Games of multicellularity.

Science.gov (United States)

Kaveh, Kamran; Veller, Carl; Nowak, Martin A

2016-08-21

Evolutionary game dynamics are often studied in the context of different population structures. Here we propose a new population structure that is inspired by simple multicellular life forms. In our model, cells reproduce but can stay together after reproduction. They reach complexes of a certain size, n, before producing single cells again. The cells within a complex derive payoff from an evolutionary game by interacting with each other. The reproductive rate of cells is proportional to their payoff. We consider all two-strategy games. We study deterministic evolutionary dynamics with mutations, and derive exact conditions for selection to favor one strategy over another. Our main result has the same symmetry as the well-known sigma condition, which has been proven for stochastic game dynamics and weak selection. For a maximum complex size of n=2 our result holds for any intensity of selection. For n≥3 it holds for weak selection. As specific examples we study the prisoner's dilemma and hawk-dove games. Our model advances theoretical work on multicellularity by allowing for frequency-dependent interactions within groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Semiotic scaffolding of multicellularity

DEFF Research Database (Denmark)

Hoffmeyer, Jesper

2015-01-01

and animals this individuation process poses very different challenges in the three kingdoms of plants, fungi and animals, and the solutions found to these differences are discussed. In the same time as multicellularity ushered life into the epoch of mortality it logically also led to the appearance...

Computational Genetic Regulatory Networks Evolvable, Self-organizing Systems

CERN Document Server

Knabe, Johannes F

2013-01-01

Genetic Regulatory Networks (GRNs) in biological organisms are primary engines for cells to enact their engagements with environments, via incessant, continually active coupling. In differentiated multicellular organisms, tremendous complexity has arisen in the course of evolution of life on earth. Engineering and science have so far achieved no working system that can compare with this complexity, depth and scope of organization. Abstracting the dynamics of genetic regulatory control to a computational framework in which artificial GRNs in artificial simulated cells differentiate while connected in a changing topology, it is possible to apply Darwinian evolution in silico to study the capacity of such developmental/differentiated GRNs to evolve. In this volume an evolutionary GRN paradigm is investigated for its evolvability and robustness in models of biological clocks, in simple differentiated multicellularity, and in evolving artificial developing 'organisms' which grow and express an ontogeny starting fr...

Thinking about Bacillus subtilis as a multicellular organism.

Science.gov (United States)

Aguilar, Claudio; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

2007-12-01

Initial attempts to use colony morphogenesis as a tool to investigate bacterial multicellularity were limited by the fact that laboratory strains often have lost many of their developmental properties. Recent advances in elucidating the molecular mechanisms underlying colony morphogenesis have been made possible through the use of undomesticated strains. In particular, Bacillus subtilis has proven to be a remarkable model system to study colony morphogenesis because of its well-characterized developmental features. Genetic screens that analyze mutants defective in colony morphology have led to the discovery of an intricate regulatory network that controls the production of an extracellular matrix. This matrix is essential for the development of complex colony architecture characterized by aerial projections that serve as preferential sites for sporulation. While much progress has been made, the challenge for future studies will be to determine the underlying mechanisms that regulate development such that differentiation occurs in a spatially and temporally organized manner.

Apprehending Dom Casmurro through Criticism Posed to Novel and Television Micro-Series

Directory of Open Access Journals (Sweden)

Alexandre de Assis Monteiro

2016-09-01

Full Text Available This paper aims to identify modalities of dialogue between the television series Capitu by Luis Fernando Carvalho and the novel Dom Casmurro by Machado de Assis. It is based on the theory of narratology, mainly on Gerard Genette's contributions. In order to consolidate the study on the nature of narratives, we propose that the texts be read based on the available scrutiny of the two pieces. Moreover, we intend to apprehend the meanings of image and time related to the television show, the process of adaptation, and the modern artistic movements that are found in the process of transmutation of the narrative from a support based on verbal code to a support based on audio-visual-verbal code.

Experimental evolution of an alternating uni- and multicellular life cycle in Chlamydomonas reinhardtii

Science.gov (United States)

Ratcliff, William C.; Herron, Matthew D.; Howell, Kathryn; Pentz, Jennifer T.; Rosenzweig, Frank; Travisano, Michael

2013-01-01

The transition to multicellularity enabled the evolution of large, complex organisms, but early steps in this transition remain poorly understood. Here we show that multicellular complexity, including development from a single cell, can evolve rapidly in a unicellular organism that has never had a multicellular ancestor. We subject the alga Chlamydomonas reinhardtii to conditions that favour multicellularity, resulting in the evolution of a multicellular life cycle in which clusters reproduce via motile unicellular propagules. While a single-cell genetic bottleneck during ontogeny is widely regarded as an adaptation to limit among-cell conflict, its appearance very early in this transition suggests that it did not evolve for this purpose. Instead, we find that unicellular propagules are adaptive even in the absence of intercellular conflict, maximizing cluster-level fecundity. These results demonstrate that the unicellular bottleneck, a trait essential for evolving multicellular complexity, can arise rapidly via co-option of the ancestral unicellular form. PMID:24193369

Organism Size Promotes the Evolution of Specialized Cells in Multicellular Digital Organisms

OpenAIRE

Willensdorfer, Martin

2007-01-01

Specialized cells are the essence of complex multicellular life. Fossils allow us to study the modification of specialized, multicellular features such as jaws, scales, and muscular appendages. But it is still unclear what organismal properties contributed to the transition from undifferentiated organisms, which contain only a single cell type, to multicellular organisms with specialized cells. Using digital organisms I study this transition. My simulations show that the transition to special...

[Self-organization in the ontogeny of multicellular organisms: a computer simulation].

Science.gov (United States)

Markov, M A; Markov, A V

2011-01-01

The progress in understanding the patterns of evolution of ontogeny is hindered by the fact that many features of ontogeny are counterintuitive (as well as the features of other processes related to self-organization, self-assembly, and spontaneous increase in complexity). The basic principle of ontogeny of multicellular organisms is that it is the process of self-assembly of ordered multicellular structures by means of coordinated behavior of many individual modules (cells), each of which follows the same set of"rules" encoded in the genome. These rules are based on the genetic regulatory networks. We hypothesize that many specific features of ontogeny that seem nontrivial or enigmatic are, in fact, the inevitable consequences of this basic principle. If so, they do not need special explanations. In order to verify this hypothesis, we developed the computer program "Evo-Devo" based on the above principle. The program is designed to model the self-assembly of ordered multicellular structures from an aggregation of dividing cells that originate from a single original cell (zygote). Each cell follows a set of rules of behavior ("genotype") that can be specified arbitrarily by the experimenter, and is the same for all cells in the embryo (each cell is programmed in exactly the same way as all other cells). It is not allowed to specify rules for groups of cells or for the whole embryo: only local rules that should be followed at the level of a single cell are possible. The analysis of phenotypic implementation of different genotypes revealed several features which are present in the ontogeny of real organisms and are regularly reproduced in the model. These include: inherent stochasticity; inescapable necessity of development of stabilizing adaptations based on negative feedback in order to decrease this stochasticity; equifinality (noise resistance) resulting from these adaptations; the ability of ontogeny to respond to major perturbations by generating new

Multicellular models of intercellular synchronization in circadian neural networks

International Nuclear Information System (INIS)

Henson, Michael A.

2013-01-01

The circadian clock generates 24 h rhythms that drive physiological and behavioral processes in a diverse range of organisms including microbes, plants, insects, and mammals. Recent experimental advances have produced improved understanding of the molecular mechanisms involved in circadian rhythm generation at the single cell level. However, the intercellular mechanisms that allow large populations of coupled pacemaker cells to synchronize and coordinate their rhythms remain poorly understood. The purpose of this article is to review recent progress in dynamic modeling of the circadian clock with a focus on multicellular models required to describe cell population synchronization. Mammalian systems are emphasized to illustrate the highly heterogeneous structure and rich dynamical behavior of multicellular circadian systems. Available multicellular models are characterized with respect to their single cell descriptions, intercellular coupling mechanisms, and network topologies. Examples drawn from our own research are used to demonstrate the advantages associated with integrating detailed single cell models within realistic multicellular networks for prediction of mammalian system dynamics. Mathematical modeling is shown to represent a powerful tool for understanding the intracellular and intercellular mechanisms utilized to robustly synchronize large populations of highly heterogeneous and sparsely coupled single cell oscillators. The article concludes with some possible directions for future research

Cellular packing, mechanical stress and the evolution of multicellularity

Science.gov (United States)

Jacobeen, Shane; Pentz, Jennifer T.; Graba, Elyes C.; Brandys, Colin G.; Ratcliff, William C.; Yunker, Peter J.

2018-03-01

The evolution of multicellularity set the stage for sustained increases in organismal complexity1-5. However, a fundamental aspect of this transition remains largely unknown: how do simple clusters of cells evolve increased size when confronted by forces capable of breaking intracellular bonds? Here we show that multicellular snowflake yeast clusters6-8 fracture due to crowding-induced mechanical stress. Over seven weeks ( 291 generations) of daily selection for large size, snowflake clusters evolve to increase their radius 1.7-fold by reducing the accumulation of internal stress. During this period, cells within the clusters evolve to be more elongated, concomitant with a decrease in the cellular volume fraction of the clusters. The associated increase in free space reduces the internal stress caused by cellular growth, thus delaying fracture and increasing cluster size. This work demonstrates how readily natural selection finds simple, physical solutions to spatial constraints that limit the evolution of group size—a fundamental step in the evolution of multicellularity.

A conceptual framework for the evolutionary origins of multicellularity

International Nuclear Information System (INIS)

Libby, Eric; B Rainey, Paul

2013-01-01

The evolution of multicellular organisms from unicellular counterparts involved a transition in Darwinian individuality from single cells to groups. A particular challenge is to understand the nature of the earliest groups, the causes of their evolution, and the opportunities for emergence of Darwinian properties. Here we outline a conceptual framework based on a logical set of possible pathways for evolution of the simplest self-replicating groups. Central to these pathways is the recognition of a finite number of routes by which genetic information can be transmitted between individual cells and groups. We describe the form and organization of each primordial group state and consider factors affecting persistence and evolution of the nascent multicellular forms. Implications arising from our conceptual framework become apparent when attempting to partition fitness effects at individual and group levels. These are discussed with reference to the evolutionary emergence of individuality and its manifestation in extant multicellular life—including those of marginal Darwinian status. (paper)

Bacterial solutions to multicellularity : a tale of biofilms, filaments and fruiting bodies

NARCIS (Netherlands)

Claessen, Dennis; Rozen, Daniel E.; Kuipers, Oscar P.; Søgaard-Andersen, Lotte; Wezel, Gilles P. van

2014-01-01

Although bacteria frequently live as unicellular organisms, many spend at least part of their lives in complex communities, and some have adopted truly multicellular lifestyles and have abandoned unicellular growth. These transitions to multicellularity have occurred independently several times for

Evolution of multicellularity coincided with increased diversification of cyanobacteria and the Great Oxidation Event

Science.gov (United States)

Schirrmeister, Bettina E.; de Vos, Jurriaan M.; Antonelli, Alexandre; Bagheri, Homayoun C.

