    1998-01-01

    The properties of GABAA receptor-mediated spontaneous IPSCs generated in hippocampal dentate granule neurones were analysed using whole-cell voltage-clamp techniques in order to explore the functional consequences of the low number (6–12) and close proximity of synaptic contacts made by single GABAergic interneurones. Spontaneous IPSCs (sIPSCs) occurred with a frequency of 14.0 ± 9.1 Hz (n = 31) and revealed a multi-modal positively skewed amplitude distribution (39.0 ± 19.8 pA, median values). The variance of 10–90 % rise times and decay kinetics between IPSCs decreased with increasing peak amplitude. Larger amplitude events had significantly faster rise times, consistent with their site of generation being proximal to the soma. The decay kinetics of sIPSCs did not significantly change with amplitude. Large amplitude sIPSCs occurred singularly or in discrete bursts, repeated regularly at low frequency. The rising phase of such sIPSCs were multi-phasic, composed of clear step-like inflections that were not a product of noise. The variability between the rising phase of individual sIPSCs was quantified by calculating their standard deviation, which produced fast rising (0.22 ± 0.05 ms time to peak, n = 16) functions with half-widths of 0.38 ± 0.10 ms, which declined to plateaux. Computer simulations demonstrated that IPSCs with properties similar to those recorded experimentally could be generated by the linear summation of groups of temporally dispersed component events. Standard deviation functions of the rising phase of simulated IPSCs accurately described distributions of the temporal dispersion of unitary components. The GABA uptake inhibitor (R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-enl-yl] nipecotic acid (tiagabine) (10 μM, n = 12) significantly prolonged the decay of mIPSCs (6.5 ± 0.8 to 8.7 ± 1.0 ms, median values) and sIPSCs (6.2 ± 0.4 to 7.3 ± 1.2 ms, median values), but failed to alter the frequency of occurrence, 10–90 % rise times or peak

  17. Conserved expression of transposon-derived non-coding transcripts in primate stem cells.

    PubMed

    Ramsay, LeeAnn; Marchetto, Maria C; Caron, Maxime; Chen, Shu-Huang; Busche, Stephan; Kwan, Tony; Pastinen, Tomi; Gage, Fred H; Bourque, Guillaume

    2017-02-28

    A significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs). Moreover, it has been shown that various long non-coding RNAs (lncRNAs), which come from the human endogenous retrovirus subfamily H (HERVH), are not only expressed but required for pluripotency in human embryonic stem cells (hESCs). To identify additional TE-derived functional non-coding transcripts, we generated RNA-seq data from induced pluripotent stem cells (iPSCs) of four primate species (human, chimpanzee, gorilla, and rhesus) and searched for transcripts whose expression was conserved. We observed that about 30% of TE instances expressed in human iPSCs had orthologous TE instances that were also expressed in chimpanzee and gorilla. Notably, our analysis revealed a number of repeat families with highly conserved expression profiles including HERVH but also MER53, which is known to be the source of a placental-specific family of microRNAs (miRNAs). We also identified a number of repeat families from all classes of TEs, including MLT1-type and Tigger families, that contributed a significant amount of sequence to primate lncRNAs whose expression was conserved. Together, these results describe TE families and TE-derived lncRNAs whose conserved expression patterns can be used to identify what are likely functional TE-derived non-coding transcripts in primate iPSCs.

  18. 7 CFR 1724.50 - Compliance with National Electrical Safety Code (NESC).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 11 2013-01-01 2013-01-01 false Compliance with National Electrical Safety Code (NESC... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC ENGINEERING, ARCHITECTURAL SERVICES AND DESIGN POLICIES AND PROCEDURES Electric System Design § 1724.50 Compliance with National Electrical Safety Code...

  19. 7 CFR 1724.50 - Compliance with National Electrical Safety Code (NESC).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Compliance with National Electrical Safety Code (NESC... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC ENGINEERING, ARCHITECTURAL SERVICES AND DESIGN POLICIES AND PROCEDURES Electric System Design § 1724.50 Compliance with National Electrical Safety Code...

  20. 7 CFR 1724.50 - Compliance with National Electrical Safety Code (NESC).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 11 2011-01-01 2011-01-01 false Compliance with National Electrical Safety Code (NESC... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC ENGINEERING, ARCHITECTURAL SERVICES AND DESIGN POLICIES AND PROCEDURES Electric System Design § 1724.50 Compliance with National Electrical Safety Code...

  1. 7 CFR 1724.50 - Compliance with National Electrical Safety Code (NESC).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 11 2012-01-01 2012-01-01 false Compliance with National Electrical Safety Code (NESC... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC ENGINEERING, ARCHITECTURAL SERVICES AND DESIGN POLICIES AND PROCEDURES Electric System Design § 1724.50 Compliance with National Electrical Safety Code...

  2. 7 CFR 1724.50 - Compliance with National Electrical Safety Code (NESC).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 11 2014-01-01 2014-01-01 false Compliance with National Electrical Safety Code (NESC... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC ENGINEERING, ARCHITECTURAL SERVICES AND DESIGN POLICIES AND PROCEDURES Electric System Design § 1724.50 Compliance with National Electrical Safety Code...

  3. From iPSC towards cardiac tissue-a road under construction.

    PubMed

    Peischard, Stefan; Piccini, Ilaria; Strutz-Seebohm, Nathalie; Greber, Boris; Seebohm, Guiscard

    2017-10-01

    The possibility to generate induced pluripotent stem cells (iPSC) opens the way to generate virtually all cell types of our human body. In combination with modern gene editing techniques like CRISPR/CAS, a new set of powerful tools becomes available for life science. Scientific fields like genotype and cell type-specific pharmacology, disease modeling, stem cell biology, and developmental biology have been dramatically fostered and their faces have been changed. However, as golden as the age of iPSC-derived cells and their manipulation has started, the shine begins to tarnish. Researchers face more and more practical problems intrinsic to the system. These problems are related to the specific culturing conditions which are not yet sufficient to mimic the natural environment of native stem cells differentiating towards adult cells. However, researchers work hard to uncover these factors. Here, we review a common standard approach to generate iPSCs and transduce these to iPSC cardiomyocytes. Further, we review recent achievements and discuss their current limitations and future perspectives. We are on track, but the road is still under construction.

  4. Generation of gene-corrected iPSC line from Parkinson's disease patient iPSC line with alpha-SNCA A53T mutation.

    PubMed

    Lee, Seo-Young; Jeong, SangKyun; Kim, Janghwan; Chung, Sun-Ku

    2018-06-09

    Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. PD can result from a mutation of alpha-synuclein (α-SNCA), such as α-SNCA A53T. Using episomal vectors, induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts with the α-SNCA A53T mutation. A huge bacterial artificial chromosome (BAC) harboring the normal α-SNCA gene successfully corrected the α-SNCA A53T-mutant iPSCs. Melting curve analysis for allelic composition indicated that the BAC DNA was precisely targeted to the α-SNCA A53T mutation allele, without random integration. The corrected PD-iPSCs displayed the normal karyotype and pluripotency, with the capability to differentiate to any cell type. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  5. Practical guide to bar coding for patient medication safety.

    PubMed

    Neuenschwander, Mark; Cohen, Michael R; Vaida, Allen J; Patchett, Jeffrey A; Kelly, Jamie; Trohimovich, Barbara

    2003-04-15

    Bar coding for the medication administration step of the drug-use process is discussed. FDA will propose a rule in 2003 that would require bar-code labels on all human drugs and biologicals. Even with an FDA mandate, manufacturer procrastination and possible shifts in product availability are likely to slow progress. Such delays should not preclude health systems from adopting bar-code-enabled point-of-care (BPOC) systems to achieve gains in patient safety. Bar-code technology is a replacement for traditional keyboard data entry. The elements of bar coding are content, which determines the meaning; data format, which refers to the embedded data and symbology, which describes the "font" in which the machine-readable code is written. For a BPOC system to deliver an acceptable level of patient protection, the hospital must first establish reliable processes for a patient identification band, caregiver badge, and medication bar coding. Medications can have either drug-specific or patient-specific bar codes. Both varieties result in the desired code that supports patient's five rights of drug administration. When medications are not available from the manufacturer in immediate-container bar-coded packaging, other means of applying the bar code must be devised, including the use of repackaging equipment, overwrapping, manual bar coding, and outsourcing. Virtually all medications should be bar coded, the bar code on the label should be easily readable, and appropriate policies, procedures, and checks should be in place. Bar coding has the potential to be not only cost-effective but to produce a return on investment. By bar coding patient identification tags, caregiver badges, and immediate-container medications, health systems can substantially increase patient safety during medication administration.

  6. Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors

    PubMed Central

    Ban, Hiroshi; Nishishita, Naoki; Fusaki, Noemi; Tabata, Toshiaki; Saeki, Koichi; Shikamura, Masayuki; Takada, Nozomi; Inoue, Makoto; Hasegawa, Mamoru; Kawamata, Shin; Nishikawa, Shin-Ichi

    2011-01-01

    After the first report of induced pluripotent stem cells (iPSCs), considerable efforts have been made to develop more efficient methods for generating iPSCs without foreign gene insertions. Here we show that Sendai virus vector, an RNA virus vector that carries no risk of integrating into the host genome, is a practical solution for the efficient generation of safer iPSCs. We improved the Sendai virus vectors by introducing temperature-sensitive mutations so that the vectors could be easily removed at nonpermissive temperatures. Using these vectors enabled the efficient production of viral/factor-free iPSCs from both human fibroblasts and CD34+ cord blood cells. Temperature-shift treatment was more effective in eliminating remaining viral vector-related genes. The resulting iPSCs expressed human embryonic stem cell markers and exhibited pluripotency. We suggest that generation of transgene-free iPSCs from cord blood cells should be an important step in providing allogeneic iPSC-derived therapy in the future. PMID:21821793

  7. 29 CFR 1910.144 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Safety color code for marking physical hazards. 1910.144... § 1910.144 Safety color code for marking physical hazards. (a) Color identification—(1) Red. Red shall be... basic color for designating caution and for marking physical hazards such as: Striking against...

  8. 29 CFR 1910.144 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 5 2013-07-01 2013-07-01 false Safety color code for marking physical hazards. 1910.144... § 1910.144 Safety color code for marking physical hazards. (a) Color identification—(1) Red. Red shall be the basic color for the identification of: (i) Fire protection equipment and apparatus. [Reserved] (ii...

  9. 29 CFR 1910.144 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Safety color code for marking physical hazards. 1910.144... § 1910.144 Safety color code for marking physical hazards. (a) Color identification—(1) Red. Red shall be the basic color for the identification of: (i) Fire protection equipment and apparatus. [Reserved] (ii...

  10. 29 CFR 1910.144 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 5 2012-07-01 2012-07-01 false Safety color code for marking physical hazards. 1910.144... § 1910.144 Safety color code for marking physical hazards. (a) Color identification—(1) Red. Red shall be the basic color for the identification of: (i) Fire protection equipment and apparatus. [Reserved] (ii...

  11. Critical-Size Calvarial Bone Defects Healing in a Mouse Model with Silk Scaffolds and SATB2- Modified iPSCs

    PubMed Central

    Ye, Jin-Hai; Xu, Yuan-Jin; Gao, Jun; Yan, Shi-Guo; Zhao, Jun; Tu, Qisheng; Zhang, Jin; Duan, Xue-Jing; Sommer, Cesar A.; Mostoslavsky, Gustavo; Kaplan, David; Wu, Yu-Nong; Zhang, Chen-Ping; Wang, Lin; Chen, Jake

    2011-01-01

    Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and thus have a great potential in application in engineered bone substitutes with bioactive scaffolds in regeneration medicine. In the current study we characterized and demonstrated the pluripotency and osteogenic differentiation of mouse iPSCs. To enhance the osteogenic differentiation of iPSCs, we then transduced the iPSCs with the potent transcription factor, nuclear matrix protein SATB2. We observed that in SATB2-overexpressing iPSCs there were increased mineral nodule formation and elevated mRNA levels of key osteogenic genes, osterix (OSX), Runx2, bone sialoprotein (BSP) and osteocalcin (OCN). Moreover, the mRNA levels of HoxA2 was reduced after SATB2 overexpression in iPSCs. The SATB2-overexpressing iPSCs were then combined with silk scaffolds and transplanted into critical-size calvarial bone defects created in nude mice. Five weeks post-surgery, radiological and micro-CT analysis revealed enhanced new bone formation in calvarial defects in SATB2 group. Histological analysis also showed increased new bone formation and mineralization in the SATB2 group. In conclusion, the results demonstrate that SATB2 facilitates the differentiation of iPSCs towards osteoblast-lineage cells by repressing HoxA2 and augmenting the functions of the osteoblast determinants Runx2, BSP and OCN. PMID:21492931

  12. Integrity of Induced Pluripotent Stem Cell (iPSC) Derived Megakaryocytes as Assessed by Genetic and Transcriptomic Analysis

    PubMed Central

    Kammers, Kai; Taub, Margaret A.; Ruczinski, Ingo; Martin, Joshua; Yanek, Lisa R.; Frazee, Alyssa; Gao, Yongxing; Hoyle, Dixie; Faraday, Nauder; Becker, Diane M.; Cheng, Linzhao; Wang, Zack Z.; Leek, Jeff T.; Becker, Lewis C.; Mathias, Rasika A.

    2017-01-01

    Previously, we have described our feeder-free, xeno-free approach to generate megakaryocytes (MKs) in culture from human induced pluripotent stem cells (iPSCs). Here, we focus specifically on the integrity of these MKs using: (1) genotype discordance between parent cell DNA to iPSC cell DNA and onward to the differentiated MK DNA; (2) genomic structural integrity using copy number variation (CNV); and (3) transcriptomic signatures of the derived MK lines compared to the iPSC lines. We detected a very low rate of genotype discordance; estimates were 0.0001%-0.01%, well below the genotyping error rate for our assay (0.37%). No CNVs were generated in the iPSCs that were subsequently passed on to the MKs. Finally, we observed highly biologically relevant gene sets as being upregulated in MKs relative to the iPSCs: platelet activation, blood coagulation, megakaryocyte development, platelet formation, platelet degranulation, and platelet aggregation. These data strongly support the integrity of the derived MK lines. PMID:28107356

  13. Non-random nature of spontaneous mIPSCs in mouse auditory brainstem neurons revealed by recurrence quantification analysis

    PubMed Central

    Leao, Richardson N; Leao, Fabricio N; Walmsley, Bruce

    2005-01-01

    A change in the spontaneous release of neurotransmitter is a useful indicator of processes occurring within presynaptic terminals. Linear techniques (e.g. Fourier transform) have been used to analyse spontaneous synaptic events in previous studies, but such methods are inappropriate if the timing pattern is complex. We have investigated spontaneous glycinergic miniature synaptic currents (mIPSCs) in principal cells of the medial nucleus of the trapezoid body. The random versus deterministic (or periodic) nature of mIPSCs was assessed using recurrence quantification analysis. Nonlinear methods were then used to quantify any detected determinism in spontaneous release, and to test for chaotic or fractal patterns. Modelling demonstrated that this procedure is much more sensitive in detecting periodicities than conventional techniques. mIPSCs were found to exhibit periodicities that were abolished by blockade of internal calcium stores with ryanodine, suggesting calcium oscillations in the presynaptic inhibitory terminals. Analysis indicated that mIPSC occurrences were chaotic in nature. Furthermore, periodicities were less evident in congenitally deaf mice than in normal mice, indicating that appropriate neural activity during development is necessary for the expression of deterministic chaos in mIPSC patterns. We suggest that chaotic oscillations of mIPSC occurrences play a physiological role in signal processing in the auditory brainstem. PMID:16271982

  14. 76 FR 11339 - Update to NFPA 101, Life Safety Code, for State Home Facilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 51 RIN 2900-AN59 Update to NFPA 101, Life Safety Code..., Life Safety Code. The change is designed to assure that State Home facilities meet current industry- wide standards regarding life safety and fire safety. DATES: Effective Date: This final rule is...

  15. Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis.

    PubMed

    Honda, Arata; Choijookhuu, Narantsog; Izu, Haruna; Kawano, Yoshihiro; Inokuchi, Mizuho; Honsho, Kimiko; Lee, Ah-Reum; Nabekura, Hiroki; Ohta, Hiroshi; Tsukiyama, Tomoyuki; Ohinata, Yasuhide; Kuroiwa, Asato; Hishikawa, Yoshitaka; Saitou, Mitinori; Jogahara, Takamichi; Koshimoto, Chihiro

    2017-05-01

    In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis , has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis , it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T. osimensis and to find a strategy to prevent its possible extinction, we have established induced pluripotent stem cells (iPSCs) and derived interspecific chimeras using mice as the hosts and recipients. Generated iPSCs are considered to be in the so-called "true naïve" state, and T. osimensis iPSCs may contribute as interspecific chimeras to several different tissues and cells in live animals. Surprisingly, female T. osimensis iPSCs not only contributed to the female germ line in the interspecific mouse ovary but also differentiated into spermatocytes and spermatids that survived in the adult interspecific mouse testes. Thus, T. osimensis cells have high sexual plasticity through which female somatic cells can be converted to male germline cells. These findings suggest flexibility in T. osimensis cells, which can adapt their germ cell sex to the gonadal niche. The probable reduction of the extinction risk of an endangered species through the use of iPSCs is indicated by this study.

  16. Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis

    PubMed Central

    Honda, Arata; Choijookhuu, Narantsog; Izu, Haruna; Kawano, Yoshihiro; Inokuchi, Mizuho; Honsho, Kimiko; Lee, Ah-Reum; Nabekura, Hiroki; Ohta, Hiroshi; Tsukiyama, Tomoyuki; Ohinata, Yasuhide; Kuroiwa, Asato; Hishikawa, Yoshitaka; Saitou, Mitinori; Jogahara, Takamichi; Koshimoto, Chihiro

    2017-01-01

    In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis, has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis, it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T. osimensis and to find a strategy to prevent its possible extinction, we have established induced pluripotent stem cells (iPSCs) and derived interspecific chimeras using mice as the hosts and recipients. Generated iPSCs are considered to be in the so-called “true naïve” state, and T. osimensis iPSCs may contribute as interspecific chimeras to several different tissues and cells in live animals. Surprisingly, female T. osimensis iPSCs not only contributed to the female germ line in the interspecific mouse ovary but also differentiated into spermatocytes and spermatids that survived in the adult interspecific mouse testes. Thus, T. osimensis cells have high sexual plasticity through which female somatic cells can be converted to male germline cells. These findings suggest flexibility in T. osimensis cells, which can adapt their germ cell sex to the gonadal niche. The probable reduction of the extinction risk of an endangered species through the use of iPSCs is indicated by this study. PMID:28508054

  17. Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters

    PubMed Central

    Andersson, Eva-Marie; Heath, Nikki; Persson-kry, Anette; Collins, Richard; Hicks, Ryan; Dekker, Niek; Forslöw, Anna

    2017-01-01

    It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs) were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC) clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications. PMID:29117231

  18. Patient-Derived iPSCs and iNs-Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases.

    PubMed

    Tang, Bor Luen

    2018-05-08

    Induced pluripotent stem cells (iPSCs) and induced neuronal (iN) cells are very much touted in terms of their potential promises in therapeutics. However, from a more fundamental perspective, iPSCs and iNs are invaluable tools for the postnatal generation of specific diseased cell types from patients, which may offer insights into disease etiology that are otherwise unobtainable with available animal or human proxies. There are two good recent examples of such important insights with diseased neurons derived via either the iPSC or iN approaches. In one, induced motor neurons (iMNs) derived from iPSCs of Amyotrophic lateral sclerosis/Frontotemporal dementia (ALS/FTD) patients with a C9orf72 repeat expansion revealed a haploinsufficiency of protein function resulting from the intronic expansion and deficiencies in motor neuron vesicular trafficking and lysosomal biogenesis that were not previously obvious in knockout mouse models. In another, striatal medium spinal neurons (MSNs) derived directly from fibroblasts of Huntington’s disease (HD) patients recapitulated age-associated disease signatures of mutant Huntingtin (mHTT) aggregation and neurodegeneration that were not prominent in neurons differentiated indirectly via iPSCs from HD patients. These results attest to the tremendous potential for pathologically accurate and mechanistically revealing disease modelling with advances in the derivation of iPSCs and iNs.

  19. Generation of Viable Mice from Induced Pluripotent Stem Cells (iPSCs) Through Tetraploid Complementation.

    PubMed

    Kang, Lan; Gao, Shaorong

    2015-01-01

    Tetraploid complementation assay is the most rigorous criteria for pluripotency characterization of pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Pluripotent stem cells could complement the developmental deficiency of tetraploid embryos and thus support the full-term mice development. Here we describe the protocol for tetraploid complementation using iPSCs to produce viable all-iPSC mice.

  20. CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs.

    PubMed

    Wang, Lixia; Yi, Fei; Fu, Lina; Yang, Jiping; Wang, Si; Wang, Zhaoxia; Suzuki, Keiichiro; Sun, Liang; Xu, Xiuling; Yu, Yang; Qiao, Jie; Belmonte, Juan Carlos Izpisua; Yang, Ze; Yuan, Yun; Qu, Jing; Liu, Guang-Hui

    2017-05-01

    Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 +/A272C and FUS +/G1566A mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 +/A272C and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.

  1. Differentiation of Mouse Induced Pluripotent Stem Cells (iPSCs) into Nucleus Pulposus-Like Cells In Vitro

    PubMed Central

    Chen, Jun; Lee, Esther J.; Jing, Liufang; Christoforou, Nicolas; Leong, Kam W.; Setton, Lori A.

    2013-01-01

    A large percentage of the population may be expected to experience painful symptoms or disability associated with intervertebral disc (IVD) degeneration – a condition characterized by diminished integrity of tissue components. Great interest exists in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient’s own somatic cells, have demonstrated their capacity to differentiate into various cell types although their potential to differentiate into an IVD cell has not yet been demonstrated. The overall objective of this study was to assess the possibility of generating iPSC-derived nucleus pulposus (NP) cells in a mouse model, a cell population that is entirely derived from notochord. This study employed magnetic activated cell sorting (MACS) to isolate a CD24+ iPSC subpopulation. Notochordal cell-related gene expression was analyzed in this CD24+ cell fraction via real time RT-PCR. CD24+ iPSCs were then cultured in a laminin-rich culture system for up to 28 days, and the mouse NP phenotype was assessed by immunostaining. This study also focused on producing a more conducive environment for NP differentiation of mouse iPSCs with addition of low oxygen tension and notochordal cell conditioned medium (NCCM) to the culture platform. iPSCs were evaluated for an ability to adopt an NP-like phenotype through a combination of immunostaining and biochemical assays. Results demonstrated that a CD24+ fraction of mouse iPSCs could be retrieved and differentiated into a population that could synthesize matrix components similar to that in native NP. Likewise, the addition of a hypoxic environment and NCCM induced a similar phenotypic result. In conclusion, this study suggests that mouse iPSCs have the potential to differentiate into NP-like cells and suggests the possibility that they may be used as a novel cell source for cellular therapy in the IVD. PMID

  2. Kayenta Township Building & Safety Department, Tribal Green Building Code Summit Presentation

    EPA Pesticide Factsheets

    Tribal Green Building Code Summit Presentation by Kayenta Township Building & Safety Department showing how they established the building department, developed a code adoption and enforcement process, and hired staff to carry out the work.

  3. Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs

    PubMed Central

    Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W

    2012-01-01

    Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238

  4. Waste IPSC : Thermal-Hydrologic-Chemical-Mechanical (THCM) modeling and simulation.

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

    Freeze, Geoffrey A.; Wang, Yifeng; Arguello, Jose Guadalupe, Jr.

    2010-10-01

    Waste IPSC Objective is to develop an integrated suite of high performance computing capabilities to simulate radionuclide movement through the engineered components and geosphere of a radioactive waste storage or disposal system: (1) with robust thermal-hydrologic-chemical-mechanical (THCM) coupling; (2) for a range of disposal system alternatives (concepts, waste form types, engineered designs, geologic settings); (3) for long time scales and associated large uncertainties; (4) at multiple model fidelities (sub-continuum, high-fidelity continuum, PA); and (5) in accordance with V&V and software quality requirements. THCM Modeling collaborates with: (1) Other Waste IPSC activities: Sub-Continuum Processes (and FMM), Frameworks and Infrastructure (and VU,more » ECT, and CT); (2) Waste Form Campaign; (3) Used Fuel Disposition (UFD) Campaign; and (4) ASCEM.« less

  5. Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    PubMed

    Shtrichman, R; Germanguz, I; Itskovitz-Eldor, J

    2013-06-01

    Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.

  6. Application of the Life Safety Code to a Historic Test Stand

    NASA Technical Reports Server (NTRS)

    Askins, Bruce; Lemke, Paul R.; Lewis, William L.; Covell, Carol C.

    2011-01-01

    NASA has conducted a study to assess alternatives to refurbishing existing launch vehicle modal test facilities as opposed to developing new test facilities to meet the demands of a very fiscally constrained test and evaluation environment. The results of this study showed that Marshall Space Flight Center (MSFC) Test Stand (TS) 4550 could be made compliant, within reasonable cost and schedule impacts, if safety processes and operational limitations were put in place to meet the safety codes and concerns of the Fire Marshall. Trades were performed with key selection criteria to ensure that appropriate levels of occupant safety are incorporated into test facility design modifications. In preparation for the ground vibration tests that were to be performed on the Ares I launch vehicle, the Ares Flight and Integrated Test Office (FITO) organization evaluated the available test facility options, which included the existing mothballed structural dynamic TS4550 used by Apollo and Shuttle, alternative ground vibration test facilities at other locations, and construction of a new dynamic test stand. After an exhaustive assessment of the alternatives, the results favored modifying the TS4550 because it was the lowest cost option and presented the least schedule risk to the NASA Constellation Program for Ares Integrated Vehicle Ground Vibration Test (IVGVT). As the renovation design plans and drawings were being developed for TS4550, a safety concern was discovered the original design for the construction of the test stand, originally built for the Apollo Program and renovated for the Shuttle Program, was completed before NASA s adoption of the currently imposed safety and building codes per National Fire Protection Association Life Safety Code [NFPA 101] and International Building Codes. The initial FITO assessment of the design changes, required to make TS4550 compliant with current safety and building standards, identified a significant cost increase and schedule impact

  7. Generation of 3D Skin Equivalents Fully Reconstituted from Human Induced Pluripotent Stem Cells (iPSCs)

    PubMed Central

    Guo, Zongyou; Liu, Liang; Higgins, Claire A.; Christiano, Angela M.

    2013-01-01

    Recent generation of patient-specific induced pluripotent stem cells (PS-iPSCs) provides significant advantages for cell- and gene-based therapy. Establishment of iPSC-based therapy for skin diseases requires efficient methodology for differentiating iPSCs into both keratinocytes and fibroblasts, the major cellular components of the skin, as well as the reconstruction of skin structures using these iPSC-derived skin components. We previously reported generation of keratinocytes from human iPSCs for use in the treatment of recessive dystrophic epidermolysis bullosa (RDEB) caused by mutations in the COL7A1 gene. Here, we developed a protocol for differentiating iPSCs into dermal fibroblasts, which also produce type VII collagen and therefore also have the potential to treat RDEB. Moreover, we generated in vitro 3D skin equivalents composed exclusively human iPSC-derived keratinocytes and fibroblasts for disease models and regenerative therapies for skin diseases, first demonstrating that iPSCs can provide the basis for modeling a human organ derived entirely from two different types of iPSC-derived cells. PMID:24147053

  8. 76 FR 77549 - Colorado River Indian Tribes-Amendment to Health & Safety Code, Article 2. Liquor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-13

    ... Health & Safety Code, Article 2. Liquor AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice. SUMMARY: This notice publishes the amendment to the Colorado River Tribal Health and Safety Code, Article... Code, Article 2, Liquor by Ordinance No. 10-03 on December 13, 2010. This notice is published in...

  9. Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives.

    PubMed

    Itakura, Go; Kawabata, Soya; Ando, Miki; Nishiyama, Yuichiro; Sugai, Keiko; Ozaki, Masahiro; Iida, Tsuyoshi; Ookubo, Toshiki; Kojima, Kota; Kashiwagi, Rei; Yasutake, Kaori; Nakauchi, Hiromitsu; Miyoshi, Hiroyuki; Nagoshi, Narihito; Kohyama, Jun; Iwanami, Akio; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki

    2017-03-14

    Human induced pluripotent stem cells (iPSCs) are promising in regenerative medicine. However, the risks of teratoma formation and the overgrowth of the transplanted cells continue to be major hurdles that must be overcome. Here, we examined the efficacy of the inducible caspase-9 (iCaspase9) gene as a fail-safe against undesired tumorigenic transformation of iPSC-derived somatic cells. We used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. In vitro, the iCaspase9 system induced apoptosis in approximately 95% of both iPSCs and iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs). To determine in vivo function, we transplanted iPSC-NS/PCs into the injured spinal cord of NOD/SCID mice. All transplanted cells whose mass effect was hindering motor function recovery were ablated upon transduction of iCaspase9. Our results suggest that the iCaspase9 system may serve as an important countermeasure against post-transplantation adverse events in stem cell transplant therapies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A simple and efficient feeder-free culture system to up-scale iPSCs on polymeric material surface for use in 3D bioprinting.

    PubMed

    Wong, Chui-Wei; Chen, You-Tzung; Chien, Chung-Liang; Yu, Tien-Yu; Rwei, Syang-Peng; Hsu, Shan-Hui

    2018-01-01

    The 3D bioprinting and cell/tissue printing techniques open new possibilities for future applications. To facilitate the 3D bioprinting process, a large amount of living cells are required. Induced pluripotent stem cells (iPSCs) represent a promising cell source for bioprinting. However, the maintenance and expansion of undifferentiated iPSCs are expensive and time consuming. Therefore, in this study a culture method to obtain a sufficient amount of healthy and undifferentiated iPSCs in a short-term period was established. The iPSCs could be passaged for twice on tissue culture polystyrene (TCPS) dish with the conditional medium and could adapt to the feeder-free environment. Feeder-free dishes were further prepared from chitosan, chitosan-hyaluronan, silk fibroin, and polyurethane (PU1 and PU2) two-dimensional substrates. The iPSCs cultured on the chitosan substrates showed a higher proliferation rate without losing the stemness feature. Among the different materials, PU2 could be prepared as a thermoresponsive hydrogel, which was a potential ink for 3D bioprinting. The iPSCs cultured on PU2 substrates well survived when further embedded in PU2 hydrogel. Moreover, PU2 hydrogel printed with iPSCs remained structural integrity. The use of PU2 hydrogel to embed iPSCs reduced the injury to iPSCs by shear stress. These results indicate that iPSCs could be expanded on chitosan or PU2 membranes without the feeder layer and then printed in PU2 hydrogel. The combination of these steps could offer a new possibility for future applications of iPSC-based 3D bioprinting in tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors.

    PubMed

    Skamagki, Maria; Correia, Cristina; Yeung, Percy; Baslan, Timour; Beck, Samuel; Zhang, Cheng; Ross, Christian A; Dang, Lam; Liu, Zhong; Giunta, Simona; Chang, Tzu-Pei; Wang, Joye; Ananthanarayanan, Aparna; Bohndorf, Martina; Bosbach, Benedikt; Adjaye, James; Funabiki, Hironori; Kim, Jonghwan; Lowe, Scott; Collins, James J; Lu, Chi-Wei; Li, Hu; Zhao, Rui; Kim, Kitai

    2017-09-01

    Induced pluripotent stem cells (iPSCs), which are used to produce transplantable tissues, may particularly benefit older patients, who are more likely to suffer from degenerative diseases. However, iPSCs generated from aged donors (A-iPSCs) exhibit higher genomic instability, defects in apoptosis and a blunted DNA damage response compared with iPSCs generated from younger donors. We demonstrated that A-iPSCs exhibit excessive glutathione-mediated reactive oxygen species (ROS) scavenging activity, which blocks the DNA damage response and apoptosis and permits survival of cells with genomic instability. We found that the pluripotency factor ZSCAN10 is poorly expressed in A-iPSCs and addition of ZSCAN10 to the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) during A-iPSC reprogramming normalizes ROS-glutathione homeostasis and the DNA damage response, and recovers genomic stability. Correcting the genomic instability of A-iPSCs will ultimately enhance our ability to produce histocompatible functional tissues from older patients' own cells that are safe for transplantation.

  12. ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors

    PubMed Central

    Skamagki, Maria; Correia, Cristina; Yeung, Percy; Baslan, Timour; Beck, Samuel; Zhang, Cheng; Ross, Christian A.; Dang, Lam; Liu, Zhong; Giunta, Simona; Chang, Tzu-Pei; Wang, Joye; Ananthanarayanan, Aparna; Bohndorf, Martina; Bosbach, Benedikt; Adjaye, James; Funabiki, Hironori; Kim, Jonghwan; Lowe, Scott; Collins, James J.; Lu, Chi-Wei; Li, Hu; Zhao, Rui; Kim, Kitai

    2018-01-01

    Induced pluripotent stem cells (iPSCs), which are used to produce transplantable tissues, may particularly benefit older patients, who are more likely to suffer from degenerative diseases. However, iPSCs generated from aged donors (A-iPSCs) exhibit higher genomic instability, defects in apoptosis and a blunted DNA damage response compared with iPSCs generated from younger donors. We demonstrated that A-iPSCs exhibit excessive glutathione-mediated reactive oxygen species (ROS) scavenging activity, which blocks the DNA damage response and apoptosis and permits survival of cells with genomic instability. We found that the pluripotency factor ZSCAN10 is poorly expressed in A-iPSCs and addition of ZSCAN10 to the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) during A-iPSC reprogramming normalizes ROS–glutathione homeostasis and the DNA damage response, and recovers genomic stability. Correcting the genomic instability of A-iPSCs will ultimately enhance our ability to produce histocompatible functional tissues from older patients’ own cells that are safe for transplantation. PMID:28846095

  13. 29 CFR 1910.35 - Compliance with NFPA 101-2000, Life Safety Code.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 5 2011-07-01 2011-07-01 false Compliance with NFPA 101-2000, Life Safety Code. 1910.35 Section 1910.35 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Means of Egress § 1910.35 Compliance...

  14. Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing.

    PubMed

    Tidball, Andrew M; Dang, Louis T; Glenn, Trevor W; Kilbane, Emma G; Klarr, Daniel J; Margolis, Joshua L; Uhler, Michael D; Parent, Jack M

    2017-09-12

    Specifically ablating genes in human induced pluripotent stem cells (iPSCs) allows for studies of gene function as well as disease mechanisms in disorders caused by loss-of-function (LOF) mutations. While techniques exist for engineering such lines, we have developed and rigorously validated a method of simultaneous iPSC reprogramming while generating CRISPR/Cas9-dependent insertions/deletions (indels). This approach allows for the efficient and rapid formation of genetic LOF human disease cell models with isogenic controls. The rate of mutagenized lines was strikingly consistent across experiments targeting four different human epileptic encephalopathy genes and a metabolic enzyme-encoding gene, and was more efficient and consistent than using CRISPR gene editing of established iPSC lines. The ability of our streamlined method to reproducibly generate heterozygous and homozygous LOF iPSC lines with passage-matched isogenic controls in a single step provides for the rapid development of LOF disease models with ideal control lines, even in the absence of patient tissue. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs.

    PubMed

    Muguruma, Keiko

    2018-02-01

    Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that cerebellar tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable cerebellar disease.

  16. 29 CFR 1910.144 - Safety color code for marking physical hazards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the basic color for the identification of: (i) Fire protection equipment and apparatus. [Reserved] (ii... 29 Labor 5 2011-07-01 2011-07-01 false Safety color code for marking physical hazards. 1910.144 Section 1910.144 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH...

  17. Quick Response codes for surgical safety: a prospective pilot study.

    PubMed

    Dixon, Jennifer L; Smythe, William Roy; Momsen, Lara S; Jupiter, Daniel; Papaconstantinou, Harry T

    2013-09-01

    Surgical safety programs have been shown to reduce patient harm; however, there is variable compliance. The purpose of this study is to determine if innovative technology such as Quick Response (QR) codes can facilitate surgical safety initiatives. We prospectively evaluated the use of QR codes during the surgical time-out for 40 operations. Feasibility and accuracy were assessed. Perceptions of the current time-out process and the QR code application were evaluated through surveys using a 5-point Likert scale and binomial yes or no questions. At baseline (n = 53), survey results from the surgical team agreed or strongly agreed that the current time-out process was efficient (64%), easy to use (77%), and provided clear information (89%). However, 65% of surgeons felt that process improvements were needed. Thirty-seven of 40 (92.5%) QR codes scanned successfully, of which 100% were accurate. Three scan failures resulted from excessive curvature or wrinkling of the QR code label on the body. Follow-up survey results (n = 33) showed that the surgical team agreed or strongly agreed that the QR program was clearer (70%), easier to use (57%), and more accurate (84%). Seventy-four percent preferred the QR system to the current time-out process. QR codes accurately transmit patient information during the time-out procedure and are preferred to the current process by surgical team members. The novel application of this technology may improve compliance, accuracy, and outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs.

    PubMed

    Fu, Lina; Xu, Xiuling; Ren, Ruotong; Wu, Jun; Zhang, Weiqi; Yang, Jiping; Ren, Xiaoqing; Wang, Si; Zhao, Yang; Sun, Liang; Yu, Yang; Wang, Zhaoxia; Yang, Ze; Yuan, Yun; Qiao, Jie; Izpisua Belmonte, Juan Carlos; Qu, Jing; Liu, Guang-Hui

    2016-03-01

    Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

  19. Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

    PubMed

    Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

    2017-05-31

    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

  20. Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging

    PubMed Central

    D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

    2017-01-01

    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging. PMID:28562315

  1. Communication overhead on the Intel iPSC-860 hypercube

    NASA Technical Reports Server (NTRS)

    Bokhari, Shahid H.

    1990-01-01

    Experiments were conducted on the Intel iPSC-860 hypercube in order to evaluate the overhead of interprocessor communication. It is demonstrated that: (1) contrary to popular belief, the distance between two communicating processors has a significant impact on communication time, (2) edge contention can increase communication time by a factor of more than 7, and (3) node contention has no measurable impact.

  2. Genetic and pharmacological correction of aberrant dopamine synthesis using patient iPSCs with BH4 metabolism disorders.

    PubMed

    Ishikawa, Taizo; Imamura, Keiko; Kondo, Takayuki; Koshiba, Yasushi; Hara, Satoshi; Ichinose, Hiroshi; Furujo, Mahoko; Kinoshita, Masako; Oeda, Tomoko; Takahashi, Jun; Takahashi, Ryosuke; Inoue, Haruhisa

    2016-12-01

    Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or dihydropteridine reductase (DHPR), respectively. Although BH4 metabolism disorders and its metabolisms have been studied, it is unclear how gene variants cause aberrant DA synthesis in patient neurons. Here, we generated induced pluripotent stem cells (iPSCs) from BH4 metabolism disorder patients with PTPS or DHPR variants, corrected the gene variant in the iPSCs using the CRISPR/Cas9 system, and differentiated the BH4 metabolism disorder patient- and isogenic control iPSCs into midbrain DA neurons. We found that by the gene correction, the BH4 amount, TH protein level and extracellular DA level were restored in DA neuronal culture using PTPS deficiency iPSCs. Furthermore, the pharmacological correction by BH4 precursor sepiapterin treatment also improved the phenotypes of PTPS deficiency. These results suggest that patient iPSCs with BH4 metabolism disorders provide an opportunity for screening substances for treating aberrant DA synthesis-related disorders. © The Author 2016. Published by Oxford University Press.

  3. Lipid Supplement in the Cultural Condition Facilitates the Porcine iPSC Derivation through cAMP/PKA/CREB Signal Pathway

    PubMed Central

    Zhang, Wei; Wang, Hanning; Zhang, Shaopeng; Zhong, Liang; Wang, Yanliang; Pei, Yangli; Cao, Suying

    2018-01-01

    Large numbers of lipids exist in the porcine oocytes and early embryos and have the positive effects on their development, suggesting that the lipids may play an important role in pluripotency establishment and maintenance in pigs. However, the effects of lipids and their metabolites, such as fatty acids on reprogramming and the pluripotency gene expression of porcine-induced pluripotent stem cells (iPSCs), are unclear. Here, we generated the porcine iPSCs that resemble the mouse embryonic stem cells (ESCs) under lipid and fatty-acid-enriched cultural conditions (supplement of AlbuMAX). These porcine iPSCs show positive for the ESCs pluripotency markers and have the differentiation abilities to all three germ layers, and importantly, have the capability of aggregation into the inner cell mass (ICM) of porcine blastocysts. We further confirmed that lipid and fatty acid enriched condition can promote the cell proliferation and improve reprogramming efficiency by elevating cAMP levels. Interestingly, this lipids supplement promotes mesenchymal–epithelial transition (MET) through the cAMP/PKA/CREB signal pathway and upregulates the E-cadherin expression during porcine somatic cell reprogramming. The lipids supplement also makes a contribution to lipid droplets accumulation in the porcine iPSCs that resemble porcine preimplantation embryos. These findings may facilitate understanding of the lipid metabolism in porcine iPSCs and lay the foundation of bona fide porcine embryonic stem cell derivation. PMID:29419748

  4. Code of Sustainable Practice in Occupational and Environmental Health and Safety for Corporations.

    PubMed

    Castleman, Barry; Allen, Barbara; Barca, Stefania; Bohme, Susanna Rankin; Henry, Emmanuel; Kaur, Amarjit; Massard-Guilbaud, Genvieve; Melling, Joseph; Menendez-Navarro, Alfredo; Renfrew, Daniel; Santiago, Myrna; Sellers, Christopher; Tweedale, Geoffrey; Zalik, Anna; Zavestoski, Stephen

    2008-01-01

    At a conference held at Stony Brook University in December 2007, "Dangerous Trade: Histories of Industrial Hazard across a Globalizing World," participants endorsed a Code of Sustainable Practice in Occupational and Environmental Health and Safety for Corporations. The Code outlines practices that would ensure corporations enact the highest health and environmentally protective measures in all the locations in which they operate. Corporations should observe international guidelines on occupational exposure to air contaminants, plant safety, air and water pollutant releases, hazardous waste disposal practices, remediation of polluted sites, public disclosure of toxic releases, product hazard labeling, sale of products for specific uses, storage and transport of toxic intermediates and products, corporate safety and health auditing, and corporate environmental auditing. Protective measures in all locations should be consonant with the most protective measures applied anywhere in the world, and should apply to the corporations' subsidiaries, contractors, suppliers, distributors, and licensees of technology. Key words: corporations, sustainability, environmental protection, occupational health, code of practice.

  5. Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.

    PubMed

    Sugai, Keiko; Fukuzawa, Ryuji; Shofuda, Tomoko; Fukusumi, Hayato; Kawabata, Soya; Nishiyama, Yuichiro; Higuchi, Yuichiro; Kawai, Kenji; Isoda, Miho; Kanematsu, Daisuke; Hashimoto-Tamaoki, Tomoko; Kohyama, Jun; Iwanami, Akio; Suemizu, Hiroshi; Ikeda, Eiji; Matsumoto, Morio; Kanemura, Yonehiro; Nakamura, Masaya; Okano, Hideyuki

    2016-09-19

    The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.

  6. Box schemes and their implementation on the iPSC/860

    NASA Technical Reports Server (NTRS)

    Chattot, J. J.; Merriam, M. L.

    1991-01-01

    Research on algoriths for efficiently solving fluid flow problems on massively parallel computers is continued in the present paper. Attention is given to the implementation of a box scheme on the iPSC/860, a massively parallel computer with a peak speed of 10 Gflops and a memory of 128 Mwords. A domain decomposition approach to parallelism is used.

  7. 75 FR 17644 - Update to NFPA 101, Life Safety Code, for State Home Facilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Part 51 RIN 2900-AN59 Update to NFPA 101, Life Safety Code... certain provisions of the 2009 edition of the National Fire Protection Association's NFPA 101, Life Safety... standards regarding life safety and fire safety. DATES: Written comments must be received by VA on or before...

  8. Ethical and Safety Issues of Stem Cell-Based Therapy.

    PubMed

    Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

    2018-01-01

    Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

  9. Ethical and Safety Issues of Stem Cell-Based Therapy

    PubMed Central

    Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

    2018-01-01

    Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells. PMID:29333086

  10. Production of Gene-Corrected Adult Beta Globin Protein in Human Erythrocytes Differentiated from Patient iPSCs After Genome Editing of the Sickle Point Mutation.

    PubMed

    Huang, Xiaosong; Wang, Ying; Yan, Wei; Smith, Cory; Ye, Zhaohui; Wang, Jing; Gao, Yongxing; Mendelsohn, Laurel; Cheng, Linzhao

    2015-05-01

    Human induced pluripotent stem cells (iPSCs) and genome editing provide a precise way to generate gene-corrected cells for disease modeling and cell therapies. Human iPSCs generated from sickle cell disease (SCD) patients have a homozygous missense point mutation in the HBB gene encoding adult β-globin proteins, and are used as a model system to improve strategies of human gene therapy. We demonstrate that the CRISPR/Cas9 system designer nuclease is much more efficient in stimulating gene targeting of the endogenous HBB locus near the SCD point mutation in human iPSCs than zinc finger nucleases and TALENs. Using a specific guide RNA and Cas9, we readily corrected one allele of the SCD HBB gene in human iPSCs by homologous recombination with a donor DNA template containing the wild-type HBB DNA and a selection cassette that was subsequently removed to avoid possible interference of HBB transcription and translation. We chose targeted iPSC clones that have one corrected and one disrupted SCD allele for erythroid differentiation assays, using an improved xeno-free and feeder-free culture condition we recently established. Erythrocytes from either the corrected or its parental (uncorrected) iPSC line were generated with similar efficiencies. Currently ∼6%-10% of these differentiated erythrocytes indeed lacked nuclei, characteristic of further matured erythrocytes called reticulocytes. We also detected the 16-kDa β-globin protein expressed from the corrected HBB allele in the erythrocytes differentiated from genome-edited iPSCs. Our results represent a significant step toward the clinical applications of genome editing using patient-derived iPSCs to generate disease-free cells for cell and gene therapies. Stem Cells 2015;33:1470-1479. © 2015 AlphaMed Press.

  11. ESAS Deliverable PS 1.1.2.3: Customer Survey on Code Generations in Safety-Critical Applications

    NASA Technical Reports Server (NTRS)

    Schumann, Johann; Denney, Ewen

    2006-01-01

    Automated code generators (ACG) are tools that convert a (higher-level) model of a software (sub-)system into executable code without the necessity for a developer to actually implement the code. Although both commercially supported and in-house tools have been used in many industrial applications, little data exists on how these tools are used in safety-critical domains (e.g., spacecraft, aircraft, automotive, nuclear). The aims of the survey, therefore, were threefold: 1) to determine if code generation is primarily used as a tool for prototyping, including design exploration and simulation, or for fiight/production code; 2) to determine the verification issues with code generators relating, in particular, to qualification and certification in safety-critical domains; and 3) to determine perceived gaps in functionality of existing tools.

  12. Demonstration of emulator-based Bayesian calibration of safety analysis codes: Theory and formulation

    DOE PAGES

    Yurko, Joseph P.; Buongiorno, Jacopo; Youngblood, Robert

    2015-05-28

    System codes for simulation of safety performance of nuclear plants may contain parameters whose values are not known very accurately. New information from tests or operating experience is incorporated into safety codes by a process known as calibration, which reduces uncertainty in the output of the code and thereby improves its support for decision-making. The work reported here implements several improvements on classic calibration techniques afforded by modern analysis techniques. The key innovation has come from development of code surrogate model (or code emulator) construction and prediction algorithms. Use of a fast emulator makes the calibration processes used here withmore » Markov Chain Monte Carlo (MCMC) sampling feasible. This study uses Gaussian Process (GP) based emulators, which have been used previously to emulate computer codes in the nuclear field. The present work describes the formulation of an emulator that incorporates GPs into a factor analysis-type or pattern recognition-type model. This “function factorization” Gaussian Process (FFGP) model allows overcoming limitations present in standard GP emulators, thereby improving both accuracy and speed of the emulator-based calibration process. Calibration of a friction-factor example using a Method of Manufactured Solution is performed to illustrate key properties of the FFGP based process.« less

  13. Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons

    PubMed Central

    Shum, Carole; Macedo, Sara C.; Warre-Cornish, Katherine; Cocks, Graham; Price, Jack; Srivastava, Deepak P.

    2015-01-01

    This article is part of a Special Issue “Estradiol and Cognition”. Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic “makeup” of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics. PMID:26143621

  14. Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway

    PubMed Central

    Szlachcic, Wojciech J.; Switonski, Pawel M.; Krzyzosiak, Wlodzimierz J.; Figlerowicz, Marek; Figiel, Maciej

    2015-01-01

    ABSTRACT Huntington disease (HD) is a brain disorder characterized by the late onset of motor and cognitive symptoms, even though the neurons in the brain begin to suffer dysfunction and degeneration long before symptoms appear. There is currently no cure. Several molecular and developmental effects of HD have been identified using neural stem cells (NSCs) and differentiated cells, such as neurons and astrocytes. Still, little is known regarding the molecular pathogenesis of HD in pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Therefore, we examined putative signaling pathways and processes involved in HD pathogenesis in pluripotent cells. We tested naïve mouse HD YAC128 iPSCs and two types of human HD iPSC that were generated from HD and juvenile-HD patients. Surprisingly, we found that a number of changes affecting cellular processes in HD were also present in undifferentiated pluripotent HD iPSCs, including the dysregulation of the MAPK and Wnt signaling pathways and the dysregulation of the expression of genes related to oxidative stress, such as Sod1. Interestingly, a common protein interactor of the huntingtin protein and the proteins in the above pathways is p53, and the expression of p53 was dysregulated in HD YAC128 iPSCs and human HD iPSCs. In summary, our findings demonstrate that multiple molecular pathways that are characteristically dysregulated in HD are already altered in undifferentiated pluripotent cells and that the pathogenesis of HD might begin during the early stages of life. PMID:26092128

  15. Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs.

    PubMed

    Yoshitoshi-Uebayashi, Elena Yukie; Toyoda, Taro; Yasuda, Katsutaro; Kotaka, Maki; Nomoto, Keiko; Okita, Keisuke; Yasuchika, Kentaro; Okamoto, Shinya; Takubo, Noriyuki; Nishikubo, Toshiya; Soga, Tomoyoshi; Uemoto, Shinji; Osafune, Kenji

    2017-05-06

    Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns. Therapeutic options are limited, and neurological sequelae may persist. To understand the pathophysiology and find novel treatments, induced pluripotent stem cells (iPSCs) were generated from a CTLN1 patient and differentiated into hepatocyte-like cells (HLCs). CTLN1-HLCs have lower ureagenesis, recapitulating part of the patient's phenotype. l-arginine, an amino acid clinically used for UCD treatment, improved this phenotype in vitro. Metabolome analysis revealed an increase in tricarboxylic acid (TCA) cycle metabolites in CTLN1, suggesting a connection between CTLN1 and the TCA cycle. This CTLN1-iPSC model improves the understanding of CTLN1 pathophysiology and can be used to pursue new therapeutic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-11-08

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

  17. Scalable 96-well Plate Based iPSC Culture and Production Using a Robotic Liquid Handling System.

    PubMed

    Conway, Michael K; Gerger, Michael J; Balay, Erin E; O'Connell, Rachel; Hanson, Seth; Daily, Neil J; Wakatsuki, Tetsuro

    2015-05-14

    Continued advancement in pluripotent stem cell culture is closing the gap between bench and bedside for using these cells in regenerative medicine, drug discovery and safety testing. In order to produce stem cell derived biopharmaceutics and cells for tissue engineering and transplantation, a cost-effective cell-manufacturing technology is essential. Maintenance of pluripotency and stable performance of cells in downstream applications (e.g., cell differentiation) over time is paramount to large scale cell production. Yet that can be difficult to achieve especially if cells are cultured manually where the operator can introduce significant variability as well as be prohibitively expensive to scale-up. To enable high-throughput, large-scale stem cell production and remove operator influence novel stem cell culture protocols using a bench-top multi-channel liquid handling robot were developed that require minimal technician involvement or experience. With these protocols human induced pluripotent stem cells (iPSCs) were cultured in feeder-free conditions directly from a frozen stock and maintained in 96-well plates. Depending on cell line and desired scale-up rate, the operator can easily determine when to passage based on a series of images showing the optimal colony densities for splitting. Then the necessary reagents are prepared to perform a colony split to new plates without a centrifugation step. After 20 passages (~3 months), two iPSC lines maintained stable karyotypes, expressed stem cell markers, and differentiated into cardiomyocytes with high efficiency. The system can perform subsequent high-throughput screening of new differentiation protocols or genetic manipulation designed for 96-well plates. This technology will reduce the labor and technical burden to produce large numbers of identical stem cells for a myriad of applications.