2013-01-01

Cyanobacteria are among the most diverse prokaryotic phyla, with morphotypes ranging from unicellular to multicellular filamentous forms, including those able to terminally (i.e., irreversibly) differentiate in form and function. It has been suggested that cyanobacteria raised oxygen levels in the atmosphere around 2.45–2.32 billion y ago during the Great Oxidation Event (GOE), hence dramatically changing life on the planet. However, little is known about the temporal evolution of cyanobacterial lineages, and possible interplay between the origin of multicellularity, diversification of cyanobacteria, and the rise of atmospheric oxygen. We estimated divergence times of extant cyanobacterial lineages under Bayesian relaxed clocks for a dataset of 16S rRNA sequences representing the entire known diversity of this phylum. We tested whether the evolution of multicellularity overlaps with the GOE, and whether multicellularity is associated with significant shifts in diversification rates in cyanobacteria. Our results indicate an origin of cyanobacteria before the rise of atmospheric oxygen. The evolution of multicellular forms coincides with the onset of the GOE and an increase in diversification rates. These results suggest that multicellularity could have played a key role in triggering cyanobacterial evolution around the GOE. PMID:23319632

A phase field approach for multicellular aggregate fusion in biofabrication.

Science.gov (United States)

Yang, Xiaofeng; Sun, Yi; Wang, Qi

2013-07-01

We present a modeling and computational approach to study fusion of multicellular aggregates during tissue and organ fabrication, which forms the foundation for the scaffold-less biofabrication of tissues and organs known as bioprinting. It is known as the phase field method, where multicellular aggregates are modeled as mixtures of multiphase complex fluids whose phase mixing or separation is governed by interphase force interactions, mimicking the cell-cell interaction in the multicellular aggregates, and intermediate range interaction mediated by the surrounding hydrogel. The material transport in the mixture is dictated by hydrodynamics as well as forces due to the interphase interactions. In a multicellular aggregate system with fixed number of cells and fixed amount of the hydrogel medium, the effect of cell differentiation, proliferation, and death are neglected in the current model, which can be readily included in the model, and the interaction between different components is dictated by the interaction energy between cell and cell as well as between cell and medium particles, respectively. The modeling approach is applicable to transient simulations of fusion of cellular aggregate systems at the time and length scale appropriate to biofabrication. Numerical experiments are presented to demonstrate fusion and cell sorting during tissue and organ maturation processes in biofabrication.

Differences in species richness patterns between unicellular and multicellular organisms.

Science.gov (United States)

Hillebrand, Helmut; Watermann, Frank; Karez, Rolf; Berninger, Ulrike-G

2001-01-01

For unicellular organisms, a lack of effects of local species richness on ecosystem function has been proposed due to their locally high species richness and their ubiquitous distribution. High dispersal ability and high individual numbers may enable unicellular taxa to occur everywhere. Using our own and published data sets on uni- and multicellular organisms, we conducted thorough statistical analyses to test whether (1) unicellular taxa show higher relative local species richness compared to multicellular taxa, (2) unicellular taxa show lower slopes of the species:area relationships and species:individuals relationships, and (3) the species composition of unicellular taxa is less influenced by geographic distance compared to multicellular taxa. We found higher local species richness compared to the global species pool for unicellular organisms than for metazoan taxa. The difference was significant if global species richness was conservatively estimated but not if extrapolated, and therefore higher richness estimates were used. Both microalgae and protozoans showed lower slopes between species richness and sample size (area or individuals) compared to macrozoobenthos, also indicating higher local species richness for unicellular taxa. The similarity of species composition of both benthic diatoms and ciliates decreased with increasing geographic distance. This indicated restricted dispersal ability of protists and the absence of ubiquity. However, a steeper slope between similarity and distance was found for polychaetes and corals, suggesting a stronger effect of distance on the dispersal of metazoans compared to unicellular taxa. In conclusion, we found partly different species richness patterns among uni- and multicellular eukaryotes, but no strict ubiquity of unicellular taxa. Therefore, the effect of local unicellular species richness on ecosystem function has to be reanalyzed. Macroecological patterns suggested for multicellular organisms may differ in

Resistance of multicellular aggregates to pharmorubicin observed in human hepatocarcinoma cells

Directory of Open Access Journals (Sweden)

Z. Jianmin

2002-02-01

Full Text Available The objective of the present study was to investigate the multicellular resistance of human hepatocarcinoma cells BEL-7402 to pharmorubicin. Cells (1 x 10(4 and 200 microcarrier Cytodex-3 beads were seeded onto a 24-well plate and cultured in RPMI 1640 medium. After the formation of multicellular aggregates, morphology and cell viability were analyzed by scanning electron microscopy, transmission electron microscopy and flow cytometry, respectively. The IC50 was determined by flow cytometry and MTT assay after the cells cultured in aggregates and monolayers were treated with pharmorubicin. The culture products exhibited structural characteristics somewhat similar to those of trabecular hepatocarcinoma in vivo. Among the microcarriers, cells were organized into several layers. Intercellular spaces were 0.5-2.0 µm wide and filled with many microvilli. The percent of viable cells was 87%. The cells cultured as multicellular aggregates were resistant to pharmorubicin with IC50 4.5-fold and 7.7-fold that of monolayer culture as determined by flow cytometry and MTT assay, respectively. This three-dimensional culture model may be used to investigate the mechanisms of multicellular drug resistance of hepatocarcinoma and to screen new anticancer drugs.

Role of multicellular aggregates in biofilm formation

DEFF Research Database (Denmark)

Kragh, Kasper N.; Hutchison, Jaime B.; Melaugh, Gavin

2016-01-01

In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. Howev...

Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa

Directory of Open Access Journals (Sweden)

Domazet-Lošo Tomislav

2010-05-01

Full Text Available Abstract Background Phylostratigraphy is a method used to correlate the evolutionary origin of founder genes (that is, functional founder protein domains of gene families with particular macroevolutionary transitions. It is based on a model of genome evolution that suggests that the origin of complex phenotypic innovations will be accompanied by the emergence of such founder genes, the descendants of which can still be traced in extant organisms. The origin of multicellularity can be considered to be a macroevolutionary transition, for which new gene functions would have been required. Cancer should be tightly connected to multicellular life since it can be viewed as a malfunction of interaction between cells in a multicellular organism. A phylostratigraphic tracking of the origin of cancer genes should, therefore, also provide insights into the origin of multicellularity. Results We find two strong peaks of the emergence of cancer related protein domains, one at the time of the origin of the first cell and the other around the time of the evolution of the multicellular metazoan organisms. These peaks correlate with two major classes of cancer genes, the 'caretakers', which are involved in general functions that support genome stability and the 'gatekeepers', which are involved in cellular signalling and growth processes. Interestingly, this phylogenetic succession mirrors the ontogenetic succession of tumour progression, where mutations in caretakers are thought to precede mutations in gatekeepers. Conclusions A link between multicellularity and formation of cancer has often been predicted. However, this has not so far been explicitly tested. Although we find that a significant number of protein domains involved in cancer predate the origin of multicellularity, the second peak of cancer protein domain emergence is, indeed, connected to a phylogenetic level where multicellular animals have emerged. The fact that we can find a strong and

A multicellular view of cytokinesis in epithelial tissue.

Science.gov (United States)

Herszterg, Sophie; Pinheiro, Diana; Bellaïche, Yohanns

2014-05-01

The study of cytokinesis in single-cell systems provided a wealth of knowledge on the molecular and biophysical mechanisms controlling daughter cell separation. In this review, we outline recent advances in the understanding of cytokinesis in epithelial tissues. These findings provide evidence for how the cytokinetic machinery adapts to a multicellular context and how the cytokinetic machinery is itself exploited by the tissue for the preservation of tissue function and architecture during proliferation. We propose that cytokinesis in epithelia should be viewed as a multicellular process, whereby the biochemical and mechanical interactions between the dividing cell and its neighbors are essential for successful daughter cell separation while defining epithelial tissue organization and preserving tissue integrity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multicellular stalk-like structures in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Engelberg, D.; Mimran, A.; Martinetto, H.; Otto, J.; Simchen, G.; Karin, M.; Fink, G.R.

1998-01-01

Stalk formation is a novel pattern of multicellular organization. Yeast cells which survive UV irradiation form colonies that grow vertically to form very long (0.5 to 3.0 cm) and thin (0.5 to 4 mm in diameter) multicellular structures. We describe the conditions required to obtain these stalk-like structures reproducibly in large numbers. Yeast mutants, mutated for control of cell polarity, developmental processes, UV response, and signal transduction cascades were tested and found capable of forming stalk-like structures. We suggest a model that explains the mechanism of stalk formation by mechanical environmental forces. We show that other microorganisms (Candida albicans, Schizosaccharomyces pombe, and Escherichia coli) also form stalks, suggesting that the ability to produce stalks may be a general property of microorganisms. Diploid yeast stalks sporulate at an elevated frequency, raising the possibility that the physiological role of stalks might be disseminating spores

Extracellular signaling and multicellularity in Bacillus subtilis.

Science.gov (United States)

Shank, Elizabeth Anne; Kolter, Roberto

2011-12-01

Bacillus subtilis regulates its ability to differentiate into distinct, co-existing cell types in response to extracellular signaling molecules produced either by itself, or present in its environment. The production of molecules by B. subtilis cells, as well as their response to these signals, is not uniform across the population. There is specificity and heterogeneity both within genetically identical populations as well as at the strain-level and species-level. This review will discuss how extracellular signaling compounds influence B. subtilis multicellularity with regard to matrix-producing cannibal differentiation, germination, and swarming behavior, as well as the specificity of the quorum-sensing peptides ComX and CSF. It will also highlight how imaging mass spectrometry can aid in identifying signaling compounds and contribute to our understanding of the functional relationship between such compounds and multicellular behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detecting tree-like multicellular life on extrasolar planets.

Science.gov (United States)

Doughty, Christopher E; Wolf, Adam

2010-11-01

Over the next two decades, NASA and ESA are planning a series of space-based observatories to find Earth-like planets and determine whether life exists on these planets. Previous studies have assessed the likelihood of detecting life through signs of biogenic gases in the atmosphere or a red edge. Biogenic gases and the red edge could be signs of either single-celled or multicellular life. In this study, we propose a technique with which to determine whether tree-like multicellular life exists on extrasolar planets. For multicellular photosynthetic organisms on Earth, competition for light and the need to transport water and nutrients has led to a tree-like body plan characterized by hierarchical branching networks. This design results in a distinct bidirectional reflectance distribution function (BRDF) that causes differing reflectance at different sun/view geometries. BRDF arises from the changing visibility of the shadows cast by objects, and the presence of tree-like structures is clearly distinguishable from flat ground with the same reflectance spectrum. We examined whether the BRDF could detect the existence of tree-like structures on an extrasolar planet by using changes in planetary albedo as a planet orbits its star. We used a semi-empirical BRDF model to simulate vegetation reflectance at different planetary phase angles and both simulated and real cloud cover to calculate disk and rotation-averaged planetary albedo for a vegetated and non-vegetated planet with abundant liquid water. We found that even if the entire planetary albedo were rendered to a single pixel, the rate of increase of albedo as a planet approaches full illumination would be comparatively greater on a vegetated planet than on a non-vegetated planet. Depending on how accurately planetary cloud cover can be resolved and the capabilities of the coronagraph to resolve exoplanets, this technique could theoretically detect tree-like multicellular life on exoplanets in 50 stellar systems.

Information transmission in genetic regulatory networks: a review

International Nuclear Information System (INIS)

Tkacik, Gasper; Walczak, Aleksandra M

2011-01-01

Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'. (topical review)

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

Science.gov (United States)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Bacterial biofilms: prokaryotic adventures in multicellularity

DEFF Research Database (Denmark)

Webb, J.S.; Givskov, Michael Christian; Kjelleberg, S.

2003-01-01

The development of bacterial biofilms includes both the initial social behavior of undifferentiated cells, as well as cell death and differentiation in the mature biofilm, and displays several striking similarities with higher organisms. Recent advances in the field provide new insight...... into differentiation and cell death events in bacterial biofilm development and propose that biofilms have an unexpected level of multicellularity....

Observation of multicellular spinning behavior of Proteus mirabilis by atomic force microscopy and multifunctional microscopy.

Science.gov (United States)

Liu, Yanxia; Deng, Yuanxin; Luo, Shuxiu; Deng, Yu; Guo, Linming; Xu, Weiwei; Liu, Lei; Liu, Junkang

2014-01-01

This study aimed to observe the multicellular spinning behavior of Proteus mirabilis by atomic force microscopy (AFM) and multifunctional microscopy in order to understand the mechanism underlying this spinning movement and its biological significance. Multifunctional microscopy with charge-coupled device (CCD) and real-time AFM showed changes in cell structure and shape of P. mirabilis during multicellular spinning movement. Specifically, the morphological characteristics of P. mirabilis, multicellular spinning dynamics, and unique movement were observed. Our findings indicate that the multicellular spinning behavior of P. mirabilis may be used to collect nutrients, perform colonization, and squeeze out competitors. The movement characteristics of P. mirabilis are vital to the organism's biological adaptability to the surrounding environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bio-electrosprayed multicellular zebrafish embryos are viable and develop normally

International Nuclear Information System (INIS)

Clarke, Jonathan D W; Jayasinghe, Suwan N

2008-01-01

Bio-electrosprays are rapidly emerging as a viable protocol for directly engineering living cells. This communication reports the bio-electrospraying of multicellular organisms, namely zebrafish embryos. The results demonstrate that the bio-electrospray protocol fails to induce any embryological perturbations. In addition to analysing overall embryo morphology, we use transgenic embryos that express green fluorescent protein in specific brain neurons to determine that neuronal numbers and organization are completely normal. These results demonstrate that the bio-electrospraying protocol does not interfere with the complex gene regulation and cell movements required for the development of a multicellular organism. (communication)

Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae.

Science.gov (United States)

Oud, Bart; Guadalupe-Medina, Victor; Nijkamp, Jurgen F; de Ridder, Dick; Pronk, Jack T; van Maris, Antonius J A; Daran, Jean-Marc

2013-11-05

Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and industrial applications of S. cerevisiae. Multicellular, fast-sedimenting lineages obtained from a haploid S. cerevisiae strain in two independent evolution experiments were analyzed by whole genome resequencing. The two evolved cell lines showed different frameshift mutations in a stretch of eight adenosines in ACE2, which encodes a transcriptional regulator involved in cell cycle control and mother-daughter cell separation. Introduction of the two ace2 mutant alleles into the haploid parental strain led to slow-sedimenting cell clusters that consisted of just a few cells, thus representing only a partial reconstruction of the evolved phenotype. In addition to single-nucleotide mutations, a whole-genome duplication event had occurred in both evolved multicellular strains. Construction of a diploid reference strain with two mutant ace2 alleles led to complete reconstruction of the multicellular-fast sedimenting phenotype. This study shows that whole-genome duplication and a frameshift mutation in ACE2 are sufficient to generate a fast-sedimenting, multicellular phenotype in S. cerevisiae. The nature of the ace2 mutations and their occurrence in two independent evolution experiments encompassing fewer than 500 generations of selective growth suggest that switching between unicellular and multicellular phenotypes may be relevant for competitiveness of S. cerevisiae in natural environments.

Trichomes: different regulatory networks lead to convergent structures.

Science.gov (United States)

Serna, Laura; Martin, Cathie

2006-06-01

Sometimes, proteins, biological structures or even organisms have similar functions and appearances but have evolved through widely divergent pathways. There is experimental evidence to suggest that different developmental pathways have converged to produce similar outgrowths of the aerial plant epidermis, referred to as trichomes. The emerging picture suggests that trichomes in Arabidopsis thaliana and, perhaps, in cotton develop through a transcriptional regulatory network that differs from those regulating trichome formation in Antirrhinum and Solanaceous species. Several lines of evidence suggest that the duplication of a gene controlling anthocyanin production and subsequent divergence might be the major force driving trichome formation in Arabidopsis, whereas the multicellular trichomes of Antirrhinum and Solanaceous species appear to have a different regulatory origin.

Cryopreservation of organotypic multicellular spheroids from human gliomas

NARCIS (Netherlands)

Kaaijk, P.; van den Berg, F.; van Amstel, P.; Troost, D.

1996-01-01

Fresh human glioma tissue can be cultured on agarose to form organotypic multicellular spheroids (OMS). The major advantage of OMS is the preservation of the cellular heterogeneity and the tumour architecture, which is lost in conventional monolayer cultures. The present study was undertaken to

THC and CBD in blood samples and seizures in Norway: Does CBD affect THC-induced impairment in apprehended subjects?

Science.gov (United States)

Havig, Stine Marie; Høiseth, Gudrun; Strand, Maren Cecilie; Karinen, Ritva Anneli; Brochmann, Gerd-Wenche; Strand, Dag Helge; Bachs, Liliana; Vindenes, Vigdis

2017-07-01

Several publications have suggested increasing cannabis potency over the last decade, which, together with lower amounts of cannabidiol (CBD), could contribute to an increase in adverse effects after cannabis smoking. Naturalistic studies on tetrahydrocannabinol (THC) and CBD in blood samples are, however, missing. This study aimed to investigate the relationship between THC- and CBD concentrations in blood samples among cannabis users, and to compare cannabinoid concentrations with the outcome of a clinical test of impairment (CTI) and between traffic accidents and non-accident driving under the influence of drugs (DUID)-cases. Assessment of THC- and CBD contents in cannabis seizures was also included. THC- and CBD concentrations in blood samples from subjects apprehended in Norway from April 2013-April 2015 were included (n=6134). A CTI result was compared with analytical findings in cases where only THC and/or CBD were detected (n=705). THC- and CBD content was measured in 41 cannabis seizures. Among THC-positive blood samples, 76% also tested positive for CBD. There was a strong correlation between THC- and CBD concentrations in blood samples (Pearson's r=0.714, pblood samples testing positive for THC, among subjects apprehended in Norway, also tested positive for CBD, suggesting frequent consumption of high CBD cannabis products. The simultaneous presence of CBD in blood does, however, not appear to affect THC-induced impairment on a CTI. Seizure sample analysis did not reveal high potency cannabis products, and while CBD content appeared high in hashish, it was almost absent in marijuana. Copyright © 2017. Published by Elsevier B.V.

Sponge cell reaggregation: Cellular structure and morphogenetic potencies of multicellular aggregates.

Science.gov (United States)

Lavrov, Andrey I; Kosevich, Igor A

2016-02-01

Sponges (phylum Porifera) are one of the most ancient extant multicellular animals and can provide valuable insights into origin and early evolution of Metazoa. High plasticity of cell differentiations and anatomical structure is characteristic feature of sponges. Present study deals with sponge cell reaggregation after dissociation as the most outstanding case of sponge plasticity. Dynamic of cell reaggregation and structure of multicellular aggregates of three demosponge species (Halichondria panicea (Pallas, 1766), Haliclona aquaeductus (Sсhmidt, 1862), and Halisarca dujardinii Johnston, 1842) were studied. Sponge tissue dissociation was performed mechanically. Resulting cell suspensions were cultured at 8-10°C for at least 5 days. Structure of multicellular aggregates was studied by light, transmission and scanning electron microscopy. Studied species share common stages of cell reaggregation-primary multicellular aggregates, early-stage primmorphs and primmorphs, but the rate of reaggregation varies considerably among species. Only cells of H. dujardinii are able to reconstruct functional and viable sponge after primmorphs formation. Sponge reconstruction in this species occurs due to active cell locomotion. Development of H. aquaeductus and H. panicea cells ceases at the stages of early primmorphs and primmorphs, respectively. Development of aggregates of these species is most likely arrested due to immobility of the majority of cells inside them. However, the inability of certain sponge species to reconstruct functional and viable individuals during cell reaggregation may be not a permanent species-specific characteristic, but depends on various factors, including the stage of the life cycle and experimental conditions. © 2016 Wiley Periodicals, Inc.

Genomic analysis of organismal complexity in the multicellular green alga Volvox carteri

Energy Technology Data Exchange (ETDEWEB)

Prochnik, Simon E.; Umen, James; Nedelcu, Aurora; Hallmann, Armin; Miller, Stephen M.; Nishii, Ichiro; Ferris, Patrick; Kuo, Alan; Mitros, Therese; Fritz-Laylin, Lillian K.; Hellsten, Uffe; Chapman, Jarrod; Simakov, Oleg; Rensing, Stefan A.; Terry, Astrid; Pangilinan, Jasmyn; Kapitonov, Vladimir; Jurka, Jerzy; Salamov, Asaf; Shapiro, Harris; Schmutz, Jeremy; Grimwood, Jane; Lindquist, Erika; Lucas, Susan; Grigoriev, Igor V.; Schmitt, Rudiger; Kirk, David; Rokhsar, Daniel S.

2010-07-01

Analysis of the Volvox carteri genome reveals that this green alga's increased organismal complexity and multicellularity are associated with modifications in protein families shared with its unicellular ancestor, and not with large-scale innovations in protein coding capacity. The multicellular green alga Volvox carteri and its morphologically diverse close relatives (the volvocine algae) are uniquely suited for investigating the evolution of multicellularity and development. We sequenced the 138 Mb genome of V. carteri and compared its {approx}14,500 predicted proteins to those of its unicellular relative, Chlamydomonas reinhardtii. Despite fundamental differences in organismal complexity and life history, the two species have similar protein-coding potentials, and few species-specific protein-coding gene predictions. Interestingly, volvocine algal-specific proteins are enriched in Volvox, including those associated with an expanded and highly compartmentalized extracellular matrix. Our analysis shows that increases in organismal complexity can be associated with modifications of lineage-specific proteins rather than large-scale invention of protein-coding capacity.

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

Science.gov (United States)

Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

2012-01-01

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to

Geometry, packing, and evolutionary paths to increased multicellular size

Science.gov (United States)

Jacobeen, Shane; Graba, Elyes C.; Brandys, Colin G.; Day, Thomas C.; Ratcliff, William C.; Yunker, Peter J.