  18. One-step genetic correction of hemoglobin E/beta-thalassemia patient-derived iPSCs by the CRISPR/Cas9 system.

    PubMed

    Wattanapanitch, Methichit; Damkham, Nattaya; Potirat, Ponthip; Trakarnsanga, Kongtana; Janan, Montira; U-Pratya, Yaowalak; Kheolamai, Pakpoom; Klincumhom, Nuttha; Issaragrisil, Surapol

    2018-02-26

    Thalassemia is the most common genetic disease worldwide; those with severe disease require lifelong blood transfusion and iron chelation therapy. The definitive cure for thalassemia is allogeneic hematopoietic stem cell transplantation, which is limited due to lack of HLA-matched donors and the risk of post-transplant complications. Induced pluripotent stem cell (iPSC) technology offers prospects for autologous cell-based therapy which could avoid the immunological problems. We now report genetic correction of the beta hemoglobin (HBB) gene in iPSCs derived from a patient with a double heterozygote for hemoglobin E and β-thalassemia (HbE/β-thalassemia), the most common thalassemia syndrome in Thailand and Southeast Asia. We used the CRISPR/Cas9 system to target the hemoglobin E mutation from one allele of the HBB gene by homology-directed repair with a single-stranded DNA oligonucleotide template. DNA sequences of the corrected iPSCs were validated by Sanger sequencing. The corrected clones were differentiated into hematopoietic progenitor and erythroid cells to confirm their multilineage differentiation potential and hemoglobin expression. The hemoglobin E mutation of HbE/β-thalassemia iPSCs was seamlessly corrected by the CRISPR/Cas9 system. The corrected clones were differentiated into hematopoietic progenitor cells under feeder-free and OP9 coculture systems. These progenitor cells were further expanded in erythroid liquid culture system and developed into erythroid cells that expressed mature HBB gene and HBB protein. Our study provides a strategy to correct hemoglobin E mutation in one step and these corrected iPSCs can be differentiated into hematopoietic stem cells to be used for autologous transplantation in patients with HbE/β-thalassemia in the future.

  19. Efficient production of erythroid, megakaryocytic and myeloid cells, using single cell-derived iPSC colony differentiation.

    PubMed

    Hansen, Marten; Varga, Eszter; Aarts, Cathelijn; Wust, Tatjana; Kuijpers, Taco; von Lindern, Marieke; van den Akker, Emile

    2018-04-28

    Hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) provide opportunities not only for fundamental research and disease modelling/drug testing but also for large-scale production of blood effector cells for future clinical application. Although there are multiple ways to differentiate human iPSCs towards hematopoietic lineages, there is a need to develop reproducible and robust protocols. Here we introduce an efficient way to produce three major blood cell types using a standardized differentiation protocol that starts with a single hematopoietic initiation step. This system is feeder-free, avoids EB-formation, starts with a hematopoietic initiation step based on a novel single cell-derived iPSC colony differentiation and produces multi-potential progenitors within 8-10 days. Followed by lineage-specific growth factor supplementation these cells can be matured into well characterized erythroid, megakaryocytic and myeloid cells with high-purity, without transcription factor overexpression or any kind of pre-purification step. This standardized differentiation system provides a simple platform to produce specific blood cells in a reproducible manner for hematopoietic development studies, disease modelling, drug testing and the potential for future therapeutic applications. Copyright © 2018. Published by Elsevier B.V.

  20. Development of Safety Assessment Code for Decommissioning of Nuclear Facilities

    NASA Astrophysics Data System (ADS)

    Shimada, Taro; Ohshima, Soichiro; Sukegawa, Takenori

    A safety assessment code, DecDose, for decommissioning of nuclear facilities has been developed, based on the experiences of the decommissioning project of Japan Power Demonstration Reactor (JPDR) at Japan Atomic Energy Research Institute (currently JAEA). DecDose evaluates the annual exposure dose of the public and workers according to the progress of decommissioning, and also evaluates the public dose at accidental situations including fire and explosion. As for the public, both the internal and the external doses are calculated by considering inhalation, ingestion, direct radiation from radioactive aerosols and radioactive depositions, and skyshine radiation from waste containers. For external dose for workers, the dose rate from contaminated components and structures to be dismantled is calculated. Internal dose for workers is calculated by considering dismantling conditions, e.g. cutting speed, cutting length of the components and exhaust velocity. Estimation models for dose rate and staying time were verified by comparison with the actual external dose of workers which were acquired during JPDR decommissioning project. DecDose code is expected to contribute the safety assessment for decommissioning of nuclear facilities.

  1. Multisystemic Disease Modeling of Liver-Derived Protein Folding Disorders Using Induced Pluripotent Stem Cells (iPSCs).

    PubMed

    Leung, Amy; Murphy, George J

    2016-01-01

    Familial transthyretin amyloidosis (ATTR) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe detailed methodologies for the directed differentiation of protein folding disease-specific iPSCs into hepatocytes that produce mutant protein, and neural-lineage cells often targeted in disease. Methodologies are also described for the construction of multisystem models and drug screening using iPSCs.

  2. Generation of human iPSCs from an essential thrombocythemia patient carrying a V501L mutation in the MPL gene.

    PubMed

    Liu, Senquan; Ye, Zhaohui; Gao, Yongxing; He, Chaoxia; Williams, Donna W; Moliterno, Alison; Spivak, Jerry; Huang, He; Cheng, Linzhao

    2017-01-01

    Activating point mutations in the MPL gene encoding the thrombopoietin receptor are found in 3%-10% of essential thrombocythemia (ET) and myelofibrosis patients. Here, we report the derivation of induced pluripotent stem cells (iPSCs) from an ET patient with a heterozygous MPL V501L mutation. Peripheral blood CD34 + progenitor cells were reprogrammed by transient plasmid expression of OCT4, SOX2, KLF4, c-MYC plus BCL2L1 (BCL-xL) genes. The derived line M494 carries a MPL V501L mutation, displays typical iPSC morphology and characteristics, are pluripotent and karyotypically normal. Upon differentiation, the iPSCs are able to differentiate into cells derived from three germ layers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Striking Similarity in the Gene Expression Levels of Individual Myc Module Members among ESCs, EpiSCs, and Partial iPSCs

    PubMed Central

    Hirasaki, Masataka; Hiraki-Kamon, Keiko; Kamon, Masayoshi; Suzuki, Ayumu; Katano, Miyuki; Nishimoto, Masazumi; Okuda, Akihiko

    2013-01-01

    Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs). Epiblast stem cells (EpiSCs) are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs) and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties. PMID:24386274

  4. Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.

    PubMed

    Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R; Greenleaf, William J; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

    2015-07-01

    Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced 'transdifferentiation' pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by various methods.

  5. Transient Acquisition of Pluripotency During Somatic Cell Transdifferentiation with iPSC Reprogramming Factors

    PubMed Central

    Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D.; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R.; Greenleaf, William J.; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H.

    2015-01-01

    Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors1,2. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation3–6. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced transdifferentiation pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by different methods. PMID:26098448

  6. Motor neuron differentiation of iPSCs obtained from peripheral blood of a mutant TARDBP ALS patient.

    PubMed

    Bossolasco, Patrizia; Sassone, Francesca; Gumina, Valentina; Peverelli, Silvia; Garzo, Maria; Silani, Vincenzo

    2018-05-17

    Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease, mainly affecting the motor neurons (MNs) and without effective therapy. Drug screening is hampered by the lack of satisfactory experimental and pre-clinical models. Induced pluripotent stem cells (iPSCs) could help to define disease mechanisms and therapeutic strategies as they could be differentiated into MNs, otherwise inaccessible from living humans. In this study, given the seminal role of TDP-43 in ALS pathophysiology, MNs were obtained from peripheral blood mononuclear cells-derived iPSCs of an ALS patient carrying a p.A382T TARDBP mutation and a healthy donor. Venous samples were preferred to fibroblasts for their ease of collection and no requirement for time consuming extended cultures before experimentation. iPSCs were characterized for expression of specific markers, spontaneously differentiated into primary germ layers and, finally, into MNs. No differences were observed between the mutated ALS patient and the control MNs with most of the cells displaying a nuclear localization of the TDP-43 protein. In conclusion, we here demonstrated for the first time that human TARDBP mutated MNs can be successfully obtained exploiting the reprogramming and differentiation ability of peripheral blood cells, an easily accessible source from any patient. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Introduction to thematic minireview series: Development of human therapeutics based on induced pluripotent stem cell (iPSC) technology.

    PubMed

    Rao, Mahendra; Gottesfeld, Joel M

    2014-02-21

    With the advent of human induced pluripotent stem cell (hiPSC) technology, it is now possible to derive patient-specific cell lines that are of great potential in both basic research and the development of new therapeutics for human diseases. Not only do hiPSCs offer unprecedented opportunities to study cellular differentiation and model human diseases, but the differentiated cell types obtained from iPSCs may become therapeutics themselves. These cells can also be used in the screening of therapeutics and in toxicology assays for potential liabilities of therapeutic agents. The remarkable achievement of transcription factor reprogramming to generate iPSCs was recognized by the award of the Nobel Prize in Medicine to Shinya Yamanaka in 2012, just 6 years after the first publication of reprogramming methods to generate hiPSCs (Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007) Cell 131, 861-872). This minireview series highlights both the promises and challenges of using iPSC technology for disease modeling, drug screening, and the development of stem cell therapeutics.

  8. Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration.

    PubMed

    Burnight, Erin R; Gupta, Manav; Wiley, Luke A; Anfinson, Kristin R; Tran, Audrey; Triboulet, Robinson; Hoffmann, Jeremy M; Klaahsen, Darcey L; Andorf, Jeaneen L; Jiao, Chunhua; Sohn, Elliott H; Adur, Malavika K; Ross, Jason W; Mullins, Robert F; Daley, George Q; Schlaeger, Thorsten M; Stone, Edwin M; Tucker, Budd A

    2017-09-06

    Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function. We developed a homology-directed repair strategy targeting a homozygous Alu insertion in exon 9 of male germ cell-associated kinase (MAK) and demonstrated restoration of the retinal transcript and protein in patient cells. We generated a CRISPR-Cas9-mediated non-homologous end joining (NHEJ) approach to excise a major contributor to Leber congenital amaurosis, the IVS26 cryptic-splice mutation in CEP290, and demonstrated correction of the transcript and protein in patient iPSCs. Lastly, we designed allele-specific CRISPR guides that selectively target the mutant Pro23His rhodopsin (RHO) allele, which, following delivery to both patient iPSCs in vitro and pig retina in vivo, created a frameshift and premature stop that would prevent transcription of the disease-causing variant. The strategies developed in this study will prove useful for correcting a wide range of genetic variants in genes that cause inherited retinal degeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  9. Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina

    PubMed Central

    Zhou, Liang; Wang, Wei; Liu, Yongqing; de Castro, Juan Fernandez; Ezashi, Toshihiko; Telugu, Bhanu Prakash V.L.; Roberts, R. Michael; Kaplan, Henry J.; Dean, Douglas C.

    2014-01-01

    Absence of a regenerative pathway for damaged retina following injury or disease has led to experiments utilizing stem cell transplantation for retinal repair, and encouraging results have been obtained in rodents. The swine eye is a closer anatomical and physiological match to the human eye, but embryonic stem cells have not been isolated from pig, and photoreceptor differentiation has not been demonstrated with swine induced pluripotent stem cells (iPSC). Here, we subjected swine iPSC to a rod photoreceptor differentiation protocol consisting of floating culture as embryoid bodies followed by differentiation in adherent culture. Real time PCR and immunostaining of differentiated cells demonstrated loss of expression of the pluripotent genes POU5F1, NANOG and SOX2 and induction of rod photoreceptor genes RCVRN, NRL, RHO and ROM1. While these differentiated cells displayed neuronal morphology, culturing on a Matrigel substratum triggered a further morphological change resulting in concentration of RHO and ROM1 in outer segment-like projections resembling those on primary cultures of rod photoreceptors. The differentiated cells were transplanted into the subretinal space of pigs treated with iodoacetic acid to eliminate rod photoreceptors. Three weeks after transplantation, engrafted RHO+ cells were evident in the outer nuclear layer where photoreceptors normally reside. A portion of these transplanted cells had generated projections resembling outer segments. These results demonstrate that swine iPSC can differentiate into photoreceptors in culture and these cells can integrate into the damaged swine neural retina thus laying a foundation for future studies using the pig as a model for retinal stem cell transplantation. PMID:21491544

  10. Scanning for safety: an integrated approach to improved bar-code medication administration.

    PubMed

    Early, Cynde; Riha, Chris; Martin, Jennifer; Lowdon, Karen W; Harvey, Ellen M

    2011-03-01

    This is a review of lessons learned in the postimplementation evaluation of a bar-code medication administration technology implemented at a major tertiary-care hospital in 2001. In 2006, with a bar-code medication administration scan compliance rate of 82%, a near-miss sentinel event prompted review of this technology as part of an institutional recommitment to a "culture of safety." Multifaceted problems with bar-code medication administration created an environment of circumventing safeguards as demonstrated by an increase in manual overrides to ensure timely medication administration. A multiprofessional team composed of nursing, pharmacy, human resources, quality, and technical services formalized. Each step in the bar-code medication administration process was reviewed. Technology, process, and educational solutions were identified and implemented systematically. Overall compliance with bar-code medication administration rose from 82% to 97%, which resulted in a calculated cost avoidance of more than $2.8 million during this time frame of the project.

  11. Interface design of VSOP'94 computer code for safety analysis

    NASA Astrophysics Data System (ADS)

    Natsir, Khairina; Yazid, Putranto Ilham; Andiwijayakusuma, D.; Wahanani, Nursinta Adi

    2014-09-01

    Today, most software applications, also in the nuclear field, come with a graphical user interface. VSOP'94 (Very Superior Old Program), was designed to simplify the process of performing reactor simulation. VSOP is a integrated code system to simulate the life history of a nuclear reactor that is devoted in education and research. One advantage of VSOP program is its ability to calculate the neutron spectrum estimation, fuel cycle, 2-D diffusion, resonance integral, estimation of reactors fuel costs, and integrated thermal hydraulics. VSOP also can be used to comparative studies and simulation of reactor safety. However, existing VSOP is a conventional program, which was developed using Fortran 65 and have several problems in using it, for example, it is only operated on Dec Alpha mainframe platforms and provide text-based output, difficult to use, especially in data preparation and interpretation of results. We develop a GUI-VSOP, which is an interface program to facilitate the preparation of data, run the VSOP code and read the results in a more user friendly way and useable on the Personal 'Computer (PC). Modifications include the development of interfaces on preprocessing, processing and postprocessing. GUI-based interface for preprocessing aims to provide a convenience way in preparing data. Processing interface is intended to provide convenience in configuring input files and libraries and do compiling VSOP code. Postprocessing interface designed to visualized the VSOP output in table and graphic forms. GUI-VSOP expected to be useful to simplify and speed up the process and analysis of safety aspects.

  12. Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome.

    PubMed

    Chin, Eunice W M; Marcy, Guillaume; Yoon, Su-In; Ma, Dongliang; Rosales, Francisco J; Augustine, George J; Goh, Eyleen L K

    2016-09-01

    Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 (R306C) and MECP2 (1155Δ32)) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amount of synaptic input, evident both as fewer Synapsin 1-positive puncta and a lower frequency of spontaneous excitatory postsynaptic currents. Supplementation of the culture media with choline rescued all of these defects. Choline supplementation may act through changes in the expression of choline acetyltransferase, an important enzyme in cholinergic signaling, and also through alterations in the lipid metabolite profiles of the RTT neurons. Our study elucidates the possible mechanistic pathways for the effect of choline on human RTT cell models, thereby illustrating the potential for using choline as a nutraceutical to treat RTT.

  13. The Potential of iPSCs for the Treatment of Premature Aging Disorders

    PubMed Central

    Compagnucci, Claudia; Bertini, Enrico

    2017-01-01

    Premature aging disorders including Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome, are a group of rare monogenic diseases leading to reduced lifespan of the patients. Importantly, these disorders mimic several features of physiological aging. Despite the interest on the study of these diseases, the underlying biological mechanisms remain unknown and no treatment is available. Recent studies on HGPS (due to mutations of the LMNA gene encoding for the nucleoskeletal proteins lamin A/C) have reported disruptions in cellular and molecular mechanisms modulating genomic stability and stem cell populations, thus giving the nuclear lamina a relevant function in nuclear organization, epigenetic regulation and in the maintenance of the stem cell pool. In this context, modeling premature aging with induced pluripotent stem cells (iPSCs) offers the possibility to study these disorders during self-renewal and differentiation into relevant cell types. iPSCs generated by cellular reprogramming from adult somatic cells allows researchers to understand pathophysiological mechanisms and enables the performance of drug screenings. Moreover, the recent development of precision genome editing offers the possibility to study the complex mechanisms underlying senescence and the possibility to correct disease phenotypes, paving the way for future therapeutic interventions. PMID:29112121

  14. The Balance of Excitatory and Inhibitory Synaptic Inputs for Coding Sound Location

    PubMed Central

    Ono, Munenori

    2014-01-01

    The localization of high-frequency sounds in the horizontal plane uses an interaural-level difference (ILD) cue, yet little is known about the synaptic mechanisms that underlie processing this cue in the inferior colliculus (IC) of mouse. Here, we study the synaptic currents that process ILD in vivo and use stimuli in which ILD varies around a constant average binaural level (ABL) to approximate sounds on the horizontal plane. Monaural stimulation in either ear produced EPSCs and IPSCs in most neurons. The temporal properties of monaural responses were well matched, suggesting connected functional zones with matched inputs. The EPSCs had three patterns in response to ABL stimuli, preference for the sound field with the highest level stimulus: (1) contralateral; (2) bilateral highly lateralized; or (3) at the center near 0 ILD. EPSCs and IPSCs were well correlated except in center-preferred neurons. Summation of the monaural EPSCs predicted the binaural excitatory response but less well than the summation of monaural IPSCs. Binaural EPSCs often showed a nonlinearity that strengthened the response to specific ILDs. Extracellular spike and intracellular current recordings from the same neuron showed that the ILD tuning of the spikes was sharper than that of the EPSCs. Thus, in the IC, balanced excitatory and inhibitory inputs may be a general feature of synaptic coding for many types of sound processing. PMID:24599475

  15. cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

    PubMed Central

    Wiley, Luke A.; Burnight, Erin R.; DeLuca, Adam P.; Anfinson, Kristin R.; Cranston, Cathryn M.; Kaalberg, Emily E.; Penticoff, Jessica A.; Affatigato, Louisa M.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

    2016-01-01

    Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

  16. BESAFE II: Accident safety analysis code for MFE reactor designs

    NASA Astrophysics Data System (ADS)

    Sevigny, Lawrence Michael

    The viability of controlled thermonuclear fusion as an alternative energy source hinges on its desirability from an economic and an environmental and safety standpoint. It is the latter which is the focus of this thesis. For magnetic fusion energy (MFE) devices, the safety concerns equate to a design's behavior during a worst-case accident scenario which is the loss of coolant accident (LOCA). In this dissertation, we examine the behavior of MFE devices during a LOCA and how this behavior relates to the safety characteristics of the machine; in particular the acute, whole-body, early dose. In doing so, we have produced an accident safety code, BESAFE II, now available to the fusion reactor design community. The Appendix constitutes the User's Manual for BESAFE II. The theory behind early dose calculations including the mobilization of activation products is presented in Chapter 2. Since mobilization of activation products is a strong function of temperature, it becomes necessary to calculate the thermal response of a design during a LOCA in order to determine the fraction of the activation products which are mobilized and thus become the source for the dose. The code BESAFE II is designed to determine the temperature history of each region of a design and determine the resulting mobilization of activation products at each point in time during the LOCA. The BESAFE II methodology is discussed in Chapter 4, followed by demonstrations of its use for two reference design cases: a PCA-Li tokamak and a SiC-He tokamak. Of these two cases, it is shown that the SiC-He tokamak is a better design from an accident safety standpoint than the PCA-Li tokamak. It is also found that doses derived from temperature-dependent mobilization data are different than those predicted using set mobilization categories such as those that involve Piet fractions. This demonstrates the need for more experimental data on fusion materials. The possibility for future improvements and modifications

  17. PharmARTS: terminology web services for drug safety data coding and retrieval.

    PubMed

    Alecu, Iulian; Bousquet, Cédric; Degoulet, Patrice; Jaulent, Marie-Christine

    2007-01-01

    MedDRA and WHO-ART are the terminologies used to encode drug safety reports. The standardisation achieved with these terminologies facilitates: 1) The sharing of safety databases; 2) Data mining for the continuous reassessment of benefit-risk ratio at national or international level or in the pharmaceutical industry. There is some debate about the capacity of these terminologies for retrieving case reports related to similar medical conditions. We have developed a resource that allows grouping similar medical conditions more effectively than WHO-ART and MedDRA. We describe here a software tool facilitating the use of this terminological resource thanks to an RDF framework with support for RDF Schema inferencing and querying. This tool eases coding and data retrieval in drug safety.

  18. FY2017 Updates to the SAS4A/SASSYS-1 Safety Analysis Code

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

    Fanning, T. H.

    The SAS4A/SASSYS-1 safety analysis software is used to perform deterministic analysis of anticipated events as well as design-basis and beyond-design-basis accidents for advanced fast reactors. It plays a central role in the analysis of U.S. DOE conceptual designs, proposed test and demonstration reactors, and in domestic and international collaborations. This report summarizes the code development activities that have taken place during FY2017. Extensions to the void and cladding reactivity feedback models have been implemented, and Control System capabilities have been improved through a new virtual data acquisition system for plant state variables and an additional Block Signal for a variablemore » lag compensator to represent reactivity feedback for novel shutdown devices. Current code development and maintenance needs are also summarized in three key areas: software quality assurance, modeling improvements, and maintenance of related tools. With ongoing support, SAS4A/SASSYS-1 can continue to fulfill its growing role in fast reactor safety analysis and help solidify DOE’s leadership role in fast reactor safety both domestically and in international collaborations.« less

  19. Generation of a human iPSC line from a patient with Leigh syndrome.

    PubMed

    Galera, Teresa; Zurita, Francisco; González-Páramos, Cristina; Moreno-Izquierdo, Ana; Fraga, Mario F; Fernández, Agustin F; Garesse, Rafael; Gallardo, M Esther

    2016-01-01

    Human iPSC line LND554SV.3 was generated from heteroplasmic fibroblasts of a patient with Leigh syndrome carrying a mutation in the MT-ND5 gene (m.13513GNA; p.D393N). Reprogramming factors Oct3/4, Sox2, Klf4,and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus.

  20. Development of the FHR advanced natural circulation analysis code and application to FHR safety analysis

    DOE PAGES

    Guo, Z.; Zweibaum, N.; Shao, M.; ...

    2016-04-19

    The University of California, Berkeley (UCB) is performing thermal hydraulics safety analysis to develop the technical basis for design and licensing of fluoride-salt-cooled, high-temperature reactors (FHRs). FHR designs investigated by UCB use natural circulation for emergency, passive decay heat removal when normal decay heat removal systems fail. The FHR advanced natural circulation analysis (FANCY) code has been developed for assessment of passive decay heat removal capability and safety analysis of these innovative system designs. The FANCY code uses a one-dimensional, semi-implicit scheme to solve for pressure-linked mass, momentum and energy conservation equations. Graph theory is used to automatically generate amore » staggered mesh for complicated pipe network systems. Heat structure models have been implemented for three types of boundary conditions (Dirichlet, Neumann and Robin boundary conditions). Heat structures can be composed of several layers of different materials, and are used for simulation of heat structure temperature distribution and heat transfer rate. Control models are used to simulate sequences of events or trips of safety systems. A proportional-integral controller is also used to automatically make thermal hydraulic systems reach desired steady state conditions. A point kinetics model is used to model reactor kinetics behavior with temperature reactivity feedback. The underlying large sparse linear systems in these models are efficiently solved by using direct and iterative solvers provided by the SuperLU code on high performance machines. Input interfaces are designed to increase the flexibility of simulation for complicated thermal hydraulic systems. In conclusion, this paper mainly focuses on the methodology used to develop the FANCY code, and safety analysis of the Mark 1 pebble-bed FHR under development at UCB is performed.« less

  1. Molecular analysis of neutrophil differentiation from human iPSCs delineates the kinetics of key regulators of hematopoiesis

    PubMed Central

    Sweeney, Colin L.; Teng, Ruifeng; Wang, Hongmei; Merling, Randall K.; Lee, Janet; Choi, Uimook; Koontz, Sherry; Wright, Daniel G.; Malech, Harry L.

    2016-01-01

    In vitro generation of mature neutrophils from human induced pluripotent stem cells (iPSCs) requires hematopoietic progenitor development followed by myeloid differentiation. The purpose of our studies was to extensively characterize this process, focusing on the critical window of development between hemogenic endothelium, hematopoietic stem/progenitor cells (HSPCs), and myeloid commitment, to identify associated regulators and markers that might enable the stem cell field to improve the efficiency and efficacy of iPSC hematopoiesis. We utilized a 4-stage differentiation protocol involving: embryoid body (EB) formation (Stage-1); EB culture with hematopoietic cytokines (Stage-2); HSPC expansion (Stage-3); and neutrophil maturation (Stage-4). CD34+CD45− putative hemogenic endothelial cells were observed in Stage-3 cultures, and expressed VEGFR-2/Flk-1/KDR and VE-cadherin endothelial markers, GATA-2, AML1/RUNX1, and SCL/TAL1 transcription factors, and endothelial/HSPC-associated microRNAs miR-24, miR-125a-3p, miR-126/126*, and miR-155. Upon further culture, CD34+CD45− cells generated CD34+CD45+ HSPCs that produced hematopoietic CFUs. Mid-Stage-3 CD34+CD45+ HSPCs exhibited increased expression of GATA-2, AML1/RUNX1, SCL/TAL1, C/EBPα, and PU.1 transcription factors, but exhibited decreased expression of HSPC-associated microRNAs, and failed to engraft in immune-deficient mice. Mid-stage-3 CD34−CD45+ cells maintained PU.1 expression and exhibited increased expression of hematopoiesis-associated miR-142-3p/5p and a trend towards increased miR-223 expression, indicating myeloid commitment. By late Stage-4, increased CD15, CD16b, and C/EBPε expression were observed, with 25–65% of cells exhibiting morphology and functions of mature neutrophils. These studies demonstrate that hematopoiesis and neutrophil differentiation from human iPSCs recapitulates many features of embryonic hematopoiesis and neutrophil production in marrow, but reveals unexpected molecular

  2. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM).

    PubMed

    Xiong, Kai; Zhou, Yan; Hyttel, Poul; Bolund, Lars; Freude, Kristine Karla; Luo, Yonglun

    2016-11-01

    Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated. These SAM-iPSCs provide a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

  3. TOOKUIL: A case study in user interface development for safety code application

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

    Gray, D.L.; Harkins, C.K.; Hoole, J.G.

    1997-07-01

    Traditionally, there has been a very high learning curve associated with using nuclear power plant (NPP) analysis codes. Even for seasoned plant analysts and engineers, the process of building or modifying an input model for present day NPP analysis codes is tedious, error prone, and time consuming. Current cost constraints and performance demands place an additional burden on today`s safety analysis community. Advances in graphical user interface (GUI) technology have been applied to obtain significant productivity and quality assurance improvements for the Transient Reactor Analysis Code (TRAC) input model development. KAPL Inc. has developed an X Windows-based graphical user interfacemore » named TOOKUIL which supports the design and analysis process, acting as a preprocessor, runtime editor, help system, and post processor for TRAC. This paper summarizes the objectives of the project, the GUI development process and experiences, and the resulting end product, TOOKUIL.« less

  4. Parallelization of Finite Element Analysis Codes Using Heterogeneous Distributed Computing

    NASA Technical Reports Server (NTRS)

    Ozguner, Fusun

    1996-01-01

    Performance gains in computer design are quickly consumed as users seek to analyze larger problems to a higher degree of accuracy. Innovative computational methods, such as parallel and distributed computing, seek to multiply the power of existing hardware technology to satisfy the computational demands of large applications. In the early stages of this project, experiments were performed using two large, coarse-grained applications, CSTEM and METCAN. These applications were parallelized on an Intel iPSC/860 hypercube. It was found that the overall speedup was very low, due to large, inherently sequential code segments present in the applications. The overall execution time T(sub par), of the application is dependent on these sequential segments. If these segments make up a significant fraction of the overall code, the application will have a poor speedup measure.

  5. Both TALENs and CRISPR/Cas9 directly target the HBB IVS2-654 (C > T) mutation in β-thalassemia-derived iPSCs.

    PubMed

    Xu, Peng; Tong, Ying; Liu, Xiu-zhen; Wang, Ting-ting; Cheng, Li; Wang, Bo-yu; Lv, Xiang; Huang, Yue; Liu, De-pei

    2015-07-09

    β-Thalassemia is one of the most common genetic blood diseases and is caused by either point mutations or deletions in the β-globin (HBB) gene. The generation of patient-specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations may be a potential therapeutic strategy for this disease. Due to the low efficiency of typical homologous recombination, endonucleases, including TALENs and CRISPR/Cas9, have been widely used to enhance the gene correction efficiency in patient-derived iPSCs. Here, we designed TALENs and CRISPR/Cas9 to directly target the intron2 mutation site IVS2-654 in the globin gene. We observed different frequencies of double-strand breaks (DSBs) at IVS2-654 loci using TALENs and CRISPR/Cas9, and TALENs mediated a higher homologous gene targeting efficiency compared to CRISPR/Cas9 when combined with the piggyBac transposon donor. In addition, more obvious off-target events were observed for CRISPR/Cas9 compared to TALENs. Finally, TALENs-corrected iPSC clones were selected for erythroblast differentiation using the OP9 co-culture system and detected relatively higher transcription of HBB than the uncorrected cells. This comparison of using TALENs or CRISPR/Cas9 to correct specific HBB mutations in patient-derived iPSCs will guide future applications of TALENs- or CRISPR/Cas9-based gene therapies in monogenic diseases.

  6. Performance of a parallel code for the Euler equations on hypercube computers

    NASA Technical Reports Server (NTRS)

    Barszcz, Eric; Chan, Tony F.; Jesperson, Dennis C.; Tuminaro, Raymond S.

    1990-01-01

    The performance of hypercubes were evaluated on a computational fluid dynamics problem and the parallel environment issues were considered that must be addressed, such as algorithm changes, implementation choices, programming effort, and programming environment. The evaluation focuses on a widely used fluid dynamics code, FLO52, which solves the two dimensional steady Euler equations describing flow around the airfoil. The code development experience is described, including interacting with the operating system, utilizing the message-passing communication system, and code modifications necessary to increase parallel efficiency. Results from two hypercube parallel computers (a 16-node iPSC/2, and a 512-node NCUBE/ten) are discussed and compared. In addition, a mathematical model of the execution time was developed as a function of several machine and algorithm parameters. This model accurately predicts the actual run times obtained and is used to explore the performance of the code in interesting but yet physically realizable regions of the parameter space. Based on this model, predictions about future hypercubes are made.

  7. Reactivation of maternal SNORD116 cluster via SETDB1 knockdown in Prader-Willi syndrome iPSCs

    PubMed Central

    Cruvinel, Estela; Budinetz, Tara; Germain, Noelle; Chamberlain, Stormy; Lalande, Marc; Martins-Taylor, Kristen

    2014-01-01

    Prader-Willi syndrome (PWS), a disorder of genomic imprinting, is characterized by neonatal hypotonia, hypogonadism, small hands and feet, hyperphagia and obesity in adulthood. PWS results from the loss of paternal copies of the cluster of SNORD116 C/D box snoRNAs and their host transcript, 116HG, on human chromosome 15q11-q13. We have investigated the mechanism of repression of the maternal SNORD116 cluster and 116HG. Here, we report that the zinc-finger protein ZNF274, in association with the histone H3 lysine 9 (H3K9) methyltransferase SETDB1, is part of a complex that binds to the silent maternal but not the active paternal alleles. Knockdown of SETDB1 in PWS-specific induced pluripotent cells (iPSCs) causes a decrease in the accumulation of H3K9 trimethylation (H3K9me3) at 116HG and corresponding accumulation of the active chromatin mark histone H3 lysine 4 dimethylation (H3K4me2). We also show that upon knockdown of SETDB1 in PWS-specific iPSCs, expression of maternally silenced 116HG RNA is partially restored. SETDB1 knockdown in PWS iPSCs also disrupts DNA methylation at the PWS-IC where a decrease in 5-methylcytosine is observed in association with a concomitant increase in 5-hydroxymethylcytosine. This observation suggests that the ZNF274/SETDB1 complex bound to the SNORD116 cluster may protect the PWS-IC from DNA demethylation during early development. Our findings reveal novel epigenetic mechanisms that function to repress the maternal 15q11-q13 region. PMID:24760766

  8. Certifying Auto-Generated Flight Code

    NASA Technical Reports Server (NTRS)

    Denney, Ewen

    2008-01-01

    Model-based design and automated code generation are being used increasingly at NASA. Many NASA projects now use MathWorks Simulink and Real-Time Workshop for at least some of their modeling and code development. However, there are substantial obstacles to more widespread adoption of code generators in safety-critical domains. Since code generators are typically not qualified, there is no guarantee that their output is correct, and consequently the generated code still needs to be fully tested and certified. Moreover, the regeneration of code can require complete recertification, which offsets many of the advantages of using a generator. Indeed, manual review of autocode can be more challenging than for hand-written code. Since the direct V&V of code generators is too laborious and complicated due to their complex (and often proprietary) nature, we have developed a generator plug-in to support the certification of the auto-generated code. Specifically, the AutoCert tool supports certification by formally verifying that the generated code is free of different safety violations, by constructing an independently verifiable certificate, and by explaining its analysis in a textual form suitable for code reviews. The generated documentation also contains substantial tracing information, allowing users to trace between model, code, documentation, and V&V artifacts. This enables missions to obtain assurance about the safety and reliability of the code without excessive manual V&V effort and, as a consequence, eases the acceptance of code generators in safety-critical contexts. The generation of explicit certificates and textual reports is particularly well-suited to supporting independent V&V. The primary contribution of this approach is the combination of human-friendly documentation with formal analysis. The key technical idea is to exploit the idiomatic nature of auto-generated code in order to automatically infer logical annotations. The annotation inference algorithm

  9. Improving radiopharmaceutical supply chain safety by implementing bar code technology.

    PubMed

    Matanza, David; Hallouard, François; Rioufol, Catherine; Fessi, Hatem; Fraysse, Marc

    2014-11-01

    The aim of this study was to describe and evaluate an approach for improving radiopharmaceutical supply chain safety by implementing bar code technology. We first evaluated the current situation of our radiopharmaceutical supply chain and, by means of the ALARM protocol, analysed two dispensing errors that occurred in our department. Thereafter, we implemented a bar code system to secure selected key stages of the radiopharmaceutical supply chain. Finally, we evaluated the cost of this implementation, from overtime, to overheads, to additional radiation exposure to workers. An analysis of the events that occurred revealed a lack of identification of prepared or dispensed drugs. Moreover, the evaluation of the current radiopharmaceutical supply chain showed that the dispensation and injection steps needed to be further secured. The bar code system was used to reinforce product identification at three selected key stages: at usable stock entry; at preparation-dispensation; and during administration, allowing to check conformity between the labelling of the delivered product (identity and activity) and the prescription. The extra time needed for all these steps had no impact on the number and successful conduct of examinations. The investment cost was reduced (2600 euros for new material and 30 euros a year for additional supplies) because of pre-existing computing equipment. With regard to the radiation exposure to workers there was an insignificant overexposure for hands with this new organization because of the labelling and scanning processes of radiolabelled preparation vials. Implementation of bar code technology is now an essential part of a global securing approach towards optimum patient management.

  10. The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice.

    PubMed

    Ou, Zhanhui; Niu, Xiaohua; He, Wenyin; Chen, Yuchang; Song, Bing; Xian, Yexing; Fan, Di; Tang, Daolin; Sun, Xiaofang

    2016-09-01

    β-thalassemia results from point mutations or small deletions in the β-globin (HBB) gene that ultimately cause anemia. The generation of induced pluripotent stem cells (iPSCs) from the somatic cells of patients in combination with subsequent homologous recombination-based gene correction provides new approaches to cure this disease. CRISPR/Cas9 is a genome editing tool that is creating a buzz in the scientific community for treating human diseases, especially genetic disorders. Here, we reported that correction of β-thalassemia mutations in patient-specific iPSCs using the CRISPR/Cas9 tool promotes hematopoietic differentiation in vivo. CRISPR/Cas9-corrected iPSC-derived hematopoietic stem cells (HSCs) were injected into sublethally-irradiated NOD-scid-IL2Rg-/- (NSI) mice. HBB expression was observed in these HSCs after hematopoietic differentiation in the NSI mice. Importantly, no tumor was found in the livers, lungs, kidneys, or bone marrow at 10 weeks in the NSI mice after implantation with these HSCs. Collectively, our findings demonstrated that CRISPR/Cas9 successfully corrects β-thalassemia mutations in patient-specific iPSCs. These CRISPR/Cas9-corrected iPSC-derived HSCs express normal HBB in mice without tumorigenic potential, suggesting a safe strategy for personalized treatment of β-thalassemia.

  11. The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs.

    PubMed

    Liu, Qidong; Wang, Guiying; Lyu, Yao; Bai, Mingliang; Jiapaer, Zeyidan; Jia, Wenwen; Han, Tong; Weng, Rong; Yang, Yiwei; Yu, Yangyang; Kang, Jiuhong

    2018-06-06

    During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (Acvr2a) is the downstream target and mediates the function of miR-590. Downregulation of Acvr2a promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shAcvr2a-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Effect of bar-code technology on the safety of medication administration.

    PubMed

    Poon, Eric G; Keohane, Carol A; Yoon, Catherine S; Ditmore, Matthew; Bane, Anne; Levtzion-Korach, Osnat; Moniz, Thomas; Rothschild, Jeffrey M; Kachalia, Allen B; Hayes, Judy; Churchill, William W; Lipsitz, Stuart; Whittemore, Anthony D; Bates, David W; Gandhi, Tejal K

    2010-05-06

    that the bar-code eMAR is an important intervention to improve medication safety. (ClinicalTrials.gov number, NCT00243373.) 2010 Massachusetts Medical Society

  13. Overview of the U.S. DOE Hydrogen Safety, Codes and Standards Program. Part 4: Hydrogen Sensors; Preprint

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

    Buttner, William J.; Rivkin, Carl; Burgess, Robert

    Hydrogen sensors are recognized as a critical element in the safety design for any hydrogen system. In this role, sensors can perform several important functions including indication of unintended hydrogen releases, activation of mitigation strategies to preclude the development of dangerous situations, activation of alarm systems and communication to first responders, and to initiate system shutdown. The functionality of hydrogen sensors in this capacity is decoupled from the system being monitored, thereby providing an independent safety component that is not affected by the system itself. The importance of hydrogen sensors has been recognized by DOE and by the Fuel Cellmore » Technologies Office's Safety and Codes Standards (SCS) program in particular, which has for several years supported hydrogen safety sensor research and development. The SCS hydrogen sensor programs are currently led by the National Renewable Energy Laboratory, Los Alamos National Laboratory, and Lawrence Livermore National Laboratory. The current SCS sensor program encompasses the full range of issues related to safety sensors, including development of advance sensor platforms with exemplary performance, development of sensor-related code and standards, outreach to stakeholders on the role sensors play in facilitating deployment, technology evaluation, and support on the proper selection and use of sensors.« less

  14. Potential Role of Induced Pluripotent Stem Cells (IPSCs) for Cell-Based Therapy of the Ocular Surface

    PubMed Central

    Casaroli-Marano, Ricardo P.; Nieto-Nicolau, Núria; Martínez-Conesa, Eva M.; Edel, Michael; Álvarez-Palomo, Ana B.

    2015-01-01

    The integrity and normal function of the corneal epithelium are crucial for maintaining the cornea’s transparency and vision. The existence of a cell population with progenitor characteristics in the limbus maintains a dynamic of constant epithelial repair and renewal. Currently, cell-based therapies for bio replacement—cultured limbal epithelial transplantation (CLET) and cultured oral mucosal epithelial transplantation (COMET)—present very encouraging clinical results for treating limbal stem cell deficiency (LSCD) and restoring vision. Another emerging therapeutic approach consists of obtaining and implementing human progenitor cells of different origins in association with tissue engineering methods. The development of cell-based therapies using stem cells, such as human adult mesenchymal or induced pluripotent stem cells (IPSCs), represent a significant breakthrough in the treatment of certain eye diseases, offering a more rational, less invasive, and better physiological treatment option in regenerative medicine for the ocular surface. This review will focus on the main concepts of cell-based therapies for the ocular surface and the future use of IPSCs to treat LSCD. PMID:26239129

  15. Both TALENs and CRISPR/Cas9 directly target the HBB IVS2–654 (C > T) mutation in β-thalassemia-derived iPSCs

    PubMed Central

    Xu, Peng; Tong, Ying; Liu, Xiu-zhen; Wang, Ting-ting; Cheng, Li; Wang, Bo-yu; Lv, Xiang; Huang, Yue; Liu, De-pei

    2015-01-01

    β-Thalassemia is one of the most common genetic blood diseases and is caused by either point mutations or deletions in the β-globin (HBB) gene. The generation of patient-specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations may be a potential therapeutic strategy for this disease. Due to the low efficiency of typical homologous recombination, endonucleases, including TALENs and CRISPR/Cas9, have been widely used to enhance the gene correction efficiency in patient-derived iPSCs. Here, we designed TALENs and CRISPR/Cas9 to directly target the intron2 mutation site IVS2-654 in the globin gene. We observed different frequencies of double-strand breaks (DSBs) at IVS2-654 loci using TALENs and CRISPR/Cas9, and TALENs mediated a higher homologous gene targeting efficiency compared to CRISPR/Cas9 when combined with the piggyBac transposon donor. In addition, more obvious off-target events were observed for CRISPR/Cas9 compared to TALENs. Finally, TALENs-corrected iPSC clones were selected for erythroblast differentiation using the OP9 co-culture system and detected relatively higher transcription of HBB than the uncorrected cells. This comparison of using TALENs or CRISPR/Cas9 to correct specific HBB mutations in patient-derived iPSCs will guide future applications of TALENs- or CRISPR/Cas9-based gene therapies in monogenic diseases. PMID:26156589

  16. Identifying the dynamics of actin and tubulin polymerization in iPSCs and in iPSC-derived neurons

    PubMed Central

    Magliocca, Valentina; Petrini, Stefania; Franchin, Tiziana; Borghi, Rossella; Niceforo, Alessia; Abbaszadeh, Zeinab; Bertini, Enrico; Compagnucci, Claudia

    2017-01-01

    The development of the nervous system requires cytoskeleton-mediated processes coordinating self-renewal, migration, and differentiation of neurons. It is not surprising that many neurodevelopmental problems and neurodegenerative disorders are caused by deficiencies in cytoskeleton-related genes. For this reason, we focus on the cytoskeletal dynamics in proliferating iPSCs and in iPSC-derived neurons to better characterize the underpinnings of cytoskeletal organization looking at actin and tubulin repolymerization studies using the cell permeable probes SiR-Actin and SiR-Tubulin. During neurogenesis, each neuron extends an axon in a complex and changing environment to reach its final target. The dynamic behavior of the growth cone and its capacity to respond to multiple spatial information allows it to find its correct target. We decided to characterize various parameters of the actin filaments and microtubules. Our results suggest that a rapid re-organization of the cytoskeleton occurs 45 minutes after treatments with de-polymerizing agents in iPSCs and 60 minutes in iPSC-derived neurons in both actin filaments and microtubules. The quantitative data confirm that the actin filaments have a primary role in the re-organization of the cytoskeleton soon after de-polymerization, while microtubules have a major function following cytoskeletal stabilization. In conclusion, we investigate the possibility that de-polymerization of the actin filaments may have an impact on microtubules organization and that de-polymerization of the microtubules may affect the stability of the actin filaments. Our results suggest that a reciprocal influence of the actin filaments occurs over the microtubules and vice versa in both in iPSCs and iPSC-derived neurons. PMID:29340040

  17. Roadmap to an Engineering-Scale Nuclear Fuel Performance & Safety Code

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

    Turner, John A; Clarno, Kevin T; Hansen, Glen A

    2009-09-01

    -development activities. Realizing the full benefits of this approach will likely take some time. However, it is important that the developmental activities for modeling and simulation be tightly coupled with the experimental activities to maximize feedback effects and accelerate both the experimental and analytical elements of the program toward a common objective. The close integration of modeling and simulation and experimental activities is key to developing a useful fuel performance simulation capability, providing a validated design and analysis tool, and understanding the uncertainties within the models and design process. The efforts of this project are integrally connected to the Transmutation Fuels Campaign (TFC), which maintains as a primary objective to formulate, fabricate, and qualify a transuranic-based fuel with added minor actinides for use in future fast reactors. Additional details of the TFC scope can be found in the Transmutation Fuels Campaign Execution Plan. This project is an integral component of the TFC modeling and simulation effort, and this multiyear plan borrowed liberally from the Transmutation Fuels Campaign Modeling and Simulation Roadmap. This document provides the multiyear staged development plan to develop a continuum-level Integrated Performance and Safety Code (IPSC) to predict the behavior of the fuel and cladding during normal reactor operations and anticipated transients up to the point of clad breach.« less

  18. Apoptosis in Porcine Pluripotent Cells: From ICM to iPSCs

    PubMed Central

    Kim, Eunhye; Hyun, Sang-Hwan

    2016-01-01

    Pigs have great potential to provide preclinical models for human disease in translational research because of their similarities with humans. In this regard, porcine pluripotent cells, which are able to differentiate into cells of all three primary germ layers, might be a suitable animal model for further development of regenerative medicine. Here, we describe the current state of knowledge on apoptosis in pluripotent cells including inner cell mass (ICM), epiblast, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Information is focused on the apoptotic phenomenon in pluripotency, maintenance, and differentiation of pluripotent stem cells and reprogramming of somatic cells in pigs. Additionally, this review examines the multiple roles of apoptosis and summarizes recent progress in porcine pluripotent cells. PMID:27626414

  19. Lymphoblast-derived integration-free iPSC line AD-TREM2-3 from a 74 year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant.

    PubMed

    Martins, Soraia; Yigit, Hatice; Bohndorf, Martina; Graffmann, Nina; Fiszl, Aurelian Robert; Wruck, Wasco; Sleegers, Kristel; Van Broeckhoven, Christine; Adjaye, James

    2018-06-01

    Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, KLF4, LIN28, L-MYC and p53 shRNA. The derived iPSC line - AD-TREM2-3 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0.940. Copyright © 2018. Published by Elsevier B.V.

  20. Deriving ICD-10 Codes for Patient Safety Indicators for Large-scale Surveillance Using Administrative Hospital Data.

    PubMed

    Southern, Danielle A; Burnand, Bernard; Droesler, Saskia E; Flemons, Ward; Forster, Alan J; Gurevich, Yana; Harrison, James; Quan, Hude; Pincus, Harold A; Romano, Patrick S; Sundararajan, Vijaya; Kostanjsek, Nenad; Ghali, William A

    2017-03-01

    Existing administrative data patient safety indicators (PSIs) have been limited by uncertainty around the timing of onset of included diagnoses. We undertook de novo PSI development through a data-driven approach that drew upon "diagnosis timing" information available in some countries' administrative hospital data. Administrative database analysis and modified Delphi rating process. All hospitalized adults in Canada in 2009. We queried all hospitalizations for ICD-10-CA diagnosis codes arising during hospital stay. We then undertook a modified Delphi panel process to rate the extent to which each of the identified diagnoses has a potential link to suboptimal quality of care. We grouped the identified quality/safety-related diagnoses into relevant clinical categories. Lastly, we queried Alberta hospital discharge data to assess the frequency of the newly defined PSI events. Among 2,416,413 national hospitalizations, we found 2590 unique ICD-10-CA codes flagged as having arisen after admission. Seven panelists evaluated these in a 2-round review process, and identified a listing of 640 ICD-10-CA diagnosis codes judged to be linked to suboptimal quality of care and thus appropriate for inclusion in PSIs. These were then grouped by patient safety experts into 18 clinically relevant PSI categories. We then analyzed data on 2,381,652 Alberta hospital discharges from 2005 through 2012, and found that 134,299 (5.2%) hospitalizations had at least 1 PSI diagnosis. The resulting work creates a foundation for a new set of PSIs for routine large-scale surveillance of hospital and health system performance.

  1. The EUCLID/V1 Integrated Code for Safety Assessment of Liquid Metal Cooled Fast Reactors. Part 1: Basic Models

    NASA Astrophysics Data System (ADS)

    Mosunova, N. A.

    2018-05-01

    The article describes the basic models included in the EUCLID/V1 integrated code intended for safety analysis of liquid metal (sodium, lead, and lead-bismuth) cooled fast reactors using fuel rods with a gas gap and pellet dioxide, mixed oxide or nitride uranium-plutonium fuel under normal operation, under anticipated operational occurrences and accident conditions by carrying out interconnected thermal-hydraulic, neutronics, and thermal-mechanical calculations. Information about the Russian and foreign analogs of the EUCLID/V1 integrated code is given. Modeled objects, equation systems in differential form solved in each module of the EUCLID/V1 integrated code (the thermal-hydraulic, neutronics, fuel rod analysis module, and the burnup and decay heat calculation modules), the main calculated quantities, and also the limitations on application of the code are presented. The article also gives data on the scope of functions performed by the integrated code's thermal-hydraulic module, using which it is possible to describe both one- and twophase processes occurring in the coolant. It is shown that, owing to the availability of the fuel rod analysis module in the integrated code, it becomes possible to estimate the performance of fuel rods in different regimes of the reactor operation. It is also shown that the models implemented in the code for calculating neutron-physical processes make it possible to take into account the neutron field distribution over the fuel assembly cross section as well as other features important for the safety assessment of fast reactors.

  2. Applications and development of communication models for the touchstone GAMMA and DELTA prototypes

    NASA Technical Reports Server (NTRS)

    Seidel, Steven R.

    1993-01-01

    The goal of this project was to develop models of the interconnection networks of the Intel iPSC/860 and DELTA multicomputers to guide the design of efficient algorithms for interprocessor communication in problems that commonly occur in CFD codes and other applications. Interprocessor communication costs of codes for message-passing architectures such as the iPSC/860 and DELTA significantly affect the level of performance that can be obtained from those machines. This project addressed several specific problems in the achievement of efficient communication on the Intel iPSC/860 hypercube and DELTA mesh. In particular, an efficient global processor synchronization algorithm was developed for the iPSC/860 and numerous broadcast algorithms were designed for the DELTA.

  3. The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model

    PubMed Central

    Murai, Kiyohito; Sun, Guoqiang; Ye, Peng; Tian, E.; Yang, Su; Cui, Qi; Sun, Guihua; Trinh, Daniel; Sun, Olivia; Hong, Teresa; Wen, Zhexing; Kalkum, Markus; Riggs, Arthur D.; Song, Hongjun; Ming, Guo-li; Shi, Yanhong

    2016-01-01

    Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation. PMID:26965827

  4. The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model.

    PubMed

    Murai, Kiyohito; Sun, Guoqiang; Ye, Peng; Tian, E; Yang, Su; Cui, Qi; Sun, Guihua; Trinh, Daniel; Sun, Olivia; Hong, Teresa; Wen, Zhexing; Kalkum, Markus; Riggs, Arthur D; Song, Hongjun; Ming, Guo-li; Shi, Yanhong

    2016-03-11

    Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation.

  5. Using Modified-ISS Model to Evaluate Medication Administration Safety During Bar Code Medication Administration Implementation in Taiwan Regional Teaching Hospital.

    PubMed

    Ma, Pei-Luen; Jheng, Yan-Wun; Jheng, Bi-Wei; Hou, I-Ching

    2017-01-01

    Bar code medication administration (BCMA) could reduce medical errors and promote patient safety. This research uses modified information systems success model (M-ISS model) to evaluate nurses' acceptance to BCMA. The result showed moderate correlation between medication administration safety (MAS) to system quality, information quality, service quality, user satisfaction, and limited satisfaction.

  6. Fire safety

    Treesearch

    Robert H. White; Mark A. Dietenberger

    1999-01-01

    Fire safety is an important concern in all types of construction. The high level of national concern for fire safety is reflected in limitations and design requirements in building codes. These code requirements are discussed in the context of fire safety design and evaluation in the initial section of this chapter. Since basic data on fire behavior of wood products...