2018-05-01

The evolutionary transition to multicellularity transformed life on earth, heralding the evolution of large, complex organisms. Recent experiments demonstrated that laboratory-evolved multicellular "snowflake yeast" readily overcome the physical barriers that limit cluster size by modifying cellular geometry [Jacobeen et al., Nat. Phys. 14, 286 (2018), 10.1038/s41567-017-0002-y]. However, it is unclear why this route to large size is observed, rather than an evolved increase in intercellular bond strength. Here, we use a geometric model of the snowflake yeast growth form to examine the geometric efficiency of increasing size by modifying geometry and bond strength. We find that changing geometry is a far more efficient route to large size than evolving increased intercellular adhesion. In fact, increasing cellular aspect ratio is on average ˜13 times more effective than increasing bond strength at increasing the number of cells in a cluster. Modifying other geometric parameters, such as the geometric arrangement of mother and daughter cells, also had larger effects on cluster size than increasing bond strength. Simulations reveal that as cells reproduce, internal stress in the cluster increases rapidly; thus, increasing bond strength provides diminishing returns in cluster size. Conversely, as cells become more elongated, cellular packing density within the cluster decreases, which substantially decreases the rate of internal stress accumulation. This suggests that geometrically imposed physical constraints may have been a key early selective force guiding the emergence of multicellular complexity.

Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

Science.gov (United States)

Ari-Wahjoedi, Bambang; Ginta, Turnad Lenggo; Parman, Setyamartana; Abustaman, Mohd Zikri Ahmad

2014-10-01

Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm-3 respectively, pore linear density of ±35 cm-1, linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively.

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

Science.gov (United States)

Woolf, N; Pearson, B E; Bondzie, P A; Meyer, R D; Lavaei, M; Belkina, A C; Chitalia, V; Rahimi, N

2017-09-18

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis.

Science.gov (United States)

López, Daniel; Fischbach, Michael A; Chu, Frances; Losick, Richard; Kolter, Roberto

2009-01-06

We report a previously undescribed quorum-sensing mechanism for triggering multicellularity in Bacillus subtilis. B. subtilis forms communities of cells known as biofilms in response to an unknown signal. We discovered that biofilm formation is stimulated by a variety of small molecules produced by bacteria--including the B. subtilis nonribosomal peptide surfactin--that share the ability to induce potassium leakage. Natural products that do not cause potassium leakage failed to induce multicellularity. Small-molecule-induced multicellularity was prevented by the addition of potassium, but not sodium or lithium. Evidence is presented that potassium leakage stimulates the activity of a membrane protein kinase, KinC, which governs the expression of genes involved in biofilm formation. We propose that KinC responds to lowered intracellular potassium concentration and that this is a quorum-sensing mechanism that enables B. subtilis to respond to related and unrelated bacteria.

Theoretical analysis of the spatio-temporal structure of bone multicellular units

International Nuclear Information System (INIS)

Buenzli, P R; Pivonka, P; Gardiner, B S; Smith, D W; Dunstan, C R; Mundy, G R

2010-01-01

Bone multicellular units (BMUs) maintain the viability of the skeletal tissue by coordinating locally the sequence of bone resorption and bone formation performed by cells of the osteoclastic and osteoblastic lineage. Understanding the emergence and the net bone balance of such structured microsystems out of the complex network of biochemical interactions between bone cells is fundamental for many bone-related diseases and the evaluation of fracture risk. Based on current experimental knowledge, we propose a spatio-temporal continuum model describing the interactions of osteoblastic and osteoclastic cells. We show that this model admits travelling-wave-like solutions with well-confined cell profiles upon specifying external conditions mimicking the environment encountered in cortical bone remodelling. The shapes of the various cell concentration profiles within this travelling structure are intrinsically linked to the parameters of the model such as differentiation, proliferation, and apoptosis rates of bone cells. The internal structure of BMUs is reproduced, allowing for experimental calibration. The spatial distribution of the key regulatory factors can also be exhibited, which in diseased states could give hints as to the biochemical agent most accountable for the disorder.

Radiosensitivity of different human tumor cells lines grown as multicellular spheroids determined from growth curves and survival data

International Nuclear Information System (INIS)

Schwachoefer, J.H.C.; Crooijmans, R.P.; van Gasteren, J.J.; Hoogenhout, J.; Jerusalem, C.R.; Kal, H.B.; Theeuwes, A.G.

1989-01-01

Five human tumor cell lines were grown as multicellular tumor spheroids (MTS) to determine whether multicellular tumor spheroids derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences paralleled clinical behavior. Multicellular tumor spheroids of two neuroblastoma, one lung adenocarcinoma, one melanoma, and a squamous cell carcinoma of the oral tongue, were studied in terms of growth delay, calculated cell survival, and spheroid control dose50 (SCD50). Growth delay and cell survival analysis for the tumor cell lines showed sensitivities that correlated well with clinical behavior of the tumor types of origin. Similar to other studies on melanoma multicellular tumor spheroids our spheroid control dose50 results for the melanoma cell line deviated from the general pattern of sensitivity. This might be due to the location of surviving cells, which prohibits proliferation of surviving cells and hence growth of melanoma multicellular tumor spheroids. This study demonstrates that radiosensitivity of human tumor cell lines can be evaluated in terms of growth delay, calculated cell survival, and spheroid control dose50 when grown as multicellular tumor spheroids. The sensitivity established from these evaluations parallels clinical behavior, thus offering a unique tool for the in vitro analysis of human tumor radiosensitivity

Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

International Nuclear Information System (INIS)

Ari-Wahjoedi, Bambang; Ginta, Turnad Lenggo; Parman, Setyamartana; Abustaman, Mohd Zikri Ahmad

2014-01-01

Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm −3 respectively, pore linear density of ±35 cm −1 , linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively

Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

Energy Technology Data Exchange (ETDEWEB)

Ari-Wahjoedi, Bambang, E-mail: bambang-ariwahjoedi@petronas.com.my [Department of Fundamental and Applied Sciences, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Centre for Intelligent Signal and Imaging Research, Universiti Teknologi PETRONAS, Bandar Seri Iskandar (Malaysia); Ginta, Turnad Lenggo [Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Centre for Intelligent Signal and Imaging Research, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tro (Malaysia); Parman, Setyamartana [Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Abustaman, Mohd Zikri Ahmad [Kebabangan Petroleum Operating Company Sdn Bhd, Lvl. 52, Tower 2, PETRONAS Twin Towers, KLCC, 50088 Kuala Lumpur (Malaysia)

2014-10-24

Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm{sup −3} respectively, pore linear density of ±35 cm{sup −1}, linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively.

Multicellular spheroids as an in vitro tumor model

International Nuclear Information System (INIS)

Kozubek, S.; Erzgraber, G.

1982-01-01

Experiments with fractionated irradiation of multicellular spheroids were performed. Our data as well as the data of other works have been evaluated by means of simple mathematical formulae on the basis of several hypothesis. The spheroids are shown to exhibit similar behaviour as in vivo carcinomas. They offer the possibility of investigation of quantitative correlations for practical purposes

Directed self-assembly of large scaffold-free multi-cellular honeycomb structures

International Nuclear Information System (INIS)

Tejavibulya, Nalin; Youssef, Jacquelyn; Bao, Brian; Ferruccio, Toni-Marie; Morgan, Jeffrey R

2011-01-01

A significant challenge to the field of biofabrication is the rapid construction of large three-dimensional (3D) living tissues and organs. Multi-cellular spheroids have been used as building blocks. In this paper, we create large multi-cellular honeycomb building blocks using directed self-assembly, whereby cell-to-cell adhesion, in the context of the shape and obstacles of a micro-mold, drives the formation of a 3D structure. Computer-aided design, rapid prototyping and replica molding were used to fabricate honeycomb-shaped micro-molds. Nonadhesive hydrogels cast from these micro-molds were equilibrated in the cell culture medium and seeded with two types of mammalian cells. The cells settled into the honeycomb recess were unable to attach to the nonadhesive hydrogel and so cell-to-cell adhesion drove the self-assembly of a large multi-cellular honeycomb within 24 h. Distinct morphological changes occurred to the honeycomb and its cells indicating the presence of significant cell-mediated tension. Unlike the spheroid, whose size is constrained by a critical diffusion distance needed to maintain cell viability, the overall size of the honeycomb is not limited. The rapid production of the honeycomb building unit, with its multiple rings of high-density cells and open lumen spaces, offers interesting new possibilities for biofabrication strategies.

Switching from a unicellular to multicellular organization in an Aspergillus niger hypha.

Science.gov (United States)

Bleichrodt, Robert-Jan; Hulsman, Marc; Wösten, Han A B; Reinders, Marcel J T

2015-03-03

Pores in fungal septa enable cytoplasmic streaming between hyphae and their compartments. Consequently, the mycelium can be considered unicellular. However, we show here that Woronin bodies close ~50% of the three most apical septa of growing hyphae of Aspergillus niger. The incidence of closure of the 9th and 10th septa was even ≥94%. Intercompartmental streaming of photoactivatable green fluorescent protein (PA-GFP) was not observed when the septa were closed, but open septa acted as a barrier, reducing the mobility rate of PA-GFP ~500 times. This mobility rate decreased with increasing septal age and under stress conditions, likely reflecting a regulatory mechanism affecting septal pore diameter. Modeling revealed that such regulation offers effective control of compound concentration between compartments. Modeling also showed that the incidence of septal closure in A. niger had an even stronger impact on cytoplasmic continuity. Cytoplasm of hyphal compartments was shown not to be in physical contact when separated by more than 4 septa. Together, data show that apical compartments of growing hyphae behave unicellularly, while older compartments have a multicellular organization. The hyphae of higher fungi are compartmentalized by porous septa that enable cytosolic streaming. Therefore, it is believed that the mycelium shares cytoplasm. However, it is shown here that the septa of Aspergillus niger are always closed in the oldest part of the hyphae, and therefore, these compartments are physically isolated from each other. In contrast, only part of the septa is closed in the youngest part of the hyphae. Still, compartments in this hyphal part are physically isolated when separated by more than 4 septa. Even open septa act as a barrier for cytoplasmic mixing. The mobility rate through such septa reduces with increasing septal age and under stress conditions. Modeling shows that the septal pore width is set such that its regulation offers maximal control of

Method for the determination of oxygen consumption rates and diffusion coefficients in multicellular spheroids

OpenAIRE

Mueller-Klieser, W.

1984-01-01

A method has been developed for the quantitative evaluation of oxygen tension (PO2) distributions in multicellular spheroids measured with O2-sensitive microelectrodes. The experimental data showed that multicellular tumor spheroids in stirred growth media were characterized by a diffusion-depleted zone surrounding the spheroids. This zone was elicited by an unstirred layer of medium next to the spheroid leading to a continuous decrease in the PO2 values from the bulk medium towards the spher...

Genome semantics, in silico multicellular systems and the Central Dogma.

Science.gov (United States)

Werner, Eric

2005-03-21

Genomes with their complexity and size present what appears to be an impossible challenge. Scientists speak in terms of decades or even centuries before we will understand how genomes and their hosts the cell and the city of cells that make up the multicellular context function. We believe that there will be surprisingly quick progress made in our understanding of genomes. The key is to stop taking the Central Dogma as the only direction in which genome research can scale the semantics of genomes. Instead a top-down approach coupled with a bottom-up approach may snare the unwieldy beast and make sense of genomes. The method we propose is to take in silico biology seriously. By developing in silico models of genomes cells and multicellular systems, we position ourselves to develop a theory of meaning for artificial genomes. Then using that develop a natural semantics of genomes.

The development and structure of thick-walled, multicellular, aerial spores in Diheterospora chlamydosporia (=Verticillium chlamydosporium).

Science.gov (United States)

Cambell, W P; Griffiths, D A

1975-07-01

The aerial, thick-walled spores in Diheterospara chlamydosporia arose as terminal swellings on erect hyphae. Repeated septation of the continuously swelling spore resulted in a multicellular structure. Immediately after the onset of septation secondary wall material was laid down between the two-layered primary wall and the plasmalemma. The presence of secondary wall material indicates that the multicellular spore is a dictyochlamydospore and not an aleuriospore. The relationship between chlamydospores and aleuriospores in other fungi is discussed.

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems.

Science.gov (United States)

Ghaffarizadeh, Ahmadreza; Heiland, Randy; Friedman, Samuel H; Mumenthaler, Shannon M; Macklin, Paul

2018-02-01

Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal "virtual laboratory" for such multicellular systems simulates both the biochemical microenvironment (the "stage") and many mechanically and biochemically interacting cells (the "players" upon the stage). PhysiCell-physics-based multicellular simulator-is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility "out of the box." The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a "cellular cargo delivery" system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also represents a significant

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems

Science.gov (United States)

Ghaffarizadeh, Ahmadreza; Mumenthaler, Shannon M.

2018-01-01

Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal “virtual laboratory” for such multicellular systems simulates both the biochemical microenvironment (the “stage”) and many mechanically and biochemically interacting cells (the “players” upon the stage). PhysiCell—physics-based multicellular simulator—is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility “out of the box.” The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a “cellular cargo delivery” system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also

On the origin of biological construction, with a focus on multicellularity.

Science.gov (United States)

van Gestel, Jordi; Tarnita, Corina E

2017-10-17

Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results from hierarchical evolutionary transitions, in which biological units (e.g., cells) form groups that evolve into new units of biological organization (e.g., multicellular organisms). Despite considerable advances, there is no bottom-up, dynamical account of how, starting from the solitary ancestor, the first groups originate and subsequently evolve the organizing principles that qualify them as new units. Guided by six central questions, we propose an integrative bottom-up approach for studying the dynamics underlying hierarchical evolutionary transitions, which builds on and synthesizes existing knowledge. This approach highlights the crucial role of the ecology and development of the solitary ancestor in the emergence and subsequent evolution of groups, and it stresses the paramount importance of the life cycle: only by evaluating groups in the context of their life cycle can we unravel the evolutionary trajectory of hierarchical transitions. These insights also provide a starting point for understanding the types of subsequent organizational complexity. The central research questions outlined here naturally link existing research programs on biological construction (e.g., on cooperation, multilevel selection, self-organization, and development) and thereby help integrate knowledge stemming from diverse fields of biology.

Bacterial stigmergy: an organising principle of multicellular collective behaviours of bacteria.

Science.gov (United States)

Gloag, Erin S; Turnbull, Lynne; Whitchurch, Cynthia B

2015-01-01

The self-organisation of collective behaviours often manifests as dramatic patterns of emergent large-scale order. This is true for relatively "simple" entities such as microbial communities and robot "swarms," through to more complex self-organised systems such as those displayed by social insects, migrating herds, and many human activities. The principle of stigmergy describes those self-organised phenomena that emerge as a consequence of indirect communication between individuals of the group through the generation of persistent cues in the environment. Interestingly, despite numerous examples of multicellular behaviours of bacteria, the principle of stigmergy has yet to become an accepted theoretical framework that describes how bacterial collectives self-organise. Here we review some examples of multicellular bacterial behaviours in the context of stigmergy with the aim of bringing this powerful and elegant self-organisation principle to the attention of the microbial research community.

Biomaterial Substrate-Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering.

Science.gov (United States)

Tseng, Ting-Chen; Wong, Chui-Wei; Hsieh, Fu-Yu; Hsu, Shan-Hui

2017-12-01

Three-dimentional (3D) multicellular aggregates (spheroids), compared to the traditional 2D monolayer cultured cells, are physiologically more similar to the cells in vivo. So far there are various techniques to generate 3D spheroids. Spheroids obtained from different methods have already been applied to regenerative medicine or cancer research. Among the cell spheroids created by different methods, the substrate-derived spheroids and their forming mechanism are unique. This review focuses on the formation of biomaterial substrate-mediated multicellular spheroids and their applications in tissue engineering and tumor models. First, the authors will describe the special chitosan substrate-derived mesenchymal stem cell (MSC) spheroids and their greater regenerative capacities in various tissues. Second, the authors will describe tumor spheroids derived on chitosan and hyaluronan substrates, which serve as a simple in vitro platform to study 3D tumor models or to perform cancer drug screening. Finally, the authors will mention the self-assembly process for substrate-derived multiple cell spheroids (co-spheroids), which may recapitulate the heterotypic cell-cell interaction for co-cultured cells or crosstalk between different types of cells. These unique multicellular mono-spheroids or co-spheroids represent a category of 3D cell culture with advantages of biomimetic cell-cell interaction, better functionalities, and imaging possibilities. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A 3D printed microfluidic perfusion device for multicellular spheroid cultures.

Science.gov (United States)

Ong, Louis Jun Ye; Islam, Anik; DasGupta, Ramanuj; Iyer, Narayanan Gopalakkrishna; Leo, Hwa Liang; Toh, Yi-Chin

2017-09-11

The advent of 3D printing technologies promises to make microfluidic organ-on-chip technologies more accessible for the biological research community. To date, hydrogel-encapsulated cells have been successfully incorporated into 3D printed microfluidic devices. However, there is currently no 3D printed microfluidic device that can support multicellular spheroid culture, which facilitates extensive cell-cell contacts important for recapitulating many multicellular functional biological structures. Here, we report a first instance of fabricating a 3D printed microfluidic cell culture device capable of directly immobilizing and maintaining the viability and functionality of 3D multicellular spheroids. We evaluated the feasibility of two common 3D printing technologies i.e. stereolithography (SLA) and PolyJet printing, and found that SLA could prototype a device comprising of cell immobilizing micro-structures that were housed within a microfluidic network with higher fidelity. We have also implemented a pump-free perfusion system, relying on gravity-driven flow to perform medium perfusion in order to reduce the complexity and footprint of the device setup, thereby improving its adaptability into a standard biological laboratory. Finally, we demonstrated the biological performance of the 3D printed device by performing pump-free perfusion cultures of patient-derived parental and metastatic oral squamous cell carcinoma tumor and liver cell (HepG2) spheroids with good cell viability and functionality. This paper presents a proof-of-concept in simplifying and integrating the prototyping and operation of a microfluidic spheroid culture device, which will facilitate its applications in various drug efficacy, metabolism and toxicity studies.

Plug-and-Play Multicellular Circuits with Time-Dependent Dynamic Responses.

Science.gov (United States)

Urrios, Arturo; Gonzalez-Flo, Eva; Canadell, David; de Nadal, Eulàlia; Macia, Javier; Posas, Francesc

2018-04-20

Synthetic biology studies aim to develop cellular devices for biomedical applications. These devices, based on living instead of electronic or electromechanic technology, might provide alternative treatments for a wide range of diseases. However, the feasibility of these devices depends, in many cases, on complex genetic circuits that must fulfill physiological requirements. In this work, we explored the potential of multicellular architectures to act as an alternative to complex circuits for implementation of new devices. As a proof of concept, we developed specific circuits for insulin or glucagon production in response to different glucose levels. Here, we show that fundamental features, such as circuit's affinity or sensitivity, are dependent on the specific configuration of the multicellular consortia, providing a method for tuning these properties without genetic engineering. As an example, we have designed and built circuits with an incoherent feed-forward loop architecture (FFL) that can be easily adjusted to generate single pulse responses. Our results might serve as a blueprint for future development of cellular devices for glycemia regulation in diabetic patients.

Role of Multicellular Aggregates in Biofilm Formation

Directory of Open Access Journals (Sweden)

Kasper N. Kragh

2016-03-01

Full Text Available In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of Pseudomonas aeruginosa biofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation.

Heavy-ion radiobiology of multicellular tumor spheroids

International Nuclear Information System (INIS)

Rodriguez, A.; Alpen, E.L.

1980-01-01

Experiments reported here were conducted with carbon ions, neon ions, and argon ions using rat brain gliosarcoma (9L) and Chinese hamster lung V79 cells grown as multicellular spheroids. Our studies were designed to evaluate high-LET radiation survival characteristics of cells grown in this relatively organized tissue-like environment. Our primary objectives were to determine the RBE values in plateau and spread Bragg peak regions of the carbon, neon, and argon beams, and evaluate with high and low LET radiation, the role of spheroid architecture in postirradiation survival of cells grown in this format

A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis.

Science.gov (United States)

Grau, Roberto R; de Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos-Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Donato, Verónica; Hölscher, Theresa; Boland, Wilhelm; Kuipers, Oscar P; Kovács, Ákos T

2015-07-07

decision to move over or stay attached to a surface controlled? Here, we use the model plant-beneficial bacterium Bacillus subtilis to answer this question. Remarkably, we discover that sessile biofilm formation and social sliding motility share the same structural components and the Spo0A regulatory network via sensor kinases, KinB and KinC. Potassium, an inhibitor of KinC-dependent biofilm formation, triggers sliding via a potassium-perceiving cytosolic domain of KinB that resembles the selectivity filter of potassium channels. The spatiotemporal response of these kinases to variable potassium levels and the gradual increase in Spo0A~Pi levels that orchestrates the activation of sliding before biofilm formation shed light on how multicellular behaviors formerly believed to be antagonistic work together to benefit the population fitness. Copyright © 2015 Grau et al.

How 5000 independent rowers coordinate their strokes in order to row into the sunlight: Phototaxis in the multicellular green alga Volvox

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Matsunaga Shigeru

2010-07-01

Full Text Available Abstract Background The evolution of multicellular motile organisms from unicellular ancestors required the utilization of previously evolved tactic behavior in a multicellular context. Volvocine green algae are uniquely suited for studying tactic responses during the transition to multicellularity because they range in complexity from unicellular to multicellular genera. Phototactic responses are essential for these flagellates because they need to orientate themselves to receive sufficient light for photosynthesis, but how does a multicellular organism accomplish phototaxis without any known direct communication among cells? Several aspects of the photoresponse have previously been analyzed in volvocine algae, particularly in the unicellular alga Chlamydomonas. Results In this study, the phototactic behavior in the spheroidal, multicellular volvocine green alga Volvox rousseletii (Volvocales, Chlorophyta was analyzed. In response to light stimuli, not only did the flagella waveform and beat frequency change, but the effective stroke was reversed. Moreover, there was a photoresponse gradient from the anterior to the posterior pole of the spheroid, and only cells of the anterior hemisphere showed an effective response. The latter caused a reverse of the fluid flow that was confined to the anterior hemisphere. The responsiveness to light is consistent with an anterior-to-posterior size gradient of eyespots. At the posterior pole, the eyespots are tiny or absent, making the corresponding cells appear to be blind. Pulsed light stimulation of an immobilized spheroid was used to simulate the light fluctuation experienced by a rotating spheroid during phototaxis. The results demonstrated that in free-swimming spheroids, only those cells of the anterior hemisphere that face toward the light source reverse the beating direction in the presence of illumination; this behavior results in phototactic turning. Moreover, positive phototaxis is facilitated by

Predictive modeling of multicellular structure formation by using Cellular Particle Dynamics simulations

Science.gov (United States)

McCune, Matthew; Shafiee, Ashkan; Forgacs, Gabor; Kosztin, Ioan

2014-03-01

Cellular Particle Dynamics (CPD) is an effective computational method for describing and predicting the time evolution of biomechanical relaxation processes of multicellular systems. A typical example is the fusion of spheroidal bioink particles during post bioprinting structure formation. In CPD cells are modeled as an ensemble of cellular particles (CPs) that interact via short-range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through integration of their equations of motion. CPD was successfully applied to describe and predict the fusion of 3D tissue construct involving identical spherical aggregates. Here, we demonstrate that CPD can also predict tissue formation involving uneven spherical aggregates whose volumes decrease during the fusion process. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images.