  7. Uniform emergency codes: will they improve safety?

    PubMed

    2005-01-01

    There are pros and cons to uniform code systems, according to emergency medicine experts. Uniformity can be a benefit when ED nurses and other staff work at several facilities. It's critical that your staff understand not only what the codes stand for, but what they must do when codes are called. If your state institutes a new system, be sure to hold regular drills to familiarize your ED staff.

  8. Efficient implementation of a 3-dimensional ADI method on the iPSC/860

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

    Van der Wijngaart, R.F.

    1993-12-31

    A comparison is made between several domain decomposition strategies for the solution of three-dimensional partial differential equations on a MIMD distributed memory parallel computer. The grids used are structured, and the numerical algorithm is ADI. Important implementation issues regarding load balancing, storage requirements, network latency, and overlap of computations and communications are discussed. Results of the solution of the three-dimensional heat equation on the Intel iPSC/860 are presented for the three most viable methods. It is found that the Bruno-Cappello decomposition delivers optimal computational speed through an almost complete elimination of processor idle time, while providing good memory efficiency.

  9. Development of Safety Analysis Code System of Beam Transport and Core for Accelerator Driven System

    NASA Astrophysics Data System (ADS)

    Aizawa, Naoto; Iwasaki, Tomohiko

    2014-06-01

    Safety analysis code system of beam transport and core for accelerator driven system (ADS) is developed for the analyses of beam transients such as the change of the shape and position of incident beam. The code system consists of the beam transport analysis part and the core analysis part. TRACE 3-D is employed in the beam transport analysis part, and the shape and incident position of beam at the target are calculated. In the core analysis part, the neutronics, thermo-hydraulics and cladding failure analyses are performed by the use of ADS dynamic calculation code ADSE on the basis of the external source database calculated by PHITS and the cross section database calculated by SRAC, and the programs of the cladding failure analysis for thermoelastic and creep. By the use of the code system, beam transient analyses are performed for the ADS proposed by Japan Atomic Energy Agency. As a result, the rapid increase of the cladding temperature happens and the plastic deformation is caused in several seconds. In addition, the cladding is evaluated to be failed by creep within a hundred seconds. These results have shown that the beam transients have caused a cladding failure.

  10. Induced pluripotent stem cell-derived gamete-associated proteins incite rejection of induced pluripotent stem cells in syngeneic mice.

    PubMed

    Kim, Eun-Mi; Manzar, Gohar; Zavazava, Nicholas

    2017-06-01

    The safety of induced pluripotent stem cells (iPSCs) in autologous recipients has been questioned after iPSCs, but not embryonic stem cells (ESCs), were reported to be rejected in syngeneic mice. This important topic has remained controversial because there has not been a mechanistic explanation for this phenomenon. Here, we hypothesize that iPSCs, but not ESCs, readily differentiate into gamete-forming cells that express meiotic antigens normally found in immune-privileged gonads. Because peripheral blood T cells are not tolerized to these antigens in the thymus, gamete-associated-proteins (GAPs) sensitize T cells leading to rejection. Here, we provide evidence that GAPs expressed in iPSC teratomas, but not in ESC teratomas, are responsible for the immunological rejection of iPSCs. Furthermore, silencing the expression of Stra8, 'the master regulator of meiosis', in iPSCs, using short hairpin RNA led to significant abrogation of the rejection of iPSCs, supporting our central hypothesis that GAPs expressed after initiation of meiosis in iPSCs were responsible for rejection. In contrast to iPSCs, iPSC-derivatives, such as haematopoietic progenitor cells, are able to engraft long-term into syngeneic recipients because they no longer express GAPs. Our findings, for the first time, provide a unifying explanation of why iPSCs, but not ESCs, are rejected in syngeneic recipients, ending the current controversy on the safety of iPSCs and their derivatives. © 2017 John Wiley & Sons Ltd.

  11. Implementation of non-condensable gases condensation suppression model into the WCOBRA/TRAC-TF2 LOCA safety evaluation code

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

    Liao, J.; Cao, L.; Ohkawa, K.

    2012-07-01

    The non-condensable gases condensation suppression model is important for a realistic LOCA safety analysis code. A condensation suppression model for direct contact condensation was previously developed by Westinghouse using first principles. The model is believed to be an accurate description of the direct contact condensation process in the presence of non-condensable gases. The Westinghouse condensation suppression model is further revised by applying a more physical model. The revised condensation suppression model is thus implemented into the WCOBRA/TRAC-TF2 LOCA safety evaluation code for both 3-D module (COBRA-TF) and 1-D module (TRAC-PF1). Parametric study using the revised Westinghouse condensation suppression model ismore » conducted. Additionally, the performance of non-condensable gases condensation suppression model is examined in the ACHILLES (ISP-25) separate effects test and LOFT L2-5 (ISP-13) integral effects test. (authors)« less

  12. Derivation of Parathyroid Gland Cells and Their Progenitors fromInduced Pluripotent Stem Cells (iPSCs) for Personalized Therapy

    DTIC Science & Technology

    2016-09-01

    parathyroid hormone and GCM2, both markers of parathyroid tissues. 15. SUBJECT TERMS Induced pluripotent stem cells, ips cells, parathyroid, Crispr ...parathyroid organogenesis. The iPSCs are being modified with CRISPR or TALEN technology for sequence specific insertion of a GFP reporter into the...cells, parathyroid, Crispr /cas9, TALENS, pluripotent stem cells, hypoparathyroidism, 2 human homolog (Gcm2/GCMB), parathyroid hormone (PTH) and

  13. Natural Language Interface for Safety Certification of Safety-Critical Software

    NASA Technical Reports Server (NTRS)

    Denney, Ewen; Fischer, Bernd

    2011-01-01

    Model-based design and automated code generation are being used increasingly at NASA. The trend is to move beyond simulation and prototyping to actual flight code, particularly in the guidance, navigation, and control domain. However, there are substantial obstacles to more widespread adoption of code generators in such safety-critical domains. Since code generators are typically not qualified, there is no guarantee that their output is correct, and consequently the generated code still needs to be fully tested and certified. The AutoCert generator plug-in supports the certification of automatically generated code by formally verifying that the generated code is free of different safety violations, by constructing an independently verifiable certificate, and by explaining its analysis in a textual form suitable for code reviews.

  14. 42 CFR 137.368 - Is the Secretary responsible for oversight and compliance of health and safety codes during...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... compliance of health and safety codes during construction projects being performed by a Self-Governance Tribe... SERVICES TRIBAL SELF-GOVERNANCE Construction Roles of the Secretary in Establishing and Implementing Construction Project Agreements § 137.368 Is the Secretary responsible for oversight and compliance of health...

  15. Towards a supported common NEAMS software stack

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

    Cormac Garvey

    2012-04-01

    The NEAMS IPSC's are developing multidimensional, multiphysics, multiscale simulation codes based on first principles that will be capable of predicting all aspects of current and future nuclear reactor systems. These new breeds of simulation codes will include rigorous verification, validation and uncertainty quantification checks to quantify the accuracy and quality of the simulation results. The resulting NEAMS IPSC simulation codes will be an invaluable tool in designing the next generation of Nuclear Reactors and also contribute to a more speedy process in the acquisition of licenses from the NRC for new Reactor designs. Due to the high resolution of themore » models, the complexity of the physics and the added computational resources to quantify the accuracy/quality of the results, the NEAMS IPSC codes will require large HPC resources to carry out the production simulation runs.« less

  16. Quantification of Retinogenesis in 3D Cultures Reveals Epigenetic Memory and Higher Efficiency in iPSCs Derived from Rod Photoreceptors.

    PubMed

    Hiler, Daniel; Chen, Xiang; Hazen, Jennifer; Kupriyanov, Sergey; Carroll, Patrick A; Qu, Chunxu; Xu, Beisi; Johnson, Dianna; Griffiths, Lyra; Frase, Sharon; Rodriguez, Alberto R; Martin, Greg; Zhang, Jiakun; Jeon, Jongrye; Fan, Yiping; Finkelstein, David; Eisenman, Robert N; Baldwin, Kristin; Dyer, Michael A

    2015-07-02

    Cell-based therapies to treat retinal degeneration are now being tested in clinical trials. However, it is not known whether the source of stem cells is important for the production of differentiated cells suitable for transplantation. To test this, we generated induced pluripotent stem cells (iPSCs) from murine rod photoreceptors (r-iPSCs) and scored their ability to make retinae by using a standardized quantitative protocol called STEM-RET. We discovered that r-iPSCs more efficiently produced differentiated retinae than did embryonic stem cells (ESCs) or fibroblast-derived iPSCs (f-iPSCs). Retinae derived from f-iPSCs had fewer amacrine cells and other inner nuclear layer cells. Integrated epigenetic analysis showed that DNA methylation contributes to the defects in f-iPSC retinogenesis and that rod-specific CTCF insulator protein-binding sites may promote r-iPSC retinogenesis. Together, our data suggest that the source of stem cells is important for producing retinal neurons in three-dimensional (3D) organ cultures. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs) to Identify Osteoclast Defects in Rare Genetic Bone Disorders

    PubMed Central

    Chen, I-Ping

    2014-01-01

    More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs) can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs) to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts. PMID:25621177

  18. Inventory of Safety-related Codes and Standards for Energy Storage Systems with some Experiences related to Approval and Acceptance

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

    Conover, David R.

    The purpose of this document is to identify laws, rules, model codes, codes, standards, regulations, specifications (CSR) related to safety that could apply to stationary energy storage systems (ESS) and experiences to date securing approval of ESS in relation to CSR. This information is intended to assist in securing approval of ESS under current CSR and to identification of new CRS or revisions to existing CRS and necessary supporting research and documentation that can foster the deployment of safe ESS.

  19. Dynamic event tree analysis with the SAS4A/SASSYS-1 safety analysis code

    DOE PAGES

    Jankovsky, Zachary K.; Denman, Matthew R.; Aldemir, Tunc

    2018-02-02

    The consequences of a transient in an advanced sodium-cooled fast reactor are difficult to capture with the traditional approach to probabilistic risk assessment (PRA). Numerous safety-relevant systems are passive and may have operational states that cannot be represented by binary success or failure. In addition, the specific order and timing of events may be crucial which necessitates the use of dynamic PRA tools such as ADAPT. The modifications to the SAS4A/SASSYS-1 sodium-cooled fast reactor safety analysis code for linking it to ADAPT to perform a dynamic PRA are described. A test case is used to demonstrate the linking process andmore » to illustrate the type of insights that may be gained with this process. Finally, newly-developed dynamic importance measures are used to assess the significance of reactor parameters/constituents on calculated consequences of initiating events.« less

  20. Dynamic event tree analysis with the SAS4A/SASSYS-1 safety analysis code

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

    Jankovsky, Zachary K.; Denman, Matthew R.; Aldemir, Tunc

    The consequences of a transient in an advanced sodium-cooled fast reactor are difficult to capture with the traditional approach to probabilistic risk assessment (PRA). Numerous safety-relevant systems are passive and may have operational states that cannot be represented by binary success or failure. In addition, the specific order and timing of events may be crucial which necessitates the use of dynamic PRA tools such as ADAPT. The modifications to the SAS4A/SASSYS-1 sodium-cooled fast reactor safety analysis code for linking it to ADAPT to perform a dynamic PRA are described. A test case is used to demonstrate the linking process andmore » to illustrate the type of insights that may be gained with this process. Finally, newly-developed dynamic importance measures are used to assess the significance of reactor parameters/constituents on calculated consequences of initiating events.« less

  1. Alternative Fuels Data Center: E85 Codes and Standards

    Science.gov Websites

    Development Equipment Options Equipment Installation Codes, Standards, & Safety Vehicles Laws & ; Incentives Ethanol Codes, Standards, and Safety The U.S. Environmental Protection Agency's (EPA) Office of -Gasoline Blends. The Occupational Safety and Health Administration (OSHA) regulates some fuel-dispensing

  2. Mechanical code comparator

    DOEpatents

    Peter, Frank J.; Dalton, Larry J.; Plummer, David W.

    2002-01-01

    A new class of mechanical code comparators is described which have broad potential for application in safety, surety, and security applications. These devices can be implemented as micro-scale electromechanical systems that isolate a secure or otherwise controlled device until an access code is entered. This access code is converted into a series of mechanical inputs to the mechanical code comparator, which compares the access code to a pre-input combination, entered previously into the mechanical code comparator by an operator at the system security control point. These devices provide extremely high levels of robust security. Being totally mechanical in operation, an access control system properly based on such devices cannot be circumvented by software attack alone.

  3. Post-test analysis of dryout test 7B' of the W-1 Sodium Loop Safety Facility Experiment with the SABRE-2P code. [LMFBR

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

    Rose, S.D.; Dearing, J.F.

    An understanding of conditions that may cause sodium boiling and boiling propagation that may lead to dryout and fuel failure is crucial in liquid-metal fast-breeder reactor safety. In this study, the SABRE-2P subchannel analysis code has been used to analyze the ultimate transient of the in-core W-1 Sodium Loop Safety Facility experiment. This code has a 3-D simple nondynamic boiling model which is able to predict the flow instability which caused dryout. In other analyses dryout has been predicted for out-of-core test bundles and so this study provides additional confirmation of the model.

  4. Improved cell therapy protocol for Parkinson’s disease based on differentiation efficiency and safety of hESC-, hiPSC and non-human primate iPSC-derived DA neurons

    PubMed Central

    Maria, Sundberg; Helle, Bogetofte; Tristan, Lawson; Gaynor, Smith; Arnar, Astradsson; Michele, Moore; Teresia, Osborn; Oliver, Cooper; Roger, Spealman; Penelope, Hallett; Ole, Isacson

    2013-01-01

    The main motor symptoms of Parkinson’s disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson’s disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA-neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for pre-clinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate-iPSC (PiPSC)-derived DA neurons. According to our results, NCAM+/CD29low sorting enriched VM DA-neurons from pluripotent stem cell-derived neural cell populations. NCAM+/CD29low DA-neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM+/CD29low DA-neurons were able to restore motor function of 6-OHDA lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future. PMID:23666606

  5. Interface requirements to couple thermal hydraulics codes to severe accident codes: ICARE/CATHARE

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

    Camous, F.; Jacq, F.; Chatelard, P.

    1997-07-01

    In order to describe with the same code the whole sequence of severe LWR accidents, up to the vessel failure, the Institute of Protection and Nuclear Safety has performed a coupling of the severe accident code ICARE2 to the thermalhydraulics code CATHARE2. The resulting code, ICARE/CATHARE, is designed to be as pertinent as possible in all the phases of the accident. This paper is mainly devoted to the description of the ICARE2-CATHARE2 coupling.

  6. Code development for ships -- A demonstration

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

    Ayyub, B.; Mansour, A.E.; White, G.

    1996-12-31

    A demonstration summary of a reliability-based structural design code for ships is presented for two ship types, a cruiser and a tanker. For both ship types, code requirements cover four failure modes: hull girder bulking, unstiffened plate yielding and buckling, stiffened plate buckling, and fatigue of critical detail. Both serviceability and ultimate limit states are considered. Because of limitation on the length, only hull girder modes are presented in this paper. Code requirements for other modes will be presented in future publication. A specific provision of the code will be a safety check expression. The design variables are to bemore » taken at their nominal values, typically values in the safe side of the respective distributions. Other safety check expressions for hull girder failure that include load combination factors, as well as consequence of failure factors, are considered. This paper provides a summary of safety check expressions for the hull girder modes.« less

  7. Experiences and results multitasking a hydrodynamics code on global and local memory machines

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

    Mandell, D.

    1987-01-01

    A one-dimensional, time-dependent Lagrangian hydrodynamics code using a Godunov solution method has been multitasked for the Cray X-MP/48, the Intel iPSC hypercube, the Alliant FX series and the IBM RP3 computers. Actual multitasking results have been obtained for the Cray, Intel and Alliant computers and simulated results were obtained for the Cray and RP3 machines. The differences in the methods required to multitask on each of the machines is discussed. Results are presented for a sample problem involving a shock wave moving down a channel. Comparisons are made between theoretical speedups, predicted by Amdahl's law, and the actual speedups obtained.more » The problems of debugging on the different machines are also described.« less

  8. Safety and Liability.

    ERIC Educational Resources Information Center

    Berthelot, Ronald J.; And Others

    1982-01-01

    This series of five articles highlights Pensacola Junior College's occupational safety course, involving simulated emergencies, Florida's standards for teacher liability, electrical safety in the classroom and laboratory, color coding for machine safety, and Florida industrial arts safety instructional materials. (SK)

  9. Safety Criticality Standards Using the French CRISTAL Code Package: Application to the AREVA NP UO{sub 2} Fuel Fabrication Plant

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

    Doucet, M.; Durant Terrasson, L.; Mouton, J.

    2006-07-01

    Criticality safety evaluations implement requirements to proof of sufficient sub critical margins outside of the reactor environment for example in fuel fabrication plants. Basic criticality data (i.e., criticality standards) are used in the determination of sub critical margins for all processes involving plutonium or enriched uranium. There are several criticality international standards, e.g., ARH-600, which is one the US nuclear industry relies on. The French Nuclear Safety Authority (DGSNR and its advising body IRSN) has requested AREVA NP to review the criticality standards used for the evaluation of its Low Enriched Uranium fuel fabrication plants with CRISTAL V0, the recentlymore » updated French criticality evaluation package. Criticality safety is a concern for every phase of the fabrication process including UF{sub 6} cylinder storage, UF{sub 6}-UO{sub 2} conversion, powder storage, pelletizing, rod loading, assembly fabrication, and assembly transportation. Until 2003, the accepted criticality standards were based on the French CEA work performed in the late seventies with the APOLLO1 cell/assembly computer code. APOLLO1 is a spectral code, used for evaluating the basic characteristics of fuel assemblies for reactor physics applications, which has been enhanced to perform criticality safety calculations. Throughout the years, CRISTAL, starting with APOLLO1 and MORET 3 (a 3D Monte Carlo code), has been improved to account for the growth of its qualification database and for increasing user requirements. Today, CRISTAL V0 is an up-to-date computational tool incorporating a modern basic microscopic cross section set based on JEF2.2 and the comprehensive APOLLO2 and MORET 4 codes. APOLLO2 is well suited for criticality standards calculations as it includes a sophisticated self shielding approach, a P{sub ij} flux determination, and a 1D transport (S{sub n}) process. CRISTAL V0 is the result of more than five years of development work focusing on

  10. Tumor-Free Transplantation of Patient-Derived Induced Pluripotent Stem Cell Progeny for Customized Islet Regeneration.

    PubMed

    El Khatib, Moustafa M; Ohmine, Seiga; Jacobus, Egon J; Tonne, Jason M; Morsy, Salma G; Holditch, Sara J; Schreiber, Claire A; Uetsuka, Koji; Fusaki, Noemi; Wigle, Dennis A; Terzic, Andre; Kudva, Yogish C; Ikeda, Yasuhiro

    2016-05-01

    Human induced pluripotent stem cells (iPSCs) and derived progeny provide invaluable regenerative platforms, yet their clinical translation has been compromised by their biosafety concern. Here, we assessed the safety of transplanting patient-derived iPSC-generated pancreatic endoderm/progenitor cells. Transplantation of progenitors from iPSCs reprogrammed by lentiviral vectors (LV-iPSCs) led to the formation of invasive teratocarcinoma-like tumors in more than 90% of immunodeficient mice. Moreover, removal of primary tumors from LV-iPSC progeny-transplanted hosts generated secondary and metastatic tumors. Combined transgene-free (TGF) reprogramming and elimination of residual pluripotent cells by enzymatic dissociation ensured tumor-free transplantation, ultimately enabling regeneration of type 1 diabetes-specific human islet structures in vivo. The incidence of tumor formation in TGF-iPSCs was titratable, depending on the oncogenic load, with reintegration of the cMYC expressing vector abolishing tumor-free transplantation. Thus, transgene-free cMYC-independent reprogramming and elimination of residual pluripotent cells are mandatory steps in achieving transplantation of iPSC progeny for customized and safe islet regeneration in vivo. Pluripotent stem cell therapy for diabetes relies on the safety as well as the quality of derived insulin-producing cells. Data from this study highlight prominent tumorigenic risks of induced pluripotent stem cell (iPSC) products, especially when reprogrammed with integrating vectors. Two major underlying mechanisms in iPSC tumorigenicity are residual pluripotent cells and cMYC overload by vector integration. This study also demonstrated that combined transgene-free reprogramming and enzymatic dissociation allows teratoma-free transplantation of iPSC progeny in the mouse model in testing the tumorigenicity of iPSC products. Further safety assessment and improvement in iPSC specification into a mature β cell phenotype would lead to

  11. Fire safety of wood construction

    Treesearch

    Robert H. White; Mark A. Dietenberger

    2010-01-01

    Fire safety is an important concern in all types of construction. The high level of national concern for fire safety is reflected in limitations and design requirements in building codes. These code requirements and related fire performance data are discussed in the context of fire safety design and evaluation in the initial section of this chapter. Because basic data...

  12. Do code of conduct audits improve chemical safety in garment factories? Lessons on corporate social responsibility in the supply chain from Fair Wear Foundation.

    PubMed

    Lindholm, Henrik; Egels-Zandén, Niklas; Rudén, Christina

    2016-10-01

    In managing chemical risks to the environment and human health in supply chains, voluntary corporate social responsibility (CSR) measures, such as auditing code of conduct compliance, play an important role. To examine how well suppliers' chemical health and safety performance complies with buyers' CSR policies and whether audited factories improve their performance. CSR audits (n = 288) of garment factories conducted by Fair Wear Foundation (FWF), an independent non-profit organization, were analyzed using descriptive statistics and statistical modeling. Forty-three per cent of factories did not comply with the FWF code of conduct, i.e. received remarks on chemical safety. Only among factories audited 10 or more times was there a significant increase in the number of factories receiving no remarks. Compliance with chemical safety requirements in garment supply chains is low and auditing is statistically correlated with improvements only at factories that have undergone numerous audits.

  13. Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by non-integrating plasmid expression

    PubMed Central

    Cheng, Linzhao; Hansen, Nancy F.; Zhao, Ling; Du, Yutao; Zou, Chunlin; Donovan, Frank X.; Chou, Bin-Kuan; Zhou, Guangyu; Li, Shijie; Dowey, Sarah N.; Ye, Zhaohui; Chandrasekharappa, Settara C.; Yang, Huanming; Mullikin, James C.; Liu, P. Paul

    2012-01-01

    Summary The utility of induced pluripotent stem cells (iPSCs) as models to study diseases and as sources for cell therapy depends on the integrity of their genomes. Despite recent publications of DNA sequence variations in the iPSCs, the true scope of such changes for the entire genome is not clear. Here we report the whole-genome sequencing of three human iPSC lines derived from two cell types of an adult donor by episomal vectors. The vector sequence was undetectable in the deeply sequenced iPSC lines. We identified 1058–1808 heterozygous single nucleotide variants (SNVs), but no copy number variants, in each iPSC line. Six to twelve of these SNVs were within coding regions in each iPSC line, but ~50% of them are synonymous changes and the remaining are not selectively enriched for known genes associated with cancers. Our data thus suggest that episome-mediated reprogramming is not inherently mutagenic during integration-free iPSC induction. PMID:22385660

  14. Do code of conduct audits improve chemical safety in garment factories? Lessons on corporate social responsibility in the supply chain from Fair Wear Foundation

    PubMed Central

    2016-01-01

    Background In managing chemical risks to the environment and human health in supply chains, voluntary corporate social responsibility (CSR) measures, such as auditing code of conduct compliance, play an important role. Objectives To examine how well suppliers’ chemical health and safety performance complies with buyers’ CSR policies and whether audited factories improve their performance. Methods CSR audits (n = 288) of garment factories conducted by Fair Wear Foundation (FWF), an independent non-profit organization, were analyzed using descriptive statistics and statistical modeling. Results Forty-three per cent of factories did not comply with the FWF code of conduct, i.e. received remarks on chemical safety. Only among factories audited 10 or more times was there a significant increase in the number of factories receiving no remarks. Conclusions Compliance with chemical safety requirements in garment supply chains is low and auditing is statistically correlated with improvements only at factories that have undergone numerous audits. PMID:27611103

  15. Generating Customized Verifiers for Automatically Generated Code

    NASA Technical Reports Server (NTRS)

    Denney, Ewen; Fischer, Bernd

    2008-01-01

    Program verification using Hoare-style techniques requires many logical annotations. We have previously developed a generic annotation inference algorithm that weaves in all annotations required to certify safety properties for automatically generated code. It uses patterns to capture generator- and property-specific code idioms and property-specific meta-program fragments to construct the annotations. The algorithm is customized by specifying the code patterns and integrating them with the meta-program fragments for annotation construction. However, this is difficult since it involves tedious and error-prone low-level term manipulations. Here, we describe an annotation schema compiler that largely automates this customization task using generative techniques. It takes a collection of high-level declarative annotation schemas tailored towards a specific code generator and safety property, and generates all customized analysis functions and glue code required for interfacing with the generic algorithm core, thus effectively creating a customized annotation inference algorithm. The compiler raises the level of abstraction and simplifies schema development and maintenance. It also takes care of some more routine aspects of formulating patterns and schemas, in particular handling of irrelevant program fragments and irrelevant variance in the program structure, which reduces the size, complexity, and number of different patterns and annotation schemas that are required. The improvements described here make it easier and faster to customize the system to a new safety property or a new generator, and we demonstrate this by customizing it to certify frame safety of space flight navigation code that was automatically generated from Simulink models by MathWorks' Real-Time Workshop.

  16. Generation of iPSC line iPSC-FH2.1 in hypoxic conditions from human foreskin fibroblasts.

    PubMed

    Questa, María; Romorini, Leonardo; Blüguermann, Carolina; Solari, Claudia María; Neiman, Gabriel; Luzzani, Carlos; Scassa, María Élida; Sevlever, Gustavo Emilio; Guberman, Alejandra Sonia; Miriuka, Santiago Gabriel

    2016-03-01

    Human foreskin fibroblasts were used to generate the iPSC line iPSC-FH2.1 using the EF1a-hSTEMCCA-loxP vector expressing OCT4, SOX2, c-MYC and KLF4, in 5% O2 culture conditions. Stemness was confirmed, as was pluripotency both in vivo and in vitro, in normoxia and hypoxia. Human Embryonic Stem Cell (hESC) line WA-09 and reprogrammed fibroblast primary culture HFF-FM were used as controls. Copyright © 2015 University of Texas at Austin Dell Medical School. Published by Elsevier B.V. All rights reserved.

  17. 76 FR 22383 - National Fire Codes: Request for Proposals for Revision of Codes and Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-21

    ... DEPARTMENT OF COMMERCE National Institute of Standards and Technology National Fire Codes: Request... publishing this notice on behalf of the National Fire Protection Association (NFPA) to announce the NFPA's proposal to revise some of its fire safety codes and standards and requests proposals from the public to...

  18. DNA Damage and Oxidative Stress in Dyskeratosis Congenita: Analysis of Pathways and Therapeutic Stategies Using CPISPR and iPSC Model Systems

    DTIC Science & Technology

    2017-06-01

    Milestone Achieved: HRPO/ACURO Approval 6 Finished Major Task 2 CRISPR knockout/RNAseq Viral infection/prep 3-6 CRISPR KO virus library prep...finished; RNA-Seq: ~75% Cell manipulation 3-6 CRISPR KO virus infection: 50%; Single cDNA infections: finished Bioinformatics 1 CRISPR KO library...characterization 1-3 Finished Update: production of iPSC clones harboring DC mutations generated by CRISPR : Design 1 Finished Update: production of

  19. Pressure Safety Program Implementation at ORNL

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

    Lower, Mark; Etheridge, Tom; Oland, C. Barry

    2013-01-01

    The Oak Ridge National Laboratory (ORNL) is a US Department of Energy (DOE) facility that is managed by UT-Battelle, LLC. In February 2006, DOE promulgated worker safety and health regulations to govern contractor activities at DOE sites. These regulations, which are provided in 10 CFR 851, Worker Safety and Health Program, establish requirements for worker safety and health program that reduce or prevent occupational injuries, illnesses, and accidental losses by providing DOE contractors and their workers with safe and healthful workplaces at DOE sites. The regulations state that contractors must achieve compliance no later than May 25, 2007. According tomore » 10 CFR 851, Subpart C, Specific Program Requirements, contractors must have a structured approach to their worker safety and health programs that at a minimum includes provisions for pressure safety. In implementing the structured approach for pressure safety, contractors must establish safety policies and procedures to ensure that pressure systems are designed, fabricated, tested, inspected, maintained, repaired, and operated by trained, qualified personnel in accordance with applicable sound engineering principles. In addition, contractors must ensure that all pressure vessels, boilers, air receivers, and supporting piping systems conform to (1) applicable American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (2004) Sections I through XII, including applicable code cases; (2) applicable ASME B31 piping codes; and (3) the strictest applicable state and local codes. When national consensus codes are not applicable because of pressure range, vessel geometry, use of special materials, etc., contractors must implement measures to provide equivalent protection and ensure a level of safety greater than or equal to the level of protection afforded by the ASME or applicable state or local codes. This report documents the work performed to address legacy pressure vessel deficiencies and

  20. Formal Safety Certification of Aerospace Software

    NASA Technical Reports Server (NTRS)

    Denney, Ewen; Fischer, Bernd

    2005-01-01

    In principle, formal methods offer many advantages for aerospace software development: they can help to achieve ultra-high reliability, and they can be used to provide evidence of the reliability claims which can then be subjected to external scrutiny. However, despite years of research and many advances in the underlying formalisms of specification, semantics, and logic, formal methods are not much used in practice. In our opinion this is related to three major shortcomings. First, the application of formal methods is still expensive because they are labor- and knowledge-intensive. Second, they are difficult to scale up to complex systems because they are based on deep mathematical insights about the behavior of the systems (t.e., they rely on the "heroic proof"). Third, the proofs can be difficult to interpret, and typically stand in isolation from the original code. In this paper, we describe a tool for formally demonstrating safety-relevant aspects of aerospace software, which largely circumvents these problems. We focus on safely properties because it has been observed that safety violations such as out-of-bounds memory accesses or use of uninitialized variables constitute the majority of the errors found in the aerospace domain. In our approach, safety means that the program will not violate a set of rules that can range for the simple memory access rules to high-level flight rules. These different safety properties are formalized as different safety policies in Hoare logic, which are then used by a verification condition generator along with the code and logical annotations in order to derive formal safety conditions; these are then proven using an automated theorem prover. Our certification system is currently integrated into a model-based code generation toolset that generates the annotations together with the code. However, this automated formal certification technology is not exclusively constrained to our code generator and could, in principle, also be

  1. Application of biomaterials to advance induced pluripotent stem cell research and therapy

    PubMed Central

    Tong, Zhixiang; Solanki, Aniruddh; Hamilos, Allison; Levy, Oren; Wen, Kendall; Yin, Xiaolei; Karp, Jeffrey M

    2015-01-01

    Derived from any somatic cell type and possessing unlimited self-renewal and differentiation potential, induced pluripotent stem cells (iPSCs) are poised to revolutionize stem cell biology and regenerative medicine research, bringing unprecedented opportunities for treating debilitating human diseases. To overcome the limitations associated with safety, efficiency, and scalability of traditional iPSC derivation, expansion, and differentiation protocols, biomaterials have recently been considered. Beyond addressing these limitations, the integration of biomaterials with existing iPSC culture platforms could offer additional opportunities to better probe the biology and control the behavior of iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of biomaterials on the iPSC field, from derivation to tissue regeneration and modeling. Although still exploratory, we envision the emerging combination of biomaterials and iPSCs will be critical in the successful application of iPSCs and their progeny for research and clinical translation. PMID:25766254

  2. Modification of the SAS4A Safety Analysis Code for Integration with the ADAPT Discrete Dynamic Event Tree Framework.

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

    Jankovsky, Zachary Kyle; Denman, Matthew R.

    It is difficult to assess the consequences of a transient in a sodium-cooled fast reactor (SFR) using traditional probabilistic risk assessment (PRA) methods, as numerous safety-related sys- tems have passive characteristics. Often there is significant dependence on the value of con- tinuous stochastic parameters rather than binary success/failure determinations. One form of dynamic PRA uses a system simulator to represent the progression of a transient, tracking events through time in a discrete dynamic event tree (DDET). In order to function in a DDET environment, a simulator must have characteristics that make it amenable to changing physical parameters midway through themore » analysis. The SAS4A SFR system analysis code did not have these characteristics as received. This report describes the code modifications made to allow dynamic operation as well as the linking to a Sandia DDET driver code. A test case is briefly described to demonstrate the utility of the changes.« less

  3. Safety Education and Science.

    ERIC Educational Resources Information Center

    Ralph, Richard

    1980-01-01

    Safety education in the science classroom is discussed, including the beginning of safe management, attitudes toward safety education, laboratory assistants, chemical and health regulation, safety aids, and a case study of a high school science laboratory. Suggestions for safety codes for science teachers, student behavior, and laboratory…

  4. Monitoring biomedical literature for post-market safety purposes by analyzing networks of text-based coded information.

    PubMed

    Botsis, Taxiarchis; Foster, Matthew; Kreimeyer, Kory; Pandey, Abhishek; Forshee, Richard

    2017-01-01

    Literature review is critical but time-consuming in the post-market surveillance of medical products. We focused on the safety signal of intussusception after the vaccination of infants with the Rotashield Vaccine in 1999 and retrieved all PubMed abstracts for rotavirus vaccines published after January 1, 1998. We used the Event-based Text-mining of Health Electronic Records system, the MetaMap tool, and the National Center for Biomedical Ontologies Annotator to process the abstracts and generate coded terms stamped with the date of publication. Data were analyzed in the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment to evaluate the intussusception-related findings before and after the release of the new rotavirus vaccines in 2006. The tight connection of intussusception with the historical signal in the first period and the absence of any safety concern for the new vaccines in the second period were verified. We demonstrated the feasibility for semi-automated solutions that may assist medical reviewers in monitoring biomedical literature.

  5. Performance of a plasma fluid code on the Intel parallel computers

    NASA Technical Reports Server (NTRS)

    Lynch, V. E.; Carreras, B. A.; Drake, J. B.; Leboeuf, J. N.; Liewer, P.

    1992-01-01

    One approach to improving the real-time efficiency of plasma turbulence calculations is to use a parallel algorithm. A parallel algorithm for plasma turbulence calculations was tested on the Intel iPSC/860 hypercube and the Touchtone Delta machine. Using the 128 processors of the Intel iPSC/860 hypercube, a factor of 5 improvement over a single-processor CRAY-2 is obtained. For the Touchtone Delta machine, the corresponding improvement factor is 16. For plasma edge turbulence calculations, an extrapolation of the present results to the Intel (sigma) machine gives an improvement factor close to 64 over the single-processor CRAY-2.

  6. EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.

    PubMed

    Ebert, Allison D; Shelley, Brandon C; Hurley, Amanda M; Onorati, Marco; Castiglioni, Valentina; Patitucci, Teresa N; Svendsen, Soshana P; Mattis, Virginia B; McGivern, Jered V; Schwab, Andrew J; Sareen, Dhruv; Kim, Ho Won; Cattaneo, Elena; Svendsen, Clive N

    2013-05-01

    We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell-cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

    PubMed Central

    Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

    2014-01-01

    Fanconi Anemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration-free induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA-patient bone marrow cells. PMID:24999918

  8. Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs.

    PubMed

    Liu, Guang-Hui; Suzuki, Keiichiro; Li, Mo; Qu, Jing; Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; Del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

    2014-07-07

    Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.

  9. Seismic Safety Of Simple Masonry Buildings

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

    Guadagnuolo, Mariateresa; Faella, Giuseppe

    2008-07-08

    Several masonry buildings comply with the rules for simple buildings provided by seismic codes. For these buildings explicit safety verifications are not compulsory if specific code rules are fulfilled. In fact it is assumed that their fulfilment ensures a suitable seismic behaviour of buildings and thus adequate safety under earthquakes. Italian and European seismic codes differ in the requirements for simple masonry buildings, mostly concerning the building typology, the building geometry and the acceleration at site. Obviously, a wide percentage of buildings assumed simple by codes should satisfy the numerical safety verification, so that no confusion and uncertainty have tomore » be given rise to designers who must use the codes. This paper aims at evaluating the seismic response of some simple unreinforced masonry buildings that comply with the provisions of the new Italian seismic code. Two-story buildings, having different geometry, are analysed and results from nonlinear static analyses performed by varying the acceleration at site are presented and discussed. Indications on the congruence between code rules and results of numerical analyses performed according to the code itself are supplied and, in this context, the obtained result can provide a contribution for improving the seismic code requirements.« less

  10. Synthesizing Certified Code

    NASA Technical Reports Server (NTRS)

    Whalen, Michael; Schumann, Johann; Fischer, Bernd

    2002-01-01

    Code certification is a lightweight approach to demonstrate software quality on a formal level. Its basic idea is to require producers to provide formal proofs that their code satisfies certain quality properties. These proofs serve as certificates which can be checked independently. Since code certification uses the same underlying technology as program verification, it also requires many detailed annotations (e.g., loop invariants) to make the proofs possible. However, manually adding theses annotations to the code is time-consuming and error-prone. We address this problem by combining code certification with automatic program synthesis. We propose an approach to generate simultaneously, from a high-level specification, code and all annotations required to certify generated code. Here, we describe a certification extension of AUTOBAYES, a synthesis tool which automatically generates complex data analysis programs from compact specifications. AUTOBAYES contains sufficient high-level domain knowledge to generate detailed annotations. This allows us to use a general-purpose verification condition generator to produce a set of proof obligations in first-order logic. The obligations are then discharged using the automated theorem E-SETHEO. We demonstrate our approach by certifying operator safety for a generated iterative data classification program without manual annotation of the code.

  11. RDS - A systematic approach towards system thermal hydraulics input code development for a comprehensive deterministic safety analysis

    NASA Astrophysics Data System (ADS)

    Salim, Mohd Faiz; Roslan, Ridha; Ibrahim, Mohd Rizal Mamat @

    2014-02-01

    Deterministic Safety Analysis (DSA) is one of the mandatory requirements conducted for Nuclear Power Plant licensing process, with the aim of ensuring safety compliance with relevant regulatory acceptance criteria. DSA is a technique whereby a set of conservative deterministic rules and requirements are applied for the design and operation of facilities or activities. Computer codes are normally used to assist in performing all required analysis under DSA. To ensure a comprehensive analysis, the conduct of DSA should follow a systematic approach. One of the methodologies proposed is the Standardized and Consolidated Reference Experimental (and Calculated) Database (SCRED) developed by University of Pisa. Based on this methodology, the use of Reference Data Set (RDS) as a pre-requisite reference document for developing input nodalization was proposed. This paper shall describe the application of RDS with the purpose of assessing its effectiveness. Two RDS documents were developed for an Integral Test Facility of LOBI-MOD2 and associated Test A1-83. Data and information from various reports and drawings were referred in preparing the RDS. The results showed that by developing RDS, it has made possible to consolidate all relevant information in one single document. This is beneficial as it enables preservation of information, promotes quality assurance, allows traceability, facilitates continuous improvement, promotes solving of contradictions and finally assisting in developing thermal hydraulic input regardless of whichever code selected. However, some disadvantages were also recognized such as the need for experience in making engineering judgments, language barrier in accessing foreign information and limitation of resources. Some possible improvements are suggested to overcome these challenges.

  12. A Comparative Study on Seismic Analysis of Bangladesh National Building Code (BNBC) with Other Building Codes

    NASA Astrophysics Data System (ADS)

    Bari, Md. S.; Das, T.

    2013-09-01

    Tectonic framework of Bangladesh and adjoining areas indicate that Bangladesh lies well within an active seismic zone. The after effect of earthquake is more severe in an underdeveloped and a densely populated country like ours than any other developed countries. Bangladesh National Building Code (BNBC) was first established in 1993 to provide guidelines for design and construction of new structure subject to earthquake ground motions in order to minimize the risk to life for all structures. A revision of BNBC 1993 is undergoing to make this up to date with other international building codes. This paper aims at the comparison of various provisions of seismic analysis as given in building codes of different countries. This comparison will give an idea regarding where our country stands when it comes to safety against earth quake. Primarily, various seismic parameters in BNBC 2010 (draft) have been studied and compared with that of BNBC 1993. Later, both 1993 and 2010 edition of BNBC codes have been compared graphically with building codes of other countries such as National Building Code of India 2005 (NBC-India 2005), American Society of Civil Engineering 7-05 (ASCE 7-05). The base shear/weight ratios have been plotted against the height of the building. The investigation in this paper reveals that BNBC 1993 has the least base shear among all the codes. Factored Base shear values of BNBC 2010 are found to have increased significantly than that of BNBC 1993 for low rise buildings (≤20 m) around the country than its predecessor. Despite revision of the code, BNBC 2010 (draft) still suggests less base shear values when compared to the Indian and American code. Therefore, this increase in factor of safety against the earthquake imposed by the proposed BNBC 2010 code by suggesting higher values of base shear is appreciable.

  13. Safety with surgical lasers.

    PubMed

    McKenzie, A L

    1984-01-01

    As the sales of surgical lasers continue to grow, the problem of laser safety in hospitals becomes increasingly more urgent. This article considers both the principles and the practice of laser safety, and indicates how safety codes should be organized within a hospital. Eye safety is of paramount importance, and the effects of different wavelengths of laser radiation on the eye are described, both for intrabeam and extended-source exposure. An account is given of the concept of Maximum Permissible Exposure (MPE) and how it depends upon wavelength and exposure duration. The standard laser classification is developed in relation to MPE. The use of laser protective eyewear is discussed for the surgeon, other theatre staff and the patient. Finally, the role of the Laser Protection Supervisor and of the Laser Protection Adviser are explained in the context of establishing a local laser safety code.

  14. Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair

    PubMed Central

    Ikeya, Makoto; Yasui, Yukihiko; Ikeda, Yasutoshi; Ebina, Kosuke; Moriguchi, Yu; Shimomura, Kazunori; Hideki, Yoshikawa

    2017-01-01

    Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage. PMID:28607560

  15. Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.

    PubMed

    Samwald, Matthias; Minarro-Giménez, José Antonio; Blagec, Kathrin; Adlassnig, Klaus-Peter

    2014-01-01

    The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.

  16. Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.

    PubMed

    Samwald, Matthias; Minarro-Giménez, José Antonio; Blagec, Kathrin; Adlassnig, Klaus-Peter

    2014-01-01

    The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, medical researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.

  17. Code manual for CONTAIN 2.0: A computer code for nuclear reactor containment analysis

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

    Murata, K.K.; Williams, D.C.; Griffith, R.O.

    1997-12-01

    The CONTAIN 2.0 computer code is an integrated analysis tool used for predicting the physical conditions, chemical compositions, and distributions of radiological materials inside a containment building following the release of material from the primary system in a light-water reactor accident. It can also predict the source term to the environment. CONTAIN 2.0 is intended to replace the earlier CONTAIN 1.12, which was released in 1991. The purpose of this Code Manual is to provide full documentation of the features and models in CONTAIN 2.0. Besides complete descriptions of the models, this Code Manual provides a complete description of themore » input and output from the code. CONTAIN 2.0 is a highly flexible and modular code that can run problems that are either quite simple or highly complex. An important aspect of CONTAIN is that the interactions among thermal-hydraulic phenomena, aerosol behavior, and fission product behavior are taken into account. The code includes atmospheric models for steam/air thermodynamics, intercell flows, condensation/evaporation on structures and aerosols, aerosol behavior, and gas combustion. It also includes models for reactor cavity phenomena such as core-concrete interactions and coolant pool boiling. Heat conduction in structures, fission product decay and transport, radioactive decay heating, and the thermal-hydraulic and fission product decontamination effects of engineered safety features are also modeled. To the extent possible, the best available models for severe accident phenomena have been incorporated into CONTAIN, but it is intrinsic to the nature of accident analysis that significant uncertainty exists regarding numerous phenomena. In those cases, sensitivity studies can be performed with CONTAIN by means of user-specified input parameters. Thus, the code can be viewed as a tool designed to assist the knowledge reactor safety analyst in evaluating the consequences of specific modeling assumptions.« less

  18. Current and anticipated uses of thermalhydraulic and neutronic codes at PSI

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

    Aksan, S.N.; Zimmermann, M.A.; Yadigaroglu, G.

    1997-07-01

    The thermalhydraulic and/or neutronic codes in use at PSI mainly provide the capability to perform deterministic safety analysis for Swiss NPPs and also serve as analysis tools for experimental facilities for LWR and ALWR simulations. In relation to these applications, physical model development and improvements, and assessment of the codes are also essential components of the activities. In this paper, a brief overview is provided on the thermalhydraulic and/or neutronic codes used for safety analysis of LWRs, at PSI, and also of some experiences and applications with these codes. Based on these experiences, additional assessment needs are indicated, together withmore » some model improvement needs. The future needs that could be used to specify both the development of a new code and also improvement of available codes are summarized.« less

  19. Bar Coding and Tracking in Pathology.

    PubMed

    Hanna, Matthew G; Pantanowitz, Liron

    2016-03-01

    Bar coding and specimen tracking are intricately linked to pathology workflow and efficiency. In the pathology laboratory, bar coding facilitates many laboratory practices, including specimen tracking, automation, and quality management. Data obtained from bar coding can be used to identify, locate, standardize, and audit specimens to achieve maximal laboratory efficiency and patient safety. Variables that need to be considered when implementing and maintaining a bar coding and tracking system include assets to be labeled, bar code symbologies, hardware, software, workflow, and laboratory and information technology infrastructure as well as interoperability with the laboratory information system. This article addresses these issues, primarily focusing on surgical pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Bar Coding and Tracking in Pathology.

    PubMed

    Hanna, Matthew G; Pantanowitz, Liron

    2015-06-01

    Bar coding and specimen tracking are intricately linked to pathology workflow and efficiency. In the pathology laboratory, bar coding facilitates many laboratory practices, including specimen tracking, automation, and quality management. Data obtained from bar coding can be used to identify, locate, standardize, and audit specimens to achieve maximal laboratory efficiency and patient safety. Variables that need to be considered when implementing and maintaining a bar coding and tracking system include assets to be labeled, bar code symbologies, hardware, software, workflow, and laboratory and information technology infrastructure as well as interoperability with the laboratory information system. This article addresses these issues, primarily focusing on surgical pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. School Dress Codes and Uniform Policies.

    ERIC Educational Resources Information Center

    Anderson, Wendell

    2002-01-01

    Opinions abound on what students should wear to class. Some see student dress as a safety issue; others see it as a student-rights issue. The issue of dress codes and uniform policies has been tackled in the classroom, the boardroom, and the courtroom. This Policy Report examines the whole fabric of the debate on dress codes and uniform policies…

  2. Posttest analysis of the FFTF inherent safety tests

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

    Padilla, A. Jr.; Claybrook, S.W.

    Inherent safety tests were performed during 1986 in the 400-MW (thermal) Fast Flux Test Facility (FFTF) reactor to demonstrate the effectiveness of an inherent shutdown device called the gas expansion module (GEM). The GEM device provided a strong negative reactivity feedback during loss-of-flow conditions by increasing the neutron leakage as a result of an expanding gas bubble. The best-estimate pretest calculations for these tests were performed using the IANUS plant analysis code (Westinghouse Electric Corporation proprietary code) and the MELT/SIEX3 core analysis code. These two codes were also used to perform the required operational safety analyses for the FFTF reactormore » and plant. Although it was intended to also use the SASSYS systems (core and plant) analysis code, the calibration of the SASSYS code for FFTF core and plant analysis was not completed in time to perform pretest analyses. The purpose of this paper is to present the results of the posttest analysis of the 1986 FFTF inherent safety tests using the SASSYS code.« less

  3. Workplace Safety and Health Topics: Safety & Prevention

    MedlinePlus

    ... Health Records (EHRs) and Patient Work Information Engineering Controls Equipment Design in Mining Falls in the Workplace Green, Safe, and Healthy Jobs – Prevention through Design Hierarchy of Controls Industry and Occupation Coding and Support Logging Safety ...

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

    BRISC is a developmental prototype for a nextgeneration “systems-level” integrated performance and safety code (IPSC) for nuclear reactors. Its development served to demonstrate how a lightweight multi-physics coupling approach can be used to tightly couple the physics models in several different physics codes (written in a variety of languages) into one integrated package for simulating accident scenarios in a liquid sodium cooled “burner” nuclear reactor. For example, the RIO Fluid Flow and Heat transfer code developed at Sandia (SNL: Chris Moen, Dept. 08005) is used in BRISC to model fluid flow and heat transfer, as well as conduction heat transfermore » in solids. Because BRISC is a prototype, its most practical application is as a foundation or starting point for developing a true production code. The sub-codes and the associated models and correlations currently employed within BRISC were chosen to cover the required application space and demonstrate feasibility, but were not optimized or validated against experimental data within the context of their use in BRISC.« less

  5. Neutronic calculation of fast reactors by the EUCLID/V1 integrated code

    NASA Astrophysics Data System (ADS)

    Koltashev, D. A.; Stakhanova, A. A.

    2017-01-01

    This article considers neutronic calculation of a fast-neutron lead-cooled reactor BREST-OD-300 by the EUCLID/V1 integrated code. The main goal of development and application of integrated codes is a nuclear power plant safety justification. EUCLID/V1 is integrated code designed for coupled neutronics, thermomechanical and thermohydraulic fast reactor calculations under normal and abnormal operating conditions. EUCLID/V1 code is being developed in the Nuclear Safety Institute of the Russian Academy of Sciences. The integrated code has a modular structure and consists of three main modules: thermohydraulic module HYDRA-IBRAE/LM/V1, thermomechanical module BERKUT and neutronic module DN3D. In addition, the integrated code includes databases with fuel, coolant and structural materials properties. Neutronic module DN3D provides full-scale simulation of neutronic processes in fast reactors. Heat sources distribution, control rods movement, reactivity level changes and other processes can be simulated. Neutron transport equation in multigroup diffusion approximation is solved. This paper contains some calculations implemented as a part of EUCLID/V1 code validation. A fast-neutron lead-cooled reactor BREST-OD-300 transient simulation (fuel assembly floating, decompression of passive feedback system channel) and cross-validation with MCU-FR code results are presented in this paper. The calculations demonstrate EUCLID/V1 code application for BREST-OD-300 simulating and safety justification.

  6. 41 CFR 128-1.8005 - Seismic safety standards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the model building codes that the Interagency Committee on Seismic Safety in Construction (ICSSC...) Uniform Building Code (UBC); (2) The 1992 Supplement to the Building Officials and Code Administrators International (BOCA) National Building Code (NBC); and (3) The 1992 Amendments to the Southern Building Code...

  7. 41 CFR 128-1.8005 - Seismic safety standards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the model building codes that the Interagency Committee on Seismic Safety in Construction (ICSSC...) Uniform Building Code (UBC); (2) The 1992 Supplement to the Building Officials and Code Administrators International (BOCA) National Building Code (NBC); and (3) The 1992 Amendments to the Southern Building Code...

  8. 41 CFR 128-1.8005 - Seismic safety standards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the model building codes that the Interagency Committee on Seismic Safety in Construction (ICSSC...) Uniform Building Code (UBC); (2) The 1992 Supplement to the Building Officials and Code Administrators International (BOCA) National Building Code (NBC); and (3) The 1992 Amendments to the Southern Building Code...

  9. 41 CFR 128-1.8005 - Seismic safety standards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the model building codes that the Interagency Committee on Seismic Safety in Construction (ICSSC...) Uniform Building Code (UBC); (2) The 1992 Supplement to the Building Officials and Code Administrators International (BOCA) National Building Code (NBC); and (3) The 1992 Amendments to the Southern Building Code...