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Assaf Zaritsky

Full Text Available Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional

Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images.

Science.gov (United States)

Zaritsky, Assaf; Natan, Sari; Horev, Judith; Hecht, Inbal; Wolf, Lior; Ben-Jacob, Eshel; Tsarfaty, Ilan

2011-01-01

Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs) is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF) on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC) images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional fluorescence single

The Emergence of Multi-Cellular Robot Organisms through On-line On-board Evolution

NARCIS (Netherlands)

Weel, B.P.M.; Haasdijk, E.W.; Eiben, A.E.

2012-01-01

We investigate whether a swarm of robots can evolve controllers that cause aggregation into 'multi-cellular' robot organisms without a specific reward to do so. To this end, we create a world where aggregated robots receive more energy than individual ones and enable robots to evolve their

Synergistic interaction between cisplatin and gemcitabine in neuroblastoma cell lines and multicellular tumor spheroids

NARCIS (Netherlands)

Besançon, Odette G.; Tytgat, Godelieve A. M.; Meinsma, Rutger; Leen, René; Hoebink, Jerry; Kalayda, Ganna V.; Jaehde, Ulrich; Caron, Huib N.; van Kuilenburg, André B. P.

2012-01-01

The efficacy and mechanism of action of cisplatin and gemcitabine were investigated in a panel of neuroblastoma cell lines and multicellular tumor spheroids. In neuroblastoma spheroids, the combination of cisplatin and gemcitabine induced a complete cytostasis at clinical relevant concentrations. A

A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis

NARCIS (Netherlands)

Grau, Roberto R; de Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos-Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Donato, Verónica; Hölscher, Theresa; Boland, Wilhelm; Kuipers, Oscar P; Kovács, Ákos T

2015-01-01

Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor

Multicellular tumor spheroid interactions with bone cells and bone

International Nuclear Information System (INIS)

Wezeman, F.H.; Guzzino, K.M.; Waxler, B.

1985-01-01

In vitro coculture techniques were used to study HSDM1C1 murine fibrosarcoma multicellular tumor spheroid (HSDM1C1-MTS) interactions with mouse calvarial bone cells having osteoblastic characteristics and mouse bone explants. HSDM1C1-MTS attached to confluent bone cell monolayers and their attachment rate was quantified. HSDM1C1-MTS interaction with bone cells was further demonstrated by the release of 3 H-deoxyuridine from prelabeled bone cells during coculture with multicellular tumor spheroids. HSDM1C1-MTS-induced cytotoxicity was mimicked by the addition of 10(-5) M prostaglandin E2 (PGE2) to 3 H-deoxyuridine-labeled bone cells. The effects of low (10(-9) M) and high (10(-5) M) concentrations of PGE2 on bone cell proliferation were also studied. Higher concentrations of PGE2 inhibited bone cell proliferation. HSDM1C1-MTS resorbed living explants in the presence of indomethacin, suggesting that other tumor cell products may also participate in bone resorption. HSDM1C1-MTS caused direct bone resorption as measured by the significantly elevated release of 45 Ca from prelabeled, devitalized calvaria. However, the growth of a confluent bone cell layer on devitalized, 45 Ca-prelabeled calvaria resulted in a significant reduction in the amount of 45 Ca released subsequent to the seeding of HSDM1C1-MTS onto the explants. Bone cells at the bone surface may act as a barrier against invasion and tumor cell-mediated bone resorption. Violation of this cellular barrier is achieved, in part, by tumor cell products

RssAB signaling coordinates early development of surface multicellularity in Serratia marcescens.

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Yu-Huan Tsai

Full Text Available Bacteria can coordinate several multicellular behaviors in response to environmental changes. Among these, swarming and biofilm formation have attracted significant attention for their correlation with bacterial pathogenicity. However, little is known about when and where the signaling occurs to trigger either swarming or biofilm formation. We have previously identified an RssAB two-component system involved in the regulation of swarming motility and biofilm formation in Serratia marcescens. Here we monitored the RssAB signaling status within single cells by tracing the location of the translational fusion protein EGFP-RssB following development of swarming or biofilm formation. RssAB signaling is specifically activated before surface migration in swarming development and during the early stage of biofilm formation. The activation results in the release of RssB from its cognate inner membrane sensor kinase, RssA, to the cytoplasm where the downstream gene promoters are located. Such dynamic localization of RssB requires phosphorylation of this regulator. By revealing the temporal activation of RssAB signaling following development of surface multicellular behavior, our findings contribute to an improved understanding of how bacteria coordinate their lifestyle on a surface.

Daunorubicin and doxorubicin but not BCNU have deleterious effects on organotypic multicellular spheroids of gliomas

NARCIS (Netherlands)

Kaaijk, P.; Troost, D.; de Boer, O. J.; van Amstel, P.; Bakker, P. J.; Leenstra, S.; Bosch, D. A.

1996-01-01

In the present study organotypic multicellular spheroids (OMS) were used to study the effects of chemotherapeutic agents on malignant gliomas. Compared with the frequently used cell line models, OMS have several advantages with respect to the preservation of the cellular heterogeneity and the

Rapid formation of size-controllable multicellular spheroids via 3D acoustic tweezers

OpenAIRE

Chen, Kejie; Wu, Mengxi; Guo, Feng; Li, Peng; Chan, Chung-Yu; Mao, Zhangming; Li, Sixing; Ren, Liqiang; Zhang, Rui; Huang, Tony Jun

2016-01-01

The multicellular spheroid is an important 3D cell culture model for drug screening, tissue engineering, and fundamental biological research. Although several spheroid formation methods have been reported, the field still lacks high-throughput and simple fabrication methods to accelerate its adoption in drug development industry. Surface acoustic wave (SAW) based cell manipulation methods, which are known to be non-invasive, flexible, and high-throughput, have not been successfully developed ...

X-ray microscopy of living multicellular organisms with the Prague Asterix Iodine Laser System

Czech Academy of Sciences Publication Activity Database

Desai, T.; Batani, D.; Bernadinello, A.; Poletti, G.; Orsini, F.; Ullschmied, Jiří; Juha, Libor; Skála, Jiří; Králiková, Božena; Krouský, Eduard; Pfeifer, Miroslav; Kadlec, Christelle; Mocek, Tomáš; Präg R., Ansgar; Renner, Oldřich; Cotelli, F.; Lamia, C. L.; Zullini, A.

2003-01-01

Roč. 21, č. 4 (2003), s. 511-516 ISSN 0263-0346 R&D Projects: GA MŠk LN00A100 Institutional research plan: CEZ:AV0Z2043910 Keywords : atomic force miscroscopy, laser-produced plasmas, multicellular microorganisms Subject RIV: BH - Optics, Masers, Lasers Impact factor: 0.646, year: 2003

Mass Spectrometry Analyses of Multicellular Tumor Spheroids.

Science.gov (United States)

Acland, Mitchell; Mittal, Parul; Lokman, Noor A; Klingler-Hoffmann, Manuela; Oehler, Martin K; Hoffmann, Peter

2018-05-01

Multicellular tumor spheroids (MCTS) are a powerful biological in vitro model, which closely mimics the 3D structure of primary avascularized tumors. Mass spectrometry (MS) has established itself as a powerful analytical tool, not only to better understand and describe the complex structure of MCTS, but also to monitor their response to cancer therapeutics. The first part of this review focuses on traditional mass spectrometry approaches with an emphasis on elucidating the molecular characteristics of these structures. Then the mass spectrometry imaging (MSI) approaches used to obtain spatially defined information from MCTS is described. Finally the analysis of primary spheroids, such as those present in ovarian cancer, and the great potential that mass spectrometry analysis of these structures has for improved understanding of cancer progression and for personalized in vitro therapeutic testing is discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Real-time viability and apoptosis kinetic detection method of 3D multicellular tumor spheroids using the Celigo Image Cytometer.

Science.gov (United States)

Kessel, Sarah; Cribbes, Scott; Bonasu, Surekha; Rice, William; Qiu, Jean; Chan, Leo Li-Ying

2017-09-01

The development of three-dimensional (3D) multicellular tumor spheroid models for cancer drug discovery research has increased in the recent years. The use of 3D tumor spheroid models may be more representative of the complex in vivo tumor microenvironments in comparison to two-dimensional (2D) assays. Currently, viability of 3D multicellular tumor spheroids has been commonly measured on standard plate-readers using metabolic reagents such as CellTiter-Glo® for end point analysis. Alternatively, high content image cytometers have been used to measure drug effects on spheroid size and viability. Previously, we have demonstrated a novel end point drug screening method for 3D multicellular tumor spheroids using the Celigo Image Cytometer. To better characterize the cancer drug effects, it is important to also measure the kinetic cytotoxic and apoptotic effects on 3D multicellular tumor spheroids. In this work, we demonstrate the use of PI and caspase 3/7 stains to measure viability and apoptosis for 3D multicellular tumor spheroids in real-time. The method was first validated by staining different types of tumor spheroids with PI and caspase 3/7 and monitoring the fluorescent intensities for 16 and 21 days. Next, PI-stained and nonstained control tumor spheroids were digested into single cell suspension to directly measure viability in a 2D assay to determine the potential toxicity of PI. Finally, extensive data analysis was performed on correlating the time-dependent PI and caspase 3/7 fluorescent intensities to the spheroid size and necrotic core formation to determine an optimal starting time point for cancer drug testing. The ability to measure real-time viability and apoptosis is highly important for developing a proper 3D model for screening tumor spheroids, which can allow researchers to determine time-dependent drug effects that usually are not captured by end point assays. This would improve the current tumor spheroid analysis method to potentially better

The Paramyxea Levine 1979: An original example of evolution towards multicellularity

Science.gov (United States)

Desportes, Isabelle

1984-03-01

The Paramyxea are parasitic in marine invertebrates. Their development is a sporulation involving the differentiation within a stem cell of several sporonts which produce spores made of cells enclosed inside each other. Three genera are recognized according to the number of spores and sporal cells, and the taxonomic position of the host (Polychaeta, Mollusca, Crustacea). The Paramyxea exhibit both protistan and metazoan characters. Their nine singlets centrioles are observed in different Protoctists whereas the fact that their sporal cells acquire distinctive cytological features may be interpreted as an evolution towards multicellularity.

Multistage model for the action of cytotoxic T lymphocytes in multicellular conjugates

International Nuclear Information System (INIS)

Macken, C.A.; Perelson, A.S.