  10. Current and anticipated uses of thermal hydraulic codes in Korea

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

    Kim, Kyung-Doo; Chang, Won-Pyo

    1997-07-01

    In Korea, the current uses of thermal hydraulic codes are categorized into 3 areas. The first application is in designing both nuclear fuel and NSSS. The codes have usually been introduced based on the technology transfer programs agreed between KAERI and the foreign vendors. Another area is in the supporting of the plant operations and licensing by the utility. The third category is research purposes. In this area assessments and some applications to the safety issue resolutions are major activities using the best estimate thermal hydraulic codes such as RELAP5/MOD3 and CATHARE2. Recently KEPCO plans to couple thermal hydraulic codesmore » with a neutronics code for the design of the evolutionary type reactor by 2004. KAERI also plans to develop its own best estimate thermal hydraulic code, however, application range is different from KEPCO developing code. Considering these activities, it is anticipated that use of the best estimate hydraulic analysis code developed in Korea may be possible in the area of safety evaluation within 10 years.« less

  11. Continuous Codes and Standards Improvement (CCSI)

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

    Rivkin, Carl H; Burgess, Robert M; Buttner, William J

    2015-10-21

    As of 2014, the majority of the codes and standards required to initially deploy hydrogen technologies infrastructure in the United States have been promulgated. These codes and standards will be field tested through their application to actual hydrogen technologies projects. Continuous codes and standards improvement (CCSI) is a process of identifying code issues that arise during project deployment and then developing codes solutions to these issues. These solutions would typically be proposed amendments to codes and standards. The process is continuous because as technology and the state of safety knowledge develops there will be a need to monitor the applicationmore » of codes and standards and improve them based on information gathered during their application. This paper will discuss code issues that have surfaced through hydrogen technologies infrastructure project deployment and potential code changes that would address these issues. The issues that this paper will address include (1) setback distances for bulk hydrogen storage, (2) code mandated hazard analyses, (3) sensor placement and communication, (4) the use of approved equipment, and (5) system monitoring and maintenance requirements.« less

  12. Patient safety principles in family medicine residency accreditation standards and curriculum objectives

    PubMed Central

    Kassam, Aliya; Sharma, Nishan; Harvie, Margot; O’Beirne, Maeve; Topps, Maureen

    2016-01-01

    Abstract Objective To conduct a thematic analysis of the College of Family Physicians of Canada’s (CFPC’s) Red Book accreditation standards and the Triple C Competency-based Curriculum objectives with respect to patient safety principles. Design Thematic content analysis of the CFPC’s Red Book accreditation standards and the Triple C curriculum. Setting Canada. Main outcome measures Coding frequency of the patient safety principles (ie, patient engagement; respectful, transparent relationships; complex systems; a just and trusting culture; responsibility and accountability for actions; and continuous learning and improvement) found in the analyzed CFPC documents. Results Within the analyzed CFPC documents, the most commonly found patient safety principle was patient engagement (n = 51 coding references); the least commonly found patient safety principles were a just and trusting culture (n = 5 coding references) and complex systems (n = 5 coding references). Other patient safety principles that were uncommon included responsibility and accountability for actions (n = 7 coding references) and continuous learning and improvement (n = 12 coding references). Conclusion Explicit inclusion of patient safety content such as the use of patient safety principles is needed for residency training programs across Canada to ensure the full spectrum of care is addressed, from community-based care to acute hospital-based care. This will ensure a patient safety culture can be cultivated from residency and sustained into primary care practice. PMID:27965349

  13. Comparison of the LLNL ALE3D and AKTS Thermal Safety Computer Codes for Calculating Times to Explosion in ODTX and STEX Thermal Cookoff Experiments

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

    Wemhoff, A P; Burnham, A K

    2006-04-05

    Cross-comparison of the results of two computer codes for the same problem provides a mutual validation of their computational methods. This cross-validation exercise was performed for LLNL's ALE3D code and AKTS's Thermal Safety code, using the thermal ignition of HMX in two standard LLNL cookoff experiments: the One-Dimensional Time to Explosion (ODTX) test and the Scaled Thermal Explosion (STEX) test. The chemical kinetics model used in both codes was the extended Prout-Tompkins model, a relatively new addition to ALE3D. This model was applied using ALE3D's new pseudospecies feature. In addition, an advanced isoconversional kinetic approach was used in the AKTSmore » code. The mathematical constants in the Prout-Tompkins code were calibrated using DSC data from hermetically sealed vessels and the LLNL optimization code Kinetics05. The isoconversional kinetic parameters were optimized using the AKTS Thermokinetics code. We found that the Prout-Tompkins model calculations agree fairly well between the two codes, and the isoconversional kinetic model gives very similar results as the Prout-Tompkins model. We also found that an autocatalytic approach in the beta-delta phase transition model does affect the times to explosion for some conditions, especially STEX-like simulations at ramp rates above 100 C/hr, and further exploration of that effect is warranted.« less

  14. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

    PubMed

    Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

    2011-04-14

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

  15. Knowledge of and attitude towards road traffic codes among commercial motorcycle riders in Anambra State.

    PubMed

    Adogu, O U; Ilika, A L

    2006-12-01

    Road traffic accidents (rtas) represent a major epidemic of non communicable disease in the country and has since escalated with the introduction of the new phenomenon of commercial motorcycle transportation such as is found in the two urban towns of nnewi and Awka of Anambra state, Nigeria. making use of a pre-tested, semi structured, interviewer administered questionnaire, relevant data on socio demographic and motorcycle characteristics were collected from a sample of commercial motorcyclists selected by systematic sampling technique. their knowledge of and attitude towards road traffic and safety codes were elicited. The result showed that the all-male commercial motorcyclists had a mean age of 30+8.9 years. one hundred and seventy six (32.6%) possessed good knowledge of road traffic codes and safety, while 35 (6.5%) exhibited good attitude towards them. both knowledge of and attitude towards traffic codes and safety improved with increase in educational level (p<0.005, p<0.001 respectively). the younger motorcyclists also possessed statistically significant better knowledge of traffic codes than their older counterparts (p<0.025). attitude to traffic codes and safety had no association with age of the motorcyclists (p>0.25). the study has provided useful information on the knowledge of and attitude towards road traffic and safety codes among commercial motorcyclists in nigeria. pursuit of knowledge through formal and informal education should run pari pasu with efforts to improve the nigerian economy in order to ensure a sustainable positive attitudinal change towards road traffic codes and safety among commercial motorcyclists.

  16. 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...

  17. iPS Cells for Post-myocardial Infarction Repair: Remarkable Opportunities and Challenges

    PubMed Central

    Lalit, Pratik A.; Hei, Derek J.; Raval, Amish N.; Kamp, Timothy J.

    2014-01-01

    Coronary artery disease with associated myocardial infarction continues to be a major cause of death and morbidity around the world despite significant advances in therapy. Patients who suffer large myocardial infarctions are at highest risk for progressive heart failure and death, and cell-based therapies offer new hope for these patients. A recently discovered cell source for cardiac repair has emerged as a result of a breakthrough reprogramming somatic cells to induced pluripotent stem cells (iPSCs). The iPSCs can proliferate indefinitely in culture and can differentiate into cardiac lineages including cardiomyocytes, smooth muscle cells, endothelial cells, and cardiac progenitors. Thus large quantities of desired cell products can be generated without being limited by cellular senescence. The iPSCs can be obtained from patients to allow autologous therapy or, alternatively, banks of HLA diverse iPSCs are possible for allogeneic therapy. Preclinical animal studies using a variety of cell preparations generated from iPSCs have shown evidence of cardiac repair. Methodology for the production of clinical grade products from human iPSCs is in place. Ongoing studies of the safety of various iPSC preparations with regard to the risk of tumor formation, immune rejection, induction of arrhythmias, and formation of stable cardiac grafts are needed as the field advances toward the first in man trials of iPSCs post-MI. PMID:24723658

  18. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells.

    PubMed

    Trevisan, Marta; Desole, Giovanna; Costanzi, Giulia; Lavezzo, Enrico; Palù, Giorgio; Barzon, Luisa

    2017-01-20

    Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs.

  19. Thermal-hydraulic interfacing code modules for CANDU reactors

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

    Liu, W.S.; Gold, M.; Sills, H.

    1997-07-01

    The approach for CANDU reactor safety analysis in Ontario Hydro Nuclear (OHN) and Atomic Energy of Canada Limited (AECL) is presented. Reflecting the unique characteristics of CANDU reactors, the procedure of coupling the thermal-hydraulics, reactor physics and fuel channel/element codes in the safety analysis is described. The experience generated in the Canadian nuclear industry may be useful to other types of reactors in the areas of reactor safety analysis.

  20. A multicenter collaborative approach to reducing pediatric codes outside the ICU.

    PubMed

    Hayes, Leslie W; Dobyns, Emily L; DiGiovine, Bruno; Brown, Ann-Marie; Jacobson, Sharon; Randall, Kelly H; Wathen, Beth; Richard, Heather; Schwab, Carolyn; Duncan, Kathy D; Thrasher, Jodi; Logsdon, Tina R; Hall, Matthew; Markovitz, Barry

    2012-03-01

    The Child Health Corporation of America formed a multicenter collaborative to decrease the rate of pediatric codes outside the ICU by 50%, double the days between these events, and improve the patient safety culture scores by 5 percentage points. A multidisciplinary pediatric advisory panel developed a comprehensive change package of process improvement strategies and measures for tracking progress. Learning sessions, conference calls, and data submission facilitated collaborative group learning and implementation. Twenty Child Health Corporation of America hospitals participated in this 12-month improvement project. Each hospital identified at least 1 noncritical care target unit in which to implement selected elements of the change package. Strategies to improve prevention, detection, and correction of the deteriorating patient ranged from relatively simple, foundational changes to more complex, advanced changes. Each hospital selected a broad range of change package elements for implementation using rapid-cycle methodologies. The primary outcome measure was reduction in codes per 1000 patient days. Secondary outcomes were days between codes and change in patient safety culture scores. Code rate for the collaborative did not decrease significantly (3% decrease). Twelve hospitals reported additional data after the collaborative and saw significant improvement in code rates (24% decrease). Patient safety culture scores improved by 4.5% to 8.5%. A complex process, such as patient deterioration, requires sufficient time and effort to achieve improved outcomes and create a deeply embedded culture of patient safety. The collaborative model can accelerate improvements achieved by individual institutions.

  1. The Italian experience on T/H best estimate codes: Achievements and perspectives

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

    Alemberti, A.; D`Auria, F.; Fiorino, E.

    1997-07-01

    Themalhydraulic system codes are complex tools developed to simulate the power plants behavior during off-normal conditions. Among the objectives of the code calculations the evaluation of safety margins, the operator training, the optimization of the plant design and of the emergency operating procedures, are mostly considered in the field of the nuclear safety. The first generation of codes was developed in the United States at the end of `60s. Since that time, different research groups all over the world started the development of their own codes. At the beginning of the `80s, the second generation codes were proposed; these differmore » from the first generation codes owing to the number of balance equations solved (six instead of three), the sophistication of the constitutive models and of the adopted numerics. The capabilities of available computers have been fully exploited during the years. The authors then summarize some of the major steps in the process of developing, modifying, and advancing the capabilities of the codes. They touch on the fact that Italian, and for that matter non-American, researchers have not been intimately involved in much of this work. They then describe the application of these codes in Italy, even though there are no operating or under construction nuclear power plants at this time. Much of this effort is directed at the general question of plant safety in the face of transient type events.« less

  2. The role of the PIRT process in identifying code improvements and executing code development

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

    Wilson, G.E.; Boyack, B.E.

    1997-07-01

    In September 1988, the USNRC issued a revised ECCS rule for light water reactors that allows, as an option, the use of best estimate (BE) plus uncertainty methods in safety analysis. The key feature of this licensing option relates to quantification of the uncertainty in the determination that an NPP has a {open_quotes}low{close_quotes} probability of violating the safety criteria specified in 10 CFR 50. To support the 1988 licensing revision, the USNRC and its contractors developed the CSAU evaluation methodology to demonstrate the feasibility of the BE plus uncertainty approach. The PIRT process, Step 3 in the CSAU methodology, wasmore » originally formulated to support the BE plus uncertainty licensing option as executed in the CSAU approach to safety analysis. Subsequent work has shown the PIRT process to be a much more powerful tool than conceived in its original form. Through further development and application, the PIRT process has shown itself to be a robust means to establish safety analysis computer code phenomenological requirements in their order of importance to such analyses. Used early in research directed toward these objectives, PIRT results also provide the technical basis and cost effective organization for new experimental programs needed to improve the safety analysis codes for new applications. The primary purpose of this paper is to describe the generic PIRT process, including typical and common illustrations from prior applications. The secondary objective is to provide guidance to future applications of the process to help them focus, in a graded approach, on systems, components, processes and phenomena that have been common in several prior applications.« less

  3. Department of Energy Construction Safety Reference Guide

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

    Not Available

    1993-09-01

    DOE has adopted the Occupational Safety and Health Administration (OSHA) regulations Title 29 Code of Federal Regulations (CFR) 1926 ``Safety and Health Regulations for Construction,`` and related parts of 29 CFR 1910, ``Occupational Safety and Health Standards.`` This nonmandatory reference guide is based on these OSHA regulations and, where appropriate, incorporates additional standards, codes, directives, and work practices that are recognized and accepted by DOE and the construction industry. It covers excavation, scaffolding, electricity, fire, signs/barricades, cranes/hoists/conveyors, hand and power tools, concrete/masonry, stairways/ladders, welding/cutting, motor vehicles/mechanical equipment, demolition, materials, blasting, steel erection, etc.

  4. Potential of Gene Editing and Induced Pluripotent Stem Cells (iPSCs) in Treatment of Retinal Diseases.

    PubMed

    Chuang, Katherine; Fields, Mark A; Del Priore, Lucian V

    2017-12-01

    The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy. This review focuses on the use of gene editing techniques and another relatively recent advent, induced pluripotent stem cells (iPSCs), and their potential for the study and treatment of retinal disease. Investment in these technologies, including overcoming challenges such as off-target mutations and low transplanted cell integration, may allow for future treatment of many debilitating inherited retinal diseases.

  5. Patient-derived iPSCs show premature neural differentiation and neuron-type specific phenotypes relevant to neurodevelopment

    PubMed Central

    Yeh, Erika; Dao, Dang Q.; Wu, Zhi Y.; Kandalam, Santoshi M.; Camacho, Federico M.; Tom, Curtis; Zhang, Wandong; Krencik, Robert; Rauen, Katherine A.; Ullian, Erik M.; Weiss, Lauren A.

    2017-01-01

    Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAFQ257R, the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation. Pharmacological PI3K/AKT pathway manipulation recapitulated cellular phenotypes in control cells and attenuated them in CFC cells. CFC cultures displayed altered cellular subtype ratios and increased intrinsic excitability. Moreover, in CFC cells, Ras/MAPK pathway activation and morphological abnormalities exhibited cell subtype-specific differences. Our results highlight the importance of exploring specific cellular subtypes and of using iPSC models to reveal relevant human-specific neurodevelopmental events. PMID:29158583

  6. RELAP-7 Code Assessment Plan and Requirement Traceability Matrix

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

    Yoo, Junsoo; Choi, Yong-joon; Smith, Curtis L.

    2016-10-01

    The RELAP-7, a safety analysis code for nuclear reactor system, is under development at Idaho National Laboratory (INL). Overall, the code development is directed towards leveraging the advancements in computer science technology, numerical solution methods and physical models over the last decades. Recently, INL has also been putting an effort to establish the code assessment plan, which aims to ensure an improved final product quality through the RELAP-7 development process. The ultimate goal of this plan is to propose a suitable way to systematically assess the wide range of software requirements for RELAP-7, including the software design, user interface, andmore » technical requirements, etc. To this end, we first survey the literature (i.e., international/domestic reports, research articles) addressing the desirable features generally required for advanced nuclear system safety analysis codes. In addition, the V&V (verification and validation) efforts as well as the legacy issues of several recently-developed codes (e.g., RELAP5-3D, TRACE V5.0) are investigated. Lastly, this paper outlines the Requirement Traceability Matrix (RTM) for RELAP-7 which can be used to systematically evaluate and identify the code development process and its present capability.« less

  7. Further Analysis of Motorcycle Helmet Effectiveness Using CODES Linked Data

    DOT National Transportation Integrated Search

    1998-01-01

    Linked data from the Crash Outcome Data Evaluation System (CODES) in seven : states was used by the National Highway Traffic Safety Administration as the : basis of a 1996 Report to Congress on the Benefits of Safety Belts and : Motorcycle Helmets (D...

  8. Energy Storage System Safety: Plan Review and Inspection Checklist

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

    Cole, Pam C.; Conover, David R.

    Codes, standards, and regulations (CSR) governing the design, construction, installation, commissioning, and operation of the built environment are intended to protect the public health, safety, and welfare. While these documents change over time to address new technology and new safety challenges, there is generally some lag time between the introduction of a technology into the market and the time it is specifically covered in model codes and standards developed in the voluntary sector. After their development, there is also a timeframe of at least a year or two until the codes and standards are adopted. Until existing model codes andmore » standards are updated or new ones are developed and then adopted, one seeking to deploy energy storage technologies or needing to verify the safety of an installation may be challenged in trying to apply currently implemented CSRs to an energy storage system (ESS). The Energy Storage System Guide for Compliance with Safety Codes and Standards1 (CG), developed in June 2016, is intended to help address the acceptability of the design and construction of stationary ESSs, their component parts, and the siting, installation, commissioning, operations, maintenance, and repair/renovation of ESS within the built environment.« less

  9. Residential building codes, affordability, and health protection: a risk-tradeoff approach.

    PubMed

    Hammitt, J K; Belsky, E S; Levy, J I; Graham, J D

    1999-12-01

    Residential building codes intended to promote health and safety may produce unintended countervailing risks by adding to the cost of construction. Higher construction costs increase the price of new homes and may increase health and safety risks through "income" and "stock" effects. The income effect arises because households that purchase a new home have less income remaining for spending on other goods that contribute to health and safety. The stock effect arises because suppression of new-home construction leads to slower replacement of less safe housing units. These countervailing risks are not presently considered in code debates. We demonstrate the feasibility of estimating the approximate magnitude of countervailing risks by combining the income effect with three relatively well understood and significant home-health risks. We estimate that a code change that increases the nationwide cost of constructing and maintaining homes by $150 (0.1% of the average cost to build a single-family home) would induce offsetting risks yielding between 2 and 60 premature fatalities or, including morbidity effects, between 20 and 800 lost quality-adjusted life years (both discounted at 3%) each year the code provision remains in effect. To provide a net health benefit, the code change would need to reduce risk by at least this amount. Future research should refine these estimates, incorporate quantitative uncertainty analysis, and apply a full risk-tradeoff approach to real-world case studies of proposed code changes.

  10. Natural and Synthetic Materials for Self-Renewal, Long-Term Maintenance, and Differentiation of Induced Pluripotent Stem Cells.

    PubMed

    Dzhoyashvili, Nina A; Shen, Sanbing; Rochev, Yury A

    2015-11-18

    Induced pluripotent stem cells (iPSCs) have attracted considerable attention from the public, clinicians, and scientists since their discovery in 2006, and raised huge expectations for regenerative medicine. One of the distinctive features of iPSCs is their propensity to differentiate into the cells of three germ lines in vitro and in vivo. The human iPSCs can be used to study the mechanisms underlying a disease and to monitor the disease progression, for testing drugs in vitro, and for cell therapy, avoiding many ethical and immunologic concerns. This technology offers the potential to take an individual approach to each patient and allows a more accurate diagnosis and specific treatment. However, there are several obstacles that impede the use of iPSCs. The derivation of fully reprogrammed iPSCs is expensive, time-consuming, and demands meticulous attention to many details. The use of biomaterials could increase the efficacy and safety while decreasing the cost of tissue engineering. The choice of a substrate utilized for iPSC culture is also important because cell-substrate contacts influence cellular behavior such as self-renewal, expansion, and differentiation. This Progress Report aims to summarize the advantages and drawbacks of natural and synthetic biomaterials, and to evaluate their role for maintenance and differentiation of iPSCs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Assessment of the safety of aquatic animal commodities for international trade: the OIE Aquatic Animal Health code.

    PubMed

    Oidtmann, B; Johnston, C; Klotins, K; Mylrea, G; Van, P T; Cabot, S; Martin, P Rosado; Ababouch, L; Berthe, F

    2013-02-01

    Trading of aquatic animals and aquatic animal products has become increasingly globalized during the last couple of decades. This commodity trade has increased the risk for the spread of aquatic animal pathogens. The World Organisation for Animal Health (OIE) is recognized as the international standard-setting organization for measures relating to international trade in animals and animal products. In this role, OIE has developed the Aquatic Animal Health Code, which provides health measures to be used by competent authorities of importing and exporting countries to avoid the transfer of agents pathogenic for animals or humans, whilst avoiding unjustified sanitary barriers. An OIE ad hoc group developed criteria for assessing the safety of aquatic animals or aquatic animal products for any purpose from a country, zone or compartment not declared free from a given disease 'X'. The criteria were based on the absence of the pathogenic agent in the traded commodity or inactivation of the pathogenic agent by the commercial processing used to produce the commodity. The group also developed criteria to assess the safety of aquatic animals or aquatic animal products for retail trade for human consumption from potentially infected areas. Such commodities were assessed considering the form and presentation of the product, the expected volume of waste tissues generated by the consumer and the likely presence of viable pathogenic agent in the waste. The ad hoc group applied the criteria to commodities listed in the individual disease chapters of the Aquatic Animal Health Code (2008 edition). Revised lists of commodities for which no additional measures should be required by the importing countries regardless of the status for disease X of the exporting country were developed and adopted by the OIE World Assembly of Delegates in May 2011. The rationale of the criteria and their application will be explained and demonstrated using examples. © 2012 Crown Copyright. Reproduced

  12. Generation of induced pluripotent stem cells from a patient with spinocerebellar ataxia type 3.

    PubMed

    Soong, Bing-Wen; Syu, Shih-Han; Wen, Cheng-Hao; Ko, Hui-Wen; Wu, Mei-Ling; Hsieh, Patrick C H; Hwang, Shiaw-Min; Lu, Huai-En

    2017-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a trinucleotide repeat (CAG) expansion in the coding region of ATXN3 gene resulting in production of ataxin-3 with an elongated polyglutamine tract. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a male patient with SCA3 by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype, retained the disease-causing ATXN3 mutation, expressed pluripotent markers and could differentiate into the three germ layers. Potentially, the iPSCs could be a useful tool for the investigation of disease mechanisms of SCA3. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. The Crash Outcome Data Evaluation System (CODES)

    DOT National Transportation Integrated Search

    1996-01-01

    The CODES Technical Report presents state-specific results from the Crash : Outcome Data Evaluation System project. These results confirm previous NHTSA : studies and show that safety belts and motorcycle helmets are effective in : reducing fatalitie...

  14. Modulation of Human Allogeneic and Syngeneic Pluripotent Stem Cells and Immunological Implications for Transplantation

    PubMed Central

    Sackett, S.D.; Brown, M.E.; Tremmel, D.M.; Ellis, T.; Burlingham, W.J.; Odorico, J.S.

    2016-01-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. PMID:26970668

  15. Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

    PubMed

    Sackett, S D; Brown, M E; Tremmel, D M; Ellis, T; Burlingham, W J; Odorico, J S

    2016-04-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Parallel spatial direct numerical simulations on the Intel iPSC/860 hypercube

    NASA Technical Reports Server (NTRS)

    Joslin, Ronald D.; Zubair, Mohammad

    1993-01-01

    The implementation and performance of a parallel spatial direct numerical simulation (PSDNS) approach on the Intel iPSC/860 hypercube is documented. The direct numerical simulation approach is used to compute spatially evolving disturbances associated with the laminar-to-turbulent transition in boundary-layer flows. The feasibility of using the PSDNS on the hypercube to perform transition studies is examined. The results indicate that the direct numerical simulation approach can effectively be parallelized on a distributed-memory parallel machine. By increasing the number of processors nearly ideal linear speedups are achieved with nonoptimized routines; slower than linear speedups are achieved with optimized (machine dependent library) routines. This slower than linear speedup results because the Fast Fourier Transform (FFT) routine dominates the computational cost and because the routine indicates less than ideal speedups. However with the machine-dependent routines the total computational cost decreases by a factor of 4 to 5 compared with standard FORTRAN routines. The computational cost increases linearly with spanwise wall-normal and streamwise grid refinements. The hypercube with 32 processors was estimated to require approximately twice the amount of Cray supercomputer single processor time to complete a comparable simulation; however it is estimated that a subgrid-scale model which reduces the required number of grid points and becomes a large-eddy simulation (PSLES) would reduce the computational cost and memory requirements by a factor of 10 over the PSDNS. This PSLES implementation would enable transition simulations on the hypercube at a reasonable computational cost.

  17. Runtime Detection of C-Style Errors in UPC Code

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

    Pirkelbauer, P; Liao, C; Panas, T

    2011-09-29

    Unified Parallel C (UPC) extends the C programming language (ISO C 99) with explicit parallel programming support for the partitioned global address space (PGAS), which provides a global memory space with localized partitions to each thread. Like its ancestor C, UPC is a low-level language that emphasizes code efficiency over safety. The absence of dynamic (and static) safety checks allows programmer oversights and software flaws that can be hard to spot. In this paper, we present an extension of a dynamic analysis tool, ROSE-Code Instrumentation and Runtime Monitor (ROSECIRM), for UPC to help programmers find C-style errors involving the globalmore » address space. Built on top of the ROSE source-to-source compiler infrastructure, the tool instruments source files with code that monitors operations and keeps track of changes to the system state. The resulting code is linked to a runtime monitor that observes the program execution and finds software defects. We describe the extensions to ROSE-CIRM that were necessary to support UPC. We discuss complications that arise from parallel code and our solutions. We test ROSE-CIRM against a runtime error detection test suite, and present performance results obtained from running error-free codes. ROSE-CIRM is released as part of the ROSE compiler under a BSD-style open source license.« less

  18. Capabilities overview of the MORET 5 Monte Carlo code

    NASA Astrophysics Data System (ADS)

    Cochet, B.; Jinaphanh, A.; Heulers, L.; Jacquet, O.

    2014-06-01

    The MORET code is a simulation tool that solves the transport equation for neutrons using the Monte Carlo method. It allows users to model complex three-dimensional geometrical configurations, describe the materials, define their own tallies in order to analyse the results. The MORET code has been initially designed to perform calculations for criticality safety assessments. New features has been introduced in the MORET 5 code to expand its use for reactor applications. This paper presents an overview of the MORET 5 code capabilities, going through the description of materials, the geometry modelling, the transport simulation and the definition of the outputs.

  19. Automatic Certification of Kalman Filters for Reliable Code Generation

    NASA Technical Reports Server (NTRS)

    Denney, Ewen; Fischer, Bernd; Schumann, Johann; Richardson, Julian

    2005-01-01

    AUTOFILTER is a tool for automatically deriving Kalman filter code from high-level declarative specifications of state estimation problems. It can generate code with a range of algorithmic characteristics and for several target platforms. The tool has been designed with reliability of the generated code in mind and is able to automatically certify that the code it generates is free from various error classes. Since documentation is an important part of software assurance, AUTOFILTER can also automatically generate various human-readable documents, containing both design and safety related information. We discuss how these features address software assurance standards such as DO-178B.

  20. Feasibility of Induced Pluripotent Stem Cell Therapies for Treatment of Type 1 Diabetes.

    PubMed

    Duffy, Caden; Prugue, Cesar; Glew, Rachel; Smith, Taryn; Howell, Calvin; Choi, Gina; Cook, Alonzo David

    2018-06-27

    Despite their potential for treating type 1 diabetes (T1D), induced pluripotent stem cells (iPSCs) have not yet been used successfully in the clinic. In this paper, advances in iPSC therapies are reviewed and compared to current methods of treating T1D. Encapsulation of iPSCs is being pursued to address such safety concerns as the possibility of immune rejection or teratoma formation, and provide for retrievability. Issues of material selection, cell differentiation, size of islet aggregates, sites of implantation, animal models, and vascularization are also being addressed. Clinical trials are being conducted to test a variety of new devices with the hope of providing additional therapies for T1D.

  1. Common Day Care Safety Renovations: Descriptions, Explanations and Cost Estimates.

    ERIC Educational Resources Information Center

    Spack, Stan

    This booklet explains some of the day care safety features specified by the new Massachusetts State Building Code (January 1, 1975) which must be met before a new day care center can be licensed. The safety features described are those which most often require renovation to meet the building code standards. Best estimates of the costs involved in…

  2. Ready for "Code Red"? Pre-Plan for Safety

    ERIC Educational Resources Information Center

    Baker, Davis E.

    2006-01-01

    In this article, the author, a principal of Buckeye Valley High School, Delaware, Ohio, focuses on how to generate a building readiness plan. He suggests that school administrators should have a readily available notebook of emergency response procedures to ensure students' safety. Among other things, he recommends creation of a building…

  3. Triangulating case-finding tools for patient safety surveillance: a cross-sectional case study of puncture/laceration.

    PubMed

    Taylor, Jennifer A; Gerwin, Daniel; Morlock, Laura; Miller, Marlene R

    2011-12-01

    To evaluate the need for triangulating case-finding tools in patient safety surveillance. This study applied four case-finding tools to error-associated patient safety events to identify and characterise the spectrum of events captured by these tools, using puncture or laceration as an example for in-depth analysis. Retrospective hospital discharge data were collected for calendar year 2005 (n=48,418) from a large, urban medical centre in the USA. The study design was cross-sectional and used data linkage to identify the cases captured by each of four case-finding tools. Three case-finding tools (International Classification of Diseases external (E) and nature (N) of injury codes, Patient Safety Indicators (PSI)) were applied to the administrative discharge data to identify potential patient safety events. The fourth tool was Patient Safety Net, a web-based voluntary patient safety event reporting system. The degree of mutual exclusion among detection methods was substantial. For example, when linking puncture or laceration on unique identifiers, out of 447 potential events, 118 were identical between PSI and E-codes, 152 were identical between N-codes and E-codes and 188 were identical between PSI and N-codes. Only 100 events that were identified by PSI, E-codes and N-codes were identical. Triangulation of multiple tools through data linkage captures potential patient safety events most comprehensively. Existing detection tools target patient safety domains differently, and consequently capture different occurrences, necessitating the integration of data from a combination of tools to fully estimate the total burden.

  4. Comparing the coding of complications in Queensland and Victorian admitted patient data.

    PubMed

    Michel, Jude L; Cheng, Diana; Jackson, Terri J

    2011-08-01

    To examine differences between Queensland and Victorian coding of hospital-acquired conditions and suggest ways to improve the usefulness of these data in the monitoring of patient safety events. Secondary analysis of admitted patient episode data collected in Queensland and Victoria. Comparison of depth of coding, and patterns in the coding of ten commonly coded complications of five elective procedures. Comparison of the mean complication codes assigned per episode revealed Victoria assigns more valid codes than Queensland for all procedures, with the difference between the states being significantly different in all cases. The proportion of the codes flagged as complications was consistently lower for Queensland when comparing 10 common complications for each of the five selected elective procedures. The estimated complication rates for the five procedures showed Victoria to have an apparently higher complication rate than Queensland for 35 of the 50 complications examined. Our findings demonstrate that the coding of complications is more comprehensive in Victoria than in Queensland. It is known that inconsistencies exist between states in routine hospital data quality. Comparative use of patient safety indicators should be viewed with caution until standards are improved across Australia. More exploration of data quality issues is needed to identify areas for improvement.

  5. Use the Bar Code System to Improve Accuracy of the Patient and Sample Identification.

    PubMed

    Chuang, Shu-Hsia; Yeh, Huy-Pzu; Chi, Kun-Hung; Ku, Hsueh-Chen

    2018-01-01

    In time and correct sample collection were highly related to patient's safety. The sample error rate was 11.1%, because misbranded patient information and wrong sample containers during January to April, 2016. We developed a barcode system of "Specimens Identify System" through process of reengineering of TRM, used bar code scanners, add sample container instructions, and mobile APP. Conclusion, the bar code systems improved the patient safety and created green environment.

  6. Characterization of human-induced pluripotent stem cell-derived cardiomyocytes: bioenergetics and utilization in safety screening.

    PubMed

    Rana, Payal; Anson, Blake; Engle, Sandra; Will, Yvonne

    2012-11-01

    Cardiotoxicity remains the number one reason for drug withdrawal from the market, and Food and Drug Administration issued black box warnings, thus demonstrating the need for more predictive preclinical safety screening, especially early in the drug discovery process when much chemical substrate is available. Whereas human-ether-a-go-go related gene screening has become routine to mitigate proarrhythmic risk, the development of in vitro assays predicting additional on- and off-target biochemical toxicities will benefit from cellular models exhibiting true cardiomyocyte characteristics such as native tissue-like mitochondrial activity. Human stem cell-derived tissue cells may provide such a model. This hypothesis was tested using a combination of flux analysis, gene and protein expression, and toxicity-profiling techniques to characterize mitochondrial function in induced pluripotent stem cell (iPSC) derived human cardiomyocytes in the presence of differing carbon sources over extended periods in cell culture. Functional analyses demonstrate that iPSC-derived cardiomyocytes are (1) capable of utilizing anaerobic or aerobic respiration depending upon the available carbon substrate and (2) bioenergetically closest to adult heart tissue cells when cultured in galactose or galactose supplemented with fatty acids. We utilized this model to test a variety of kinase inhibitors with known clinical cardiac liabilities for their potential toxicity toward these cells. We found that the kinase inhibitors showed a dose-dependent toxicity to iPSC cardiomyocytes grown in galactose and that oxygen consumption rates were significantly more affected than adenosine triphosphate production. Sorafenib was found to have the most effect, followed by sunitinib, dasatinib, imatinib, lapatinib, and nioltinib.

  7. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

  8. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

  9. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

  10. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

  11. 7 CFR Exhibit E to Subpart A of... - Voluntary National Model Building Codes

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Voluntary National Model Building Codes E Exhibit E... National Model Building Codes The following documents address the health and safety aspects of buildings and related structures and are voluntary national model building codes as defined in § 1924.4(h)(2) of...

  12. 7 CFR Exhibit E to Subpart A of... - Voluntary National Model Building Codes

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Voluntary National Model Building Codes E Exhibit E to... Model Building Codes The following documents address the health and safety aspects of buildings and related structures and are voluntary national model building codes as defined in § 1924.4(h)(2) of this...

  13. 7 CFR Exhibit E to Subpart A of... - Voluntary National Model Building Codes

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Voluntary National Model Building Codes E Exhibit E... National Model Building Codes The following documents address the health and safety aspects of buildings and related structures and are voluntary national model building codes as defined in § 1924.4(h)(2) of...

  14. Industry and Occupation in the Electronic Health Record: An Investigation of the National Institute for Occupational Safety and Health Industry and Occupation Computerized Coding System

    PubMed Central

    2016-01-01

    Background Inclusion of information about a patient’s work, industry, and occupation, in the electronic health record (EHR) could facilitate occupational health surveillance, better health outcomes, prevention activities, and identification of workers’ compensation cases. The US National Institute for Occupational Safety and Health (NIOSH) has developed an autocoding system for “industry” and “occupation” based on 1990 Bureau of Census codes; its effectiveness requires evaluation in conjunction with promoting the mandatory addition of these variables to the EHR. Objective The objective of the study was to evaluate the intercoder reliability of NIOSH’s Industry and Occupation Computerized Coding System (NIOCCS) when applied to data collected in a community survey conducted under the Affordable Care Act; to determine the proportion of records that are autocoded using NIOCCS. Methods Standard Occupational Classification (SOC) codes are used by several federal agencies in databases that capture demographic, employment, and health information to harmonize variables related to work activities among these data sources. There are 359 industry and occupation responses that were hand coded by 2 investigators, who came to a consensus on every code. The same variables were autocoded using NIOCCS at the high and moderate criteria level. Results Kappa was .84 for agreement between hand coders and between the hand coder consensus code versus NIOCCS high confidence level codes for the first 2 digits of the SOC code. For 4 digits, NIOCCS coding versus investigator coding ranged from kappa=.56 to .70. In this study, NIOCCS was able to achieve production rates (ie, to autocode) 31%-36% of entered variables at the “high confidence” level and 49%-58% at the “medium confidence” level. Autocoding (production) rates are somewhat lower than those reported by NIOSH. Agreement between manually coded and autocoded data are “substantial” at the 2-digit level, but only

  15. Industry and Occupation in the Electronic Health Record: An Investigation of the National Institute for Occupational Safety and Health Industry and Occupation Computerized Coding System.

    PubMed

    Schmitz, Matthew; Forst, Linda

    2016-02-15

    Inclusion of information about a patient's work, industry, and occupation, in the electronic health record (EHR) could facilitate occupational health surveillance, better health outcomes, prevention activities, and identification of workers' compensation cases. The US National Institute for Occupational Safety and Health (NIOSH) has developed an autocoding system for "industry" and "occupation" based on 1990 Bureau of Census codes; its effectiveness requires evaluation in conjunction with promoting the mandatory addition of these variables to the EHR. The objective of the study was to evaluate the intercoder reliability of NIOSH's Industry and Occupation Computerized Coding System (NIOCCS) when applied to data collected in a community survey conducted under the Affordable Care Act; to determine the proportion of records that are autocoded using NIOCCS. Standard Occupational Classification (SOC) codes are used by several federal agencies in databases that capture demographic, employment, and health information to harmonize variables related to work activities among these data sources. There are 359 industry and occupation responses that were hand coded by 2 investigators, who came to a consensus on every code. The same variables were autocoded using NIOCCS at the high and moderate criteria level. Kappa was .84 for agreement between hand coders and between the hand coder consensus code versus NIOCCS high confidence level codes for the first 2 digits of the SOC code. For 4 digits, NIOCCS coding versus investigator coding ranged from kappa=.56 to .70. In this study, NIOCCS was able to achieve production rates (ie, to autocode) 31%-36% of entered variables at the "high confidence" level and 49%-58% at the "medium confidence" level. Autocoding (production) rates are somewhat lower than those reported by NIOSH. Agreement between manually coded and autocoded data are "substantial" at the 2-digit level, but only "fair" to "good" at the 4-digit level. This work serves as a

  16. Current and anticipated uses of the CATHARE code at EDF and FRAMATOME

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

    Gandrille, J.L.; Vacher, J.L.; Poizat, F.

    1997-07-01

    This paper presents current industrial applications of the CATHARE code in the fields of Safety Studies and Simulators where the code is intensively used by FRAMATOME, EDF and CEA, the development partners of CATHARE. Future needs in these fields are also recapitulated.

  17. Generating Code Review Documentation for Auto-Generated Mission-Critical Software

    NASA Technical Reports Server (NTRS)

    Denney, Ewen; Fischer, Bernd

    2009-01-01

    Model-based design and automated code generation are increasingly used at NASA to produce actual flight code, particularly in the Guidance, Navigation, and Control domain. However, since code generators are typically not qualified, there is no guarantee that their output is correct, and consequently auto-generated code still needs to be fully tested and certified. We have thus developed AUTOCERT, a generator-independent plug-in that supports the certification of auto-generated code. AUTOCERT takes a set of mission safety requirements, and formally verifies that the autogenerated code satisfies these requirements. It generates a natural language report that explains why and how the code complies with the specified requirements. The report is hyper-linked to both the program and the verification conditions and thus provides a high-level structured argument containing tracing information for use in code reviews.

  18. Recent improvements of reactor physics codes in MHI

    NASA Astrophysics Data System (ADS)

    Kosaka, Shinya; Yamaji, Kazuya; Kirimura, Kazuki; Kamiyama, Yohei; Matsumoto, Hideki

    2015-12-01

    This paper introduces recent improvements for reactor physics codes in Mitsubishi Heavy Industries, Ltd(MHI). MHI has developed a new neutronics design code system Galaxy/Cosmo-S(GCS) for PWR core analysis. After TEPCO's Fukushima Daiichi accident, it is required to consider design extended condition which has not been covered explicitly by the former safety licensing analyses. Under these circumstances, MHI made some improvements for GCS code system. A new resonance calculation model of lattice physics code and homogeneous cross section representative model for core simulator have been developed to apply more wide range core conditions corresponding to severe accident status such like anticipated transient without scram (ATWS) analysis and criticality evaluation of dried-up spent fuel pit. As a result of these improvements, GCS code system has very wide calculation applicability with good accuracy for any core conditions as far as fuel is not damaged. In this paper, the outline of GCS code system is described briefly and recent relevant development activities are presented.

  19. Development of photovoltaic array and module safety requirements

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Safety requirements for photovoltaic module and panel designs and configurations likely to be used in residential, intermediate, and large-scale applications were identified and developed. The National Electrical Code and Building Codes were reviewed with respect to present provisions which may be considered to affect the design of photovoltaic modules. Limited testing, primarily in the roof fire resistance field was conducted. Additional studies and further investigations led to the development of a proposed standard for safety for flat-plate photovoltaic modules and panels. Additional work covered the initial investigation of conceptual approaches and temporary deployment, for concept verification purposes, of a differential dc ground-fault detection circuit suitable as a part of a photovoltaic array safety system.

  20. [QR-Code based patient tracking: a cost-effective option to improve patient safety].

    PubMed

    Fischer, M; Rybitskiy, D; Strauß, G; Dietz, A; Dressler, C R

    2013-03-01

    Hospitals are implementing a risk management system to avoid patient or surgery mix-ups. The trend is to use preoperative checklists. This work deals specifically with a type of patient identification, which is realized by storing patient data on a patient-fixed medium. In 127 ENT surgeries data relevant for patient identification were encrypted in a 2D-QR-Code. The code, as a separate document coming with the patient chart or as a patient wristband, has been decrypted in the OR and the patient data were presented visible for all persons. The decoding time, the compliance of the patient data, as well as the duration of the patient identification was compared with the traditional patient identification by inspection of the patient chart. A total of 125 QR codes were read. The time for the decrypting of QR-Code was 5.6 s, the time for the screen view for patient identification was 7.9 s, and for a comparison group of 75 operations traditional patient identification was 27.3 s. Overall, there were 6 relevant information errors in the two parts of the experiment. This represents a ratio of 0.6% for 8 relevant classes per each encrypted QR code. This work allows a cost effective way to technically support patient identification based on electronic patient data. It was shown that the use in the clinical routine is possible. The disadvantage is a potential misinformation from incorrect or missing information in the HIS, or due to changes of the data after the code was created. The QR-code-based patient tracking is seen as a useful complement to the already widely used identification wristband. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases.

    PubMed

    Wiley, Luke A; Burnight, Erin R; Songstad, Allison E; Drack, Arlene V; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2015-01-01

    Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement. Copyright © 2014. Published by Elsevier Ltd.

  2. 36 CFR 910.37 - Fire and life safety.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Fire and life safety. 910.37... DEVELOPMENT AREA Standards Uniformly Applicable to the Development Area § 910.37 Fire and life safety. As a... recommended that all new development be guided by standards of the NFPA Codes for fire and life safety and...

  3. 36 CFR 910.37 - Fire and life safety.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Fire and life safety. 910.37... DEVELOPMENT AREA Standards Uniformly Applicable to the Development Area § 910.37 Fire and life safety. As a... recommended that all new development be guided by standards of the NFPA Codes for fire and life safety and...

  4. SCALE Code System

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

    Rearden, Bradley T.; Jessee, Matthew Anderson

    The SCALE Code System is a widely-used modeling and simulation suite for nuclear safety analysis and design that is developed, maintained, tested, and managed by the Reactor and Nuclear Systems Division (RNSD) of Oak Ridge National Laboratory (ORNL). SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor and lattice physics, radiation shielding, spent fuel and radioactive source term characterization, and sensitivity and uncertainty analysis. Since 1980, regulators, licensees, and research institutions around the world have used SCALE for safety analysis and design. SCALE provides an integrated framework with dozens of computational modules including three deterministicmore » and three Monte Carlo radiation transport solvers that are selected based on the desired solution strategy. SCALE includes current nuclear data libraries and problem-dependent processing tools for continuous-energy (CE) and multigroup (MG) neutronics and coupled neutron-gamma calculations, as well as activation, depletion, and decay calculations. SCALE includes unique capabilities for automated variance reduction for shielding calculations, as well as sensitivity and uncertainty analysis. SCALE’s graphical user interfaces assist with accurate system modeling, visualization of nuclear data, and convenient access to desired results.« less

  5. 7 CFR Exhibit E to Subpart A of... - Voluntary National Model Building Codes

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... National Model Building Codes The following documents address the health and safety aspects of buildings... International, Inc., 4051 West Flossmoor Road, Country Club Hills, Illinois 60477. 2 Southern Building Code Congress International, Inc., 900 Montclair Road, Birmingham, Alabama 35213-1206. 3 International...

  6. Current and anticipated uses of thermal-hydraulic codes in Germany

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

    Teschendorff, V.; Sommer, F.; Depisch, F.

    1997-07-01

    In Germany, one third of the electrical power is generated by nuclear plants. ATHLET and S-RELAP5 are successfully applied for safety analyses of the existing PWR and BWR reactors and possible future reactors, e.g. EPR. Continuous development and assessment of thermal-hydraulic codes are necessary in order to meet present and future needs of licensing organizations, utilities, and vendors. Desired improvements include thermal-hydraulic models, multi-dimensional simulation, computational speed, interfaces to coupled codes, and code architecture. Real-time capability will be essential for application in full-scope simulators. Comprehensive code validation and quantification of uncertainties are prerequisites for future best-estimate analyses.

  7. Safety and health in the construction of fixed offshore installations in the petroleum industry

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

    Not Available

    1981-01-01

    A meeting convened by the ILO (International Labor Office) on safety problems in the offshore petroleum industry recommended the preparation of a code of practice setting out standards for safety and health during the construction of fixed offshore installations. Such a code, to be prepared by the ILO in co-operation with other bodies, including the Inter-Governmental Maritime Consultative Organisation (IMCO), was to take into consideration existing standards applicable to offshore construction activities and to supplement the ILO codes of practice on safety and health in building and civil engineering work, shipbuilding and ship repairing. (Copyright (c) International Labour Organisation 1981.)

  8. Review of current nuclear fallout codes.

    PubMed

    Auxier, Jerrad P; Auxier, John D; Hall, Howard L

    2017-05-01

    The importance of developing a robust nuclear forensics program to combat the illicit use of nuclear material that may be used as an improvised nuclear device is widely accepted. In order to decrease the threat to public safety and improve governmental response, government agencies have developed fallout-analysis codes to predict the fallout particle size, dose, and dispersion and dispersion following a detonation. This paper will review the different codes that have been developed for predicting fallout from both chemical and nuclear weapons. This will decrease the response time required for the government to respond to the event. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. The Nuremberg Code subverts human health and safety by requiring animal modeling

    PubMed Central

    2012-01-01

    Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented. PMID:22769234

  10. The Nuremberg Code subverts human health and safety by requiring animal modeling.

    PubMed

    Greek, Ray; Pippus, Annalea; Hansen, Lawrence A

    2012-07-08

    The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.

  11. Building codes: An often overlooked determinant of health.

    PubMed

    Chauvin, James; Pauls, Jake; Strobl, Linda

    2016-05-01

    Although the vast majority of the world's population spends most of their time in buildings, building codes are not often thought of as 'determinants of health'. The standards that govern the design, construction, and use of buildings affect our health, security, safety, and well-being. This is true for dwellings, schools, and universities, shopping centers, places of recreation, places of worship, health-care facilities, and workplaces. We urge proactive engagement by the global public health community in developing these codes, and in the design and implementation of health protection and health promotion activities intended to reduce the risk of injury, disability, and death, particularly when due to poor building code adoption/adaption, application, and enforcement.

  12. Patient safety incidents in hospice care: observations from interdisciplinary case conferences.

    PubMed

    Oliver, Debra Parker; Demiris, George; Wittenberg-Lyles, Elaine; Gage, Ashley; Dewsnap-Dreisinger, Mariah L; Luetkemeyer, Jamie

    2013-12-01

    In the home hospice environment, issues arise every day presenting challenges to the safety, care, and quality of the dying experience. The literature pertaining to the safety challenges in this environment is limited. The study explored two research questions; 1) What types of patient safety incidents occur in the home hospice setting? 2) How many of these incidents are recognized by the hospice staff and/or the patient or caregiver as a patient safety incident? Video-recordings of hospice interdisciplinary team case conferences were reviewed and coded for patient safety incidents. Patient safety incidents were defined as any event or circumstance that could have resulted or did result in unnecessary harm to the patient or caregiver, or that could have resulted or did result in a negative impact on the quality of the dying experience for the patient. Codes for categories of patient safety incidents were based on the International Classification for Patient Safety. The setting for the study included two rural hospice programs in one Midwestern state in the United States. One hospice team had two separately functioning teams, the second hospice had three teams. 54 video-recordings were reviewed and coded. Patient safety incidents were identified that involved issues in clinical process, medications, falls, family or caregiving, procedural problems, documentation, psychosocial issues, administrative challenges and accidents. This study distinguishes categories of patient safety events that occur in home hospice care. Although the scope and definition of potential patient safety incidents in hospice is unique, the events observed in this study are similar to those observed with in other settings. This study identifies an operating definition and a potential classification for further research on patient safety incidents in hospice. Further research and consensus building of the definition of patient safety incidents and patient safety incidents in this setting is

  13. Recent improvements of reactor physics codes in MHI

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

    Kosaka, Shinya, E-mail: shinya-kosaka@mhi.co.jp; Yamaji, Kazuya; Kirimura, Kazuki

    2015-12-31

    This paper introduces recent improvements for reactor physics codes in Mitsubishi Heavy Industries, Ltd(MHI). MHI has developed a new neutronics design code system Galaxy/Cosmo-S(GCS) for PWR core analysis. After TEPCO’s Fukushima Daiichi accident, it is required to consider design extended condition which has not been covered explicitly by the former safety licensing analyses. Under these circumstances, MHI made some improvements for GCS code system. A new resonance calculation model of lattice physics code and homogeneous cross section representative model for core simulator have been developed to apply more wide range core conditions corresponding to severe accident status such like anticipatedmore » transient without scram (ATWS) analysis and criticality evaluation of dried-up spent fuel pit. As a result of these improvements, GCS code system has very wide calculation applicability with good accuracy for any core conditions as far as fuel is not damaged. In this paper, the outline of GCS code system is described briefly and recent relevant development activities are presented.« less

  14. Rural School District Dress Code Implementation: Perceptions of Stakeholders after First Year

    ERIC Educational Resources Information Center

    Wright, Krystal M.

    2012-01-01

    Schools are continuously searching for solutions to solve truancy, academic, behavioral, safety, and climate issues. One of the latest trends in education is requiring students to adhere to dress codes as a solution to these issues. Dress codes can range from slightly restrictive clothing to the requiring of a uniform. Many school district…

  15. Characterizing PCDH19 in human induced pluripotent stem cells (iPSCs) and iPSC-derived developing neurons: emerging role of a protein involved in controlling polarity during neurogenesis

    PubMed Central

    Compagnucci, Claudia; Petrini, Stefania; Higuraschi, Norimichi; Trivisano, Marina; Specchio, Nicola; Hirose, Shinichi; Bertini, Enrico; Terracciano, Alessandra

    2015-01-01

    PCDH19 (Protocadherin 19), a member of the cadherin superfamily, is involved in the pathogenic mechanism of an X-linked model of neurological disease. The biological function of PCHD19 in human neurons and during neurogenesis is currently unknown. Therefore, we decided to use the model of the induced pluripotent stem cells (iPSCs) to characterize the location and timing of expression of PCDH19 during cortical neuronal differentiation. Our data show that PCDH19 is expressed in pluripotent cells before differentiation in a homogeneous pattern, despite its localization is often limited to one pole of the cell. During neuronal differentiation, positional information on the progenitor cells assumes an important role in acquiring polarization. The proper control of the cell orientation ensures a fine balancing between symmetric (giving rise to two progenitor sister cells) versus asymmetric (giving rise to one progenitor cell and one newborn neuron) division. This process results in the polar organization of the neural tube with a lumen indicating the basal part of the polarized neuronal progenitor cell; in the iPSC model the cells are organized in the ‘neural rosette’ and interestingly, PCDH19 is located at the center of the rosette, with other well-known markers of the lumen (N-cadherin and ZO-1). These data suggest that PCDH19 has a role in instructing the apico-basal polarity of the progenitor cells, thus regulating the development of a properly organized human brain. PMID:26450854

  16. Post-licensure rapid immunization safety monitoring program (PRISM) data characterization.

    PubMed

    Baker, Meghan A; Nguyen, Michael; Cole, David V; Lee, Grace M; Lieu, Tracy A

    2013-12-30

    The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program is the immunization safety monitoring component of FDA's Mini-Sentinel project, a program to actively monitor the safety of medical products using electronic health information. FDA sought to assess the surveillance capabilities of this large claims-based distributed database for vaccine safety surveillance by characterizing the underlying data. We characterized data available on vaccine exposures in PRISM, estimated how much additional data was gained by matching with select state and local immunization registries, and compared vaccination coverage estimates based on PRISM data with other available data sources. We generated rates of computerized codes representing potential health outcomes relevant to vaccine safety monitoring. Standardized algorithms including ICD-9 codes, number of codes required, exclusion criteria and location of the encounter were used to obtain the background rates. The majority of the vaccines routinely administered to infants, children, adolescents and adults were well captured by claims data. Immunization registry data in up to seven states comprised between 5% and 9% of data for all vaccine categories with the exception of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively. Vaccination coverage estimates based on PRISM's computerized data were similar to but lower than coverage estimates from the National Immunization Survey and Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of interest studied, the rates of potential outcomes based on ICD-9 codes were generally higher than rates described in the literature, which are typically clinically confirmed cases. PRISM program's data on vaccine exposures and health outcomes appear complete enough to support robust safety monitoring. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 7 CFR Exhibit E to Subpart A of... - Voluntary National Model Building Codes

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Voluntary National Model Building Codes E Exhibit E... HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY... National Model Building Codes The following documents address the health and safety aspects of buildings...

  18. Medicare and Medicaid Programs; Fire Safety Requirements for Certain Health Care Facilities. Final rule.

    PubMed

    2016-05-04

    This final rule will amend the fire safety standards for Medicare and Medicaid participating hospitals, critical access hospitals (CAHs), long-term care facilities, intermediate care facilities for individuals with intellectual disabilities (ICF-IID), ambulatory surgery centers (ASCs), hospices which provide inpatient services, religious non-medical health care institutions (RNHCIs), and programs of all-inclusive care for the elderly (PACE) facilities. Further, this final rule will adopt the 2012 edition of the Life Safety Code (LSC) and eliminate references in our regulations to all earlier editions of the Life Safety Code. It will also adopt the 2012 edition of the Health Care Facilities Code, with some exceptions.

  19. Establishment of a translational endothelial cell model using directed differentiation of induced pluripotent stem cells from Cynomolgus monkey.

    PubMed

    Thoma, Eva C; Heckel, Tobias; Keller, David; Giroud, Nicolas; Leonard, Brian; Christensen, Klaus; Roth, Adrian; Bertinetti-Lapatki, Cristina; Graf, Martin; Patsch, Christoph

    2016-10-25

    Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models for various applications. While human PSC-based cellular models are already advanced, similar systems for non-human primates (NHPs) are still lacking. However, as NHPs are the most appropriate animals for evaluating the safety of many novel pharmaceuticals, the availability of in vitro systems would be extremely useful to bridge the gap between cellular and animal models. Here, we present a NHP in vitro endothelial cell system using induced pluripotent stem cells (IPSCs) from Cynomolgus monkey (Macaca fascicularis). Based on an adapted protocol for human IPSCs, we directly differentiated macaque IPSCs into endothelial cells under chemically defined conditions. The resulting endothelial cells can be enriched using immuno-magnetic cell sorting and display endothelial marker expression and function. RNA sequencing revealed that the differentiation process closely resembled vasculogenesis. Moreover, we showed that endothelial cells derived from macaque and human IPSCs are highly similar with respect to gene expression patterns and key endothelial functions, such as inflammatory responses. These data demonstrate the power of IPSC differentiation technology to generate defined cell types for use as translational in vitro models to compare cell type-specific responses across species.

  20. The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions.

    PubMed

    Liu, H; Yang, L; Yu, F F; Wang, S; Wu, C; Qu, C; Lammi, M J; Guo, X

    2017-05-01

    The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. Patient-Specific Pluripotent Stem Cells in Neurological Diseases

    PubMed Central

    Durnaoglu, Serpen; Genc, Sermin; Genc, Kursad

    2011-01-01

    Many human neurological diseases are not currently curable and result in devastating neurologic sequelae. The increasing availability of induced pluripotent stem cells (iPSCs) derived from adult human somatic cells provides new prospects for cellreplacement strategies and disease-related basic research in a broad spectrum of human neurologic diseases. Patient-specific iPSC-based modeling of neurogenetic and neurodegenerative diseases is an emerging efficient tool for in vitro modeling to understand disease and to screen for genes and drugs that modify the disease process. With the exponential increase in iPSC research in recent years, human iPSCs have been successfully derived with different technologies and from various cell types. Although there remain a great deal to learn about patient-specific iPSC safety, the reprogramming mechanisms, better ways to direct a specific reprogramming, ideal cell source for cellular grafts, and the mechanisms by which transplanted stem cells lead to an enhanced functional recovery and structural reorganization, the discovery of the therapeutic potential of iPSCs offers new opportunities for the treatment of incurable neurologic diseases. However, iPSC-based therapeutic strategies need to be thoroughly evaluated in preclinical animal models of neurological diseases before they can be applied in a clinical setting. PMID:21776279

  2. 32 CFR 634.25 - Installation traffic codes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... riding in a POV whether on or off the installation. (iv) Infant/child restraint devices (car seats) will be required in POVs for children 4 years old or under and not exceeding 45 pounds in weight. (v... development and publication of installation traffic codes will be based on the following: (1) Highway Safety...

  3. 32 CFR 634.25 - Installation traffic codes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... riding in a POV whether on or off the installation. (iv) Infant/child restraint devices (car seats) will be required in POVs for children 4 years old or under and not exceeding 45 pounds in weight. (v... development and publication of installation traffic codes will be based on the following: (1) Highway Safety...

  4. Progress of IRSN R&D on ITER Safety Assessment

    NASA Astrophysics Data System (ADS)

    Van Dorsselaere, J. P.; Perrault, D.; Barrachin, M.; Bentaib, A.; Gensdarmes, F.; Haeck, W.; Pouvreau, S.; Salat, E.; Seropian, C.; Vendel, J.

    2012-08-01

    The French "Institut de Radioprotection et de Sûreté Nucléaire" (IRSN), in support to the French "Autorité de Sûreté Nucléaire", is analysing the safety of ITER fusion installation on the basis of the ITER operator's safety file. IRSN set up a multi-year R&D program in 2007 to support this safety assessment process. Priority has been given to four technical issues and the main outcomes of the work done in 2010 and 2011 are summarized in this paper: for simulation of accident scenarios in the vacuum vessel, adaptation of the ASTEC system code; for risk of explosion of gas-dust mixtures in the vacuum vessel, adaptation of the TONUS-CFD code for gas distribution, development of DUST code for dust transport, and preparation of IRSN experiments on gas inerting, dust mobilization, and hydrogen-dust mixtures explosion; for evaluation of the efficiency of the detritiation systems, thermo-chemical calculations of tritium speciation during transport in the gas phase and preparation of future experiments to evaluate the most influent factors on detritiation; for material neutron activation, adaptation of the VESTA Monte Carlo depletion code. The first results of these tasks have been used in 2011 for the analysis of the ITER safety file. In the near future, this R&D global programme may be reoriented to account for the feedback of the latter analysis or for new knowledge.

  5. Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.

    PubMed

    Omole, Adekunle Ebenezer; Fakoya, Adegbenro Omotuyi John

    2018-01-01

    The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and

  6. Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

    PubMed Central

    2018-01-01

    The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and

  7. Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment.

    PubMed

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

    2017-06-20

    Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.

  8. Assessment and Application of the ROSE Code for Reactor Outage Thermal-Hydraulic and Safety Analysis

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

    Liang, Thomas K.S.; Ko, F.-K.; Dai, L.-C

    The currently available tools, such as RELAP5, RETRAN, and others, cannot easily and correctly perform the task of analyzing the system behavior during plant outages. Therefore, a medium-sized program aiming at reactor outage simulation and evaluation, such as midloop operation (MLO) with loss of residual heat removal (RHR), has been developed. Important thermal-hydraulic processes involved during MLO with loss of RHR can be properly simulated by the newly developed reactor outage simulation and evaluation (ROSE) code. The two-region approach with a modified two-fluid model has been adopted to be the theoretical basis of the ROSE code.To verify the analytical modelmore » in the first step, posttest calculations against the integral midloop experiments with loss of RHR have been performed. The excellent simulation capacity of the ROSE code against the Institute of Nuclear Energy Research Integral System Test Facility test data is demonstrated. To further mature the ROSE code in simulating a full-sized pressurized water reactor, assessment against the WGOTHIC code and the Maanshan momentary-loss-of-RHR event has been undertaken. The successfully assessed ROSE code is then applied to evaluate the abnormal operation procedure (AOP) with loss of RHR during MLO (AOP 537.4) for the Maanshan plant. The ROSE code also has been successfully transplanted into the Maanshan training simulator to support operator training. How the simulator was upgraded by the ROSE code for MLO will be presented in the future.« less

  9. A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells

    PubMed Central

    Saxena, Pratik; Heng, Boon Chin; Bai, Peng; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

    2016-01-01

    Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON). This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets. Synthetic lineage-control networks may provide the missing link to genetically programme somatic cells into autologous cell phenotypes for regenerative medicine. PMID:27063289

  10. Interface requirements for coupling a containment code to a reactor system thermal hydraulic codes

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

    Baratta, A.J.

    1997-07-01

    To perform a complete analysis of a reactor transient, not only the primary system response but the containment response must also be accounted for. Such transients and accidents as a loss of coolant accident in both pressurized water and boiling water reactors and inadvertent operation of safety relief valves all challenge the containment and may influence flows because of containment feedback. More recently, the advanced reactor designs put forth by General Electric and Westinghouse in the US and by Framatome and Seimens in Europe rely on the containment to act as the ultimate heat sink. Techniques used by analysts andmore » engineers to analyze the interaction of the containment and the primary system were usually iterative in nature. Codes such as RELAP or RETRAN were used to analyze the primary system response and CONTAIN or CONTEMPT the containment response. The analysis was performed by first running the system code and representing the containment as a fixed pressure boundary condition. The flows were usually from the primary system to the containment initially and generally under choked conditions. Once the mass flows and timing are determined from the system codes, these conditions were input into the containment code. The resulting pressures and temperatures were then calculated and the containment performance analyzed. The disadvantage of this approach becomes evident when one performs an analysis of a rapid depressurization or a long term accident sequence in which feedback from the containment can occur. For example, in a BWR main steam line break transient, the containment heats up and becomes a source of energy for the primary system. Recent advances in programming and computer technology are available to provide an alternative approach. The author and other researchers have developed linkage codes capable of transferring data between codes at each time step allowing discrete codes to be coupled together.« less

  11. 77 FR 54836 - Federal Motor Vehicle Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... DEPARTMENT OF TRANSPORTATION National Highway Traffic Safety Administration 49 CFR Part 571 Federal Motor Vehicle Safety Standards CFR Correction 0 In Title 49 of the Code of Federal Regulations... read as follows: Sec. 571.119 Standard No. 119; New pneumatic tires for motor vehicles with a GVWR of...

  12. Modeling Guidelines for Code Generation in the Railway Signaling Context

    NASA Technical Reports Server (NTRS)

    Ferrari, Alessio; Bacherini, Stefano; Fantechi, Alessandro; Zingoni, Niccolo

    2009-01-01

    Modeling guidelines constitute one of the fundamental cornerstones for Model Based Development. Their relevance is essential when dealing with code generation in the safety-critical domain. This article presents the experience of a railway signaling systems manufacturer on this issue. Introduction of Model-Based Development (MBD) and code generation in the industrial safety-critical sector created a crucial paradigm shift in the development process of dependable systems. While traditional software development focuses on the code, with MBD practices the focus shifts to model abstractions. The change has fundamental implications for safety-critical systems, which still need to guarantee a high degree of confidence also at code level. Usage of the Simulink/Stateflow platform for modeling, which is a de facto standard in control software development, does not ensure by itself production of high-quality dependable code. This issue has been addressed by companies through the definition of modeling rules imposing restrictions on the usage of design tools components, in order to enable production of qualified code. The MAAB Control Algorithm Modeling Guidelines (MathWorks Automotive Advisory Board)[3] is a well established set of publicly available rules for modeling with Simulink/Stateflow. This set of recommendations has been developed by a group of OEMs and suppliers of the automotive sector with the objective of enforcing and easing the usage of the MathWorks tools within the automotive industry. The guidelines have been published in 2001 and afterwords revisited in 2007 in order to integrate some additional rules developed by the Japanese division of MAAB [5]. The scope of the current edition of the guidelines ranges from model maintainability and readability to code generation issues. The rules are conceived as a reference baseline and therefore they need to be tailored to comply with the characteristics of each industrial context. Customization of these

  13. Patient complaints in healthcare systems: a systematic review and coding taxonomy

    PubMed Central

    Reader, Tom W; Gillespie, Alex; Roberts, Jane

    2014-01-01

    Background Patient complaints have been identified as a valuable resource for monitoring and improving patient safety. This article critically reviews the literature on patient complaints, and synthesises the research findings to develop a coding taxonomy for analysing patient complaints. Methods The PubMed, Science Direct and Medline databases were systematically investigated to identify patient complaint research studies. Publications were included if they reported primary quantitative data on the content of patient-initiated complaints. Data were extracted and synthesised on (1) basic study characteristics; (2) methodological details; and (3) the issues patients complained about. Results 59 studies, reporting 88 069 patient complaints, were included. Patient complaint coding methodologies varied considerably (eg, in attributing single or multiple causes to complaints). In total, 113 551 issues were found to underlie the patient complaints. These were analysed using 205 different analytical codes which when combined represented 29 subcategories of complaint issue. The most common issues complained about were ‘treatment’ (15.6%) and ‘communication’ (13.7%). To develop a patient complaint coding taxonomy, the subcategories were thematically grouped into seven categories, and then three conceptually distinct domains. The first domain related to complaints on the safety and quality of clinical care (representing 33.7% of complaint issues), the second to the management of healthcare organisations (35.1%) and the third to problems in healthcare staff–patient relationships (29.1%). Conclusions Rigorous analyses of patient complaints will help to identify problems in patient safety. To achieve this, it is necessary to standardise how patient complaints are analysed and interpreted. Through synthesising data from 59 patient complaint studies, we propose a coding taxonomy for supporting future research and practice in the analysis of patient complaint data

  14. Characterization of porcine partially reprogrammed iPSCs from adipose-derived stem cells.

    PubMed

    Wei, Chao; Li, Xia; Zhang, Pengfei; Zhang, Yu; Liu, Tong; Jiang, Shaoshuai; Han, Fei; Zhang, Yunhai

    2015-05-01

    Partially reprogrammed induced pluripotent stem cells (PiPSCs) have great potential for investigating reprogramming mechanisms and represent an alternative potential material for making genetically modified animals and regenerative medicine. To date, PiPSCs have scarcely been reported in detail when compared with mice and humans. In this study, we obtained PiPSCs from porcine adipose-derived stem cells (pADSCs) by ectopic expression of human transcription factors (OCT4, SOX2, c-MYC, and KLF4) in feeder-free condition. The morphology and proliferation activity of porcine PiPSCs (pPiPSCs) were similar to those of porcine fully reprogrammed iPSCs (pFiPSCs); furthermore, pPiPSCs expressed higher levels of the typical surface molecules (CD29) found in pADSCs. However, pPiPSCs were negative for key proteins (NANOG) connected with stemness and possessed lower differentiation ability in vivo and in vitro. When differentiation-inhibiting factors were withdrawn, pPiPSCs-derived cells (pPiPSC-DCs) showed similar features to pADSCs in many aspects, including proliferation, differentiation, and immunosuppression. When both types of cells were used to produce cloned embryos, we found that the blastocyst formation rate of 19DC (one of the pPiPSC-DC cell lines)-derived cloned embryos was obviously higher than that of others. The total cell number of 19DC-derived blastocysts was significantly higher than the 30DC (one pFiPSC-DC cell line)-derived blastocysts. In all, through limited differentiation ability, the proliferation activity of pPiPSCs is similar to that of pFiPSCs, and pPiPSCs can retain several of the features of pADSCs, which are beneficial to cell therapy. Furthermore, the differentiation of pPiPSCs is more favorable for producing high-quality reconstructed embryos. © 2015 Society for Reproduction and Fertility.

  15. Methodology, status, and plans for development and assessment of the RELAP5 code

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

    Johnson, G.W.; Riemke, R.A.

    1997-07-01

    RELAP/MOD3 is a computer code used for the simulation of transients and accidents in light-water nuclear power plants. The objective of the program to develop and maintain RELAP5 was and is to provide the U.S. Nuclear Regulatory Commission with an independent tool for assessing reactor safety. This paper describes code requirements, models, solution scheme, language and structure, user interface validation, and documentation. The paper also describes the current and near term development program and provides an assessment of the code`s strengths and limitations.

  16. Development of a three-dimensional transient code for reactivity-initiated events of BWRs (boiling water reactors) - Models and code verifications

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

    Uematsu, Hitoshi; Yamamoto, Toru; Izutsu, Sadayuki

    1990-06-01

    A reactivity-initiated event is a design-basis accident for the safety analysis of boiling water reactors. It is defined as a rapid transient of reactor power caused by a reactivity insertion of over $1.0 due to a postulated drop or abnormal withdrawal of the control rod from the core. Strong space-dependent feedback effects are associated with the local power increase due to control rod movement. A realistic treatment of the core status in a transient by a code with a detailed core model is recommended in evaluating this event. A three-dimensional transient code, ARIES, has been developed to meet this need.more » The code simulates the event with three-dimensional neutronics, coupled with multichannel thermal hydraulics, based on a nonequilibrium separated flow model. The experimental data obtained in reactivity accident tests performed with the SPERT III-E core are used to verify the entire code, including thermal-hydraulic models.« less

  17. Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function.

    PubMed

    Lai, Frank Pui-Ling; Lau, Sin-Ting; Wong, John Kwong-Leong; Gui, Hongsheng; Wang, Reeson Xu; Zhou, Tingwen; Lai, Wing Hon; Tse, Hung-Fat; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Ngan, Elly Sau-Wai

    2017-07-01

    Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% of HSCR patients have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factors. We sought to identify mutations associated with S-HSCR, and used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system to determine how mutations affect ENCC function. We created induced pluripotent stem cell (iPSC) lines from 1 patient with total colonic aganglionosis (with the G731del mutation in RET) and from 2 patients with S-HSCR (without a RET mutation), as well as RET +/- and RET -/- iPSCs. IMR90-iPSC cells were used as the control cell line. Migration and differentiation capacities of iPSC-derived ENCCs were analyzed in differentiation and migration assays. We searched for mutation(s) associated with S-HSCR by combining genetic and transcriptome data from patient blood- and iPSC-derived ENCCs, respectively. Mutations in the iPSCs were corrected using the CRISPR/Cas9 system. ENCCs derived from all iPSC lines, but not control iPSCs, had defects in migration and neuronal lineage differentiation. RET mutations were associated with differentiation and migration defects of ENCCs in vitro. Genetic and transcriptome analyses associated a mutation in the vinculin gene (VCL M209L) with S-HSCR. CRISPR/Cas9 correction of the RET G731del and VCL M209L mutations in iPSCs restored the differentiation and migration capacities of ENCCs. We identified mutations in VCL associated with S-HSCR. Correction of this mutation in iPSC using CRISPR/Cas9 editing, as well as the RET G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored ENCC function. Our study demonstrates how human iPSCs can

  18. Using narrative text and coded data to develop hazard scenarios for occupational injury interventions

    PubMed Central

    Lincoln, A; Sorock, G; Courtney, T; Wellman, H; Smith, G; Amoroso, P

    2004-01-01

    Objective: To determine whether narrative text in safety reports contains sufficient information regarding contributing factors and precipitating mechanisms to prioritize occupational back injury prevention strategies. Design, setting, subjects, and main outcome measures: Nine essential data elements were identified in narratives and coded sections of safety reports for each of 94 cases of back injuries to United States Army truck drivers reported to the United States Army Safety Center between 1987 and 1997. The essential elements of each case were used to reconstruct standardized event sequences. A taxonomy of the event sequences was then developed to identify common hazard scenarios and opportunities for primary interventions. Results: Coded data typically only identified five data elements (broad activity, task, event/exposure, nature of injury, and outcomes) while narratives provided additional elements (contributing factor, precipitating mechanism, primary source) essential for developing our taxonomy. Three hazard scenarios were associated with back injuries among Army truck drivers accounting for 83% of cases: struck by/against events during motor vehicle crashes; falls resulting from slips/trips or loss of balance; and overexertion from lifting activities. Conclusions: Coded data from safety investigations lacked sufficient information to thoroughly characterize the injury event. However, the combination of existing narrative text (similar to that collected by many injury surveillance systems) and coded data enabled us to develop a more complete taxonomy of injury event characteristics and identify common hazard scenarios. This study demonstrates that narrative text can provide the additional information on contributing factors and precipitating mechanisms needed to target prevention strategies. PMID:15314055

  19. Delay Analysis of Car-to-Car Reliable Data Delivery Strategies Based on Data Mulling with Network Coding

    NASA Astrophysics Data System (ADS)

    Park, Joon-Sang; Lee, Uichin; Oh, Soon Young; Gerla, Mario; Lun, Desmond Siumen; Ro, Won Woo; Park, Joonseok

    Vehicular ad hoc networks (VANET) aims to enhance vehicle navigation safety by providing an early warning system: any chance of accidents is informed through the wireless communication between vehicles. For the warning system to work, it is crucial that safety messages be reliably delivered to the target vehicles in a timely manner and thus reliable and timely data dissemination service is the key building block of VANET. Data mulling technique combined with three strategies, network codeing, erasure coding and repetition coding, is proposed for the reliable and timely data dissemination service. Particularly, vehicles in the opposite direction on a highway are exploited as data mules, mobile nodes physically delivering data to destinations, to overcome intermittent network connectivity cause by sparse vehicle traffic. Using analytic models, we show that in such a highway data mulling scenario the network coding based strategy outperforms erasure coding and repetition based strategies.

  20. The SAS4A/SASSYS-1 Safety Analysis Code System, Version 5

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

    Fanning, T. H.; Brunett, A. J.; Sumner, T.

    The SAS4A/SASSYS-1 computer code is developed by Argonne National Laboratory for thermal, hydraulic, and neutronic analysis of power and flow transients in liquidmetal- cooled nuclear reactors (LMRs). SAS4A was developed to analyze severe core disruption accidents with coolant boiling and fuel melting and relocation, initiated by a very low probability coincidence of an accident precursor and failure of one or more safety systems. SASSYS-1, originally developed to address loss-of-decay-heat-removal accidents, has evolved into a tool for margin assessment in design basis accident (DBA) analysis and for consequence assessment in beyond-design-basis accident (BDBA) analysis. SAS4A contains detailed, mechanistic models of transientmore » thermal, hydraulic, neutronic, and mechanical phenomena to describe the response of the reactor core, its coolant, fuel elements, and structural members to accident conditions. The core channel models in SAS4A provide the capability to analyze the initial phase of core disruptive accidents, through coolant heat-up and boiling, fuel element failure, and fuel melting and relocation. Originally developed to analyze oxide fuel clad with stainless steel, the models in SAS4A have been extended and specialized to metallic fuel with advanced alloy cladding. SASSYS-1 provides the capability to perform a detailed thermal/hydraulic simulation of the primary and secondary sodium coolant circuits and the balance-ofplant steam/water circuit. These sodium and steam circuit models include component models for heat exchangers, pumps, valves, turbines, and condensers, and thermal/hydraulic models of pipes and plena. SASSYS-1 also contains a plant protection and control system modeling capability, which provides digital representations of reactor, pump, and valve controllers and their response to input signal changes.« less

  1. 42 CFR 403.744 - Condition of participation: Life safety from fire.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Condition of participation: Life safety from fire... safety from fire. (a) General. An RNHCI must meet the following conditions: (1) Except as otherwise... Safety Code of the National Fire Protection Association. The Director of the Office of the Federal...

  2. Improving the safety of street-vended food.

    PubMed

    Moy, G; Hazzard, A; Käferstein, F

    1997-01-01

    An integrated plan of action for improving street food involving health and other regulatory authorities, vendors and consumers should address not only food safety, but also environmental health management, including consideration of inadequate sanitation and waste management, possible environmental pollution, congestion and disturbances to traffic. However, WHO cautions that, in view of their importance in the diets of urban populations, particularly the socially disadvantaged, every effort should be made to preserve the benefits provided by varied, inexpensive and often nutritious street food. Therefore, authorities concerned with street food management must balance efforts aimed at reducing the negative aspects on the environment with the benefits of street food and its important role in the community. Health authorities charged with responsibility for food safety control should match risk management action to the level of assessed risk. The rigorous application of codes and enforcement of regulations more suited to larger and permanent food service establishments is unlikely to be justifiable. Such rigorous application of codes and regulations may result in disappearance of the trade with consequent aggravation of hunger and malnutrition. Moreover, most codes and regulations have not been based on any systematic identification and assessment of health hazards associated with different types of foods and operations as embodied in the HACCP approach which has been recognized by Codex as the most cost-effective means for promoting food safety. WHO encourages the development of regulations that empower vendors to take greater responsibility for the preparation of safe food, and of codes of practice based on the HACCP system.

  3. Nuclear criticality safety: 5-day training course

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

    Schlesser, J.A.

    1992-11-01

    This compilation of notes is presented as a source reference for the criticality safety course. It represents the contributions of many people, particularly Tom McLaughlin, the course's primary instructor. At the completion of this training course, the attendee will: be able to define terms commonly used in nuclear criticality safety; be able to appreciate the fundamentals of nuclear criticality safety; be able to identify factors which affect nuclear criticality safety; be able to identify examples of criticality controls as used at Los Alamos; be able to identify examples of circumstances present during criticality accidents; be able to identify examples ofmore » computer codes used by the nuclear criticality safety specialist; be able to identify examples of safety consciousness required in nuclear criticality safety.« less

  4. The science behind codes and standards for safe walkways: changes in level, stairways, stair handrails and slip resistance.

    PubMed

    Nemire, Kenneth; Johnson, Daniel A; Vidal, Keith

    2016-01-01

    Walkway codes and standards are often created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and empirical data. The authors maintain that in the formulation of codes and standards that impact pedestrian safety, the results of pertinent scientific research should be given significant weight. This article examines many elements of common walkway codes and standards related to changes in level, stairways, stair handrails, and slip resistance. It identifies which portions are based on or supported by empirical data; and which could benefit from additional scientific research. This article identifies areas in which additional research, codes, and standards may be beneficial to enhance pedestrian safety. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  5. A proto-code of ethics and conduct for European nurse directors.

    PubMed

    Stievano, Alessandro; De Marinis, Maria Grazia; Kelly, Denise; Filkins, Jacqueline; Meyenburg-Altwarg, Iris; Petrangeli, Mauro; Tschudin, Verena

    2012-03-01

    The proto-code of ethics and conduct for European nurse directors was developed as a strategic and dynamic document for nurse managers in Europe. It invites critical dialogue, reflective thinking about different situations, and the development of specific codes of ethics and conduct by nursing associations in different countries. The term proto-code is used for this document so that specifically country-orientated or organization-based and practical codes can be developed from it to guide professionals in more particular or situation-explicit reflection and values. The proto-code of ethics and conduct for European nurse directors was designed and developed by the European Nurse Directors Association's (ENDA) advisory team. This article gives short explanations of the code' s preamble and two main parts: Nurse directors' ethical basis, and Principles of professional practice, which is divided into six specific points: competence, care, safety, staff, life-long learning and multi-sectorial working.

  6. Generating Safety-Critical PLC Code From a High-Level Application Software Specification

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The benefits of automatic-application code generation are widely accepted within the software engineering community. These benefits include raised abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at Kennedy Space Center recognized the need for PLC code generation while developing the new ground checkout and launch processing system, called the Launch Control System (LCS). Engineers developed a process and a prototype software tool that automatically translates a high-level representation or specification of application software into ladder logic that executes on a PLC. All the computer hardware in the LCS is planned to be commercial off the shelf (COTS), including industrial controllers or PLCs that are connected to the sensors and end items out in the field. Most of the software in LCS is also planned to be COTS, with only small adapter software modules that must be developed in order to interface between the various COTS software products. A domain-specific language (DSL) is a programming language designed to perform tasks and to solve problems in a particular domain, such as ground processing of launch vehicles. The LCS engineers created a DSL for developing test sequences of ground checkout and launch operations of future launch vehicle and spacecraft elements, and they are developing a tabular specification format that uses the DSL keywords and functions familiar to the ground and flight system users. The tabular specification format, or tabular spec, allows most ground and flight system users to document how the application software is intended to function and requires little or no software programming knowledge or experience. A small sample from a prototype tabular spec application is

  7. Derivation and Characterization of Induced Pluripotent Stem Cells from Equine Fibroblasts

    PubMed Central

    Breton, Amandine; Sharma, Ruchi; Diaz, Andrea Catalina; Parham, Alea Gillian; Graham, Audrey; Neil, Claire; Whitelaw, Christopher Bruce; Milne, Elspeth

    2013-01-01

    Pluripotent stem cells offer unprecedented potential not only for human medicine but also for veterinary medicine, particularly in relation to the horse. Induced pluripotent stem cells (iPSCs) are particularly promising, as they are functionally similar to embryonic stem cells and can be generated in vitro in a patient-specific manner. In this study, we report the generation of equine iPSCs from skin fibroblasts obtained from a foal and reprogrammed using viral vectors coding for murine Oct4, Sox2, c-Myc, and Klf4 sequences. The reprogrammed cell lines were morphologically similar to iPSCs reported from other species and could be stably maintained over more than 30 passages. Immunostaining and polymerase chain reaction analyses revealed that these cell lines expressed an array of endogenous markers associated with pluripotency, including OCT4, SOX2, NANOG, REX1, LIN28, SSEA1, SSEA4, and TRA1-60. Furthermore, under the appropriate conditions, the equine iPSCs readily formed embryoid bodies and differentiated in vitro into cells expressing markers of ectoderm, mesoderm, and endoderm, and when injected into immunodeficient mice, gave raise to tumors containing differentiated derivatives of the 3 germ layers. Finally, we also reprogrammed fibroblasts from a 2-year-old horse. The reprogrammed cells were similar to iPSCs derived from neonatal fibroblasts in terms of morphology, expression of pluripotency markers, and differentiation ability. The generation of these novel cell lines constitutes an important step toward the understanding of pluripotency in the horse, and paves the way for iPSC technology to potentially become a powerful research and clinical tool in veterinary biomedicine. PMID:22897112

  8. Generating code adapted for interlinking legacy scalar code and extended vector code

    DOEpatents

    Gschwind, Michael K

    2013-06-04

    Mechanisms for intermixing code are provided. Source code is received for compilation using an extended Application Binary Interface (ABI) that extends a legacy ABI and uses a different register configuration than the legacy ABI. First compiled code is generated based on the source code, the first compiled code comprising code for accommodating the difference in register configurations used by the extended ABI and the legacy ABI. The first compiled code and second compiled code are intermixed to generate intermixed code, the second compiled code being compiled code that uses the legacy ABI. The intermixed code comprises at least one call instruction that is one of a call from the first compiled code to the second compiled code or a call from the second compiled code to the first compiled code. The code for accommodating the difference in register configurations is associated with the at least one call instruction.

  9. 78 FR 11092 - Safety and Health Regulations for Construction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... LABOR DEPARTMENT Occupational Safety and Health Administration 29 CFR Part 1926 Safety and Health Regulations for Construction CFR Correction In Title 29 of the Code of Federal Regulations, Part 1926, revised as of July 1, 2012, on page 225, in Sec. 1926.152, paragraph (c)(16) is added to read as follows: Sec...

  10. Colour coding scrubs as a means of improving perioperative communication.

    PubMed

    Litak, Dominika

    2011-05-01

    Effective communication within the operating department is essential for achieving patient safety. A large part of the perioperative communication is non-verbal. One type of non-verbal communication is 'object communication', the most common form of which is clothing. The colour coding of clothing such as scrubs has the potential to optimise perioperative communication with the patients and between the staff. A colour contains a coded message, and is a visual cue for an immediate identification of personnel. This is of key importance in the perioperative environment. The idea of colour coded scrubs in the perioperative setting has not been much explored to date and, given the potential contributiontowards improvement of patient outcomes, deserves consideration.

  11. Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells.

    PubMed

    Hong, So Gun; Dunbar, Cynthia E; Winkler, Thomas

    2013-02-01

    Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced.

  12. Road safety practices among commercial motorcyclists in a rural town in Nigeria: implications for health education.

    PubMed

    Amoran, O E; Eme, Owoaje; Giwa, O A; Gbolahan, O B

    This cross-sectional, community-based study was carried out among commercial motorcyclists in Igboora. All the commercial motor parks in Igboora were visited and all the commercial motorcyclists who consented to participate in the study were interviewed. Information on the respondents' socio-demographic characteristics, and the practice of road safety measures was collected using an interviewer administered questionnaire. A total of 299 motorcyclists were interviewed. All (100%) of them were males. The mean age of the respondents was 27.4 +/- 7.4 years. One hundred eighty-two (60.7%) of the motorcyclists had the correct knowledge of the purpose of Highway Code. Only 70 (23.3%) could recognize more than half of the currently used road safety codes and 47 (15.7%) obey these road safety codes more than half of the time they see it. Only 183 (61.2%) of them had a driving license and 72 (24.1%) were able to produce these licenses on demand. All (100%) of the respondents did not use any protective helmet. Those who have longer years of working experience, higher level of education and higher knowledge of the safety codes practice it more regularly (r = 0.198, p = 0.001, chi2= 9.31, p = 0.025, and r = 0.28, p = 0.001 respectively). One hundred thirty-six (45.5%) have been involved in at least one accident in the preceding year. The overall incidence of road traffic accident was 2.16 per 1,000. There was however on statistically significant association between the practice of road safety codes and the occurrence of road traffic accidents (chi2= 0.176, p = 0.916). The study shows that the practice of road safety measures was low in this rural Nigerian community and was not associated with the incidence of road traffic accidents. Introducing road safety education particularly targeted at educating the motorcyclists on the importance and practice of road safety measures would lead to an increase in the practice of the safety measures and hopefully a reduction in the incidence

  13. Performance of Compiler-Assisted Memory Safety Checking

    DTIC Science & Technology

    2014-08-01

    software developer has in mind a particular object to which the pointer should point, the intended referent. A memory access error occurs when an ac...Performance of Compiler-Assisted Memory Safety Checking David Keaton Robert C. Seacord August 2014 TECHNICAL NOTE CMU/SEI-2014-TN...based memory safety checking tool and the performance that can be achieved with two such tools whose source code is freely available. The note then

  14. The Nuclear Energy Advanced Modeling and Simulation Enabling Computational Technologies FY09 Report

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

    Diachin, L F; Garaizar, F X; Henson, V E

    2009-10-12

    In this document we report on the status of the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Enabling Computational Technologies (ECT) effort. In particular, we provide the context for ECT In the broader NEAMS program and describe the three pillars of the ECT effort, namely, (1) tools and libraries, (2) software quality assurance, and (3) computational facility (computers, storage, etc) needs. We report on our FY09 deliverables to determine the needs of the integrated performance and safety codes (IPSCs) in these three areas and lay out the general plan for software quality assurance to meet the requirements of DOE andmore » the DOE Advanced Fuel Cycle Initiative (AFCI). We conclude with a brief description of our interactions with the Idaho National Laboratory computer center to determine what is needed to expand their role as a NEAMS user facility.« less

  15. An Extended Proof-Carrying Code Framework for Security Enforcement

    NASA Astrophysics Data System (ADS)

    Pirzadeh, Heidar; Dubé, Danny; Hamou-Lhadj, Abdelwahab

    The rapid growth of the Internet has resulted in increased attention to security to protect users from being victims of security threats. In this paper, we focus on security mechanisms that are based on Proof-Carrying Code (PCC) techniques. In a PCC system, a code producer sends a code along with its safety proof to the consumer. The consumer executes the code only if the proof is valid. Although PCC has been shown to be a useful security framework, it suffers from the sheer size of typical proofs -proofs of even small programs can be considerably large. In this paper, we propose an extended PCC framework (EPCC) in which, instead of the proof, a proof generator for the program in question is transmitted. This framework enables the execution of the proof generator and the recovery of the proof on the consumer's side in a secure manner using a newly created virtual machine called the VEP (Virtual Machine for Extended PCC).

  16. Safety Issues with Hydrogen as a Vehicle Fuel

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

    Cadwallader, Lee Charles; Herring, James Stephen

    1999-10-01

    This report is an initial effort to identify and evaluate safety issues associated with the use of hydrogen as a vehicle fuel in automobiles. Several forms of hydrogen have been considered: gas, liquid, slush, and hydrides. The safety issues have been discussed, beginning with properties of hydrogen and the phenomenology of hydrogen combustion. Safety-related operating experiences with hydrogen vehicles have been summarized to identify concerns that must be addressed in future design activities and to support probabilistic risk assessment. Also, applicable codes, standards, and regulations pertaining to hydrogen usage and refueling have been identified and are briefly discussed. This reportmore » serves as a safety foundation for any future hydrogen safety work, such as a safety analysis or a probabilistic risk assessment.« less

  17. Safety Issues with Hydrogen as a Vehicle Fuel

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

    L. C. Cadwallader; J. S. Herring

    1999-09-01

    This report is an initial effort to identify and evaluate safety issues associated with the use of hydrogen as a vehicle fuel in automobiles. Several forms of hydrogen have been considered: gas, liquid, slush, and hydrides. The safety issues have been discussed, beginning with properties of hydrogen and the phenomenology of hydrogen combustion. Safety-related operating experiences with hydrogen vehicles have been summarized to identify concerns that must be addressed in future design activities and to support probabilistic risk assessment. Also, applicable codes, standards, and regulations pertaining to hydrogen usage and refueling have been identified and are briefly discussed. This reportmore » serves as a safety foundation for any future hydrogen safety work, such as a safety analysis or a probabilistic risk assessment.« less

  18. The First ASME Code Stamped Cryomodule at SNS

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

    Howell, M P; Crofford, M T; Douglas, D L

    The first spare cryomodule for the Spallation Neutron Source (SNS) has been designed, fabricated, and tested by SNS personnel. The approach to design for this cryomodule was to hold critical design features identical to the original design such as bayonet positions, coupler positions, cold mass assembly, and overall footprint. However, this is the first SNS cryomodule that meets the pressure requirements put forth in the 10 CFR 851: Worker Safety and Health Program. The most significant difference is that Section VIII of the ASME Boiler and Pressure Vessel Code was applied to the vacuum vessel of this cryomodule. Applying themore » pressure code to the helium vessels within the cryomodule was considered. However, it was determined to be schedule prohibitive because it required a code case for materials that are not currently covered by the code. Good engineering practice was applied to the internal components to verify the quality and integrity of the entire cryomodule. The design of the cryomodule, fabrication effort, and cryogenic test results will be reported in this paper.« less

  19. MELCOR computer code manuals

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

    Summers, R.M.; Cole, R.K. Jr.; Smith, R.C.

    1995-03-01

    MELCOR is a fully integrated, engineering-level computer code that models the progression of severe accidents in light water reactor nuclear power plants. MELCOR is being developed at Sandia National Laboratories for the U.S. Nuclear Regulatory Commission as a second-generation plant risk assessment tool and the successor to the Source Term Code Package. A broad spectrum of severe accident phenomena in both boiling and pressurized water reactors is treated in MELCOR in a unified framework. These include: thermal-hydraulic response in the reactor coolant system, reactor cavity, containment, and confinement buildings; core heatup, degradation, and relocation; core-concrete attack; hydrogen production, transport, andmore » combustion; fission product release and transport; and the impact of engineered safety features on thermal-hydraulic and radionuclide behavior. Current uses of MELCOR include estimation of severe accident source terms and their sensitivities and uncertainties in a variety of applications. This publication of the MELCOR computer code manuals corresponds to MELCOR 1.8.3, released to users in August, 1994. Volume 1 contains a primer that describes MELCOR`s phenomenological scope, organization (by package), and documentation. The remainder of Volume 1 contains the MELCOR Users Guides, which provide the input instructions and guidelines for each package. Volume 2 contains the MELCOR Reference Manuals, which describe the phenomenological models that have been implemented in each package.« less

  20. Data Analysis Approaches for the Risk-Informed Safety Margins Characterization Toolkit

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

    Mandelli, Diego; Alfonsi, Andrea; Maljovec, Daniel P.

    2016-09-01

    In the past decades, several numerical simulation codes have been employed to simulate accident dynamics (e.g., RELAP5-3D, RELAP-7, MELCOR, MAAP). In order to evaluate the impact of uncertainties into accident dynamics, several stochastic methodologies have been coupled with these codes. These stochastic methods range from classical Monte-Carlo and Latin Hypercube sampling to stochastic polynomial methods. Similar approaches have been introduced into the risk and safety community where stochastic methods (such as RAVEN, ADAPT, MCDET, ADS) have been coupled with safety analysis codes in order to evaluate the safety impact of timing and sequencing of events. These approaches are usually calledmore » Dynamic PRA or simulation-based PRA methods. These uncertainties and safety methods usually generate a large number of simulation runs (database storage may be on the order of gigabytes or higher). The scope of this paper is to present a broad overview of methods and algorithms that can be used to analyze and extract information from large data sets containing time dependent data. In this context, “extracting information” means constructing input-output correlations, finding commonalities, and identifying outliers. Some of the algorithms presented here have been developed or are under development within the RAVEN statistical framework.« less

  1. Automated Source-Code-Based Testing of Object-Oriented Software

    NASA Astrophysics Data System (ADS)

    Gerlich, Ralf; Gerlich, Rainer; Dietrich, Carsten

    2014-08-01

    With the advent of languages such as C++ and Java in mission- and safety-critical space on-board software, new challenges for testing and specifically automated testing arise. In this paper we discuss some of these challenges, consequences and solutions based on an experiment in automated source- code-based testing for C++.

  2. Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier.

    PubMed

    Vatine, Gad D; Al-Ahmad, Abraham; Barriga, Bianca K; Svendsen, Soshana; Salim, Ariel; Garcia, Leslie; Garcia, Veronica J; Ho, Ritchie; Yucer, Nur; Qian, Tongcheng; Lim, Ryan G; Wu, Jie; Thompson, Leslie M; Spivia, Weston R; Chen, Zhaohui; Van Eyk, Jennifer; Palecek, Sean P; Refetoff, Samuel; Shusta, Eric V; Svendsen, Clive N

    2017-06-01

    Inactivating mutations in the thyroid hormone (TH) transporter Monocarboxylate transporter 8 (MCT8) cause severe psychomotor retardation in children. Animal models do not reflect the biology of the human disease. Using patient-specific induced pluripotent stem cells (iPSCs), we generated MCT8-deficient neural cells that showed normal TH-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype. To test potential BBB involvement, we generated an iPSC-based BBB model of MCT8 deficiency, and we found that MCT8 was necessary for polarized influx of the active form of TH across the BBB. We also found that a candidate drug did not appreciably cross the mutant BBB. Our results therefore clarify the underlying physiological basis of this disorder, and they suggest that circumventing the diseased BBB to deliver active TH to the brain could be a viable therapeutic strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Measuring patient safety culture in maternal and child health institutions in China: a qualitative study.

    PubMed

    Wang, Yuanyuan; Liu, Weiwei; Shi, Huifeng; Liu, Chaojie; Wang, Yan

    2017-07-12

    Patient safety culture (PSC) plays a critical role in ensuring safe and quality care. Extensive PSC studies have been undertaken in hospitals. However, little is known about PSC in maternal and child health (MCH) institutions in China, which provide both population-based preventive services as well as individual care for patients. This study aimed to develop a theoretical framework for conceptualising PSC in MCH institutions in China. The study was undertaken in six MCH institutions (three in Hebei and three in Beijing). Participants (n=118) were recruited through stratified purposive sampling: 20 managers/administrators, 59 care providers and 39 patients. In-depth interviews were conducted with the participants. The interview data were coded using both inductive (based on the existing PSC theory developed by the Agency for Healthcare Research and Quality) and deductive (open coding arising from data) approaches. A PSC framework was formulated through axial coding that connected initial codes and selective coding that extracted a small number of themes. The interviewees considered patient safety in relation to six aspects: safety and security in public spaces, safety of medical services, privacy and information security, financial security, psychological safety and gap in services. A 12-dimensional PSC framework was developed, containing 69 items. While the existing PSC theory was confirmed by this study, some new themes emerged from the data. Patients expressed particular concerns about psychological safety and financial security. Defensive medical practices emerged as a PSC dimension that is associated with not only medical safety but also financial security and psychological safety. Patient engagement was also valued by the interviewees, especially the patients, as part of PSC. Although there are some common features in PSC across different healthcare delivery systems, PSC can also be context specific. In MCH settings in China, the meaning of 'patient safety

  4. Bleacher Safety: What Do We Look for? What Can We Do?

    ERIC Educational Resources Information Center

    IEA Environmental Consultant, 1999

    1999-01-01

    Discusses safety issues surrounding aging bleacher systems, highlighting the following three primary safety considerations: space between seats and footboards; guardrails; and the structural provisions of the 1997 Uniform Building Code. Tips for bleacher accident-prevention assessment and excerpts from federal and Minnesota legislation on bleacher…

  5. Methodology, status and plans for development and assessment of Cathare code

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

    Bestion, D.; Barre, F.; Faydide, B.

    1997-07-01

    This paper presents the methodology, status and plans for the development, assessment and uncertainty evaluation of the Cathare code. Cathare is a thermalhydraulic code developed by CEA (DRN), IPSN, EDF and FRAMATOME for PWR safety analysis. First, the status of the code development and assessment is presented. The general strategy used for the development and the assessment of the code is presented. Analytical experiments with separate effect tests, and component tests are used for the development and the validation of closure laws. Successive Revisions of constitutive laws are implemented in successive Versions of the code and assessed. System tests ormore » integral tests are used to validate the general consistency of the Revision. Each delivery of a code Version + Revision is fully assessed and documented. A methodology is being developed to determine the uncertainty on all constitutive laws of the code using calculations of many analytical tests and applying the Discrete Adjoint Sensitivity Method (DASM). At last, the plans for the future developments of the code are presented. They concern the optimization of the code performance through parallel computing - the code will be used for real time full scope plant simulators - the coupling with many other codes (neutronic codes, severe accident codes), the application of the code for containment thermalhydraulics. Also, physical improvements are required in the field of low pressure transients and in the modeling for the 3-D model.« less

  6. Methodology, status and plans for development and assessment of TUF and CATHENA codes

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

    Luxat, J.C.; Liu, W.S.; Leung, R.K.

    1997-07-01

    An overview is presented of the Canadian two-fluid computer codes TUF and CATHENA with specific focus on the constraints imposed during development of these codes and the areas of application for which they are intended. Additionally a process for systematic assessment of these codes is described which is part of a broader, industry based initiative for validation of computer codes used in all major disciplines of safety analysis. This is intended to provide both the licensee and the regulator in Canada with an objective basis for assessing the adequacy of codes for use in specific applications. Although focused specifically onmore » CANDU reactors, Canadian experience in developing advanced two-fluid codes to meet wide-ranging application needs while maintaining past investment in plant modelling provides a useful contribution to international efforts in this area.« less

  7. The three Rs of fire safety, emergency action, and fire prevention planning: promoting safety at the worksite.

    PubMed

    Thompson, Marcella R

    2003-04-01

    Fire safety is of paramount importance for everyone. In many workplaces, the occupational health nurse's scope of practice encompasses safety related activities. Included within this role is the responsibility for fire safety, emergency action, and fire prevention planning. The Three Rs of fire safety, emergency action, and fire prevention plans are rules, responsibilities, and resources. Myriad building and fire safety codes, regulations, and standards exist with which an employer must comply. An employer's responsibility for installing, testing, inspecting, and maintaining fire safety related equipment is extensive. Emergency action and fire prevention planning begins with conducting a detailed physical survey and preparing site maps. It includes making key policy decisions, writing procedures, and training employees in those procedures by practicing and executing site drills. The best resources available for emergency planning are the local fire department and the property insurer. Planning ahead means an efficient emergency response if disaster strikes. It saves lives, limits property damage, and preserves the environment.

  8. Boating Safety Training Manual.

    ERIC Educational Resources Information Center

    Coast Guard, Washington, DC.

    The training manual serves as the text for the Coast Guard's boating safety 32-hour course and for the D-8 Qualification Code Recertification Course. The manual is designed for self-study or for use with an instructor-led course. Each chapter concludes with a quiz to be used as a review of chaper content. Opening chapters review the use of the…

  9. Analysis of the technology acceptance model in examining hospital nurses' behavioral intentions toward the use of bar code medication administration.

    PubMed

    Song, Lunar; Park, Byeonghwa; Oh, Kyeung Mi

    2015-04-01

    Serious medication errors continue to exist in hospitals, even though there is technology that could potentially eliminate them such as bar code medication administration. Little is known about the degree to which the culture of patient safety is associated with behavioral intention to use bar code medication administration. Based on the Technology Acceptance Model, this study evaluated the relationships among patient safety culture and perceived usefulness and perceived ease of use, and behavioral intention to use bar code medication administration technology among nurses in hospitals. Cross-sectional surveys with a convenience sample of 163 nurses using bar code medication administration were conducted. Feedback and communication about errors had a positive impact in predicting perceived usefulness (β=.26, P<.01) and perceived ease of use (β=.22, P<.05). In a multiple regression model predicting for behavioral intention, age had a negative impact (β=-.17, P<.05); however, teamwork within hospital units (β=.20, P<.05) and perceived usefulness (β=.35, P<.01) both had a positive impact on behavioral intention. The overall bar code medication administration behavioral intention model explained 24% (P<.001) of the variance. Identified factors influencing bar code medication administration behavioral intention can help inform hospitals to develop tailored interventions for RNs to reduce medication administration errors and increase patient safety by using this technology.

  10. Qualification of Simulation Software for Safety Assessment of Sodium Cooled Fast Reactors. Requirements and Recommendations

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

    Brown, Nicholas R.; Pointer, William David; Sieger, Matt

    2016-04-01

    The goal of this review is to enable application of codes or software packages for safety assessment of advanced sodium-cooled fast reactor (SFR) designs. To address near-term programmatic needs, the authors have focused on two objectives. First, the authors have focused on identification of requirements for software QA that must be satisfied to enable the application of software to future safety analyses. Second, the authors have collected best practices applied by other code development teams to minimize cost and time of initial code qualification activities and to recommend a path to the stated goal.

  11. Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells.

    PubMed

    He, Qiong; Wang, Hui-Hui; Cheng, Tao; Yuan, Wei-Ping; Ma, Yu-Po; Jiang, Yong-Ping; Ren, Zhi-Hua

    2017-09-27

    Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay. Results The cell line bore a missense mutation in the 6 th coding exon (c.676 C>T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.

  12. Safety engineering: KTA code of practice. Lifting mechanisms in nuclear plant

    NASA Astrophysics Data System (ADS)

    Lifting mechanisms safety requirements are discussed in accordance with the present state of development of science and engineering for the protection of life, health, and assets against the dangers of nuclear energy and the ill effects of ionizing radiation.

  13. Patient safety with blood products administration using wireless and bar-code technology.

    PubMed

    Porcella, Aleta; Walker, Kristy

    2005-01-01

    Supported by a grant from the Agency for Healthcare Research and Quality, a University of Iowa Hospitals and Clinics interdisciplinary research team created an online data-capture-response tool utilizing wireless mobile devices and bar code technology to track and improve blood products administration process. The tool captures 1) sample collection, 2) sample arrival in the blood bank, 3) blood product dispense from blood bank, and 4) administration. At each step, the scanned patient wristband ID bar code is automatically compared to scanned identification barcode on requisition, sample, and/or product, and the system presents either a confirmation or an error message to the user. Following an eight-month, 5 unit, staged pilot, a 'big bang,' hospital-wide implementation occurred on February 7, 2005. Preliminary results from pilot data indicate that the new barcode process captures errors 3 to 10 times better than the old manual process.

  14. Site-Specific Genome Engineering in Human Pluripotent Stem Cells.

    PubMed

    Merkert, Sylvia; Martin, Ulrich

    2016-06-24

    The possibility to generate patient-specific induced pluripotent stem cells (iPSCs) offers an unprecedented potential of applications in clinical therapy and medical research. Human iPSCs and their differentiated derivatives are tools for diseases modelling, drug discovery, safety pharmacology, and toxicology. Moreover, they allow for the engineering of bioartificial tissue and are promising candidates for cellular therapies. For many of these applications, the ability to genetically modify pluripotent stem cells (PSCs) is indispensable, but efficient site-specific and safe technologies for genetic engineering of PSCs were developed only recently. By now, customized engineered nucleases provide excellent tools for targeted genome editing, opening new perspectives for biomedical research and cellular therapies.

  15. An exploratory study of the relationship between socioeconomic status and motor vehicle safety features.

    PubMed

    Girasek, Deborah C; Taylor, Brett

    2010-04-01

    The purpose of this study was to assess the association between motor vehicle owners' socioeconomic status (SES) and the safety of their motor vehicles. Truncated vehicle identification numbers (VINs) were obtained from the Maryland Motor Vehicle Administration office. ZIP code-level income and educational data were assigned to each VIN. Software was used to identify safety-related vehicle characteristics including crash test rating, availability of electronic stability control and side impact air bags, age, and weight. Correlations and analyses of variance were performed to assess whether a ZIP code's median household income and educational level were associated with its proportion of registered vehicles with safety features. For 13 of the 16 correlations performed, SES was significantly associated with the availability of vehicle safety features in a direction that favored upper-income individuals. Vehicle weight was not associated with income or education. When ZIP codes were divided into median household income quintiles, their mean proportions of safety features also differed significantly, in the same direction, for availability of electronic stability control, side impact air bags, vehicle age, and crash test ratings. Safer motor vehicles appear to be distributed along socioeconomic lines, with lower income groups experiencing more risk. This previously unidentified mechanism of disparity merits further study and the attention of policy makers.

  16. Maternal worries, home safety behaviors, and perceived difficulties.

    PubMed

    Hendrickson, Sherry Garrett

    2008-01-01

    The aim of the study was to explore the worries, safety behaviors, and perceived difficulties in keeping children safe at home in a purposive sample of low-income, predominantly non-English speaking mothers as a foundation for later nursing interventions. This study was a qualitative, descriptive design with content analysis to identify maternal concerns, behaviors, and perceptions of home safety as part of a larger study. Eighty-two mothers, 64% of whom were monolingual Spanish-speakers, responded in writing to three semistructured interview questions. When mothers were unable to read and write the researcher wrote the responses, then read the content aloud for verification. A standardized probe for each question was posed to obtain richer responses. Data management included use of the software program NUD*IST and coding analyses following the Miles and Huberman guidelines (1994). Interpretations were translated into English for this report. The major worries were falling, health, kidnapping, and being hit by a car. The leading maternal behaviors were coded as being physically, verbally, and environmentally preventive. Mothers said that it was their role to provide safety, and that this role could be wearisome, such that constant supervision was difficult. Low-income mothers described their worries for their 1 to 4 year-old children, explored their behaviors for preventing injury, and discussed what made keeping children from harm difficult. Understanding how mothers keep children safe, the barriers to home safety, and effective safety behaviors are important to the health of children. The clinical relevance of this study includes building trust as clinicians plan assessment, intervention and evaluation of home safety to encourage dialog about concerns, safety behaviors, and barriers to keeping children from injury.

  17. Coupling Legacy and Contemporary Deterministic Codes to Goldsim for Probabilistic Assessments of Potential Low-Level Waste Repository Sites

    NASA Astrophysics Data System (ADS)

    Mattie, P. D.; Knowlton, R. G.; Arnold, B. W.; Tien, N.; Kuo, M.

    2006-12-01

    Sandia National Laboratories (Sandia), a U.S. Department of Energy National Laboratory, has over 30 years experience in radioactive waste disposal and is providing assistance internationally in a number of areas relevant to the safety assessment of radioactive waste disposal systems. International technology transfer efforts are often hampered by small budgets, time schedule constraints, and a lack of experienced personnel in countries with small radioactive waste disposal programs. In an effort to surmount these difficulties, Sandia has developed a system that utilizes a combination of commercially available codes and existing legacy codes for probabilistic safety assessment modeling that facilitates the technology transfer and maximizes limited available funding. Numerous codes developed and endorsed by the United States Nuclear Regulatory Commission and codes developed and maintained by United States Department of Energy are generally available to foreign countries after addressing import/export control and copyright requirements. From a programmatic view, it is easier to utilize existing codes than to develop new codes. From an economic perspective, it is not possible for most countries with small radioactive waste disposal programs to maintain complex software, which meets the rigors of both domestic regulatory requirements and international peer review. Therefore, re-vitalization of deterministic legacy codes, as well as an adaptation of contemporary deterministic codes, provides a creditable and solid computational platform for constructing probabilistic safety assessment models. External model linkage capabilities in Goldsim and the techniques applied to facilitate this process will be presented using example applications, including Breach, Leach, and Transport-Multiple Species (BLT-MS), a U.S. NRC sponsored code simulating release and transport of contaminants from a subsurface low-level waste disposal facility used in a cooperative technology transfer

  18. Results of comparative RBMK neutron computation using VNIIEF codes (cell computation, 3D statics, 3D kinetics). Final report

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

    Grebennikov, A.N.; Zhitnik, A.K.; Zvenigorodskaya, O.A.

    1995-12-31

    In conformity with the protocol of the Workshop under Contract {open_quotes}Assessment of RBMK reactor safety using modern Western Codes{close_quotes} VNIIEF performed a neutronics computation series to compare western and VNIIEF codes and assess whether VNIIEF codes are suitable for RBMK type reactor safety assessment computation. The work was carried out in close collaboration with M.I. Rozhdestvensky and L.M. Podlazov, NIKIET employees. The effort involved: (1) cell computations with the WIMS, EKRAN codes (improved modification of the LOMA code) and the S-90 code (VNIIEF Monte Carlo). Cell, polycell, burnup computation; (2) 3D computation of static states with the KORAT-3D and NEUmore » codes and comparison with results of computation with the NESTLE code (USA). The computations were performed in the geometry and using the neutron constants presented by the American party; (3) 3D computation of neutron kinetics with the KORAT-3D and NEU codes. These computations were performed in two formulations, both being developed in collaboration with NIKIET. Formulation of the first problem maximally possibly agrees with one of NESTLE problems and imitates gas bubble travel through a core. The second problem is a model of the RBMK as a whole with imitation of control and protection system controls (CPS) movement in a core.« less

  19. National Electrical Code in Power Engineering Course for Electrical Engineering Curriculum

    ERIC Educational Resources Information Center

    Azizur, Rahman M. M.

    2011-01-01

    In order to ensure the safety of their inhabitants and properties, the residential, industrial and business installations require complying with NEC (national electrical code) for electrical systems. Electrical design engineers and technicians rely heavily on these very important design guidelines. However, these design guidelines are not formally…

  20. Proceedings of the Third International Workshop on Proof-Carrying Code and Software Certification

    NASA Technical Reports Server (NTRS)

    Ewen, Denney, W. (Editor); Jensen, Thomas (Editor)

    2009-01-01

    This NASA conference publication contains the proceedings of the Third International Workshop on Proof-Carrying Code and Software Certification, held as part of LICS in Los Angeles, CA, USA, on August 15, 2009. Software certification demonstrates the reliability, safety, or security of software systems in such a way that it can be checked by an independent authority with minimal trust in the techniques and tools used in the certification process itself. It can build on existing validation and verification (V&V) techniques but introduces the notion of explicit software certificates, Vvilich contain all the information necessary for an independent assessment of the demonstrated properties. One such example is proof-carrying code (PCC) which is an important and distinctive approach to enhancing trust in programs. It provides a practical framework for independent assurance of program behavior; especially where source code is not available, or the code author and user are unknown to each other. The workshop wiII address theoretical foundations of logic-based software certification as well as practical examples and work on alternative application domains. Here "certificate" is construed broadly, to include not just mathematical derivations and proofs but also safety and assurance cases, or any fonnal evidence that supports the semantic analysis of programs: that is, evidence about an intrinsic property of code and its behaviour that can be independently checked by any user, intermediary, or third party. These guarantees mean that software certificates raise trust in the code itself, distinct from and complementary to any existing trust in the creator of the code, the process used to produce it, or its distributor. In addition to the contributed talks, the workshop featured two invited talks, by Kelly Hayhurst and Andrew Appel. The PCC 2009 website can be found at http://ti.arc.nasa.gov /event/pcc 091.

  1. Implementation of ASME Code, Section XI, Code Case N-770, on Alternative Examination Requirements for Class 1 Butt Welds Fabricated with Alloy 82/182

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

    Sullivan, Edmund J.; Anderson, Michael T.

    In May 2010, the NRC issued a proposed notice of rulemaking that includes a provision to add a new section to its rules to require licensees to implement ASME Code Case N-770, ‘‘Alternative Examination Requirements and Acceptance Standards for Class 1 PWR Piping and Vessel Nozzle Butt Welds Fabricated with UNS N06082 or UNS W86182 Weld Filler Material With or Without the Application of Listed Mitigation Activities, Section XI, Division 1,’’ with 15 conditions. Code Case N-770 contains baseline and inservice inspection (ISI) requirements for unmitigated butt welds fabricated with Alloy 82/182 material and preservice and ISI requirements for mitigatedmore » butt welds. The NRC stated that application of ASME Code Case N-770 is necessary because the inspections currently required by the ASME Code, Section XI, were not written to address stress corrosion cracking Alloy 82/182 butt welds, and the safety consequences of inadequate inspections can be significant. The NRC expects to issue the final rule incorporating this code case into its regulations in the spring 2011 time frame. This paper discusses the new examination requirements, the conditions that NRC is imposing , and the major concerns with implementation of the new Code Case.« less

  2. Ten Fire Safety Tips for Schools.

    ERIC Educational Resources Information Center

    Lake, James D.

    1999-01-01

    Provides 10 basic tips, compiled from the National Fire Protection Association's Life Safety Code 101, to ensure that educational facilities are fire safe. Tips include use of frequent and unexpected fire drills, limiting wall space of student artwork and teaching materials, being alert to preventing arson, planning speedy and safe emergency…

  3. 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.

  4. Current and anticipated uses of thermal hydraulic codes at the Japan Atomic Energy Research Institute

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

    Akimoto, Hajime; Kukita; Ohnuki, Akira

    1997-07-01

    The Japan Atomic Energy Research Institute (JAERI) is conducting several research programs related to thermal-hydraulic and neutronic behavior of light water reactors (LWRs). These include LWR safety research projects, which are conducted in accordance with the Nuclear Safety Commission`s research plan, and reactor engineering projects for the development of innovative reactor designs or core/fuel designs. Thermal-hydraulic and neutronic codes are used for various purposes including experimental analysis, nuclear power plant (NPP) safety analysis, and design assessment.

  5. Revenue sources for financing transportation safety activities in Virginia : phase two, state sources.

    DOT National Transportation Integrated Search

    1980-01-01

    Senate Bill 85, an action of the 1978 General Assembly, amended the Code of Virginia to provide, in part, that the Division of Highway Safety be succeeded by the newly created Department of Transportation Safety effective July 1, 1978. In its Declara...

  6. Making Homes Healthy: International Code Council Processes and Patterns.

    PubMed

    Coyle, Edward C; Isett, Kimberley R; Rondone, Joseph; Harris, Rebecca; Howell, M Claire Batten; Brandus, Katherine; Hughes, Gwendolyn; Kerfoot, Richard; Hicks, Diana

    2016-01-01

    Americans spend more than 90% of their time indoors, so it is important that homes are healthy environments. Yet many homes contribute to preventable illnesses via poor air quality, pests, safety hazards, and others. Efforts have been made to promote healthy housing through code changes, but results have been mixed. In support of such efforts, we analyzed International Code Council's (ICC) building code change process to uncover patterns of content and context that may contribute to successful adoptions of model codes. Discover patterns of facilitators and barriers to code amendments proposals. Mixed methods study of ICC records of past code change proposals. N = 2660. N/A. N/A. There were 4 possible outcomes for each code proposal studied: accepted as submitted, accepted as modified, accepted as modified by public comment, and denied. We found numerous correlates for final adoption of model codes proposed to the ICC. The number of proponents listed on a proposal was inversely correlated with success. Organizations that submitted more than 15 proposals had a higher chance of success than those that submitted fewer than 15. Proposals submitted by federal agencies correlated with a higher chance of success. Public comments in favor of a proposal correlated with an increased chance of success, while negative public comment had an even stronger negative correlation. To increase the chance of success, public health officials should submit their code changes through internal ICC committees or a federal agency, limit the number of cosponsors of the proposal, work with (or become) an active proposal submitter, and encourage public comment in favor of passage through their broader coalition.

  7. SCALE Code System 6.2.1

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

    Rearden, Bradley T.; Jessee, Matthew Anderson

    The SCALE Code System is a widely-used modeling and simulation suite for nuclear safety analysis and design that is developed, maintained, tested, and managed by the Reactor and Nuclear Systems Division (RNSD) of Oak Ridge National Laboratory (ORNL). SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor and lattice physics, radiation shielding, spent fuel and radioactive source term characterization, and sensitivity and uncertainty analysis. Since 1980, regulators, licensees, and research institutions around the world have used SCALE for safety analysis and design. SCALE provides an integrated framework with dozens of computational modules including three deterministicmore » and three Monte Carlo radiation transport solvers that are selected based on the desired solution strategy. SCALE includes current nuclear data libraries and problem-dependent processing tools for continuous-energy (CE) and multigroup (MG) neutronics and coupled neutron-gamma calculations, as well as activation, depletion, and decay calculations. SCALE includes unique capabilities for automated variance reduction for shielding calculations, as well as sensitivity and uncertainty analysis. SCALE’s graphical user interfaces assist with accurate system modeling, visualization of nuclear data, and convenient access to desired results.« less

  8. Items Supporting the Hanford Internal Dosimetry Program Implementation of the IMBA Computer Code

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

    Carbaugh, Eugene H.; Bihl, Donald E.

    2008-01-07

    The Hanford Internal Dosimetry Program has adopted the computer code IMBA (Integrated Modules for Bioassay Analysis) as its primary code for bioassay data evaluation and dose assessment using methodologies of ICRP Publications 60, 66, 67, 68, and 78. The adoption of this code was part of the implementation plan for the June 8, 2007 amendments to 10 CFR 835. This information release includes action items unique to IMBA that were required by PNNL quality assurance standards for implementation of safety software. Copie of the IMBA software verification test plan and the outline of the briefing given to new users aremore » also included.« less

  9. Concatenated Coding Using Trellis-Coded Modulation

    NASA Technical Reports Server (NTRS)

    Thompson, Michael W.

    1997-01-01

    In the late seventies and early eighties a technique known as Trellis Coded Modulation (TCM) was developed for providing spectrally efficient error correction coding. Instead of adding redundant information in the form of parity bits, redundancy is added at the modulation stage thereby increasing bandwidth efficiency. A digital communications system can be designed to use bandwidth-efficient multilevel/phase modulation such as Amplitude Shift Keying (ASK), Phase Shift Keying (PSK), Differential Phase Shift Keying (DPSK) or Quadrature Amplitude Modulation (QAM). Performance gain can be achieved by increasing the number of signals over the corresponding uncoded system to compensate for the redundancy introduced by the code. A considerable amount of research and development has been devoted toward developing good TCM codes for severely bandlimited applications. More recently, the use of TCM for satellite and deep space communications applications has received increased attention. This report describes the general approach of using a concatenated coding scheme that features TCM and RS coding. Results have indicated that substantial (6-10 dB) performance gains can be achieved with this approach with comparatively little bandwidth expansion. Since all of the bandwidth expansion is due to the RS code we see that TCM based concatenated coding results in roughly 10-50% bandwidth expansion compared to 70-150% expansion for similar concatenated scheme which use convolution code. We stress that combined coding and modulation optimization is important for achieving performance gains while maintaining spectral efficiency.

  10. Current advances in the generation of human iPS cells: implications in cell-based regenerative medicine.

    PubMed

    Revilla, Ana; González, Clara; Iriondo, Amaia; Fernández, Bárbara; Prieto, Cristina; Marín, Carlos; Liste, Isabel

    2016-11-01

    Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells.

    PubMed

    Wang, Linli; Chen, Yuehua; Guan, Chunyan; Zhao, Zhiju; Li, Qiang; Yang, Jianguo; Mo, Jian; Wang, Bin; Wu, Wei; Yang, Xiaohui; Song, Libing; Li, Jun

    2017-11-02

    Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important. To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system's feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses. We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system. The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

  12. Generating induced pluripotent stem cell derived endothelial cells and induced endothelial cells for cardiovascular disease modelling and therapeutic angiogenesis.

    PubMed

    Clayton, Z E; Sadeghipour, S; Patel, S

    2015-10-15

    Standard therapy for atherosclerotic coronary and peripheral arterial disease is insufficient in a significant number of patients because extensive disease often precludes effective revascularization. Stem cell therapy holds promise as a supplementary treatment for these patients, as pre-clinical and clinical research has shown transplanted cells can promote angiogenesis via direct and paracrine mechanisms. Induced pluripotent stem cells (iPSCs) are a novel cell type obtained by reprogramming somatic cells using exogenous transcription factor cocktails, which have been introduced to somatic cells via viral or plasmid constructs, modified mRNA or small molecules. IPSCs are now being used in disease modelling and drug testing and are undergoing their first clinical trial, but despite recent advances, the inefficiency of the reprogramming process remains a major limitation, as does the lack of consensus regarding the optimum transcription factor combination and delivery method and the uncertainty surrounding the genetic and epigenetic stability of iPSCs. IPSCs have been successfully differentiated into vascular endothelial cells (iPSC-ECs) and, more recently, induced endothelial cells (iECs) have also been generated by direct differentiation, which bypasses the pluripotent intermediate. IPSC-ECs and iECs demonstrate endothelial functionality in vitro and have been shown to promote neovessel growth and enhance blood flow recovery in animal models of myocardial infarction and peripheral arterial disease. Challenges remain in optimising the efficiency, safety and fidelity of the reprogramming and endothelial differentiation processes and establishing protocols for large-scale production of clinical-grade, patient-derived cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Highly efficient Cas9-mediated transcriptional programming

    DOE PAGES

    Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; ...

    2015-03-02

    The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. Here we describe an improved transcriptional regulator through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. Here, we demonstrate its utility in activating endogenous coding and non-coding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).

  14. Telepharmacy and bar-code technology in an i.v. chemotherapy admixture area.

    PubMed

    O'Neal, Brian C; Worden, John C; Couldry, Rick J

    2009-07-01

    A program using telepharmacy and bar-code technology to increase the presence of the pharmacist at a critical risk point during chemotherapy preparation is described. Telepharmacy hardware and software were acquired, and an inspection camera was placed in a biological safety cabinet to allow the pharmacy technician to take digital photographs at various stages of the chemotherapy preparation process. Once the pharmacist checks the medication vials' agreement with the work label, the technician takes the product into the biological safety cabinet, where the appropriate patient is selected from the pending work list, a queue of patient orders sent from the pharmacy information system. The technician then scans the bar code on the vial. Assuming the bar code matches, the technician photographs the work label, vials, diluents and fluids to be used, and the syringe (before injecting the contents into the bag) along with the vial. The pharmacist views all images as a part of the final product-checking process. This process allows the pharmacist to verify that the correct quantity of medication was transferred from the primary source to a secondary container without being physically present at the time of transfer. Telepharmacy and bar coding provide a means to improve the accuracy of chemotherapy preparation by decreasing the likelihood of using the incorrect product or quantity of drug. The system facilitates the reading of small product labels and removes the need for a pharmacist to handle contaminated syringes and vials when checking the final product.

  15. New "Risk-Targeted" Seismic Maps Introduced into Building Codes

    USGS Publications Warehouse

    Luco, Nicholas; Garrett, B.; Hayes, J.

    2012-01-01

    Throughout most municipalities of the United States, structural engineers design new buildings using the U.S.-focused International Building Code (IBC). Updated editions of the IBC are published every 3 years. The latest edition (2012) contains new "risk-targeted maximum considered earthquake" (MCER) ground motion maps, which are enabling engineers to incorporate a more consistent and better defined level of seismic safety into their building designs.

  16. Guidelines for pressure vessel safety assessment

    NASA Astrophysics Data System (ADS)

    Yukawa, S.

    1990-04-01

    A technical overview and information on metallic pressure containment vessels and tanks is given. The intent is to provide Occupational Safety and Health Administration (OSHA) personnel and other persons with information to assist in the evaluation of the safety of operating pressure vessels and low pressure storage tanks. The scope is limited to general industrial application vessels and tanks constructed of carbon or low alloy steels and used at temperatures between -75 and 315 C (-100 and 600 F). Information on design codes, materials, fabrication processes, inspection and testing applicable to the vessels and tanks are presented. The majority of the vessels and tanks are made to the rules and requirements of ASME Code Section VIII or API Standard 620. The causes of deterioration and damage in operation are described and methods and capabilities of detecting serious damage and cracking are discussed. Guidelines and recommendations formulated by various groups to inspect for the damages being found and to mitigate the causes and effects of the problems are presented.

  17. Combustion Safety for Appliances Using Indoor Air (Fact Sheet)

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

    Not Available

    2014-05-01

    This measure guideline covers how to assess and carry out the combustion safety procedures for appliances and heating equipment that uses indoor air for combustion in low-rise residential buildings. Only appliances installed in the living space, or in an area freely communicating with the living space, vented alone or in tandem with another appliance are considered here. A separate measure guideline addresses combustion appliances located either within the living space in enclosed closets or side rooms or outside the living space in an adjacent area like an attic or garage that use outdoor air for combustion. This document is formore » inspectors, auditors, and technicians working in homes where energy upgrades are being conducted whether or not air infiltration control is included in the package of measures being applied. In the indoor combustion air case, guidelines summarized here are based on language provided in several of the codes to establish minimum requirements for the space using simplified prescriptive measures. In addition, building performance testing procedures are provided by testing agencies. The codes in combination with the test procedures offer comprehensive combustion safety coverage to address safety concerns, allowing inexperienced residential energy retrofit inspectors to effectively address combustion safety issues and allow energy retrofits to proceed.« less

  18. Racial/ethnic differences in obesity and comorbidities between safety-net- and non safety-net integrated health systems

    PubMed Central

    Balasubramanian, Bijal A.; Garcia, Michael P.; Corley, Douglas A.; Doubeni, Chyke A.; Haas, Jennifer S.; Kamineni, Aruna; Quinn, Virginia P.; Wernli, Karen; Zheng, Yingye; Skinner, Celette Sugg

    2017-01-01

    Abstract Previous research shows that patients in integrated health systems experience fewer racial disparities compared with more traditional healthcare systems. Little is known about patterns of racial/ethnic disparities between safety-net and non safety-net integrated health systems. We evaluated racial/ethnic differences in body mass index (BMI) and the Charlson comorbidity index from 3 non safety-net- and 1 safety-net integrated health systems in a cross-sectional study. Multinomial logistic regression modeled comorbidity and BMI on race/ethnicity and health care system type adjusting for age, sex, insurance, and zip-code-level income The study included 1.38 million patients. Higher proportions of safety-net versus non safety-net patients had comorbidity score of 3+ (11.1% vs. 5.0%) and BMI ≥35 (27.7% vs. 15.8%). In both types of systems, blacks and Hispanics were more likely than whites to have higher BMIs. Whites were more likely than blacks or Hispanics to have higher comorbidity scores in a safety net system, but less likely to have higher scores in the non safety-nets. The odds of comorbidity score 3+ and BMI 35+ in blacks relative to whites were significantly lower in safety-net than in non safety-net settings. Racial/ethnic differences were present within both safety-net and non safety-net integrated health systems, but patterns differed. Understanding patterns of racial/ethnic differences in health outcomes in safety-net and non safety-net integrated health systems is important to tailor interventions to eliminate racial/ethnic disparities in health and health care. PMID:28296752

  19. Keeping a common bawdy house becomes a "serious offence" under Criminal Code.

    PubMed

    2010-10-01

    New federal regulations targeting organized crime will make keeping a common bawdy house a "serious offence" under the Criminal Code. Sex work advocates reacted by calling the measure a serious step back that will undermine the protection of sex workers' human rights, safety, dignity and health.

  20. In Vitro and In Vivo Development of Horse Cloned Embryos Generated with iPSCs, Mesenchymal Stromal Cells and Fetal or Adult Fibroblasts as Nuclear Donors.

    PubMed

    Olivera, Ramiro; Moro, Lucia Natalia; Jordan, Roberto; Luzzani, Carlos; Miriuka, Santiago; Radrizzani, Martin; Donadeu, F Xavier; Vichera, Gabriel

    2016-01-01

    The demand for equine cloning as a tool to preserve high genetic value is growing worldwide; however, nuclear transfer efficiency is still very low. To address this issue, we first evaluated the effects of time from cell fusion to activation (<1h, n = 1261; 1-2h, n = 1773; 2-3h, n = 1647) on in vitro and in vivo development of equine embryos generated by cloning. Then, we evaluated the effects of using different nuclear donor cell types in two successive experiments: I) induced pluripotent stem cells (iPSCs) vs. adult fibroblasts (AF) fused to ooplasts injected with the pluripotency-inducing genes OCT4, SOX2, MYC and KLF4, vs. AF alone as controls; II) umbilical cord-derived mesenchymal stromal cells (UC-MSCs) vs. fetal fibroblasts derived from an unborn cloned foetus (FF) vs. AF from the original individual. In the first experiment, both blastocyst production and pregnancy rates were higher in the 2-3h group (11.5% and 9.5%, respectively), respect to <1h (5.2% and 2%, respectively) and 1-2h (5.6% and 4.7%, respectively) groups (P<0.05). However, percentages of born foals/pregnancies were similar when intervals of 2-3h (35.2%) or 1-2h (35.7%) were used. In contrast to AF, the iPSCs did not generate any blastocyst-stage embryos. Moreover, injection of oocytes with the pluripotency-inducing genes did not improve blastocyst production nor pregnancy rates respect to AF controls. Finally, higher blastocyst production was obtained using UC-MSC (15.6%) than using FF (8.9%) or AF (9.3%), (P<0.05). Despite pregnancy rates were similar for these 3 groups (17.6%, 18.2% and 22%, respectively), viable foals (two) were obtained only by using FF. In summary, optimum blastocyst production rates can be obtained using a 2-3h interval between cell fusion and activation as well as using UC-MSCs as nuclear donors. Moreover, FF line can improve the efficiency of an inefficient AF line. Overall, 24 healthy foals were obtained from a total of 29 born foals.

  1. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs)

    NASA Technical Reports Server (NTRS)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This report contains the outcome of the assessment and the findings, observations, and NESC recommendations to the Agency and individual NASA Centers.

  2. Evaluation of liquefaction potential for building code

    NASA Astrophysics Data System (ADS)

    Nunziata, C.; De Nisco, G.; Panza, G. F.

    2008-07-01

    The standard approach for the evaluation of the liquefaction susceptibility is based on the estimation of a safety factor between the cyclic shear resistance to liquefaction and the earthquake induced shear stress. Recently, an updated procedure based on shear-wave velocities (Vs) has been proposed which could be more easily applied. These methods have been applied at La Plaja beach of Catania, that experienced liquefaction because of the 1693 earthquake. The detailed geotechnical and Vs information and the realistic ground motion computed for the 1693 event let us compare the two approaches. The successful application of the Vs procedure, slightly modified to fit historical and safety factor information, even if additional field performances are needed, encourages the development of a guide for liquefaction potential analysis, based on well defined Vs profiles to be included in the italian seismic code.

  3. An examination of some safety issues among commercial motorcyclists in Nigeria: a case study.

    PubMed

    Arosanyin, Godwin Tunde; Olowosulu, Adekunle Taiwo; Oyeyemi, Gafar Matanmi

    2013-01-01

    The reduction of road crashes and injuries among motorcyclists in Nigeria requires a system inquiry into some safety issues at pre-crash, crash and post-crash stages to guide action plans. This paper examines safety issues such as age restriction, motorcycle engine capacity, highway code awareness, licence holding, helmet usage, crash involvement, rescue and payment for treatment among commercial motorcyclists. The primary data derived from a structured questionnaire administered to 334 commercial motorcyclists in Samaru, Zaria were analysed using descriptive statistics and logistic regression technique. There was total compliance with age restriction and motorcycle engine capacity. About 41.8% of the operators were not aware of the existence of the highway code. The odds of licence holding increased with highway code awareness, education with above senior secondary as the reference category and earnings. The odds of crash involvement decreased with highway code awareness, earnings and mode of operation. About 84% of the motorcyclists did not use crash helmet, in spite of being aware of the benefit, and 65.4% of motorcycle crashes was found to be with other road users. The promotion of safety among motorcyclists therefore requires strict traffic law enforcement and modification of road design to segregate traffic and protect pedestrians.

  4. Establishment and assessment of code scaling capability

    NASA Astrophysics Data System (ADS)

    Lim, Jaehyok

    In this thesis, a method for using RELAP5/MOD3.3 (Patch03) code models is described to establish and assess the code scaling capability and to corroborate the scaling methodology that has been used in the design of the Purdue University Multi-Dimensional Integral Test Assembly for ESBWR applications (PUMA-E) facility. It was sponsored by the United States Nuclear Regulatory Commission (USNRC) under the program "PUMA ESBWR Tests". PUMA-E facility was built for the USNRC to obtain data on the performance of the passive safety systems of the General Electric (GE) Nuclear Energy Economic Simplified Boiling Water Reactor (ESBWR). Similarities between the prototype plant and the scaled-down test facility were investigated for a Gravity-Driven Cooling System (GDCS) Drain Line Break (GDLB). This thesis presents the results of the GDLB test, i.e., the GDLB test with one Isolation Condenser System (ICS) unit disabled. The test is a hypothetical multi-failure small break loss of coolant (SB LOCA) accident scenario in the ESBWR. The test results indicated that the blow-down phase, Automatic Depressurization System (ADS) actuation, and GDCS injection processes occurred as expected. The GDCS as an emergency core cooling system provided adequate supply of water to keep the Reactor Pressure Vessel (RPV) coolant level well above the Top of Active Fuel (TAF) during the entire GDLB transient. The long-term cooling phase, which is governed by the Passive Containment Cooling System (PCCS) condensation, kept the reactor containment system that is composed of Drywell (DW) and Wetwell (WW) below the design pressure of 414 kPa (60 psia). In addition, the ICS continued participating in heat removal during the long-term cooling phase. A general Code Scaling, Applicability, and Uncertainty (CSAU) evaluation approach was discussed in detail relative to safety analyses of Light Water Reactor (LWR). The major components of the CSAU methodology that were highlighted particularly focused on the

  5. 49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Pt. 229, App. C...

  6. 49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Pt. 229, App. C...

  7. 49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Pt. 229, App. C...

  8. Validation and verification of the laser range safety tool (LRST)

    NASA Astrophysics Data System (ADS)

    Kennedy, Paul K.; Keppler, Kenneth S.; Thomas, Robert J.; Polhamus, Garrett D.; Smith, Peter A.; Trevino, Javier O.; Seaman, Daniel V.; Gallaway, Robert A.; Crockett, Gregg A.

    2003-06-01

    The U.S. Dept. of Defense (DOD) is currently developing and testing a number of High Energy Laser (HEL) weapons systems. DOD range safety officers now face the challenge of designing safe methods of testing HEL's on DOD ranges. In particular, safety officers need to ensure that diffuse and specular reflections from HEL system targets, as well as direct beam paths, are contained within DOD boundaries. If both the laser source and the target are moving, as they are for the Airborne Laser (ABL), a complex series of calculations is required and manual calculations are impractical. Over the past 5 years, the Optical Radiation Branch of the Air Force Research Laboratory (AFRL/HEDO), the ABL System Program Office, Logicon-RDA, and Northrup-Grumman, have worked together to develop a computer model called teh Laser Range Safety Tool (LRST), specifically designed for HEL reflection hazard analyses. The code, which is still under development, is currently tailored to support the ABL program. AFRL/HEDO has led an LRST Validation and Verification (V&V) effort since 1998, in order to determine if code predictions are accurate. This paper summarizes LRST V&V efforts to date including: i) comparison of code results with laboratory measurements of reflected laser energy and with reflection measurements made during actual HEL field tests, and ii) validation of LRST's hazard zone computations.

  9. Tritium safety study using Caisson Assembly (CATS) at TPL/JAEA

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

    Hayashi, T.; Kobayashi, K.; Iwai, Y.

    Tritium confinement is required as the most important safety Junction for a fusion reactor. In order to demonstrate the confinement performance experimentally, an unique equipment, called CATS: Caisson Assembly for Tritium Safety study, was installed in Tritium Process Laboratory of Japan Atomic Energy Agency and operated for about 10 years. Tritium confinement and migration data in CATS have been accumulated and dynamic simulation code was accumulated using these data. Contamination and decontamination behavior on various materials and new safety equipment functions have been investigated under collaborations with a lot of laboratories and universities. (authors)

  10. 3 CFR 8672 - Proclamation 8672 of May 9, 2011. National Building Safety Month, 2011

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... public and private sectors—to implement effective standards and codes that sustain safe and resilient structures. We need innovation and partnerships at all levels of society to develop transformative... Proclamation Building safety is a critical component of our homeland security, our personal and public safety...

  11. Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9.

    PubMed

    Li, Hongmei Lisa; Fujimoto, Naoko; Sasakawa, Noriko; Shirai, Saya; Ohkame, Tokiko; Sakuma, Tetsushi; Tanaka, Michihiro; Amano, Naoki; Watanabe, Akira; Sakurai, Hidetoshi; Yamamoto, Takashi; Yamanaka, Shinya; Hotta, Akitsu

    2015-01-13

    Duchenne muscular dystrophy (DMD) is a severe muscle-degenerative disease caused by a mutation in the dystrophin gene. Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined. Using a unique k-mer database, we systematically identified a unique target region that reduces off-target sites. To restore the dystrophin protein, we performed three correction methods (exon skipping, frameshifting, and exon knockin) in DMD-patient-derived iPSCs, and found that exon knockin was the most effective approach. We further investigated the genomic integrity by karyotyping, copy number variation array, and exome sequencing to identify clones with a minimal mutation load. Finally, we differentiated the corrected iPSCs toward skeletal muscle cells and successfully detected the expression of full-length dystrophin protein. These results provide an important framework for developing iPSC-based gene therapy for genetic disorders using programmable nucleases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. The application of the psychological contract to workplace safety.

    PubMed

    Walker, Arlene; Hutton, Dorothy M

    2006-01-01

    Psychological contracts of safety are conceptualized as the beliefs of individuals about reciprocal safety obligations inferred from implicit or explicit promises. Although the literature on psychological contracts is growing, the existence of psychological contracts in relation to safety has not been established. The research sought to identify psychological contracts in the conversations of employees about safety, by demonstrating reciprocity in relation to employer and employee safety obligations. The identified safety obligations were used to develop a measure of psychological contracts of safety. The participants were 131 employees attending safety training sessions in retail and manufacturing organizations. Non-participant observation was used to collect the data during safety training sessions. Content analysis was used to analyze the data. Categories for coding were established through identification of language markers that demonstrated contingencies or other implied obligations. Direct evidence of reciprocity between employer safety obligations and employee safety obligations was found in statements from the participants demonstrating psychological contracts. A comprehensive list of perceived employer and employee safety obligations was compiled and developed into a measure of psychological contracts of safety. A small sample of 33 safety personnel was used to validate the safety obligations. CONCLUSIONS AND IMPACT ON INDUSTRY: Implications of these findings for safety and psychological contract research are discussed.

  13. Self-complementary circular codes in coding theory.

    PubMed

    Fimmel, Elena; Michel, Christian J; Starman, Martin; Strüngmann, Lutz

    2018-04-01

    Self-complementary circular codes are involved in pairing genetic processes. A maximal [Formula: see text] self-complementary circular code X of trinucleotides was identified in genes of bacteria, archaea, eukaryotes, plasmids and viruses (Michel in Life 7(20):1-16 2017, J Theor Biol 380:156-177, 2015; Arquès and Michel in J Theor Biol 182:45-58 1996). In this paper, self-complementary circular codes are investigated using the graph theory approach recently formulated in Fimmel et al. (Philos Trans R Soc A 374:20150058, 2016). A directed graph [Formula: see text] associated with any code X mirrors the properties of the code. In the present paper, we demonstrate a necessary condition for the self-complementarity of an arbitrary code X in terms of the graph theory. The same condition has been proven to be sufficient for codes which are circular and of large size [Formula: see text] trinucleotides, in particular for maximal circular codes ([Formula: see text] trinucleotides). For codes of small-size [Formula: see text] trinucleotides, some very rare counterexamples have been constructed. Furthermore, the length and the structure of the longest paths in the graphs associated with the self-complementary circular codes are investigated. It has been proven that the longest paths in such graphs determine the reading frame for the self-complementary circular codes. By applying this result, the reading frame in any arbitrary sequence of trinucleotides is retrieved after at most 15 nucleotides, i.e., 5 consecutive trinucleotides, from the circular code X identified in genes. Thus, an X motif of a length of at least 15 nucleotides in an arbitrary sequence of trinucleotides (not necessarily all of them belonging to X) uniquely defines the reading (correct) frame, an important criterion for analyzing the X motifs in genes in the future.

  14. Fusion Safety Program annual report, fiscal year 1994

    NASA Astrophysics Data System (ADS)

    Longhurst, Glen R.; Cadwallader, Lee C.; Dolan, Thomas J.; Herring, J. Stephen; McCarthy, Kathryn A.; Merrill, Brad J.; Motloch, Chester C.; Petti, David A.

    1995-03-01

    This report summarizes the major activities of the Fusion Safety Program in fiscal year 1994. The Idaho National Engineering Laboratory (INEL) is the designated lead laboratory and Lockheed Idaho Technologies Company is the prime contractor for this program. The Fusion Safety Program was initiated in 1979. Activities are conducted at the INEL, at other DOE laboratories, and at other institutions, including the University of Wisconsin. The technical areas covered in this report include tritium safety, beryllium safety, chemical reactions and activation product release, safety aspects of fusion magnet systems, plasma disruptions, risk assessment failure rate data base development, and thermalhydraulics code development and their application to fusion safety issues. Much of this work has been done in support of the International Thermonuclear Experimental Reactor (ITER). Also included in the report are summaries of the safety and environmental studies performed by the Fusion Safety Program for the Tokamak Physics Experiment and the Tokamak Fusion Test Reactor and of the technical support for commercial fusion facility conceptual design studies. A major activity this year has been work to develop a DOE Technical Standard for the safety of fusion test facilities.

  15. Crash Outcome Data Evaluation System (CODES) Project Safety Belt and Helmet Analyses

    DOT National Transportation Integrated Search

    1996-02-15

    Analyses of the benefits of safety belt and helmet use were undertaken for a : Report that was sent to Congress February, 1996. NHTSA awarded grants to link : crash and injury state data and perform the analyses upon which the report was : based. The...

  16. SCALE Code System 6.2.2

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

    Rearden, Bradley T.; Jessee, Matthew Anderson

    The SCALE Code System is a widely used modeling and simulation suite for nuclear safety analysis and design that is developed, maintained, tested, and managed by the Reactor and Nuclear Systems Division (RNSD) of Oak Ridge National Laboratory (ORNL). SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor physics, radiation shielding, radioactive source term characterization, and sensitivity and uncertainty analysis. Since 1980, regulators, licensees, and research institutions around the world have used SCALE for safety analysis and design. SCALE provides an integrated framework with dozens of computational modules including 3 deterministic and 3 Monte Carlomore » radiation transport solvers that are selected based on the desired solution strategy. SCALE includes current nuclear data libraries and problem-dependent processing tools for continuous-energy (CE) and multigroup (MG) neutronics and coupled neutron-gamma calculations, as well as activation, depletion, and decay calculations. SCALE includes unique capabilities for automated variance reduction for shielding calculations, as well as sensitivity and uncertainty analysis. SCALE’s graphical user interfaces assist with accurate system modeling, visualization of nuclear data, and convenient access to desired results. SCALE 6.2 represents one of the most comprehensive revisions in the history of SCALE, providing several new capabilities and significant improvements in many existing features.« less

  17. Immunization safety in US print media, 1995-2005.

    PubMed

    Hussain, Hamidah; Omer, Saad B; Manganello, Jennifer A; Kromm, Elizabeth Edsall; Carter, Terrell C; Kan, Lilly; Stokley, Shannon; Halsey, Neal A; Salmon, Daniel A

    2011-05-01

    To identify and describe vaccine safety in US newspaper articles. Articles (1147) from 44 states and Washington, DC, between January 1, 1995, and July 15, 2005, were identified by using the search terms "immunize or vaccine" and "adverse events or safety or exemption or danger or risk or damage or injury or side effect" and were coded by using a standardized data-collection instrument. The mean number of vaccine-safety articles per state was 26. Six (not mutually exclusive) topics were identified: vaccine-safety concerns (46%); vaccine policy (44%); vaccines are safe (20%); immunizations are required (10%); immunizations are not required (8%); and state/school exemption (8%). Three spikes in the number of newspaper articles about vaccine-safety issues were observed: in 1999 regarding rotavirus vaccine and in 2002 and 2003 regarding smallpox vaccine. Excluding articles that referred to rotavirus and smallpox vaccines, 37% of the articles had a negative take-home message. Ongoing monitoring of news on vaccine safety may help the content and framing of vaccine-safety messages.

  18. Evaluation of Safety, Quality and Productivity in Construction

    NASA Astrophysics Data System (ADS)

    Usmen, M. A.; Vilnitis, M.

    2015-11-01

    This paper examines the success indicators of construction projects, safety, quality and productivity, in terms of their implications and impacts during and after construction. First safety is considered during construction with a focus on hazard identification and the prevention of occupational accidents and injuries on worksites. The legislation mandating safety programs, training and compliance with safety standards is presented and discussed. Consideration of safety at the design stage is emphasized. Building safety and the roles of building codes in prevention of structural failures are also covered in the paper together with factors affecting building failures and methods for their prevention. Quality is introduced in the paper from the perspective of modern total quality management. Concepts of quality management, quality control, quality assurance and Six Sigma and how they relate to building quality and structural integrity are discussed with examples. Finally, productivity concepts are presented with emphasis on effective project management to minimize loss of productivity, complimented by lean construction and lean Six Sigma principles. The paper concludes by synthesizing the relationships between safety, quality and productivity.

  19. Coset Codes Viewed as Terminated Convolutional Codes

    NASA Technical Reports Server (NTRS)

    Fossorier, Marc P. C.; Lin, Shu

    1996-01-01

    In this paper, coset codes are considered as terminated convolutional codes. Based on this approach, three new general results are presented. First, it is shown that the iterative squaring construction can equivalently be defined from a convolutional code whose trellis terminates. This convolutional code determines a simple encoder for the coset code considered, and the state and branch labelings of the associated trellis diagram become straightforward. Also, from the generator matrix of the code in its convolutional code form, much information about the trade-off between the state connectivity and complexity at each section, and the parallel structure of the trellis, is directly available. Based on this generator matrix, it is shown that the parallel branches in the trellis diagram of the convolutional code represent the same coset code C(sub 1), of smaller dimension and shorter length. Utilizing this fact, a two-stage optimum trellis decoding method is devised. The first stage decodes C(sub 1), while the second stage decodes the associated convolutional code, using the branch metrics delivered by stage 1. Finally, a bidirectional decoding of each received block starting at both ends is presented. If about the same number of computations is required, this approach remains very attractive from a practical point of view as it roughly doubles the decoding speed. This fact is particularly interesting whenever the second half of the trellis is the mirror image of the first half, since the same decoder can be implemented for both parts.

  20. Examination of adult and child bicyclist safety-relevant events using naturalistic bicycling methodology.

    PubMed

    Hamann, Cara J; Peek-Asa, Corinne

    2017-05-01

    Among roadway users, bicyclists are considered vulnerable due to their high risk for injury when involved in a crash. Little is known about the circumstances leading to near crashes, crashes, and related injuries or how these vary by age and gender. The purpose of this study was to examine the rates and characteristics of safety-relevant events (crashes, near crashes, errors, and traffic violations) among adult and child bicyclists. Bicyclist trips were captured using Pedal Portal, a data acquisition and coding system which includes a GPS-enabled video camera and graphical user interface. A total of 179 safety-relevant events were manually coded from trip videos. Overall, child errors and traffic violations occurred at a rate of 1.9 per 100min of riding, compared to 6.3 for adults. However, children rode on the sidewalk 56.4% of the time, compared with 12.7% for adults. For both adults and children, the highest safety-relevant event rates occurred on paved roadways with no bicycle facilities present (Adults=8.6 and Children=7.2, per 100min of riding). Our study, the first naturalistic study to compare safety-relevant events among adults and children, indicates large variation in riding behavior and exposure between child and adult bicyclists. The majority of identified events were traffic violations and we were not able to code all risk-relevant data (e.g., subtle avoidance behaviors, failure to check for traffic, probability of collision). Future naturalistic cycling studies would benefit from enhanced instrumentation (e.g., additional camera views) and coding protocols able to fill these gaps. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Java Source Code Analysis for API Migration to Embedded Systems

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

    Winter, Victor; McCoy, James A.; Guerrero, Jonathan

    Embedded systems form an integral part of our technological infrastructure and oftentimes play a complex and critical role within larger systems. From the perspective of reliability, security, and safety, strong arguments can be made favoring the use of Java over C in such systems. In part, this argument is based on the assumption that suitable subsets of Java’s APIs and extension libraries are available to embedded software developers. In practice, a number of Java-based embedded processors do not support the full features of the JVM. For such processors, source code migration is a mechanism by which key abstractions offered bymore » APIs and extension libraries can made available to embedded software developers. The analysis required for Java source code-level library migration is based on the ability to correctly resolve element references to their corresponding element declarations. A key challenge in this setting is how to perform analysis for incomplete source-code bases (e.g., subsets of libraries) from which types and packages have been omitted. This article formalizes an approach that can be used to extend code bases targeted for migration in such a manner that the threats associated the analysis of incomplete code bases are eliminated.« less

  2. Current and anticipated uses of thermal-hydraulic codes in Spain

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

    Pelayo, F.; Reventos, F.

    1997-07-01

    Spanish activities in the field of Applied Thermal-Hydraulics are steadily increasing as the codes are becoming practicable enough to efficiently sustain engineering decision in the Nuclear Power industry. Before reaching this point, a lot of effort has been devoted to achieve this goal. This paper briefly describes this process, points at the current applications and draws conclusions on the limitations. Finally it establishes the applications where the use of T-H codes would be worth in the future, this in turn implies further development of the codes to widen the scope of application and improve the general performance. Due to themore » different uses of the codes, the applications mainly come from the authority, industry, universities and research institutions. The main conclusion derived from this paper establishes that further code development is justified if the following requisites are considered: (1) Safety relevance of scenarios not presently covered is established. (2) A substantial gain in margins or the capability to use realistic assumptions is obtained. (3) A general consensus on the licensability and methodology for application is reached. The role of Regulatory Body is stressed, as the most relevant outcome of the project may be related to the evolution of the licensing frame.« less

  3. Combinatorial neural codes from a mathematical coding theory perspective.

    PubMed

    Curto, Carina; Itskov, Vladimir; Morrison, Katherine; Roth, Zachary; Walker, Judy L

    2013-07-01

    Shannon's seminal 1948 work gave rise to two distinct areas of research: information theory and mathematical coding theory. While information theory has had a strong influence on theoretical neuroscience, ideas from mathematical coding theory have received considerably less attention. Here we take a new look at combinatorial neural codes from a mathematical coding theory perspective, examining the error correction capabilities of familiar receptive field codes (RF codes). We find, perhaps surprisingly, that the high levels of redundancy present in these codes do not support accurate error correction, although the error-correcting performance of receptive field codes catches up to that of random comparison codes when a small tolerance to error is introduced. However, receptive field codes are good at reflecting distances between represented stimuli, while the random comparison codes are not. We suggest that a compromise in error-correcting capability may be a necessary price to pay for a neural code whose structure serves not only error correction, but must also reflect relationships between stimuli.

  4. A cloud medication safety support system using QR code and Web services for elderly outpatients.

    PubMed

    Tseng, Ming-Hseng; Wu, Hui-Ching

    2014-01-01

    Drug is an important part of disease treatment, but medication errors happen frequently and have significant clinical and financial consequences. The prevalence of prescription medication use among the ambulatory adult population increases with advancing age. Because of the global aging society, outpatients need to improve medication safety more than inpatients. The elderly with multiple chronic conditions face the complex task of medication management. To reduce the medication errors for the elder outpatients with chronic diseases, a cloud medication safety supporting system is designed, demonstrated and evaluated. The proposed system is composed of a three-tier architecture: the front-end tier, the mobile tier and the cloud tier. The mobile tier will host the personalized medication safety supporting application on Android platforms that provides some primary functions including reminders for medication, assistance with pill-dispensing, recording of medications, position of medications and notices of forgotten medications for elderly outpatients. Finally, the hybrid technology acceptance model is employed to understand the intention and satisfaction level of the potential users to use this mobile medication safety support application system. The result of the system acceptance testing indicates that this developed system, implementing patient-centered services, is highly accepted by the elderly. This proposed M-health system could assist elderly outpatients' homecare in preventing medication errors and improving their medication safety.

  5. Modeling of Flow Blockage in a Liquid Metal-Cooled Reactor Subassembly with a Subchannel Analysis Code

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

    Jeong, Hae-Yong; Ha, Kwi-Seok; Chang, Won-Pyo

    The local blockage in a subassembly of a liquid metal-cooled reactor (LMR) is of importance to the plant safety because of the compact design and the high power density of the core. To analyze the thermal-hydraulic parameters in a subassembly of a liquid metal-cooled reactor with a flow blockage, the Korea Atomic Energy Research Institute has developed the MATRA-LMR-FB code. This code uses the distributed resistance model to describe the sweeping flow formed by the wire wrap around the fuel rods and to model the recirculation flow after a blockage. The hybrid difference scheme is also adopted for the descriptionmore » of the convective terms in the recirculating wake region of low velocity. Some state-of-the-art turbulent mixing models were implemented in the code, and the models suggested by Rehme and by Zhukov are analyzed and found to be appropriate for the description of the flow blockage in an LMR subassembly. The MATRA-LMR-FB code predicts accurately the experimental data of the Oak Ridge National Laboratory 19-pin bundle with a blockage for both the high-flow and low-flow conditions. The influences of the distributed resistance model, the hybrid difference method, and the turbulent mixing models are evaluated step by step with the experimental data. The appropriateness of the models also has been evaluated through a comparison with the results from the COMMIX code calculation. The flow blockage for the KALIMER design has been analyzed with the MATRA-LMR-FB code and is compared with the SABRE code to guarantee the design safety for the flow blockage.« less

  6. Safety Alerts: An Observational Study in Portugal.

    PubMed

    Soares, Sara; Roque, Fátima; Teixeira Rodrigues, António; Figueiras, Adolfo; Herdeiro, Maria Teresa

    2015-09-01

    The information that is available when marketing authorizations are approved is limited. Pharmacovigilance has an important role during the postauthorization period, and alerts published by national authorities allow health care professionals to be informed about new data on safety profiles. This study therefore sought to analyze all safety alerts published by the Portuguese National Authority of Medicines and Health Products I.P. (INFARMED). We conducted an observational study of all alerts published on the INFARMED website from January 2002 through December 2014. From the data included in the alerts, the following information was abstracted: active substance name (and trade name), event that led to the alert, and the resulting safety measures. Active substances were classified according to the Anatomical Therapeutic Chemical (ATC) code. A total of 562 alerts were published, and 304 were eligible for inclusion. The musculoskeletal system was the ATC code with more alerts (n = 53), followed by the nervous system (n = 42). Communication of the information and recommendations to the health care professionals and the public in general was the most frequent safety measure (n = 128), followed by changes in the Summary of the Product Characteristics and package information leaflet (n = 66). During the study period, 26 marketing authorizations were temporarily suspended and 10 were revoked. The knowledge of the alerts published during the postmarketing period is very useful to the health care professionals for improving prescription and use of medicines and to the scientific community for the development of new researches. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  7. Recent Updates to the MELCOR 1.8.2 Code for ITER Applications

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

    Merrill, Brad J

    This report documents recent changes made to the MELCOR 1.8.2 computer code for application to the International Thermonuclear Experimental Reactor (ITER), as required by ITER Task Agreement ITA 81-18. There are four areas of change documented by this report. The first area is the addition to this code of a model for transporting HTO. The second area is the updating of the material oxidation correlations to match those specified in the ITER Safety Analysis Data List (SADL). The third area replaces a modification to an aerosol tranpsort subroutine that specified the nominal aerosol density internally with one that now allowsmore » the user to specify this density through user input. The fourth area corrected an error that existed in an air condensation subroutine of previous versions of this modified MELCOR code. The appendices of this report contain FORTRAN listings of the coding for these modifications.« less

  8. Software Certification - Coding, Code, and Coders

    NASA Technical Reports Server (NTRS)

    Havelund, Klaus; Holzmann, Gerard J.

    2011-01-01

    We describe a certification approach for software development that has been adopted at our organization. JPL develops robotic spacecraft for the exploration of the solar system. The flight software that controls these spacecraft is considered to be mission critical. We argue that the goal of a software certification process cannot be the development of "perfect" software, i.e., software that can be formally proven to be correct under all imaginable and unimaginable circumstances. More realistically, the goal is to guarantee a software development process that is conducted by knowledgeable engineers, who follow generally accepted procedures to control known risks, while meeting agreed upon standards of workmanship. We target three specific issues that must be addressed in such a certification procedure: the coding process, the code that is developed, and the skills of the coders. The coding process is driven by standards (e.g., a coding standard) and tools. The code is mechanically checked against the standard with the help of state-of-the-art static source code analyzers. The coders, finally, are certified in on-site training courses that include formal exams.

  9. Discussion on LDPC Codes and Uplink Coding

    NASA Technical Reports Server (NTRS)

    Andrews, Ken; Divsalar, Dariush; Dolinar, Sam; Moision, Bruce; Hamkins, Jon; Pollara, Fabrizio

    2007-01-01

    This slide presentation reviews the progress that the workgroup on Low-Density Parity-Check (LDPC) for space link coding. The workgroup is tasked with developing and recommending new error correcting codes for near-Earth, Lunar, and deep space applications. Included in the presentation is a summary of the technical progress of the workgroup. Charts that show the LDPC decoder sensitivity to symbol scaling errors are reviewed, as well as a chart showing the performance of several frame synchronizer algorithms compared to that of some good codes and LDPC decoder tests at ESTL. Also reviewed is a study on Coding, Modulation, and Link Protocol (CMLP), and the recommended codes. A design for the Pseudo-Randomizer with LDPC Decoder and CRC is also reviewed. A chart that summarizes the three proposed coding systems is also presented.

  10. Construction safety program for the National Ignition Facility, July 30, 1999 (NIF-0001374-OC)

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

    Benjamin, D W

    1999-07-30

    These rules apply to all LLNL employees, non-LLNL employees (including contract labor, supplemental labor, vendors, personnel matrixed/assigned from other National Laboratories, participating guests, visitors and students) and contractors/subcontractors. The General Rules-Code of Safe Practices shall be used by management to promote accident prevention through indoctrination, safety and health training and on-the-job application. As a condition for contracts award, all contractors and subcontractors and their employees must certify on Form S and H A-l that they have read and understand, or have been briefed and understand, the National Ignition Facility OCIP Project General Rules-Code of Safe Practices. (An interpreter must briefmore » those employees who do not speak or read English fluently.) In addition, all contractors and subcontractors shall adopt a written General Rules-Code of Safe Practices that relates to their operations. The General Rules-Code of Safe Practices must be posted at a conspicuous location at the job site office or be provided to each supervisory employee who shall have it readily available. Copies of the General Rules-Code of Safe Practices can also be included in employee safety pamphlets.« less

  11. 75 FR 33696 - Safety Zone: July Firework Display in Captain of the Port, Puget Sound AOR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ...-AA00 Safety Zone: July Firework Display in Captain of the Port, Puget Sound AOR AGENCY: Coast Guard... Captain of the Port, Puget Sound AOR. (a) Safety Zone. The following area is a designated safety zone: all..., Captain of the Port, Puget Sound. [FR Doc. 2010-14294 Filed 6-14-10; 8:45 am] BILLING CODE 9110-04-P ...

  12. Globalization of ASME Nuclear Codes and Standards

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

    Swayne, Rick; Erler, Bryan A.

    2006-07-01

    With the globalization of the nuclear industry, it is clear that the reactor suppliers are based in many countries around the world (such as United States, France, Japan, Canada, South Korea, South Africa) and they will be marketing their reactors to many countries around the world (such as US, China, South Korea, France, Canada, Finland, Taiwan). They will also be fabricating their components in many different countries around the world. With this situation, it is clear that the requirements of ASME Nuclear Codes and Standards need to be adjusted to accommodate the regulations, fabricating processes, and technology of various countriesmore » around the world. It is also very important for the American Society of Mechanical Engineers (ASME) to be able to assure that products meeting the applicable ASME Code requirements will provide the same level of safety and quality assurance as those products currently fabricated under the ASME accreditation process. To do this, many countries are in the process of establishing or changing their regulations, and it is important for ASME to interface with the appropriate organizations in those countries, in order to ensure there is effective use of ASME Codes and standards around the world. (authors)« less

  13. Practices in Code Discoverability: Astrophysics Source Code Library

    NASA Astrophysics Data System (ADS)

    Allen, A.; Teuben, P.; Nemiroff, R. J.; Shamir, L.

    2012-09-01

    Here we describe the Astrophysics Source Code Library (ASCL), which takes an active approach to sharing astrophysics source code. ASCL's editor seeks out both new and old peer-reviewed papers that describe methods or experiments that involve the development or use of source code, and adds entries for the found codes to the library. This approach ensures that source codes are added without requiring authors to actively submit them, resulting in a comprehensive listing that covers a significant number of the astrophysics source codes used in peer-reviewed studies. The ASCL now has over 340 codes in it and continues to grow. In 2011, the ASCL has on average added 19 codes per month. An advisory committee has been established to provide input and guide the development and expansion of the new site, and a marketing plan has been developed and is being executed. All ASCL source codes have been used to generate results published in or submitted to a refereed journal and are freely available either via a download site or from an identified source. This paper provides the history and description of the ASCL. It lists the requirements for including codes, examines the advantages of the ASCL, and outlines some of its future plans.

  14. New quantum codes constructed from quaternary BCH codes

    NASA Astrophysics Data System (ADS)

    Xu, Gen; Li, Ruihu; Guo, Luobin; Ma, Yuena

    2016-10-01

    In this paper, we firstly study construction of new quantum error-correcting codes (QECCs) from three classes of quaternary imprimitive BCH codes. As a result, the improved maximal designed distance of these narrow-sense imprimitive Hermitian dual-containing quaternary BCH codes are determined to be much larger than the result given according to Aly et al. (IEEE Trans Inf Theory 53:1183-1188, 2007) for each different code length. Thus, families of new QECCs are newly obtained, and the constructed QECCs have larger distance than those in the previous literature. Secondly, we apply a combinatorial construction to the imprimitive BCH codes with their corresponding primitive counterpart and construct many new linear quantum codes with good parameters, some of which have parameters exceeding the finite Gilbert-Varshamov bound for linear quantum codes.

  15. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs) . Volume 2; Appendices

    NASA Technical Reports Server (NTRS)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This document contains the appendices to the main report.

  16. Perception of School Safety of a Local School

    ERIC Educational Resources Information Center

    Massey-Jones, Darla

    2013-01-01

    This qualitative case study investigated the perception of school safety, what current policies and procedures were effective, and what policies and procedures should be implemented. Data were collected in two steps, by survey and focus group interview. Analysis determined codes that revealed several themes relevant to the perception of school…

  17. Bayesian decision support for coding occupational injury data.

    PubMed

    Nanda, Gaurav; Grattan, Kathleen M; Chu, MyDzung T; Davis, Letitia K; Lehto, Mark R

    2016-06-01

    Studies on autocoding injury data have found that machine learning algorithms perform well for categories that occur frequently but often struggle with rare categories. Therefore, manual coding, although resource-intensive, cannot be eliminated. We propose a Bayesian decision support system to autocode a large portion of the data, filter cases for manual review, and assist human coders by presenting them top k prediction choices and a confusion matrix of predictions from Bayesian models. We studied the prediction performance of Single-Word (SW) and Two-Word-Sequence (TW) Naïve Bayes models on a sample of data from the 2011 Survey of Occupational Injury and Illness (SOII). We used the agreement in prediction results of SW and TW models, and various prediction strength thresholds for autocoding and filtering cases for manual review. We also studied the sensitivity of the top k predictions of the SW model, TW model, and SW-TW combination, and then compared the accuracy of the manually assigned codes to SOII data with that of the proposed system. The accuracy of the proposed system, assuming well-trained coders reviewing a subset of only 26% of cases flagged for review, was estimated to be comparable (86.5%) to the accuracy of the original coding of the data set (range: 73%-86.8%). Overall, the TW model had higher sensitivity than the SW model, and the accuracy of the prediction results increased when the two models agreed, and for higher prediction strength thresholds. The sensitivity of the top five predictions was 93%. The proposed system seems promising for coding injury data as it offers comparable accuracy and less manual coding. Accurate and timely coded occupational injury data is useful for surveillance as well as prevention activities that aim to make workplaces safer. Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.

  18. Running an ethical trial 60 years after the Nuremberg Code.

    PubMed

    Markman, Jonathan R; Markman, Maurie

    2007-12-01

    The Nuremberg Code has served as a foundation for ethical clinical research since its publication 60 years ago. This landmark document, developed in response to the horrors of human experimentation done by Nazi physicians and investigators, focused crucial attention on the fundamental rights of research participants and on the responsibilities of investigators. Although the Nuremberg Code has provided an important framework for discussions on the requirements of ethical clinical research, and has resulted in the development of other initiatives-eg, the Declaration of Helsinki and the Belmont Report-designed to ensure the rights and safety of human beings taking part in medical research, knowledge of both past events and the current complexity of research suggests further improvements are necessary in the existing approaches to human clinical research.

  19. Software Model Checking Without Source Code

    NASA Technical Reports Server (NTRS)

    Chaki, Sagar; Ivers, James

    2009-01-01

    We present a framework, called AIR, for verifying safety properties of assembly language programs via software model checking. AIR extends the applicability of predicate abstraction and counterexample guided abstraction refinement to the automated verification of low-level software. By working at the assembly level, AIR allows verification of programs for which source code is unavailable-such as legacy and COTS software-and programs that use features-such as pointers, structures, and object-orientation-that are problematic for source-level software verification tools. In addition, AIR makes no assumptions about the underlying compiler technology. We have implemented a prototype of AIR and present encouraging results on several non-trivial examples.

  20. 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

  1. Measure Guideline: Combustion Safety for Natural Draft Appliances Using Indoor Air

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

    Brand, L.

    2014-04-01

    This measure guideline covers how to assess and carry out the combustion safety procedures for appliances and heating equipment that uses indoor air for combustion in low-rise residential buildings. Only appliances installed in the living space, or in an area freely communicating with the living space, vented alone or in tandem with another appliance are considered here. A separate measure guideline addresses combustion appliances located either within the living space in enclosed closets or side rooms or outside the living space in an adjacent area like an attic or garage that use outdoor air for combustion. This document is formore » inspectors, auditors, and technicians working in homes where energy upgrades are being conducted whether or not air infiltration control is included in the package of measures being applied. In the indoor combustion air case, guidelines summarized here are based on language provided in several of the codes to establish minimum requirements for the space using simplified prescriptive measures. In addition, building performance testing procedures are provided by testing agencies. The codes in combination with the test procedures offer comprehensive combustion safety coverage to address safety concerns, allowing inexperienced residential energy retrofit inspectors to effectively address combustion safety issues and allow energy retrofits to proceed.« less

  2. Assessment of tissue allograft safety monitoring with administrative healthcare databases: a pilot project using Medicare data.

    PubMed

    Dhakal, Sanjaya; Burwen, Dale R; Polakowski, Laura L; Zinderman, Craig E; Wise, Robert P

    2014-03-01

    Assess whether Medicare data are useful for monitoring tissue allograft safety and utilization. We used health care claims (billing) data from 2007 for 35 million fee-for-service Medicare beneficiaries, a predominantly elderly population. Using search terms for transplant-related procedures, we generated lists of ICD-9-CM and CPT(®) codes and assessed the frequency of selected allograft procedures. Step 1 used inpatient data and ICD-9-CM procedure codes. Step 2 added non-institutional provider (e.g., physician) claims, outpatient institutional claims, and CPT codes. We assembled preliminary lists of diagnosis codes for infections after selected allograft procedures. Many ICD-9-CM codes were ambiguous as to whether the procedure involved an allograft. Among 1.3 million persons with a procedure ascertained using the list of ICD-9-CM codes, only 1,886 claims clearly involved an allograft. CPT codes enabled better ascertainment of some allograft procedures (over 17,000 persons had corneal transplants and over 2,700 had allograft skin transplants). For spinal fusion procedures, CPT codes improved specificity for allografts; of nearly 100,000 patients with ICD-9-CM codes for spinal fusions, more than 34,000 had CPT codes indicating allograft use. Monitoring infrequent events (infections) after infrequent exposures (tissue allografts) requires large study populations. A strength of the large Medicare databases is the substantial number of certain allograft procedures. Limitations include lack of clinical detail and donor information. Medicare data can potentially augment passive reporting systems and may be useful for monitoring tissue allograft safety and utilization where codes clearly identify allograft use and coding algorithms can effectively screen for infections.

  3. 76 FR 70414 - National Fire Protection Association (NFPA) Proposes To Revise Codes and Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... DEPARTMENT OF COMMERCE National Institute of Standards and Technology National Fire Protection... publishing this notice on behalf of the National Fire Protection Association (NFPA) to announce the NFPA's proposal to revise some of its fire safety codes and standards and requests proposals from the public to...

  4. Quantitative and Qualitative Analysis of Nutrition and Food Safety Information in School Science Textbooks of India

    ERIC Educational Resources Information Center

    Subba Rao, G. M.; Vijayapushapm, T.; Venkaiah, K.; Pavarala, V.

    2012-01-01

    Objective: To assess quantity and quality of nutrition and food safety information in science textbooks prescribed by the Central Board of Secondary Education (CBSE), India for grades I through X. Design: Content analysis. Methods: A coding scheme was developed for quantitative and qualitative analyses. Two investigators independently coded the…

  5. Fission yield and criticality excursion code

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

    Blanchard, A.

    2000-06-30

    The ANSI/ANS 8.3 standard allows a maximum yield not to exceed 2 x 10 fissions to calculate requiring the alarm system to be effective. It is common practice to use this allowance or to develop some other yield based on past criticality accident history or excursion experiments. The literature on the subject of yields discusses maximum yields larger and somewhat smaller than the ANS 8.3 permissive value. The ability to model criticality excursions and vary the various parameters to determine a credible maximum yield for operational specific cases has been available for some time but is not in common usemore » by criticality safety specialists. The topic of yields for various solution, metal, oxide powders, etc. in various geometry's and containers has been published by laboratory specialists or university staff and students for many decades but have not been available to practitioners. The need for best-estimate calculations of fission yields with a well-validated criticality excursion code has long been recognized. But no coordinated effort has been made so far to develop a generalized and well-validated excursion code for different types of systems. In this paper, the current practices to estimate fission yields are summarized along with its shortcomings for the 12-Rad zone (at SRS) and Criticality Alarm System (CAS) calculations. Finally the need for a user-friendly excursion code is reemphasized.« less

  6. Development of an integrated thermal-hydraulics capability incorporating RELAP5 and PANTHER neutronics code

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

    Page, R.; Jones, J.R.

    1997-07-01

    Ensuring that safety analysis needs are met in the future is likely to lead to the development of new codes and the further development of existing codes. It is therefore advantageous to define standards for data interfaces and to develop software interfacing techniques which can readily accommodate changes when they are made. Defining interface standards is beneficial but is necessarily restricted in application if future requirements are not known in detail. Code interfacing methods are of particular relevance with the move towards automatic grid frequency response operation where the integration of plant dynamic, core follow and fault study calculation toolsmore » is considered advantageous. This paper describes the background and features of a new code TALINK (Transient Analysis code LINKage program) used to provide a flexible interface to link the RELAP5 thermal hydraulics code with the PANTHER neutron kinetics and the SIBDYM whole plant dynamic modelling codes used by Nuclear Electric. The complete package enables the codes to be executed in parallel and provides an integrated whole plant thermal-hydraulics and neutron kinetics model. In addition the paper discusses the capabilities and pedigree of the component codes used to form the integrated transient analysis package and the details of the calculation of a postulated Sizewell `B` Loss of offsite power fault transient.« less

  7. Discrimination of Stem Cell Status after Subjecting Cynomolgus Monkey Pluripotent Stem Cells to Naïve Conversion

    PubMed Central

    Honda, Arata; Kawano, Yoshihiro; Izu, Haruna; Choijookhuu, Narantsog; Honsho, Kimiko; Nakamura, Tomonori; Yabuta, Yukihiro; Yamamoto, Takuya; Takashima, Yasuhiro; Hirose, Michiko; Sankai, Tadashi; Hishikawa, Yoshitaka; Ogura, Atsuo; Saitou, Mitinori

    2017-01-01

    Experimental animal models have played an indispensable role in the development of human induced pluripotent stem cell (iPSC) research. The derivation of high-quality (so-called “true naïve state”) iPSCs of non-human primates enhances their application and safety for human regenerative medicine. Although several attempts have been made to convert human and non-human primate PSCs into a truly naïve state, it is unclear which evaluation methods can discriminate them as being truly naïve. Here we attempted to derive naïve cynomolgus monkey (Cm) (Macaca fascicularis) embryonic stem cells (ESCs) and iPSCs. Several characteristics of naïve Cm ESCs including colony morphology, appearance of naïve-related mRNAs and proteins, leukaemia inhibitory factor dependency, and mitochondrial respiration were confirmed. Next, we generated Cm iPSCs and converted them to a naïve state. Transcriptomic comparison of PSCs with early Cm embryos elucidated the partial achievement (termed naïve-like) of their conversion. When these were subjected to in vitro neural differentiation, enhanced differentiating capacities were observed after naïve-like conversion, but some lines exhibited heterogeneity. The difficulty of achieving contribution to chimeric mouse embryos was also demonstrated. These results suggest that Cm PSCs could ameliorate their in vitro neural differentiation potential even though they could not display true naïve characteristics. PMID:28349944

  8. Low Density Parity Check Codes: Bandwidth Efficient Channel Coding

    NASA Technical Reports Server (NTRS)

    Fong, Wai; Lin, Shu; Maki, Gary; Yeh, Pen-Shu

    2003-01-01

    Low Density Parity Check (LDPC) Codes provide near-Shannon Capacity performance for NASA Missions. These codes have high coding rates R=0.82 and 0.875 with moderate code lengths, n=4096 and 8176. Their decoders have inherently parallel structures which allows for high-speed implementation. Two codes based on Euclidean Geometry (EG) were selected for flight ASIC implementation. These codes are cyclic and quasi-cyclic in nature and therefore have a simple encoder structure. This results in power and size benefits. These codes also have a large minimum distance as much as d,,, = 65 giving them powerful error correcting capabilities and error floors less than lo- BER. This paper will present development of the LDPC flight encoder and decoder, its applications and status.

  9. LNG Safety Research: FEM3A Model Development

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

    Iraj A. Salehi

    This quarterly report for DE-FG26-04NT42030 covers a period from July 1, 2004 to September 30, 2004. Activity during this period included preparation of a CD containing the FEM3a FORTRAN code for distribution and organization of an LNG safety workshop. Contract negotiation between GTI and University of Arkansas continued.

  10. 75 FR 37310 - Health and Safety Data Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 716 Health and Safety Data Reporting CFR Correction In Title 40 of the Code of Federal Regulations, Parts 700 to 789, revised as of July 1, 2009, make the following corrections: 1. At the bottom of page 86, in Sec. 716.20, paragraph (a) introductory text, in the...

  11. Guide for the Development of Safety Assessment Report (SAR)

    DTIC Science & Technology

    1987-08-01

    Di ’:t ib ityioe I A,;!i~abiiity Codes Dist SpdIt ora bloe INSia OEapy r TABLE OF CONTENTS PAGE III SAFETY ASSESSMENT REPORT...above. Potential hazards associated with the maintenance of the turbine engine (i.e., use of cleaning agents ) are not addressed .in the accompanying

  12. Error-correction coding

    NASA Technical Reports Server (NTRS)

    Hinds, Erold W. (Principal Investigator)

    1996-01-01

    This report describes the progress made towards the completion of a specific task on error-correcting coding. The proposed research consisted of investigating the use of modulation block codes as the inner code of a concatenated coding system in order to improve the overall space link communications performance. The study proposed to identify and analyze candidate codes that will complement the performance of the overall coding system which uses the interleaved RS (255,223) code as the outer code.

  13. TEMPEST code modifications and testing for erosion-resisting sludge simulations

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

    Onishi, Y.; Trent, D.S.

    The TEMPEST computer code has been used to address many waste retrieval operational and safety questions regarding waste mobilization, mixing, and gas retention. Because the amount of sludge retrieved from the tank is directly related to the sludge yield strength and the shear stress acting upon it, it is important to incorporate the sludge yield strength into simulations of erosion-resisting tank waste retrieval operations. This report describes current efforts to modify the TEMPEST code to simulate pump jet mixing of erosion-resisting tank wastes and the models used to test for erosion of waste sludge with yield strength. Test results formore » solid deposition and diluent/slurry jet injection into sludge layers in simplified tank conditions show that the modified TEMPEST code has a basic ability to simulate both the mobility and immobility of the sludges with yield strength. Further testing, modification, calibration, and verification of the sludge mobilization/immobilization model are planned using erosion data as they apply to waste tank sludges.« less

  14. Improvements and applications of COBRA-TF for stand-alone and coupled LWR safety analyses

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

    Avramova, M.; Cuervo, D.; Ivanov, K.

    2006-07-01

    The advanced thermal-hydraulic subchannel code COBRA-TF has been recently improved and applied for stand-alone and coupled LWR core calculations at the Pennsylvania State Univ. in cooperation with AREVA NP GmbH (Germany)) and the Technical Univ. of Madrid. To enable COBRA-TF for academic and industrial applications including safety margins evaluations and LWR core design analyses, the code programming, numerics, and basic models were revised and substantially improved. The code has undergone through an extensive validation, verification, and qualification program. (authors)

  15. Error correcting coding-theory for structured light illumination systems

    NASA Astrophysics Data System (ADS)

    Porras-Aguilar, Rosario; Falaggis, Konstantinos; Ramos-Garcia, Ruben

    2017-06-01

    Intensity discrete structured light illumination systems project a series of projection patterns for the estimation of the absolute fringe order using only the temporal grey-level sequence at each pixel. This work proposes the use of error-correcting codes for pixel-wise correction of measurement errors. The use of an error correcting code is advantageous in many ways: it allows reducing the effect of random intensity noise, it corrects outliners near the border of the fringe commonly present when using intensity discrete patterns, and it provides a robustness in case of severe measurement errors (even for burst errors where whole frames are lost). The latter aspect is particular interesting in environments with varying ambient light as well as in critical safety applications as e.g. monitoring of deformations of components in nuclear power plants, where a high reliability is ensured even in case of short measurement disruptions. A special form of burst errors is the so-called salt and pepper noise, which can largely be removed with error correcting codes using only the information of a given pixel. The performance of this technique is evaluated using both simulations and experiments.

  16. Rate-compatible punctured convolutional codes (RCPC codes) and their applications

    NASA Astrophysics Data System (ADS)

    Hagenauer, Joachim

    1988-04-01

    The concept of punctured convolutional codes is extended by punctuating a low-rate 1/N code periodically with period P to obtain a family of codes with rate P/(P + l), where l can be varied between 1 and (N - 1)P. A rate-compatibility restriction on the puncturing tables ensures that all code bits of high rate codes are used by the lower-rate codes. This allows transmission of incremental redundancy in ARQ/FEC (automatic repeat request/forward error correction) schemes and continuous rate variation to change from low to high error protection within a data frame. Families of RCPC codes with rates between 8/9 and 1/4 are given for memories M from 3 to 6 (8 to 64 trellis states) together with the relevant distance spectra. These codes are almost as good as the best known general convolutional codes of the respective rates. It is shown that the same Viterbi decoder can be used for all RCPC codes of the same M. The application of RCPC codes to hybrid ARQ/FEC schemes is discussed for Gaussian and Rayleigh fading channels using channel-state information to optimize throughput.

  17. Current and anticipated uses of the thermal hydraulics codes at the NRC

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

    Caruso, R.

    1997-07-01

    The focus of Thermal-Hydraulic computer code usage in nuclear regulatory organizations has undergone a considerable shift since the codes were originally conceived. Less work is being done in the area of {open_quotes}Design Basis Accidents,{close_quotes}, and much more emphasis is being placed on analysis of operational events, probabalistic risk/safety assessment, and maintenance practices. All of these areas need support from Thermal-Hydraulic computer codes to model the behavior of plant fluid systems, and they all need the ability to perform large numbers of analyses quickly. It is therefore important for the T/H codes of the future to be able to support thesemore » needs, by providing robust, easy-to-use, tools that produce easy-to understand results for a wider community of nuclear professionals. These tools need to take advantage of the great advances that have occurred recently in computer software, by providing users with graphical user interfaces for both input and output. In addition, reduced costs of computer memory and other hardware have removed the need for excessively complex data structures and numerical schemes, which make the codes more difficult and expensive to modify, maintain, and debug, and which increase problem run-times. Future versions of the T/H codes should also be structured in a modular fashion, to allow for the easy incorporation of new correlations, models, or features, and to simplify maintenance and testing. Finally, it is important that future T/H code developers work closely with the code user community, to ensure that the code meet the needs of those users.« less

  18. Amino acid codes in mitochondria as possible clues to primitive codes

    NASA Technical Reports Server (NTRS)

    Jukes, T. H.

    1981-01-01

    Differences between mitochondrial codes and the universal code indicate that an evolutionary simplification has taken place, rather than a return to a more primitive code. However, these differences make it evident that the universal code is not the only code possible, and therefore earlier codes may have differed markedly from the previous code. The present universal code is probably a 'frozen accident.' The change in CUN codons from leucine to threonine (Neurospora vs. yeast mitochondria) indicates that neutral or near-neutral changes occurred in the corresponding proteins when this code change took place, caused presumably by a mutation in a tRNA gene.

  19. ASME code considerations for the compact heat exchanger

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

    Nestell, James; Sham, Sam

    2015-08-31

    robustness. Classic shell and tube designs will be large and costly, and may only be appropriate in steam generator service in the SHX where boiling inside the tubes occurs. For other energy conversion systems, all of these features can be met in a compact heat exchanger design. This report will examine some of the ASME Code issues that will need to be addressed to allow use of a Code-qualified compact heat exchanger in IHX or SHX nuclear service. Most effort will focus on the IHX, since the safety-related (Class A) design rules are more extensive than those for important-to-safety (Class B) or commercial rules that are relevant to the SHX.« less

  20. Energy efficient rateless codes for high speed data transfer over free space optical channels

    NASA Astrophysics Data System (ADS)

    Prakash, Geetha; Kulkarni, Muralidhar; Acharya, U. S.

    2015-03-01

    Terrestrial Free Space Optical (FSO) links transmit information by using the atmosphere (free space) as a medium. In this paper, we have investigated the use of Luby Transform (LT) codes as a means to mitigate the effects of data corruption induced by imperfect channel which usually takes the form of lost or corrupted packets. LT codes, which are a class of Fountain codes, can be used independent of the channel rate and as many code words as required can be generated to recover all the message bits irrespective of the channel performance. Achieving error free high data rates with limited energy resources is possible with FSO systems if error correction codes with minimal overheads on the power can be used. We also employ a combination of Binary Phase Shift Keying (BPSK) with provision for modification of threshold and optimized LT codes with belief propagation for decoding. These techniques provide additional protection even under strong turbulence regimes. Automatic Repeat Request (ARQ) is another method of improving link reliability. Performance of ARQ is limited by the number of retransmissions and the corresponding time delay. We prove through theoretical computations and simulations that LT codes consume less energy per bit. We validate the feasibility of using energy efficient LT codes over ARQ for FSO links to be used in optical wireless sensor networks within the eye safety limits.

  1. 77 FR 61513 - Information Disclosure Under Section 6(b) of the Consumer Product Safety Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-10

    ... CONSUMER PRODUCT SAFETY COMMISSION 16 CFR Part 1101 Information Disclosure Under Section 6(b) of the Consumer Product Safety Act CFR Correction 0 In Title 16 of the Code of Federal Regulations, Part 1000 to End, revised as of January 1, 2012, on page 147, in Sec. 1101.25 (a) and (b), the words ``5...

  2. Analysis of quantum error-correcting codes: Symplectic lattice codes and toric codes

    NASA Astrophysics Data System (ADS)

    Harrington, James William

    Quantum information theory is concerned with identifying how quantum mechanical resources (such as entangled quantum states) can be utilized for a number of information processing tasks, including data storage, computation, communication, and cryptography. Efficient quantum algorithms and protocols have been developed for performing some tasks (e.g. , factoring large numbers, securely communicating over a public channel, and simulating quantum mechanical systems) that appear to be very difficult with just classical resources. In addition to identifying the separation between classical and quantum computational power, much of the theoretical focus in this field over the last decade has been concerned with finding novel ways of encoding quantum information that are robust against errors, which is an important step toward building practical quantum information processing devices. In this thesis I present some results on the quantum error-correcting properties of oscillator codes (also described as symplectic lattice codes) and toric codes. Any harmonic oscillator system (such as a mode of light) can be encoded with quantum information via symplectic lattice codes that are robust against shifts in the system's continuous quantum variables. I show the existence of lattice codes whose achievable rates match the one-shot coherent information over the Gaussian quantum channel. Also, I construct a family of symplectic self-dual lattices and search for optimal encodings of quantum information distributed between several oscillators. Toric codes provide encodings of quantum information into two-dimensional spin lattices that are robust against local clusters of errors and which require only local quantum operations for error correction. Numerical simulations of this system under various error models provide a calculation of the accuracy threshold for quantum memory using toric codes, which can be related to phase transitions in certain condensed matter models. I also present

  3. Technology Infusion of CodeSonar into the Space Network Ground Segment (RII07)

    NASA Technical Reports Server (NTRS)

    Benson, Markland

    2008-01-01

    The NASA Software Assurance Research Program (in part) performs studies as to the feasibility of technologies for improving the safety, quality, reliability, cost, and performance of NASA software. This study considers the application of commercial automated source code analysis tools to mission critical ground software that is in the operations and sustainment portion of the product lifecycle.

  4. Revenue sources for financing transportation safety activities in Virginia : phase three, feasibility of a surcharge on traffic fines.

    DOT National Transportation Integrated Search

    1981-01-01

    Senate Bill 85, an action of the 1978 General Assembly, amended the Code of Virginia to provide, in part, that the Division of Highway Safety be succeeded by the newly created Department of Transportation Safety effective July 1, 1978. In its Declara...

  5. The ADVANCE Code of Conduct for collaborative vaccine studies.

    PubMed

    Kurz, Xavier; Bauchau, Vincent; Mahy, Patrick; Glismann, Steffen; van der Aa, Lieke Maria; Simondon, François

    2017-04-04

    Lessons learnt from the 2009 (H1N1) flu pandemic highlighted factors limiting the capacity to collect European data on vaccine exposure, safety and effectiveness, including lack of rapid access to available data sources or expertise, difficulties to establish efficient interactions between multiple parties, lack of confidence between private and public sectors, concerns about possible or actual conflicts of interest (or perceptions thereof) and inadequate funding mechanisms. The Innovative Medicines Initiative's Accelerated Development of VAccine benefit-risk Collaboration in Europe (ADVANCE) consortium was established to create an efficient and sustainable infrastructure for rapid and integrated monitoring of post-approval benefit-risk of vaccines, including a code of conduct and governance principles for collaborative studies. The development of the code of conduct was guided by three core and common values (best science, strengthening public health, transparency) and a review of existing guidance and relevant published articles. The ADVANCE Code of Conduct includes 45 recommendations in 10 topics (Scientific integrity, Scientific independence, Transparency, Conflicts of interest, Study protocol, Study report, Publication, Subject privacy, Sharing of study data, Research contract). Each topic includes a definition, a set of recommendations and a list of additional reading. The concept of the study team is introduced as a key component of the ADVANCE Code of Conduct with a core set of roles and responsibilities. It is hoped that adoption of the ADVANCE Code of Conduct by all partners involved in a study will facilitate and speed-up its initiation, design, conduct and reporting. Adoption of the ADVANCE Code of Conduct should be stated in the study protocol, study report and publications and journal editors are encouraged to use it as an indication that good principles of public health, science and transparency were followed throughout the study. Copyright © 2017

  6. Number of minimum-weight code words in a product code

    NASA Technical Reports Server (NTRS)

    Miller, R. L.

    1978-01-01

    Consideration is given to the number of minimum-weight code words in a product code. The code is considered as a tensor product of linear codes over a finite field. Complete theorems and proofs are presented.

  7. Capabilities needed for the next generation of thermo-hydraulic codes for use in real time applications

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

    Arndt, S.A.

    1997-07-01

    The real-time reactor simulation field is currently at a crossroads in terms of the capability to perform real-time analysis using the most sophisticated computer codes. Current generation safety analysis codes are being modified to replace simplified codes that were specifically designed to meet the competing requirement for real-time applications. The next generation of thermo-hydraulic codes will need to have included in their specifications the specific requirement for use in a real-time environment. Use of the codes in real-time applications imposes much stricter requirements on robustness, reliability and repeatability than do design and analysis applications. In addition, the need for codemore » use by a variety of users is a critical issue for real-time users, trainers and emergency planners who currently use real-time simulation, and PRA practitioners who will increasingly use real-time simulation for evaluating PRA success criteria in near real-time to validate PRA results for specific configurations and plant system unavailabilities.« less

  8. Code Status Reconciliation to Improve Identification and Documentation of Code Status in Electronic Health Records.

    PubMed

    Jain, Viral G; Greco, Peter J; Kaelber, David C

    2017-03-08

    Code status (CS) of a patient (part of their end-of-life wishes) can be critical information in healthcare delivery, which can change over time, especially at transitions of care. Although electronic health record (EHR) tools exist for medication reconciliation across transitions of care, much less attention is given to CS, and standard EHR tools have not been implemented for CS reconciliation (CSR). Lack of CSR creates significant potential patient safety and quality of life issues. To study the tools, workflow, and impact of clinical decision support (CDS) for CSR. We established rules for CS implementation in our EHR. At admission, a CS is required as part of a patient's admission order set. Using standard CDS tools in our EHR, we built an interruptive alert for CSR at discharge if a patient did not have the same inpatient (current) CS at discharge as that prior to admission CS. Of 80,587 admissions over a four year period (2 years prior to and post CSR implementation), CS discordance was seen in 3.5% of encounters which had full code status prior to admission, but Do Not Resuscitate (DNR) CS at discharge. In addition, 1.4% of the encounters had a different variant of the DNR CS at discharge when compared with CS prior to admission. On pre-post CSR implementation analysis, DNR CS per 1000 admissions per month increased significantly among patients discharged and in patients being admitted (mean ± SD: 85.36 ± 13.69 to 399.85 ± 182.86, p<0.001; and 1.99 ± 1.37 vs 16.70 ± 4.51, p<0.001, respectively). EHR enabled CSR is effective and represents a significant informatics opportunity to help honor patients' end-of-life wishes. CSR represents one example of non-medication reconciliation at transitions of care that should be considered in all EHRs to improve care quality and patient safety.

  9. Patient safety awareness among Undergraduate Medical Students in Pakistani Medical School.

    PubMed

    Kamran, Rizwana; Bari, Attia; Khan, Rehan Ahmed; Al-Eraky, Mohamed

    2018-01-01

    To measure the level of awareness of patient safety among undergraduate medical students in Pakistani Medical School and to find the difference with respect to gender and prior experience with medical error. This cross-sectional study was conducted at the University of Lahore (UOL), Pakistan from January to March 2017, and comprised final year medical students. Data was collected using a questionnaire 'APSQ- III' on 7 point Likert scale. Eight questions were reverse coded. Survey was anonymous. SPSS package 20 was used for statistical analysis. Questionnaire was filled by 122 students, with 81% response rate. The best score 6.17 was given for the 'team functioning', followed by 6.04 for 'long working hours as a cause of medical error'. The domains regarding involvement of patient, confidence to report medical errors and role of training and learning on patient safety scored high in the agreed range of >5. Reverse coded questions about 'professional incompetence as an error cause' and 'disclosure of errors' showed negative perception. No significant differences of perceptions were found with respect to gender and prior experience with medical error (p= >0.05). Undergraduate medical students at UOL had a positive attitude towards patient safety. However, there were misconceptions about causes of medical errors and error disclosure among students and patient safety education needs to be incorporated in medical curriculum of Pakistan.

  10. Safety Identifying of Integral Abutment Bridges under Seismic and Thermal Loads

    PubMed Central

    Easazadeh Far, Narges; Barghian, Majid

    2014-01-01

    Integral abutment bridges (IABs) have many advantages over conventional bridges in terms of strength and maintenance cost. Due to the integrity of these structures uniform thermal and seismic loads are known important ones on the structure performance. Although all bridge design codes consider temperature and earthquake loads separately in their load combinations for conventional bridges, the thermal load is an “always on” load and, during the occurrence of an earthquake, these two important loads act on bridge simultaneously. Evaluating the safety level of IABs under combination of these loads becomes important. In this paper, the safety of IABs—designed by AASHTO LRFD bridge design code—under combination of thermal and seismic loads is studied. To fulfill this aim, first the target reliability indexes under seismic load have been calculated. Then, these analyses for the same bridge under combination of thermal and seismic loads have been repeated and the obtained reliability indexes are compared with target indexes. It is shown that, for an IAB designed by AASHTO LRFD, the indexes have been reduced under combined effects. So, the target level of safety during its design life is not provided and the code's load combination should be changed. PMID:25405232

  11. [Topics of occupational medicine and environment in codes and social accountability standards of business].

    PubMed

    Denisov, E I; Golovaneva, G V; Potapenko, A A

    2005-01-01

    The problems of social accountability as applied to the occupational safety, health and environment are discussed. Russian and international codes and standards in the field are reviewed. Legal duties and rights of employers in occupational risk management for workers' health are considered. Some ethical aspects including health protection of female workers are discussed.

  12. The Role of Leadership in Safety Performance and Results

    NASA Astrophysics Data System (ADS)

    Caravello, Halina E.

    Employee injury rates in U.S. land-based operations in the energy industry are 2 to 3 times higher relative to other regions in the world. Although a rich literature exists on drivers of safety performance, no previous studies investigated factors influencing this elevated rate. Leadership has been identified as a key contributor to safety outcomes and this grounded theory study drew upon the full range leadership model, situational leadership, and leader-member exchange theories for the conceptual framework. Leadership aspects influencing safety performance were investigated through guided interviews of 27 study participants; data analyses included open and axial coding, and constant comparisons identified higher-level categories. Selective coding integrated categories into the theoretical framework that developed the idealized, transformational leader traits motivating safe behaviors of leading by example, expressing care and concern for employees' well-being, celebrating successes, and communicating the importance of safety (other elements included visibility and commitment). Employee and supervisor participants reported similar views on the idealized leader traits, but low levels of these qualities may be driving elevated injury rates. Identifying these key elements provides the foundation to creating strategies and action plans enabling energy sector companies to prevent employee injuries and fatalities in an industry where tens of thousands of employees are subjected to significant hazards and elevated risks. Creating safer workplaces for U.S. employees by enhancing leaders' skills, building knowledge, and improving behaviors will improve the employees' and their families' lives by reducing the pain and suffering resulting from injuries and fatalities.

  13. Uplink Coding

    NASA Technical Reports Server (NTRS)

    Pollara, Fabrizio; Hamkins, Jon; Dolinar, Sam; Andrews, Ken; Divsalar, Dariush

    2006-01-01

    This viewgraph presentation reviews uplink coding. The purpose and goals of the briefing are (1) Show a plan for using uplink coding and describe benefits (2) Define possible solutions and their applicability to different types of uplink, including emergency uplink (3) Concur with our conclusions so we can embark on a plan to use proposed uplink system (4) Identify the need for the development of appropriate technology and infusion in the DSN (5) Gain advocacy to implement uplink coding in flight projects Action Item EMB04-1-14 -- Show a plan for using uplink coding, including showing where it is useful or not (include discussion of emergency uplink coding).

  14. An Innovative Hybrid Loop-Pool SFR Design and Safety Analysis Methods: Today and Tomorrow

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

    Hongbin Zhang; Haihua Zhao; Vincent Mousseau

    2008-04-01

    Investment in commercial sodium cooled fast reactor (SFR) power plants will become possible only if SFRs achieve economic competitiveness as compared to light water reactors and other Generation IV reactors. Toward that end, we have launched efforts to improve the economics and safety of SFRs from the thermal design and safety analyses perspectives at Idaho National Laboratory. From the thermal design perspective, an innovative hybrid loop-pool SFR design has been proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to further improve economics and safety. From the safety analysesmore » perspective, we have initiated an effort to develop a high fidelity reactor system safety code.« less

  15. Multiple component codes based generalized LDPC codes for high-speed optical transport.

    PubMed

    Djordjevic, Ivan B; Wang, Ting

    2014-07-14

    A class of generalized low-density parity-check (GLDPC) codes suitable for optical communications is proposed, which consists of multiple local codes. It is shown that Hamming, BCH, and Reed-Muller codes can be used as local codes, and that the maximum a posteriori probability (MAP) decoding of these local codes by Ashikhmin-Lytsin algorithm is feasible in terms of complexity and performance. We demonstrate that record coding gains can be obtained from properly designed GLDPC codes, derived from multiple component codes. We then show that several recently proposed classes of LDPC codes such as convolutional and spatially-coupled codes can be described using the concept of GLDPC coding, which indicates that the GLDPC coding can be used as a unified platform for advanced FEC enabling ultra-high speed optical transport. The proposed class of GLDPC codes is also suitable for code-rate adaption, to adjust the error correction strength depending on the optical channel conditions.

  16. Image processing for safety assessment in civil engineering.

    PubMed

    Ferrer, Belen; Pomares, Juan C; Irles, Ramon; Espinosa, Julian; Mas, David

    2013-06-20

    Behavior analysis of construction safety systems is of fundamental importance to avoid accidental injuries. Traditionally, measurements of dynamic actions in civil engineering have been done through accelerometers, but high-speed cameras and image processing techniques can play an important role in this area. Here, we propose using morphological image filtering and Hough transform on high-speed video sequence as tools for dynamic measurements on that field. The presented method is applied to obtain the trajectory and acceleration of a cylindrical ballast falling from a building and trapped by a thread net. Results show that safety recommendations given in construction codes can be potentially dangerous for workers.

  17. Gorlin syndrome-derived induced pluripotent stem cells are hypersensitive to hedgehog-mediated osteogenic induction.

    PubMed

    Hasegawa, Daigo; Ochiai-Shino, Hiromi; Onodera, Shoko; Nakamura, Takashi; Saito, Akiko; Onda, Takeshi; Watanabe, Katsuhito; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Kosaki, Kenjiro; Yamaguchi, Akira; Shibahara, Takahiko; Azuma, Toshifumi

    2017-01-01

    Gorlin syndrome is an autosomal dominant inherited syndrome that predisposes a patient to the formation of basal cell carcinomas, odontogenic keratocysts, and skeletal anomalies. Causative mutations in several genes associated with the sonic hedgehog (SHH) signaling pathway, including PTCH1, have been identified in Gorlin syndrome patients. However, no definitive genotype-phenotype correlations are evident in these patients, and their clinical presentation varies greatly, often leading to delayed diagnosis and treatment. We generated iPSCs from four unrelated Gorlin syndrome patients with loss-of-function mutations in PTCH1 using the Sendai virus vector (SeVdp(KOSM)302). The patient-derived iPSCs exhibited basic iPSC features, including stem cell marker expression, totipotency, and the ability to form teratomas. GLI1 expression levels were greater in fibroblasts and patient-derived iPSCs than in the corresponding control cells. Patient-derived iPSCs expressed lower basal levels than control iPSCs of the genes encoding the Hh ligands Indian Hedgehog (IHH) and SHH, the Hh acetyltransferase HHAT, Wnt proteins, BMP4, and BMP6. Most of these genes were upregulated in patient-derived iPSCs grown in osteoblast differentiation medium (OBM) and downregulated in control iPSCs cultured in OBM. The expression of GLI1 and GLI2 substantially decreased in both control and patient-derived iPSCs cultured in OBM, whereas GLI3, SHH, and IHH were upregulated in patient-derived iPSCs and downregulated in control iPSCs grown in OBM. Activation of Smoothened by SAG in cells grown in OBM significantly enhanced alkaline phosphatase activity in patient-derived iPSCs compared with control iPSC lines. In summary, patient-derived iPSCs expressed lower basal levels than the control iPSCs of the genes encoding Hh, Wnt, and bone morphogenetic proteins, but their expression of these genes strongly increased under osteogenic conditions. These findings indicate that patient-derived iPSCs are

  18. Sustaining engineering codes of ethics for the twenty-first century.

    PubMed

    Michelfelder, Diane; Jones, Sharon A

    2013-03-01

    How much responsibility ought a professional engineer to have with regard to supporting basic principles of sustainable development? While within the United States, professional engineering societies, as reflected in their codes of ethics, differ in their responses to this question, none of these professional societies has yet to put the engineer's responsibility toward sustainability on a par with commitments to public safety, health, and welfare. In this paper, we aim to suggest that sustainability should be included in the paramountcy clause because it is a necessary condition to ensure the safety, health, and welfare of the public. Part of our justification rests on the fact that to engineer sustainably means among many things to consider social justice, understood as the fair and equitable distribution of social goods, as a design constraint similar to technical, economic, and environmental constraints. This element of social justice is not explicit in the current paramountcy clause. Our argument rests on demonstrating that social justice in terms of both inter- and intra-generational equity is an important dimension of sustainability (and engineering). We also propose that embracing sustainability in the codes while recognizing the role that social justice plays may elevate the status of the engineer as public intellectual and agent of social good. This shift will then need to be incorporated in how we teach undergraduate engineering students about engineering ethics.

  19. Shielding calculation and criticality safety analysis of spent fuel transportation cask in research reactors.

    PubMed

    Mohammadi, A; Hassanzadeh, M; Gharib, M

    2016-02-01

    In this study, shielding calculation and criticality safety analysis were carried out for general material testing reactor (MTR) research reactors interim storage and relevant transportation cask. During these processes, three major terms were considered: source term, shielding, and criticality calculations. The Monte Carlo transport code MCNP5 was used for shielding calculation and criticality safety analysis and ORIGEN2.1 code for source term calculation. According to the results obtained, a cylindrical cask with body, top, and bottom thicknesses of 18, 13, and 13 cm, respectively, was accepted as the dual-purpose cask. Furthermore, it is shown that the total dose rates are below the normal transport criteria that meet the standards specified. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Model Children's Code.

    ERIC Educational Resources Information Center

    New Mexico Univ., Albuquerque. American Indian Law Center.

    The Model Children's Code was developed to provide a legally correct model code that American Indian tribes can use to enact children's codes that fulfill their legal, cultural and economic needs. Code sections cover the court system, jurisdiction, juvenile offender procedures, minor-in-need-of-care, and termination. Almost every Code section is…

  1. Coding "We-ness" in couple's relationship stories: A method for assessing mutuality in couple therapy.

    PubMed

    Gildersleeve, Sara; Singer, Jefferson A; Skerrett, Karen; Wein, Shelter

    2017-05-01

    "We-ness," a couple's mutual investment in their relationship and in each other, has been found to be a potent dimension of couple resilience. This study examined the development of a method to capture We-ness in psychotherapy through the coding of relationship narratives co-constructed by couples ("We-Stories"). It used a coding system to identify the core thematic elements that make up these narratives. Couples that self-identified as "happy" (N = 53) generated We-Stories and completed measures of relationship satisfaction and mutuality. These stories were then coded using the We-Stories coding manual. Findings indicated that security, an element that involves aspects of safety, support, and commitment, was most common, appearing in 58.5% of all narratives. This element was followed by the elements of pleasure (49.1%) and shared meaning/vision (37.7%). The number of "We-ness" elements was also correlated with and predictive of discrepancy scores on measures of relationship mutuality, indicating the validity of the We-Stories coding manual. Limitations and future directions are discussed.

  2. New quantum codes derived from a family of antiprimitive BCH codes

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Li, Ruihu; Lü, Liangdong; Guo, Luobin

    The Bose-Chaudhuri-Hocquenghem (BCH) codes have been studied for more than 57 years and have found wide application in classical communication system and quantum information theory. In this paper, we study the construction of quantum codes from a family of q2-ary BCH codes with length n=q2m+1 (also called antiprimitive BCH codes in the literature), where q≥4 is a power of 2 and m≥2. By a detailed analysis of some useful properties about q2-ary cyclotomic cosets modulo n, Hermitian dual-containing conditions for a family of non-narrow-sense antiprimitive BCH codes are presented, which are similar to those of q2-ary primitive BCH codes. Consequently, via Hermitian Construction, a family of new quantum codes can be derived from these dual-containing BCH codes. Some of these new antiprimitive quantum BCH codes are comparable with those derived from primitive BCH codes.

  3. Promoting personal safety of building service workers: issues and challenges.

    PubMed

    Chen, Shelley I; Skillen, D Lynn

    2006-06-01

    This exploratory, descriptive study conducted at a large western Canadian university solicited perceptions of personal safety among building service workers who perform night shift work alone. Ten semi-structured interviews were conducted at approximately 10:00 p.m. or 7:00 a.m with a convenience sample of night building service workers in private or semi-private locations on the university campus. Transcribed interview data were subjected to inductive content analysis using descriptive, interpretive, and pattern coding (Miles & Huberman, 1994). Results suggest that building service night shift workers are exposed to personal safety hazards in their physical and psychosocial work environments. In addition, culturally and linguistically appropriate delivery of safety training and education about policies and procedures is required for culturally diverse building service workers. Promotion of personal safety in this heterogeneous worker population requires due diligence, assessment, and advocacy.

  4. Surface acoustic wave coding for orthogonal frequency coded devices

    NASA Technical Reports Server (NTRS)

    Malocha, Donald (Inventor); Kozlovski, Nikolai (Inventor)

    2011-01-01

    Methods and systems for coding SAW OFC devices to mitigate code collisions in a wireless multi-tag system. Each device producing plural stepped frequencies as an OFC signal with a chip offset delay to increase code diversity. A method for assigning a different OCF to each device includes using a matrix based on the number of OFCs needed and the number chips per code, populating each matrix cell with OFC chip, and assigning the codes from the matrix to the devices. The asynchronous passive multi-tag system includes plural surface acoustic wave devices each producing a different OFC signal having the same number of chips and including a chip offset time delay, an algorithm for assigning OFCs to each device, and a transceiver to transmit an interrogation signal and receive OFC signals in response with minimal code collisions during transmission.

  5. Agile Methods for Open Source Safety-Critical Software.

    PubMed

    Gary, Kevin; Enquobahrie, Andinet; Ibanez, Luis; Cheng, Patrick; Yaniv, Ziv; Cleary, Kevin; Kokoori, Shylaja; Muffih, Benjamin; Heidenreich, John

    2011-08-01

    The introduction of software technology in a life-dependent environment requires the development team to execute a process that ensures a high level of software reliability and correctness. Despite their popularity, agile methods are generally assumed to be inappropriate as a process family in these environments due to their lack of emphasis on documentation, traceability, and other formal techniques. Agile methods, notably Scrum, favor empirical process control, or small constant adjustments in a tight feedback loop. This paper challenges the assumption that agile methods are inappropriate for safety-critical software development. Agile methods are flexible enough to encourage the rightamount of ceremony; therefore if safety-critical systems require greater emphasis on activities like formal specification and requirements management, then an agile process will include these as necessary activities. Furthermore, agile methods focus more on continuous process management and code-level quality than classic software engineering process models. We present our experiences on the image-guided surgical toolkit (IGSTK) project as a backdrop. IGSTK is an open source software project employing agile practices since 2004. We started with the assumption that a lighter process is better, focused on evolving code, and only adding process elements as the need arose. IGSTK has been adopted by teaching hospitals and research labs, and used for clinical trials. Agile methods have matured since the academic community suggested they are not suitable for safety-critical systems almost a decade ago, we present our experiences as a case study for renewing the discussion.

  6. Use of the Means/Ends Test to Evaluate Public School Dress-Code Policies

    ERIC Educational Resources Information Center

    Workman, Jane E.; Studak, Cathryn M.

    2008-01-01

    The purpose of this article is to explain how a means/ends test can be adapted for the school environment. Public school officials can use a means/ends test to document an analysis of whether dress-code policies will be effective in diminishing risks to the health, safety, or morality of the school population. Elements of policy evaluation--ends,…

  7. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to... 13/4″. (C)(1) Rim thickness is 11/16″ or less; (2) Rim thickness is 5/8″ or less; (3) Rim thickness...

  8. Knowledge management: Role of the the Radiation Safety Information Computational Center (RSICC)

    NASA Astrophysics Data System (ADS)

    Valentine, Timothy

    2017-09-01

    The Radiation Safety Information Computational Center (RSICC) at Oak Ridge National Laboratory (ORNL) is an information analysis center that collects, archives, evaluates, synthesizes and distributes information, data and codes that are used in various nuclear technology applications. RSICC retains more than 2,000 software packages that have been provided by code developers from various federal and international agencies. RSICC's customers (scientists, engineers, and students from around the world) obtain access to such computing codes (source and/or executable versions) and processed nuclear data files to promote on-going research, to ensure nuclear and radiological safety, and to advance nuclear technology. The role of such information analysis centers is critical for supporting and sustaining nuclear education and training programs both domestically and internationally, as the majority of RSICC's customers are students attending U.S. universities. Additionally, RSICC operates a secure CLOUD computing system to provide access to sensitive export-controlled modeling and simulation (M&S) tools that support both domestic and international activities. This presentation will provide a general review of RSICC's activities, services, and systems that support knowledge management and education and training in the nuclear field.

  9. Program for developing and implementing a new approach to designing for fire safety in buildings

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The traditional method of providing for fire safety in buildings through reliance on codes and standards that prescribe specific measures to be taken in the design and construction of buildings to minimize the potential for a fire occurring and to protect property and life should a fire occur was evaluated. A new approach to designing for fire safety in buildings is outlined.

  10. Probabilistic approach for decay heat uncertainty estimation using URANIE platform and MENDEL depletion code

    NASA Astrophysics Data System (ADS)

    Tsilanizara, A.; Gilardi, N.; Huynh, T. D.; Jouanne, C.; Lahaye, S.; Martinez, J. M.; Diop, C. M.

    2014-06-01

    The knowledge of the decay heat quantity and the associated uncertainties are important issues for the safety of nuclear facilities. Many codes are available to estimate the decay heat. ORIGEN, FISPACT, DARWIN/PEPIN2 are part of them. MENDEL is a new depletion code developed at CEA, with new software architecture, devoted to the calculation of physical quantities related to fuel cycle studies, in particular decay heat. The purpose of this paper is to present a probabilistic approach to assess decay heat uncertainty due to the decay data uncertainties from nuclear data evaluation like JEFF-3.1.1 or ENDF/B-VII.1. This probabilistic approach is based both on MENDEL code and URANIE software which is a CEA uncertainty analysis platform. As preliminary applications, single thermal fission of uranium 235, plutonium 239 and PWR UOx spent fuel cell are investigated.

  11. Understanding Mixed Code and Classroom Code-Switching: Myths and Realities

    ERIC Educational Resources Information Center

    Li, David C. S.

    2008-01-01

    Background: Cantonese-English mixed code is ubiquitous in Hong Kong society, and yet using mixed code is widely perceived as improper. This paper presents evidence of mixed code being socially constructed as bad language behavior. In the education domain, an EDB guideline bans mixed code in the classroom. Teachers are encouraged to stick to…

  12. Preliminary LOCA analysis of the westinghouse small modular reactor using the WCOBRA/TRAC-TF2 thermal-hydraulics code

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

    Liao, J.; Kucukboyaci, V. N.; Nguyen, L.

    2012-07-01

    The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (> 225 MWe) integral pressurized water reactor (iPWR) with all primary components, including the steam generator and the pressurizer located inside the reactor vessel. The reactor core is based on a partial-height 17x17 fuel assembly design used in the AP1000{sup R} reactor core. The Westinghouse SMR utilizes passive safety systems and proven components from the AP1000 plant design with a compact containment that houses the integral reactor vessel and the passive safety systems. A preliminary loss of coolant accident (LOCA) analysis of the Westinghouse SMR has been performed using themore » WCOBRA/TRAC-TF2 code, simulating a transient caused by a double ended guillotine (DEG) break in the direct vessel injection (DVI) line. WCOBRA/TRAC-TF2 is a new generation Westinghouse LOCA thermal-hydraulics code evolving from the US NRC licensed WCOBRA/TRAC code. It is designed to simulate PWR LOCA events from the smallest break size to the largest break size (DEG cold leg). A significant number of fluid dynamics models and heat transfer models were developed or improved in WCOBRA/TRAC-TF2. A large number of separate effects and integral effects tests were performed for a rigorous code assessment and validation. WCOBRA/TRAC-TF2 was introduced into the Westinghouse SMR design phase to assist a quick and robust passive cooling system design and to identify thermal-hydraulic phenomena for the development of the SMR Phenomena Identification Ranking Table (PIRT). The LOCA analysis of the Westinghouse SMR demonstrates that the DEG DVI break LOCA is mitigated by the injection and venting from the Westinghouse SMR passive safety systems without core heat up, achieving long term core cooling. (authors)« less

  13. Current status of treating neurodegenerative disease with induced pluripotent stem cells.

    PubMed

    Pen, A E; Jensen, U B

    2017-01-01

    Degenerative diseases of the brain have proven challenging to treat, let alone cure. One of the treatment options is the use of stem cell therapy, which has been under investigation for several years. However, treatment with stem cells comes with a number of drawbacks, for instance the source of these cells. Currently, a number of options are tested to produce stem cells, although the main issues of quantity and ethics remain for most of them. Over recent years, the potential of induced pluripotent stem cells (iPSCs) has been widely investigated and these cells seem promising for production of numerous different tissues both in vitro and in vivo. One of the major advantages of iPSCs is that they can be made autologous and can provide a sufficient quantity of cells by culturing, making the use of other stem cell sources unnecessary. As the first descriptions of iPSC production with the transcription factors Sox2, Klf4, Oct4 and C-Myc, called the Yamanaka factors, a variety of methods has been developed to convert somatic cells from all germ layers to pluripotent stem cells. Improvement of these methods is necessary to increase the efficiency of reprogramming, the quality of pluripotency and the safety of these cells before use in human trials. This review focusses on the current accomplishments and remaining challenges in the production and use of iPSCs for treatment of neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Rescue of ATP7B function in hepatocyte-like cells from Wilson's disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin.

    PubMed

    Zhang, Shiqiang; Chen, Shen; Li, Wen; Guo, Xiangpeng; Zhao, Ping; Xu, Jianyong; Chen, Yan; Pan, Qiong; Liu, Xiaorong; Zychlinski, Daniela; Lu, Hai; Tortorella, Micky D; Schambach, Axel; Wang, Yan; Pei, Duanqing; Esteban, Miguel A

    2011-08-15

    Directed hepatocyte differentiation from human induced pluripotent stem cells (iPSCs) potentially provides a unique platform for modeling liver genetic diseases and performing drug-toxicity screening in vitro. Wilson's disease is a genetic disease caused by mutations in the ATP7B gene, whose product is a liver transporter protein responsible for coordinated copper export into bile and blood. Interestingly, the spectrum of ATP7B mutations is vast and can influence clinical presentation (a variable spectrum of hepatic and neural manifestations), though the reason is not well understood. We describe the generation of iPSCs from a Chinese patient with Wilson's disease that bears the R778L Chinese hotspot mutation in the ATP7B gene. These iPSCs were pluripotent and could be readily differentiated into hepatocyte-like cells that displayed abnormal cytoplasmic localization of mutated ATP7B and defective copper transport. Moreover, gene correction using a self-inactivating lentiviral vector that expresses codon optimized-ATP7B or treatment with the chaperone drug curcumin could reverse the functional defect in vitro. Hence, our work describes an attractive model for studying the pathogenesis of Wilson's disease that is valuable for screening compounds or gene therapy approaches aimed to correct the abnormality. In the future, once relevant safety concerns (including the stability of the mature liver-like phenotype) and technical issues for the transplantation procedure are solved, hepatocyte-like cells from similarly genetically corrected iPSCs could be an option for autologous transplantation in Wilson's disease.

  15. Case-crossover analysis of heat-coded deaths and vulnerable subpopulations: Oklahoma, 1990-2011

    NASA Astrophysics Data System (ADS)

    Moore, Brianna F.; Brooke Anderson, G.; Johnson, Matthew G.; Brown, Sheryll; Bradley, Kristy K.; Magzamen, Sheryl

    2017-11-01

    The extent of the association between temperature and heat-coded deaths, for which heat is the primary cause of death, remains largely unknown. We explored the association between temperature and heat-coded deaths and potential interactions with various demographic and environmental factors. A total of 335 heat-coded deaths that occurred in Oklahoma from 1990 through 2011 were identified using heat-related International Classification of Diseases codes, cause-of-death nomenclature, and narrative descriptions. Conditional logistic regression models examined the association between temperature and heat index on heat-coded deaths. Interaction by demographic factors (age, sex, marital status, living alone, outdoor/heavy labor occupations) and environmental factors (ozone, PM10, PM2.5) was also explored. Temperatures ≥99 °F (the median value) were associated with approximately five times higher odds of a heat-coded death as compared to temperatures <99 °F (adjusted OR = 4.9, 95% CI 3.3, 7.2). The effect estimates were attenuated when exposure to heat was characterized by heat index. The interaction results suggest that effect of temperature on heat-coded deaths may depend on sex and occupation. For example, the odds of a heat-coded death among outdoor/heavy labor workers exposed to temperatures ≥99 °F was greater than expected based on the sum of the individual effects (observed OR = 14.0, 95% CI 2.7, 72.0; expected OR = 4.1 [2.8 + 2.3-1.0]). Our results highlight the extent of the association between temperature and heat-coded deaths and emphasize the need for a comprehensive, multisource definition of heat-coded deaths. Furthermore, based on the interaction results, we recommend that states implement or expand heat safety programs to protect vulnerable subpopulations, such as outdoor workers.

  16. Computation of Thermodynamic Equilibria Pertinent to Nuclear Materials in Multi-Physics Codes

    NASA Astrophysics Data System (ADS)

    Piro, Markus Hans Alexander

    Nuclear energy plays a vital role in supporting electrical needs and fulfilling commitments to reduce greenhouse gas emissions. Research is a continuing necessity to improve the predictive capabilities of fuel behaviour in order to reduce costs and to meet increasingly stringent safety requirements by the regulator. Moreover, a renewed interest in nuclear energy has given rise to a "nuclear renaissance" and the necessity to design the next generation of reactors. In support of this goal, significant research efforts have been dedicated to the advancement of numerical modelling and computational tools in simulating various physical and chemical phenomena associated with nuclear fuel behaviour. This undertaking in effect is collecting the experience and observations of a past generation of nuclear engineers and scientists in a meaningful way for future design purposes. There is an increasing desire to integrate thermodynamic computations directly into multi-physics nuclear fuel performance and safety codes. A new equilibrium thermodynamic solver is being developed with this matter as a primary objective. This solver is intended to provide thermodynamic material properties and boundary conditions for continuum transport calculations. There are several concerns with the use of existing commercial thermodynamic codes: computational performance; limited capabilities in handling large multi-component systems of interest to the nuclear industry; convenient incorporation into other codes with quality assurance considerations; and, licensing entanglements associated with code distribution. The development of this software in this research is aimed at addressing all of these concerns. The approach taken in this work exploits fundamental principles of equilibrium thermodynamics to simplify the numerical optimization equations. In brief, the chemical potentials of all species and phases in the system are constrained by estimates of the chemical potentials of the system

  17. QR Codes 101

    ERIC Educational Resources Information Center

    Crompton, Helen; LaFrance, Jason; van 't Hooft, Mark

    2012-01-01

    A QR (quick-response) code is a two-dimensional scannable code, similar in function to a traditional bar code that one might find on a product at the supermarket. The main difference between the two is that, while a traditional bar code can hold a maximum of only 20 digits, a QR code can hold up to 7,089 characters, so it can contain much more…

  18. Evaluation of Key Factors Impacting Feeding Safety in the Neonatal Intensive Care Unit: A Systematic Review.

    PubMed

    Matus, Bethany A; Bridges, Kayla M; Logomarsino, John V

    2018-06-21

    Individualized feeding care plans and safe handling of milk (human or formula) are critical in promoting growth, immune function, and neurodevelopment in the preterm infant. Feeding errors and disruptions or limitations to feeding processes in the neonatal intensive care unit (NICU) are associated with negative safety events. Feeding errors include contamination of milk and delivery of incorrect or expired milk and may result in adverse gastrointestinal illnesses. The purpose of this review was to evaluate the effect(s) of centralized milk preparation, use of trained technicians, use of bar code-scanning software, and collaboration between registered dietitians and registered nurses on feeding safety in the NICU. A systematic review of the literature was completed, and 12 articles were selected as relevant to search criteria. Study quality was evaluated using the Downs and Black scoring tool. An evaluation of human studies indicated that the use of centralized milk preparation, trained technicians, bar code-scanning software, and possible registered dietitian involvement decreased feeding-associated error in the NICU. A state-of-the-art NICU includes a centralized milk preparation area staffed by trained technicians, care supported by bar code-scanning software, and utilization of a registered dietitian to improve patient safety. These resources will provide nurses more time to focus on nursing-specific neonatal care. Further research is needed to evaluate the impact of factors related to feeding safety in the NICU as well as potential financial benefits of these quality improvement opportunities.

  19. Aluminum Data Measurements and Evaluation for Criticality Safety Applications

    NASA Astrophysics Data System (ADS)

    Leal, L. C.; Guber, K. H.; Spencer, R. R.; Derrien, H.; Wright, R. Q.

    2002-12-01

    The Defense Nuclear Facility Safety Board (DNFSB) Recommendation 93-2 motivated the US Department of Energy (DOE) to develop a comprehensive criticality safety program to maintain and to predict the criticality of systems throughout the DOE complex. To implement the response to the DNFSB Recommendation 93-2, a Nuclear Criticality Safety Program (NCSP) was created including the following tasks: Critical Experiments, Criticality Benchmarks, Training, Analytical Methods, and Nuclear Data. The Nuclear Data portion of the NCSP consists of a variety of differential measurements performed at the Oak Ridge Electron Linear Accelerator (ORELA) at the Oak Ridge National Laboratory (ORNL), data analysis and evaluation using the generalized least-squares fitting code SAMMY in the resolved, unresolved, and high energy ranges, and the development and benchmark testing of complete evaluations for a nuclide for inclusion into the Evaluated Nuclear Data File (ENDF/B). This paper outlines the work performed at ORNL to measure, evaluate, and test the nuclear data for aluminum for applications in criticality safety problems.

  20. The random coding bound is tight for the average code.

    NASA Technical Reports Server (NTRS)

    Gallager, R. G.

    1973-01-01

    The random coding bound of information theory provides a well-known upper bound to the probability of decoding error for the best code of a given rate and block length. The bound is constructed by upperbounding the average error probability over an ensemble of codes. The bound is known to give the correct exponential dependence of error probability on block length for transmission rates above the critical rate, but it gives an incorrect exponential dependence at rates below a second lower critical rate. Here we derive an asymptotic expression for the average error probability over the ensemble of codes used in the random coding bound. The result shows that the weakness of the random coding bound at rates below the second critical rate is due not to upperbounding the ensemble average, but rather to the fact that the best codes are much better than the average at low rates.

  1. Making your code citable with the Astrophysics Source Code Library

    NASA Astrophysics Data System (ADS)

    Allen, Alice; DuPrie, Kimberly; Schmidt, Judy; Berriman, G. Bruce; Hanisch, Robert J.; Mink, Jessica D.; Nemiroff, Robert J.; Shamir, Lior; Shortridge, Keith; Taylor, Mark B.; Teuben, Peter J.; Wallin, John F.

    2016-01-01

    The Astrophysics Source Code Library (ASCL, ascl.net) is a free online registry of codes used in astronomy research. With nearly 1,200 codes, it is the largest indexed resource for astronomy codes in existence. Established in 1999, it offers software authors a path to citation of their research codes even without publication of a paper describing the software, and offers scientists a way to find codes used in refereed publications, thus improving the transparency of the research. It also provides a method to quantify the impact of source codes in a fashion similar to the science metrics of journal articles. Citations using ASCL IDs are accepted by major astronomy journals and if formatted properly are tracked by ADS and other indexing services. The number of citations to ASCL entries increased sharply from 110 citations in January 2014 to 456 citations in September 2015. The percentage of code entries in ASCL that were cited at least once rose from 7.5% in January 2014 to 17.4% in September 2015. The ASCL's mid-2014 infrastructure upgrade added an easy entry submission form, more flexible browsing, search capabilities, and an RSS feeder for updates. A Changes/Additions form added this past fall lets authors submit links for papers that use their codes for addition to the ASCL entry even if those papers don't formally cite the codes, thus increasing the transparency of that research and capturing the value of their software to the community.

  2. 76 FR 77549 - Lummi Nation-Title 20-Code of Laws-Liquor Code

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-13

    ... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Lummi Nation--Title 20--Code of Laws--Liquor... amendment to Lummi Nation's Title 20--Code of Laws--Liquor Code. The Code regulates and controls the... this amendment to Title 20--Lummi Nation Code of Laws--Liquor Code by Resolution 2011-038 on March 1...

  3. New French Regulation for NPPs and Code Consequences

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

    Faidy, Claude

    2006-07-01

    On December 2005, the French regulator issued a new regulation for French nuclear power plants, in particular for pressure equipment (PE). This regulation need first to agree with non-nuclear PE regulation and add to that some specific requirements, in particular radiation protection requirements. Different advantages are in these proposal, it's more qualitative risk oriented and it's an important link with non-nuclear industry. Only few components are nuclear specific. But, the general philosophy of the existing Codes (RCC-M [15], KTA [16] or ASME [17]) have to be improved. For foreign Codes, it's plan to define the differences in the user specifications.more » In parallel to that, a new safety classification has been developed by French utility. The consequences is the need to cross all these specifications to define a minimum quality level for each components or systems. In the same time a new concept has been developed to replace the well known 'Leak Before Break methodology': the 'Break Exclusion' methodology. This paper will summarize the key aspects of these different topics. (authors)« less

  4. Recent Accomplishments and Future Directions in US Fusion Safety & Environmental Program

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

    David A. Petti; Brad J. Merrill; Phillip Sharpe

    2006-07-01

    The US fusion program has long recognized that the safety and environmental (S&E) potential of fusion can be attained by prudent materials selection, judicious design choices, and integration of safety requirements into the design of the facility. To achieve this goal, S&E research is focused on understanding the behavior of the largest sources of radioactive and hazardous materials in a fusion facility, understanding how energy sources in a fusion facility could mobilize those materials, developing integrated state of the art S&E computer codes and risk tools for safety assessment, and evaluating S&E issues associated with current fusion designs. In thismore » paper, recent accomplishments are reviewed and future directions outlined.« less

  5. Parents' experience with child safety restraint in China.

    PubMed

    Chen, Xiaojun; Yang, Jingzhen; Peek-Asa, Corinne; Li, Liping

    2014-04-07

    Child safety restraints are effective measures in protecting children from an injury while traveling in a car. However, the rate of child restraint use is extremely low in Chinese cities. Parent drivers could play an important role in promoting child safety restraint use, but not all of them take active responsibility. This study used a qualitative approach and included 14 in-depth interviews among parents with a child, under the age of 6, living in Shantou City (7 child safety restraint users and 7 non-users). Purposive sampling was used to recruit eligible parent drivers who participated in a previous observation study. Interview data were collected from March to April 2013. The audio taped and transcribed data were coded and analyzed to identify key themes. Four key themes on child safety restraint emerged from the in-depth interviews with parents. These included 1) Having a child safety restraint installed in the rear seat with an adult sitting next to the restrained child is ideal, and child safety restraint is seen as an alternative when adult accompaniment is not available; 2) Having effective parental education strategies could help make a difference in child safety restraint use; 3) Inadequate promotion and parents' poor safety awareness contribute to the low rate of child safety restraint in China; 4) Mandatory legislation on child safety restraint use could be an effective approach. Inadequate promotion and low awareness of safe traveling by parents were closely linked to low child safety seat usage under the circumstance of no mandatory legislation. Future intervention efforts need to focus on increasing parents' safe travel awareness combined with CSS product promotion before the laws are enacted.

  6. Make safety awareness a priority: Use a login software in your research facility

    DOE PAGES

    Camino, Fernando E.

    2017-01-21

    We report on a facility login software, whose objective is to improve safety in multi-user research facilities. Its most important safety features are: 1) blocks users from entering the lab after being absent for more than a predetermined number of days; 2) gives users a random safety quiz question, which they need to answer satisfactorily in order to use the facility; 3) blocks unauthorized users from using the facility afterhours; and 4) displays the current users in the facility. Besides restricting access to unauthorized users, the software keeps users mindful of key safety concepts. In addition, integration of the softwaremore » with a door controller system can convert it into an effective physical safety mechanism. Depending on DOE approval, the code may be available as open source.« less

  7. Make safety awareness a priority: Use a login software in your research facility

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

    Camino, Fernando E.

    We report on a facility login software, whose objective is to improve safety in multi-user research facilities. Its most important safety features are: 1) blocks users from entering the lab after being absent for more than a predetermined number of days; 2) gives users a random safety quiz question, which they need to answer satisfactorily in order to use the facility; 3) blocks unauthorized users from using the facility afterhours; and 4) displays the current users in the facility. Besides restricting access to unauthorized users, the software keeps users mindful of key safety concepts. In addition, integration of the softwaremore » with a door controller system can convert it into an effective physical safety mechanism. Depending on DOE approval, the code may be available as open source.« less

  8. Patient safety awareness among Undergraduate Medical Students in Pakistani Medical School

    PubMed Central

    Kamran, Rizwana; Bari, Attia; Khan, Rehan Ahmed; Al-Eraky, Mohamed

    2018-01-01

    Objective: To measure the level of awareness of patient safety among undergraduate medical students in Pakistani Medical School and to find the difference with respect to gender and prior experience with medical error. Methods: This cross-sectional study was conducted at the University of Lahore (UOL), Pakistan from January to March 2017, and comprised final year medical students. Data was collected using a questionnaire ‘APSQ- III’ on 7 point Likert scale. Eight questions were reverse coded. Survey was anonymous. SPSS package 20 was used for statistical analysis. Results: Questionnaire was filled by 122 students, with 81% response rate. The best score 6.17 was given for the ‘team functioning’, followed by 6.04 for ‘long working hours as a cause of medical error’. The domains regarding involvement of patient, confidence to report medical errors and role of training and learning on patient safety scored high in the agreed range of >5. Reverse coded questions about ‘professional incompetence as an error cause’ and ‘disclosure of errors’ showed negative perception. No significant differences of perceptions were found with respect to gender and prior experience with medical error (p= >0.05). Conclusion: Undergraduate medical students at UOL had a positive attitude towards patient safety. However, there were misconceptions about causes of medical errors and error disclosure among students and patient safety education needs to be incorporated in medical curriculum of Pakistan. PMID:29805398

  9. Read-Write-Codes: An Erasure Resilient Encoding System for Flexible Reading and Writing in Storage Networks

    NASA Astrophysics Data System (ADS)

    Mense, Mario; Schindelhauer, Christian

    We introduce the Read-Write-Coding-System (RWC) - a very flexible class of linear block codes that generate efficient and flexible erasure codes for storage networks. In particular, given a message x of k symbols and a codeword y of n symbols, an RW code defines additional parameters k ≤ r,w ≤ n that offer enhanced possibilities to adjust the fault-tolerance capability of the code. More precisely, an RWC provides linear left(n,k,dright)-codes that have (a) minimum distance d = n - r + 1 for any two codewords, and (b) for each codeword there exists a codeword for each other message with distance of at most w. Furthermore, depending on the values r,w and the code alphabet, different block codes such as parity codes (e.g. RAID 4/5) or Reed-Solomon (RS) codes (if r = k and thus, w = n) can be generated. In storage networks in which I/O accesses are very costly and redundancy is crucial, this flexibility has considerable advantages as r and w can optimally be adapted to read or write intensive applications; only w symbols must be updated if the message x changes completely, what is different from other codes which always need to rewrite y completely as x changes. In this paper, we first state a tight lower bound and basic conditions for all RW codes. Furthermore, we introduce special RW codes in which all mentioned parameters are adjustable even online, that is, those RW codes are adaptive to changing demands. At last, we point out some useful properties regarding safety and security of the stored data.

  10. Medicare and Medicaid programs; fire safety requirements for certain health care facilities. Final rule.

    PubMed

    2003-01-10

    This final rule amends the fire safety standards for hospitals, long-term care facilities, intermediate care facilities for the mentally retarded, ambulatory surgery centers, hospices that provide inpatient services, religious nonmedical health care institutions, critical access hospitals, and Programs of All-Inclusive Care for the Elderly facilities. Further, this final rule adopts the 2000 edition of the Life Safety Code and eliminates references in our regulations to all earlier editions.

  11. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, A.; Divsalar, D.; Yao, K.

    2004-01-01

    In this paper we propose an innovative channel coding scheme called Accumulate Repeat Accumulate codes. This class of codes can be viewed as trubo-like codes, namely a double serial concatenation of a rate-1 accumulator as an outer code, a regular or irregular repetition as a middle code, and a punctured accumulator as an inner code.

  12. Metabolome Profiling of Partial and Fully Reprogrammed Induced Pluripotent Stem Cells.

    PubMed

    Park, Soon-Jung; Lee, Sang A; Prasain, Nutan; Bae, Daekyeong; Kang, Hyunsu; Ha, Taewon; Kim, Jong Soo; Hong, Ki-Sung; Mantel, Charlie; Moon, Sung-Hwan; Broxmeyer, Hal E; Lee, Man Ryul

    2017-05-15

    Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs. In this study, we characterized the metabolites of human fully reprogrammed iPSCs, partially reprogrammed iPSCs, and embryonic stem cells (ESCs). Using capillary electrophoresis time-of-flight mass spectrometry-based metabolomics, we found that 89% of analyzed metabolites were similarly expressed in fully reprogrammed iPSCs and human ESCs (hESCs), whereas partially reprogrammed iPSCs shared only 74% similarly expressed metabolites with hESCs. Metabolomic profiling analysis suggested that converting mitochondrial respiration to glycolytic flux is critical for reprogramming of somatic cells into fully reprogrammed iPSCs. This characterization of metabolic reprogramming in iPSCs may enable the development of new reprogramming parameters for enhancing the generation of fully reprogrammed human iPSCs.

  13. Reprogramming of fibroblasts from older women with pelvic floor disorders alters cellular behavior associated with donor age.

    PubMed

    Wen, Yan; Wani, Prachi; Zhou, Lu; Baer, Tom; Phadnis, Smruti Madan; Reijo Pera, Renee A; Chen, Bertha

    2013-02-01

    We aimed to derive induced pluripotent stem cell (iPSC) lines from vaginal fibroblasts from older women with pelvic organ prolapse. We examined the effect of donor age on iPSCs and on the cells redifferentiated from these iPSCs. Vaginal fibroblasts were isolated from younger and older subjects for reprogramming. iPSCs were generated simultaneously using an excisable polycistronic lentiviral vector expressing Oct4, Klf4, Sox2, and cMyc. The pluripotent markers of iPSCs were confirmed by immunocytochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spectral karyotyping was performed. The ability of the iPSCs to differentiate into three germ layers was confirmed by embryoid body and teratoma formation. Senescence marker (p21, p53, and Bax) expressions were determined by qRT-PCR and Western blot. The iPSCs were redifferentiated to fibroblasts and were evaluated with senescence-associated β-galactosidase (SA) activity and mitotic index using time-lapse dark-field microscopy. iPSCs derived from both the younger and older subjects expressed pluripotency markers and showed normal karyotype and positive teratoma assays. There was no significant difference in expression of senescence and apoptosis markers (p21, p53, and Bax) in iPSCs derived from the younger subject compared with the older subject. Furthermore, fibroblasts redifferentiated from these iPSCs did not differ in SA activity or mitotic index. We report successful derivation of iPSCs from women with pelvic organ prolapse. Older age did not interfere with successful reprogramming. Donor age differences were not observed in these iPSCs using standard senescence markers, and donor age did not appear to affect cell mitotic activity in fibroblasts redifferentiated from iPSCs.

  14. Interprofessional, psycho-social intervention to facilitate resilience and reduce supportive care needs for patients with cancer: Results of a noncomparative, randomized phase II trial.

    PubMed

    Eicher, Manuela; Ribi, Karin; Senn-Dubey, Catherine; Senn, Stefanie; Ballabeni, Pierluigi; Betticher, Daniel

    2018-04-14

    We developed 2 intensity levels of a complex intervention for interprofessional supportive care in cancer (IPSC-C) to facilitate resilience and reduce unmet supportive care needs. We aimed to test the feasibility, acceptability, and preliminary effectiveness of both intensity levels in routine practice. In a randomized, noncomparative phase II trial, newly diagnosed patients received either low (LI-IPSC-C) or high (HI-IPSC-C) intensity interventions. Low-intensity-interprofessional supportive care in cancer (LI-IPSC-C) consisted of 3 electronic assessments of resilience, unmet supportive care needs, mood, and coping effort over 16 weeks with an immediate feedback to clinicians including tailored intervention recommendations to facilitate resilience and supportive care. High-intensity-interprofessional supportive care in cancer (HI-IPSC-C) added 5 structured consultations (face-to-face and telephone) provided by specialized nurses. Primary outcome was a change ≥5 in resilience score on the Connor-Davidson Resilience Scale (CD-RISC). Secondary outcomes were unmet supportive care needs, mood, and coping effort. We assessed feasibility by clinician-provided tailored interventions as recommended and acceptability through qualitative interviews with clinicians and patients. In the LI-IPSC-C arm, 11 of 41, in the HI-IPSC-C arm 17 of 43, patients increased resilience scores by ≥5. Relatively more patients decreased unmet needs in HI-IPSC-C arm. Mood, in both arms, and coping effort, in HI-IPSC-C arm, improved meaningfully. Feasibility was limited for the LI-IPSC-C arm, mainly due to lack of time; acceptability was high in both arms. Neither LI-IPSC-C nor HI-IPSC-C interventions reached the desired threshold. HI-IPSC-C showed positive effects on secondary outcomes and was feasible. Resilience as measured by the CD-RISC may not be the optimal outcome measure for this intervention. Copyright © 2018 John Wiley & Sons, Ltd.

  15. Reactivity Coefficient Calculation for AP1000 Reactor Using the NODAL3 Code

    NASA Astrophysics Data System (ADS)

    Pinem, Surian; Malem Sembiring, Tagor; Tukiran; Deswandri; Sunaryo, Geni Rina

    2018-02-01

    The reactivity coefficient is a very important parameter for inherent safety and stability of nuclear reactors operation. To provide the safety analysis of the reactor, the calculation of changes in reactivity caused by temperature is necessary because it is related to the reactor operation. In this paper, the temperature reactivity coefficients of fuel and moderator of the AP1000 core are calculated, as well as the moderator density and boron concentration. All of these coefficients are calculated at the hot full power condition (HFP). All neutron diffusion constant as a function of temperature, water density and boron concentration were generated by the SRAC2006 code. The core calculations for determination of the reactivity coefficient parameter are done by using NODAL3 code. The calculation results show that the fuel temperature, moderator temperature and boron reactivity coefficients are in the range between -2.613 pcm/°C to -4.657pcm/°C, -1.00518 pcm/°C to 1.00649 pcm/°C and -9.11361 pcm/ppm to -8.0751 pcm/ppm, respectively. For the water density reactivity coefficients, the positive reactivity occurs at the water temperature less than 190 °C. The calculation results show that the reactivity coefficients are accurate because the results have a very good agreement with the design value.

  16. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  17. Error floor behavior study of LDPC codes for concatenated codes design

    NASA Astrophysics Data System (ADS)

    Chen, Weigang; Yin, Liuguo; Lu, Jianhua

    2007-11-01

    Error floor behavior of low-density parity-check (LDPC) codes using quantized decoding algorithms is statistically studied with experimental results on a hardware evaluation platform. The results present the distribution of the residual errors after decoding failure and reveal that the number of residual error bits in a codeword is usually very small using quantized sum-product (SP) algorithm. Therefore, LDPC code may serve as the inner code in a concatenated coding system with a high code rate outer code and thus an ultra low error floor can be achieved. This conclusion is also verified by the experimental results.

  18. Lecture Notes on Criticality Safety Validation Using MCNP & Whisper

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

    Brown, Forrest B.; Rising, Michael Evan; Alwin, Jennifer Louise

    Training classes for nuclear criticality safety, MCNP documentation. The need for, and problems surrounding, validation of computer codes and data area considered first. Then some background for MCNP & Whisper is given--best practices for Monte Carlo criticality calculations, neutron spectra, S(α,β) thermal neutron scattering data, nuclear data sensitivities, covariance data, and correlation coefficients. Whisper is computational software designed to assist the nuclear criticality safety analyst with validation studies with the Monte Carlo radiation transport package MCNP. Whisper's methodology (benchmark selection – C k's, weights; extreme value theory – bias, bias uncertainty; MOS for nuclear data uncertainty – GLLS) and usagemore » are discussed.« less

  19. SER assistant: An expert system for safety evaluation reports

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

    DeChaine, M.D.; Levine, S.H.; Feltus, M.A.

    1993-01-01

    The SER Assistant is an expert system that assists engineers to write safety evaluation reports (SERs). Section 50.59 of the Code of Federal Regulations allows modifications to be made to nuclear power plants without prior US Nuclear Regulatory Commission approval if two conditions are satisfied. First, the change must not affect the technical specifications of the plant. Second, the modification must not affect a part of the plant described in the final safety analysis report, or if it does, it must not create an unreviewed safety question. The purpose of an SER is to ensure that these conditions are satisfiedmore » for the proposed modification. The SER Assistant aids this process by providing relevant, but directed, questions and information as well as giving engineers an organized environment to document their thought processes.« less

  20. The EDIT-COMGEOM Code

    DTIC Science & Technology

    1975-09-01

    This report assumes a familiarity with the GIFT and MAGIC computer codes. The EDIT-COMGEOM code is a FORTRAN computer code. The EDIT-COMGEOM code...converts the target description data which was used in the MAGIC computer code to the target description data which can be used in the GIFT computer code

  1. Agile Methods for Open Source Safety-Critical Software

    PubMed Central

    Enquobahrie, Andinet; Ibanez, Luis; Cheng, Patrick; Yaniv, Ziv; Cleary, Kevin; Kokoori, Shylaja; Muffih, Benjamin; Heidenreich, John

    2011-01-01

    The introduction of software technology in a life-dependent environment requires the development team to execute a process that ensures a high level of software reliability and correctness. Despite their popularity, agile methods are generally assumed to be inappropriate as a process family in these environments due to their lack of emphasis on documentation, traceability, and other formal techniques. Agile methods, notably Scrum, favor empirical process control, or small constant adjustments in a tight feedback loop. This paper challenges the assumption that agile methods are inappropriate for safety-critical software development. Agile methods are flexible enough to encourage the right amount of ceremony; therefore if safety-critical systems require greater emphasis on activities like formal specification and requirements management, then an agile process will include these as necessary activities. Furthermore, agile methods focus more on continuous process management and code-level quality than classic software engineering process models. We present our experiences on the image-guided surgical toolkit (IGSTK) project as a backdrop. IGSTK is an open source software project employing agile practices since 2004. We started with the assumption that a lighter process is better, focused on evolving code, and only adding process elements as the need arose. IGSTK has been adopted by teaching hospitals and research labs, and used for clinical trials. Agile methods have matured since the academic community suggested they are not suitable for safety-critical systems almost a decade ago, we present our experiences as a case study for renewing the discussion. PMID:21799545

  2. Computer codes for checking, plotting and processing of neutron cross-section covariance data and their application

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

    Sartori, E.; Roussin, R.W.

    This paper presents a brief review of computer codes concerned with checking, plotting, processing and using of covariances of neutron cross-section data. It concentrates on those available from the computer code information centers of the United States and the OECD/Nuclear Energy Agency. Emphasis will be placed also on codes using covariances for specific applications such as uncertainty analysis, data adjustment and data consistency analysis. Recent evaluations contain neutron cross section covariance information for all isotopes of major importance for technological applications of nuclear energy. It is therefore important that the available software tools needed for taking advantage of this informationmore » are widely known as hey permit the determination of better safety margins and allow the optimization of more economic, I designs of nuclear energy systems.« less

  3. Surface code implementation of block code state distillation.

    PubMed

    Fowler, Austin G; Devitt, Simon J; Jones, Cody

    2013-01-01

    State distillation is the process of taking a number of imperfect copies of a particular quantum state and producing fewer better copies. Until recently, the lowest overhead method of distilling states produced a single improved [formula: see text] state given 15 input copies. New block code state distillation methods can produce k improved [formula: see text] states given 3k + 8 input copies, potentially significantly reducing the overhead associated with state distillation. We construct an explicit surface code implementation of block code state distillation and quantitatively compare the overhead of this approach to the old. We find that, using the best available techniques, for parameters of practical interest, block code state distillation does not always lead to lower overhead, and, when it does, the overhead reduction is typically less than a factor of three.

  4. Surface code implementation of block code state distillation

    PubMed Central

    Fowler, Austin G.; Devitt, Simon J.; Jones, Cody

    2013-01-01

    State distillation is the process of taking a number of imperfect copies of a particular quantum state and producing fewer better copies. Until recently, the lowest overhead method of distilling states produced a single improved |A〉 state given 15 input copies. New block code state distillation methods can produce k improved |A〉 states given 3k + 8 input copies, potentially significantly reducing the overhead associated with state distillation. We construct an explicit surface code implementation of block code state distillation and quantitatively compare the overhead of this approach to the old. We find that, using the best available techniques, for parameters of practical interest, block code state distillation does not always lead to lower overhead, and, when it does, the overhead reduction is typically less than a factor of three. PMID:23736868

  5. Implications of electronic health record downtime: an analysis of patient safety event reports.

    PubMed

    Larsen, Ethan; Fong, Allan; Wernz, Christian; Ratwani, Raj M

    2018-02-01

    We sought to understand the types of clinical processes, such as image and medication ordering, that are disrupted during electronic health record (EHR) downtime periods by analyzing the narratives of patient safety event report data. From a database of 80 381 event reports, 76 reports were identified as explicitly describing a safety event associated with an EHR downtime period. These reports were analyzed and categorized based on a developed code book to identify the clinical processes that were impacted by downtime. We also examined whether downtime procedures were in place and followed. The reports were coded into categories related to their reported clinical process: Laboratory, Medication, Imaging, Registration, Patient Handoff, Documentation, History Viewing, Delay of Procedure, and General. A majority of reports (48.7%, n = 37) were associated with lab orders and results, followed by medication ordering and administration (14.5%, n = 11). Incidents commonly involved patient identification and communication of clinical information. A majority of reports (46%, n = 35) indicated that downtime procedures either were not followed or were not in place. Only 27.6% of incidents (n = 21) indicated that downtime procedures were successfully executed. Patient safety report data offer a lens into EHR downtime-related safety hazards. Important areas of risk during EHR downtime periods were patient identification and communication of clinical information; these should be a focus of downtime procedure planning to reduce safety hazards. EHR downtime events pose patient safety hazards, and we highlight critical areas for downtime procedure improvement. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. [Agricultural biotechnology safety assessment].

    PubMed

    McClain, Scott; Jones, Wendelyn; He, Xiaoyun; Ladics, Gregory; Bartholomaeus, Andrew; Raybould, Alan; Lutter, Petra; Xu, Haibin; Wang, Xue

    2015-01-01

    Genetically modified (GM) crops were first introduced to farmers in 1995 with the intent to provide better crop yield and meet the increasing demand for food and feed. GM crops have evolved to include a thorough safety evaluation for their use in human food and animal feed. Safety considerations begin at the level of DNA whereby the inserted GM DNA is evaluated for its content, position and stability once placed into the crop genome. The safety of the proteins coded by the inserted DNA and potential effects on the crop are considered, and the purpose is to ensure that the transgenic novel proteins are safe from a toxicity, allergy, and environmental perspective. In addition, the grain that provides the processed food or animal feed is also tested to evaluate its nutritional content and identify unintended effects to the plant composition when warranted. To provide a platform for the safety assessment, the GM crop is compared to non-GM comparators in what is typically referred to as composition equivalence testing. New technologies, such as mass spectrometry and well-designed antibody-based methods, allow better analytical measurements of crop composition, including endogenous allergens. Many of the analytical methods and their intended uses are based on regulatory guidance documents, some of which are outlined in globally recognized documents such as Codex Alimentarius. In certain cases, animal models are recommended by some regulatory agencies in specific countries, but there is typically no hypothesis or justification of their use in testing the safety of GM crops. The quality and standardization of testing methods can be supported, in some cases, by employing good laboratory practices (GLP) and is recognized in China as important to ensure quality data. Although the number of recommended, in some cases, required methods for safety testing are increasing in some regulatory agencies, it should be noted that GM crops registered to date have been shown to be

  7. Using Coding Apps to Support Literacy Instruction and Develop Coding Literacy

    ERIC Educational Resources Information Center

    Hutchison, Amy; Nadolny, Larysa; Estapa, Anne

    2016-01-01

    In this article the authors present the concept of Coding Literacy and describe the ways in which coding apps can support the development of Coding Literacy and disciplinary and digital literacy skills. Through detailed examples, we describe how coding apps can be integrated into literacy instruction to support learning of the Common Core English…

  8. Performance analysis of a cascaded coding scheme with interleaved outer code

    NASA Technical Reports Server (NTRS)

    Lin, S.

    1986-01-01

    A cascaded coding scheme for a random error channel with a bit-error rate is analyzed. In this scheme, the inner code C sub 1 is an (n sub 1, m sub 1l) binary linear block code which is designed for simultaneous error correction and detection. The outer code C sub 2 is a linear block code with symbols from the Galois field GF (2 sup l) which is designed for correcting both symbol errors and erasures, and is interleaved with a degree m sub 1. A procedure for computing the probability of a correct decoding is presented and an upper bound on the probability of a decoding error is derived. The bound provides much better results than the previous bound for a cascaded coding scheme with an interleaved outer code. Example schemes with inner codes ranging from high rates to very low rates are evaluated. Several schemes provide extremely high reliability even for very high bit-error rates say 10 to the -1 to 10 to the -2 power.

  9. High rate concatenated coding systems using bandwidth efficient trellis inner codes

    NASA Technical Reports Server (NTRS)

    Deng, Robert H.; Costello, Daniel J., Jr.

    1989-01-01

    High-rate concatenated coding systems with bandwidth-efficient trellis inner codes and Reed-Solomon (RS) outer codes are investigated for application in high-speed satellite communication systems. Two concatenated coding schemes are proposed. In one the inner code is decoded with soft-decision Viterbi decoding, and the outer RS code performs error-correction-only decoding (decoding without side information). In the other, the inner code is decoded with a modified Viterbi algorithm, which produces reliability information along with the decoded output. In this algorithm, path metrics are used to estimate the entire information sequence, whereas branch metrics are used to provide reliability information on the decoded sequence. This information is used to erase unreliable bits in the decoded output. An errors-and-erasures RS decoder is then used for the outer code. The two schemes have been proposed for high-speed data communication on NASA satellite channels. The rates considered are at least double those used in current NASA systems, and the results indicate that high system reliability can still be achieved.

  10. Industrial Code Development

    NASA Technical Reports Server (NTRS)

    Shapiro, Wilbur

    1991-01-01

    The industrial codes will consist of modules of 2-D and simplified 2-D or 1-D codes, intended for expeditious parametric studies, analysis, and design of a wide variety of seals. Integration into a unified system is accomplished by the industrial Knowledge Based System (KBS), which will also provide user friendly interaction, contact sensitive and hypertext help, design guidance, and an expandable database. The types of analysis to be included with the industrial codes are interfacial performance (leakage, load, stiffness, friction losses, etc.), thermoelastic distortions, and dynamic response to rotor excursions. The first three codes to be completed and which are presently being incorporated into the KBS are the incompressible cylindrical code, ICYL, and the compressible cylindrical code, GCYL.

  11. Parents’ experience with child safety restraint in China

    PubMed Central

    2014-01-01

    Background Child safety restraints are effective measures in protecting children from an injury while traveling in a car. However, the rate of child restraint use is extremely low in Chinese cities. Parent drivers could play an important role in promoting child safety restraint use, but not all of them take active responsibility. Methods This study used a qualitative approach and included 14 in-depth interviews among parents with a child, under the age of 6, living in Shantou City (7 child safety restraint users and 7 non-users). Purposive sampling was used to recruit eligible parent drivers who participated in a previous observation study. Interview data were collected from March to April 2013. The audio taped and transcribed data were coded and analyzed to identify key themes. Results Four key themes on child safety restraint emerged from the in-depth interviews with parents. These included 1) Having a child safety restraint installed in the rear seat with an adult sitting next to the restrained child is ideal, and child safety restraint is seen as an alternative when adult accompaniment is not available; 2) Having effective parental education strategies could help make a difference in child safety restraint use; 3) Inadequate promotion and parents’ poor safety awareness contribute to the low rate of child safety restraint in China; 4) Mandatory legislation on child safety restraint use could be an effective approach. Conclusion Inadequate promotion and low awareness of safe traveling by parents were closely linked to low child safety seat usage under the circumstance of no mandatory legislation. Future intervention efforts need to focus on increasing parents’ safe travel awareness combined with CSS product promotion before the laws are enacted. PMID:24708776

  12. New optimal asymmetric quantum codes constructed from constacyclic codes

    NASA Astrophysics Data System (ADS)

    Xu, Gen; Li, Ruihu; Guo, Luobin; Lü, Liangdong

    2017-02-01

    In this paper, we propose the construction of asymmetric quantum codes from two families of constacyclic codes over finite field 𝔽q2 of code length n, where for the first family, q is an odd prime power with the form 4t + 1 (t ≥ 1 is integer) or 4t - 1 (t ≥ 2 is integer) and n1 = q2+1 2; for the second family, q is an odd prime power with the form 10t + 3 or 10t + 7 (t ≥ 0 is integer) and n2 = q2+1 5. As a result, families of new asymmetric quantum codes [[n,k,dz/dx

  13. Quantum error-correcting codes from algebraic geometry codes of Castle type

    NASA Astrophysics Data System (ADS)

    Munuera, Carlos; Tenório, Wanderson; Torres, Fernando

    2016-10-01

    We study algebraic geometry codes producing quantum error-correcting codes by the CSS construction. We pay particular attention to the family of Castle codes. We show that many of the examples known in the literature in fact belong to this family of codes. We systematize these constructions by showing the common theory that underlies all of them.

  14. Imprinted expression of UBE3A in non-neuronal cells from a Prader–Willi syndrome patient with an atypical deletion

    PubMed Central

    Martins-Taylor, Kristen; Hsiao, Jack S.; Chen, Pin-Fang; Glatt-Deeley, Heather; De Smith, Adam J.; Blakemore, Alexandra I.F.; Lalande, Marc; Chamberlain, Stormy J.

    2014-01-01

    Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are two neurodevelopmental disorders most often caused by deletions of the same region of paternally inherited and maternally inherited human chromosome 15q, respectively. AS is a single gene disorder, caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, while PWS is still considered a contiguous gene disorder. Rare individuals with PWS who carry atypical microdeletions on chromosome 15q have narrowed the critical region for this disorder to a 108 kb region that includes the SNORD116 snoRNA cluster and the Imprinted in Prader–Willi (IPW) non-coding RNA. Here we report the derivation of induced pluripotent stem cells (iPSCs) from a PWS patient with an atypical microdeletion that spans the PWS critical region. We show that these iPSCs express brain-specific portions of the transcripts driven by the PWS imprinting center, including the UBE3A antisense transcript (UBE3A-ATS). Furthermore, UBE3A expression is imprinted in most of these iPSCs. These data suggest that UBE3A imprinting in neurons only requires UBE3A-ATS expression, and no other neuron-specific factors. These data also suggest that a boundary element lying within the PWS critical region prevents UBE3A-ATS expression in non-neural tissues. PMID:24363065

  15. Laser hazards and safety in the military environment. Lecture series

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

    Not Available

    The Lecture Series is intended to provide an understanding of the safety problems associated with the military use of lasers. The most important hazard is the inadvertent irradiation of the eye and so the series will include contributions from the physical and biological sciences, as well as from ophthalmologists. Those involved with laser safety come from many backgrounds -- from physics to engineering and from vision physiology to clinical ophthalmology and it is essential that each understands the contribution of the other. The lectures include an introductory part and from this, the more advanced aspects of each subject are covered,more » leading to the issues involved in the design of safety codes and the control of laser hazards. The final session deals with medical surveillance of laser personnel. The Series is of value to both military and civilian personnel involved with safety, whether they are concerned with land, sea or airborne laser systems. (GRA)« less

  16. Schroedinger’s code: Source code availability and transparency in astrophysics

    NASA Astrophysics Data System (ADS)

    Ryan, PW; Allen, Alice; Teuben, Peter

    2018-01-01

    Astronomers use software for their research, but how many of the codes they use are available as source code? We examined a sample of 166 papers from 2015 for clearly identified software use, then searched for source code for the software packages mentioned in these research papers. We categorized the software to indicate whether source code is available for download and whether there are restrictions to accessing it, and if source code was not available, whether some other form of the software, such as a binary, was. Over 40% of the source code for the software used in our sample was not available for download.As URLs have often been used as proxy citations for software, we also extracted URLs from one journal’s 2015 research articles, removed those from certain long-term, reliable domains, and tested the remainder to determine what percentage of these URLs were still accessible in September and October, 2017.

  17. Two-terminal video coding.

    PubMed

    Yang, Yang; Stanković, Vladimir; Xiong, Zixiang; Zhao, Wei

    2009-03-01

    Following recent works on the rate region of the quadratic Gaussian two-terminal source coding problem and limit-approaching code designs, this paper examines multiterminal source coding of two correlated, i.e., stereo, video sequences to save the sum rate over independent coding of both sequences. Two multiterminal video coding schemes are proposed. In the first scheme, the left sequence of the stereo pair is coded by H.264/AVC and used at the joint decoder to facilitate Wyner-Ziv coding of the right video sequence. The first I-frame of the right sequence is successively coded by H.264/AVC Intracoding and Wyner-Ziv coding. An efficient stereo matching algorithm based on loopy belief propagation is then adopted at the decoder to produce pixel-level disparity maps between the corresponding frames of the two decoded video sequences on the fly. Based on the disparity maps, side information for both motion vectors and motion-compensated residual frames of the right sequence are generated at the decoder before Wyner-Ziv encoding. In the second scheme, source splitting is employed on top of classic and Wyner-Ziv coding for compression of both I-frames to allow flexible rate allocation between the two sequences. Experiments with both schemes on stereo video sequences using H.264/AVC, LDPC codes for Slepian-Wolf coding of the motion vectors, and scalar quantization in conjunction with LDPC codes for Wyner-Ziv coding of the residual coefficients give a slightly lower sum rate than separate H.264/AVC coding of both sequences at the same video quality.

  18. More box codes

    NASA Technical Reports Server (NTRS)

    Solomon, G.

    1992-01-01

    A new investigation shows that, starting from the BCH (21,15;3) code represented as a 7 x 3 matrix and adding a row and column to add even parity, one obtains an 8 x 4 matrix (32,15;8) code. An additional dimension is obtained by specifying odd parity on the rows and even parity on the columns, i.e., adjoining to the 8 x 4 matrix, the matrix, which is zero except for the fourth column (of all ones). Furthermore, any seven rows and three columns will form the BCH (21,15;3) code. This box code has the same weight structure as the quadratic residue and BCH codes of the same dimensions. Whether there exists an algebraic isomorphism to either code is as yet unknown.

  19. Eighteen years of recommendations to prevent industrial chemical incidents: results and lessons learned of the US Chemical Safety Board.

    PubMed

    Tinney, V A; Anenberg, S C; Kaszniak, M; Robinson, B

    2016-10-01

    The US Chemical Safety Board (CSB), a federal agency that investigates significant chemical incidents and hazards, is interested in determining the impact of the recommendations resulting from its investigations, and how to better more effective recommendations to prevent chemical incidents. This is a descriptive study of the US Chemical Safety Board's safety recommendations. The CSB coded and analysed its safety recommendations according to potential impact on reducing incidents, implementation status, purpose and recipient type. As of March 31, 2015, the CSB has issued 733 recommendations, 75% (548) of which are closed and 25% (185) of which remain open. For recommendations categorised as having high, medium, and low impact, 38% (78), 76% (160), and 78% (245) were implemented, respectively. CSB recommendations have led to important and lasting safety changes through regulations, industry guidance and voluntary consensus standards, and individual companies; however, coding recommendations by potential impact do not fully capture the influence of CSB recommendations. While this methodology serves as a preliminary way to determine the effect of recommendations, further data are needed to determine the extent to which these safety changes have reduced the frequency or severity of industrial accidents. Copyright © 2016 The Royal Society for Public Health. All rights reserved.

  20. Coding in Muscle Disease.

    PubMed

    Jones, Lyell K; Ney, John P

    2016-12-01

    Accurate coding is critically important for clinical practice and research. Ongoing changes to diagnostic and billing codes require the clinician to stay abreast of coding updates. Payment for health care services, data sets for health services research, and reporting for medical quality improvement all require accurate administrative coding. This article provides an overview of administrative coding for patients with muscle disease and includes a case-based review of diagnostic and Evaluation and Management (E/M) coding principles in patients with myopathy. Procedural coding for electrodiagnostic studies and neuromuscular ultrasound is also reviewed.