1984-01-01

The authors propose a multistage stochastic model to explain data on the kinetics of target cell lysis by cytotoxic T lymphocytes in multicellular conjugates. A novel feature of this model is that the authors explicitly consider both the lethal hitting stage and the target cell disintegration stage of the cytolytic process. Further, the authors allow for the possibility that target cell disintegration is itself a complex process composed of many events. The comparison of this model with the data of other investigators suggests that cytotoxic T cells deliver lethal hits at random to undamage target cells. Having received a lethal hit, the target cell disintegrates over a variable length of time. The disintegration times of target cells from different conjugates appear to be randomly distributed and to be consistent with a model in which disintegration occurs by at least two major, sequential, rate-limiting events. For conjugates containing one lymphocyte and multiple target cells, the mean rate at which a lethally hit target cell disintegrates is found to be independent of the total number of target cells in the conjugate. This model predicts that in such multicellular conjugates, individual target cells lyse one by one, on average at approximately 30-min intervals, thus agreeing closely with previously reported experimental observations. 35 references, 3 figures, 2 tables

Cytolytic effects of autologous lymphokine-activated killer cells on organotypic multicellular spheroids of gliomas in vitro

NARCIS (Netherlands)

Kaaijk, P.; Troost, D.; Dast, P. K.; van den Berg, F.; Leenstra, S.; Bosch, D. A.

1995-01-01

Knowledge about lymphokine-activated killer (LAK) cell infiltration and LAK cell cytotoxicity is essential to improve the effectiveness of LAK cell therapy against gliomas. In the present study, organotypic multicellular spheroids (OMS) of glioma tissue were used as a culture model to study the

Tissues development in stems of Aristolochia clematitis L. in the point of view of multicellular complexes formation

Directory of Open Access Journals (Sweden)

Zofia Puławska

2014-01-01

Full Text Available After cytokinesis the cells do not separate but remain within the wall of the mother cell. After a series of divisions a multicellular complex arises. In the stems of Aristolochia clematitis procambium is closer related to protoxylem than to protophloem, and metaphloem is closer related to metaxylem than to protophloem. Since protophloem has a closer common origin with fibre primordia than with the remaining tissues, it cannot be decided unequivocally what is the origin of the fibres or when procambium differentiates. The common origin of the primary vascular tissues is visible in the pattern of the multicellular complexes, whereas the common origin of the secondary vascular tissue developing in the underground several-year-old parts of the stem can be traced in the arrangement of the single radial tiers. Some characteristics of symplastic growth are discussed.

Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

Science.gov (United States)

Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

2017-01-01

Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids

Directory of Open Access Journals (Sweden)

Annkathrin Hornung

2015-09-01

Full Text Available Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT employing superparamagnetic iron oxide nanoparticles (SPION loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPIONMTO are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo.

The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution.

Science.gov (United States)

Fidler, Aaron L; Boudko, Sergei P; Rokas, Antonis; Hudson, Billy G

2018-04-09

The cellular microenvironment, characterized by an extracellular matrix (ECM), played an essential role in the transition from unicellularity to multicellularity in animals (metazoans), and in the subsequent evolution of diverse animal tissues and organs. A major ECM component are members of the collagen superfamily -comprising 28 types in vertebrates - that exist in diverse supramolecular assemblies ranging from networks to fibrils. Each assembly is characterized by a hallmark feature, a protein structure called a triple helix. A current gap in knowledge is understanding the mechanisms of how the triple helix encodes and utilizes information in building scaffolds on the outside of cells. Type IV collagen, recently revealed as the evolutionarily most ancient member of the collagen superfamily, serves as an archetype for a fresh view of fundamental structural features of a triple helix that underlie the diversity of biological activities of collagens. In this Opinion, we argue that the triple helix is a protein structure of fundamental importance in building the extracellular matrix, which enabled animal multicellularity and tissue evolution. © 2018. Published by The Company of Biologists Ltd.

Generation of multicellular tumor spheroids by the hanging-drop method.

Science.gov (United States)

Timmins, Nicholas E; Nielsen, Lars K

2007-01-01

Owing to their in vivo-like characteristics, three-dimensional (3D) multicellular tumor spheroid (MCTS) cultures are gaining increasing popularity as an in vitro model of tumors. A straightforward and simple approach to the cultivation of these MCTS is the hanging-drop method. Cells are suspended in droplets of medium, where they develop into coherent 3D aggregates and are readily accessed for analysis. In addition to being simple, the method eliminates surface interactions with an underlying substratum (e.g., polystyrene plastic or agarose), requires only a low number of starting cells, and is highly reproducible. This method has also been applied to the co-cultivation of mixed cell populations, including the co-cultivation of endothelial cells and tumor cells as a model of early tumor angiogenesis.

Rapid formation of size-controllable multicellular spheroids via 3D acoustic tweezers.

Science.gov (United States)

Chen, Kejie; Wu, Mengxi; Guo, Feng; Li, Peng; Chan, Chung Yu; Mao, Zhangming; Li, Sixing; Ren, Liqiang; Zhang, Rui; Huang, Tony Jun

2016-07-05

The multicellular spheroid is an important 3D cell culture model for drug screening, tissue engineering, and fundamental biological research. Although several spheroid formation methods have been reported, the field still lacks high-throughput and simple fabrication methods to accelerate its adoption in drug development industry. Surface acoustic wave (SAW) based cell manipulation methods, which are known to be non-invasive, flexible, and high-throughput, have not been successfully developed for fabricating 3D cell assemblies or spheroids, due to the limited understanding on SAW-based vertical levitation. In this work, we demonstrated the capability of fabricating multicellular spheroids in the 3D acoustic tweezers platform. Our method used drag force from microstreaming to levitate cells in the vertical direction, and used radiation force from Gor'kov potential to aggregate cells in the horizontal plane. After optimizing the device geometry and input power, we demonstrated the rapid and high-throughput nature of our method by continuously fabricating more than 150 size-controllable spheroids and transferring them to Petri dishes every 30 minutes. The spheroids fabricated by our 3D acoustic tweezers can be cultured for a week with good cell viability. We further demonstrated that spheroids fabricated by this method could be used for drug testing. Unlike the 2D monolayer model, HepG2 spheroids fabricated by the 3D acoustic tweezers manifested distinct drug resistance, which matched existing reports. The 3D acoustic tweezers based method can serve as a novel bio-manufacturing tool to fabricate complex 3D cell assembles for biological research, tissue engineering, and drug development.

Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model

DEFF Research Database (Denmark)

Bendtsen, Kristian Moss; Juul, Jeppe Søgaard; Trusina, Ala

2012-01-01

increases the amount of unrepaired DNA damage. Despite this vicious circle, we ask, can cells maintain a high DNA repair capacity for some time or is repair capacity bound to continuously decline with age? We here present a simple mathematical model for ageing in multicellular systems where cells subjected...... to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity. Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity......DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn...

Coupling gene expression and multicellular morphogenesis during fruiting body formation in Myxococcus xanthus

DEFF Research Database (Denmark)

Søgaard-Andersen, L.; Overgaard, M.; Lobedanz, S.

2003-01-01

xanthus illustrates this coupling in the construction of a multicellular structure. Fruiting body formation involves two stages: aggregation of cells into mounds and the position-specific sporulation of cells that have accumulated inside mounds. Developmental gene expression propels these two processes...... morphogenesis. Accumulation of the C-signal is tightly regulated and involves transcriptional activation of the csgA gene and proteolysis of the full-length CsgA protein to produce the shorter cell surface-associated 17 kDa C-signal protein. The C-signal induces aggregation, sporulation and developmental gene...

Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

Science.gov (United States)

Aghighi, Alireza; Comtois, Philippe

2017-09-01

Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

From cat's eyes to disjoint multicellular natural convection flow in tall tilted cavities

Energy Technology Data Exchange (ETDEWEB)

Nicolas, Alfredo, E-mail: anc@xanum.uam.mx [Depto. Matematicas, 3er Piso Ed. AT-Diego Bricio, UAM-I, 09340 Mexico D.F. (Mexico); Baez, Elsa [Depto. Matematicas Aplicadas y Sistemas, UAM-C, 01120 Mexico D.F. (Mexico); Bermudez, Blanca [Facultad de C. de la Computacion, BUAP, 72570 Puebla, Pue. (Mexico)

2011-07-11

Numerical results of two-dimensional natural convection problems, in air-filled tall cavities, are reported to study the change of the cat's eyes flow as some parameters vary, the aspect ratio A and the angle of inclination φ of the cavity, with the Rayleigh number Ra mostly fixed; explicitly, the range of the variation is given by 12≤A≤20 and 0{sup o}≤φ≤270{sup o}; about Ra=1.1x10{sup 4}. A novelty contribution of this work is the transition from the cat's eyes changes, as A varies, to a disjoint multicellular flow, as φ varies. These flows may be modeled by the unsteady Boussinesq approximation in stream function and vorticity variables which is solved with a fixed point iterative process applied to the nonlinear elliptic system that results after time discretization. The validation of the results relies on mesh size and time-step independence studies. -- Highlights: → Fixed point iterative method for solving symmetric linear elliptic problems. → Robust method to study effects as aspect ratio and angle of inclination vary. → Interest on the dynamics and evolution of the fluid flow and on heat transfer. → Study of transition from cat's eyes instability to a disjoint multicellular flow.

Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

NARCIS (Netherlands)

Kaaijk, P.; Troost, D.; Sminia, P.; Hulshof, M. C.; van der Kracht, A. H.; Leenstra, S.; Bosch, D. A.

1997-01-01

The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the

Generation of Multicellular Tumor Spheroids with Microwell-Based Agarose Scaffolds for Drug Testing.

Directory of Open Access Journals (Sweden)

Xue Gong

Full Text Available Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold prepared with the template containing uniform-sized micro-wells in commercially available cell culture plates. The agarose scaffold allows for good adjustment of MCTS size and large-scale production of MCTS. Transparent agarose scaffold also allows for monitoring of spheroid formation under an optical microscopy. The formation of MCTS from MCF-7 cells was prepared using different-size-well templates and systematically investigated in terms of spheroid growth curve, circularity, and cell viability. The doxorubicin cytotoxicity against MCF-7 spheroid and MCF-7 monolayer cells was compared. The drug penetration behavior, cell cycle distribution, cell apoptosis, and gene expression were also evaluated in MCF-7 spheroid. The findings of this study indicate that, compared with cellular monolayer, MCTS provides a valuable platform for the assessment of therapeutic candidates in an in vivo-mimic microenvironment, and thus has great potential for use in drug discovery and tumor biology research.

Ability of multicellular salt glands in Tamarix species to secrete Na+ and K+ selectively.

Science.gov (United States)

Ma, Haiyan; Tian, Changyan; Feng, Gu; Yuan, Junfeng

2011-03-01

The present study aimed to determine the mechanism of cation-selective secretion by multicellular salt glands. Using a hydroponic culture system, the secretion and accumulation of Na(+) and K(+) in Tamarix ramosissima and T. laxa under different salt stresses (NaCl, KCl and NaCl+KCl) were studied. Additionally, the effects of salt gland inhibitors (orthovanadate, Ba(2+), ouabain, tetraethylammonium (TEA) and verapamil) on Na(+) and K(+) secretion and accumulation were examined. Treatment with NaCl (at 0-200 mmol L(-1) levels) significantly increased Na(+) secretion, whereas KCl treatment (at 0-200 mmol L(-1) levels) significantly increased K(+) secretion. The ratio of secretion to accumulation of Na(+) was higher than that of K(+). The changes in Na(+) and K(+) secretion differed after adding different ions into the single-salt solutions. Addition of NaCl to the KCl solution (at 100 mmol L(-1) level, respectively) led to a significant decrease in K(+) secretion rate, whereas addition of KCl to the NaCl solution (at 100 mmol L(-1) level, respectively) had little impact on the Na(+) secretion rate. These results indicated that Na+ secretion in Tamarix was highly selective. In addition, Na(+) secretion was significantly inhibited by orthovanadate, ouabain, TEA and verapamil, and K(+) secretion was significantly inhibited by ouabain, TEA and verapamil. The different impacts of orthovanadate on Na(+) and K(+) secretion might be the primary cause for the different Na(+) and K(+) secretion abilities of multicellular salt glands in Tamarix.

Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.

Directory of Open Access Journals (Sweden)

Dario Barbone

Full Text Available When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression

Science.gov (United States)

Barbone, Dario; Cheung, Priscilla; Battula, Sailaja; Busacca, Sara; Gray, Steven G.; Longley, Daniel B.; Bueno, Raphael; Sugarbaker, David J.; Fennell, Dean A.; Broaddus, V. Courtney

2012-01-01

When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies. PMID:23300762

Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

Energy Technology Data Exchange (ETDEWEB)

Wang, Jian-Zheng, E-mail: wppzheng@126.com [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Zhu, Yu-Xia [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang [Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Meng, Yue-Zhong [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275 (China)

2016-05-01

In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

International Nuclear Information System (INIS)

Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

2016-01-01

In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

The phosphatomes of the multicellular myxobacteria Myxococcus xanthus and Sorangium cellulosum in comparison with other prokaryotic genomes.

Directory of Open Access Journals (Sweden)

Anke Treuner-Lange

Full Text Available BACKGROUND: Analysis of the complete genomes from the multicellular myxobacteria Myxococcus xanthus and Sorangium cellulosum identified the highest number of eukaryotic-like protein kinases (ELKs compared to all other genomes analyzed. High numbers of protein phosphatases (PPs could therefore be anticipated, as reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes. METHODOLOGY: Here we report an intensive analysis of the phosphatomes of M. xanthus and S. cellulosum in which we constructed phylogenetic trees to position these sequences relative to PPs from other prokaryotic organisms. PRINCIPAL FINDINGS: PREDOMINANT OBSERVATIONS WERE: (i M. xanthus and S. cellulosum possess predominantly Ser/Thr PPs; (ii S. cellulosum encodes the highest number of PP2c-type phosphatases so far reported for a prokaryotic organism; (iii in contrast to M. xanthus only S. cellulosum encodes high numbers of SpoIIE-like PPs; (iv there is a significant lack of synteny among M. xanthus and S. cellulosum, and (v the degree of co-organization between kinase and phosphatase genes is extremely low in these myxobacterial genomes. CONCLUSIONS: We conclude that there has been a greater expansion of ELKs than PPs in multicellular myxobacteria.

Differential thermo-resistance of multicellular tumor spheroids

International Nuclear Information System (INIS)

Khoei, S.; Goliaei, B.; Neshasteh-Rize, A.

2004-01-01

Many cell lines, when cultured under proper conditions, can form three dimensional structures called multicellular spheroids. These spheroids resemble in vivo tumor models in several aspects. Therefore, studying growth characteristics and behavior of spheroids is beneficial in understanding the behavior of tumors under various experimental conditions. In this work, we have studied the growth properties, along with the thermal characteristics of spheroids of Du 145 human prostate carcinoma cell lines and compared the results to monolayer cultures of these cells. For this purpose, The Du 145 cells were cultured either as monolayer or spheroids. At various times after initiation of cultures, the growth properties of spheroids as a function of seeding cell number was determined. To evaluate the thermal characteristics of spheroids, they were heated at various stages of growth at 43 d ig c for various periods. The thermal response was judged by the survival fraction of colony forming cells in spheroids or monolayer culture following heat treatment. The results showed spheroids were more resistant to heat than monolayer cultures at all stages of development. However, the extent of this thermal resistant was dependent on the age, and consequently, the size of the spheroid. The result suggests that the differential thermal resistance of the spheroid cultures develop gradually during the growth of spheroid cultures of Du 145 cell line

LNA-FISH for detection of microRNAs in frozen sections

DEFF Research Database (Denmark)

Silahtaroglu, Asli N

2010-01-01

MicroRNAs (miRNAs) are small ( approximately 22 nt) noncoding RNA molecules that regulate the expression of protein coding genes either by cleavage or translational repression. miRNAs comprise one of the most abundant classes of gene regulatory molecules in multicellular organisms. Yet, the funct......MicroRNAs (miRNAs) are small ( approximately 22 nt) noncoding RNA molecules that regulate the expression of protein coding genes either by cleavage or translational repression. miRNAs comprise one of the most abundant classes of gene regulatory molecules in multicellular organisms. Yet...

Numerical modeling of working of a multicellular proportional counter aimed to individual dosimetry of neutrons

International Nuclear Information System (INIS)

Bordy, J.M.; Barthe, J.; Boutruche, B.

1993-01-01

The use of a personal dosimeter imposes severe constraints, particularly for tension of polarization and tolerable dimensions. That why a numerical modeling of this detector working is an appreciable help for conception. It allows to determine quickly the influence of modification of different parameters (nature and pressure of gas, dimension of electrodes, dimension of channels, tension of polarization,...) without having to make new prototypes. The aim of this report is to give some numerical results got with a multicellular counter with a cylindrical geometry. 6 figs

The Role of Functional Amyloids in Multicellular Growth and Development of Gram-Positive Bacteria

DEFF Research Database (Denmark)

Dragoš, Anna; Kovács, Ákos T.; Claessen, Dennis

2017-01-01

Amyloid fibrils play pivotal roles in all domains of life. In bacteria, these fibrillar structures are often part of an extracellular matrix that surrounds the producing organism and thereby provides protection to harsh environmental conditions. Here, we discuss the role of amyloid fibrils...... in the two distant Gram-positive bacteria, Streptomyces coelicolor and Bacillus subtilis. We describe how amyloid fibrils contribute to a multitude of developmental processes in each of these systems, including multicellular growth and community development. Despite this variety of tasks, we know...... surprisingly little about how their assembly is organized to fulfill all these roles....

Inter-specific coral chimerism: Genetically distinct multicellular structures associated with tissue loss in Montipora capitata

Science.gov (United States)

Work, Thierry M.; Forsman, Zac H.; Szabo, Zoltan; Lewis, Teresa D.; Aeby, Greta S.; Toonen, Robert J.

2011-01-01

Montipora white syndrome (MWS) results in tissue-loss that is often lethal to Montipora capitata, a major reef building coral that is abundant and dominant in the Hawai'ian Archipelago. Within some MWS-affected colonies in Kane'ohe Bay, Oahu, Hawai'i, we saw unusual motile multicellular structures within gastrovascular canals (hereafter referred to as invasive gastrovascular multicellular structure-IGMS) that were associated with thinning and fragmentation of the basal body wall. IGMS were in significantly greater densities in coral fragments manifesting tissue-loss compared to paired normal fragments. Mesenterial filaments from these colonies yielded typical M. capitata mitochondrial haplotypes (CO1, CR), while IGMS from the same colony consistently yielded distinct haplotypes previously only found in a different Montipora species (Montipora flabellata). Protein profiles showed consistent differences between paired mesenterial filaments and IGMS from the same colonies as did seven microsatellite loci that also exhibited an excess of alleles per locus inconsistent with a single diploid organism. We hypothesize that IGMS are a parasitic cellular lineage resulting from the chimeric fusion between M. capitata and M. flabellata larvae followed by morphological reabsorption of M. flabellata and subsequent formation of cell-lineage parasites. We term this disease Montiporaiasis. Although intra-specific chimerism is common in colonial animals, this is the first suspected inter-specific example and the first associated with tissue loss.

Colloquium: Modeling the dynamics of multicellular systems: Application to tissue engineering

Science.gov (United States)

Kosztin, Ioan; Vunjak-Novakovic, Gordana; Forgacs, Gabor

2012-10-01

Tissue engineering is a rapidly evolving discipline that aims at building functional tissues to improve or replace damaged ones. To be successful in such an endeavor, ideally, the engineering of tissues should be based on the principles of developmental biology. Recent progress in developmental biology suggests that the formation of tissues from the composing cells is often guided by physical laws. Here a comprehensive computational-theoretical formalism is presented that is based on experimental input and incorporates biomechanical principles of developmental biology. The formalism is described and it is shown that it correctly reproduces and predicts the quantitative characteristics of the fundamental early developmental process of tissue fusion. Based on this finding, the formalism is then used toward the optimization of the fabrication of tubular multicellular constructs, such as a vascular graft, by bioprinting, a novel tissue engineering technology.

Cell shedding from X-irradiated multicellular spheroids of human lung carcinomas

International Nuclear Information System (INIS)

Sakata, K.; Okada, S.; Suzuki, N.; Majima, H.

1991-01-01

We studied the effect of radiation on cell shedding from the surface of multicellular spheroids. Spheroids were produced from two human lung cell lines, one adenocarcinoma (LCT1) and the other small cell carcinoma (LCT2), by using a liquid overlay culture technique. The number of cells shed from both kinds of spheroids did not change significantly when they were irradiated. The number of clonogenic cells shed from both kinds of irradiated spheroids decreased sharply as the dose of irradiation increases. There were no significant differences in clonogenic cell shedding per spheroid between LCT1 and LCT2 spheroids. 400 μm spheroids were more radioresistant to inhibition of clonogenic cell shedding than 250 μm spheroids. Shed cells were more radiosensitive than speroid cells. In these experiments, we did not obtain any results indicating that radiation enchances metastasis. (orig.) [de

Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms

DEFF Research Database (Denmark)

Klausen, Mikkel; Aaes-Jorgensen, A.; Molin, Søren

2003-01-01

development, we have performed an investigation with time-lapse confocal laser scanning microscopy of biofilms formed by various combinations of colour-coded P. aeruginosa wild type and motility mutants. We show that mushroom-shaped multicellular structures in P. aeruginosa biofilms can form in a sequential...... process involving a non-motile bacterial subpopulation and a migrating bacterial subpopulation. The non-motile bacteria form the mushroom stalks by growth in certain foci of the biofilm. The migrating bacteria form the mushroom caps by climbing the stalks and aggregating on the tops in a process which...

Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia

Science.gov (United States)

Urrios, Arturo; de Nadal, Eulàlia; Solé, Ricard; Posas, Francesc

2016-01-01

Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit’s complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined. PMID:26829588

Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

Energy Technology Data Exchange (ETDEWEB)

Theumer, Anja; Gräfe, Christine; Bähring, Franziska [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Bergemann, Christian [Chemicell GmbH, Eresburgstrasse 22–23, 12103 Berlin (Germany); Hochhaus, Andreas [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Clement, Joachim H., E-mail: joachim.clement@med.uni-jena.de [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany)

2015-04-15

The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood–brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 µg/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles.

Integrated biocircuits: engineering functional multicellular circuits and devices

Science.gov (United States)

Prox, Jordan; Smith, Tory; Holl, Chad; Chehade, Nick; Guo, Liang

2018-04-01

Objective. Implantable neurotechnologies have revolutionized neuromodulatory medicine for treating the dysfunction of diseased neural circuitry. However, challenges with biocompatibility and lack of full control over neural network communication and function limits the potential to create more stable and robust neuromodulation devices. Thus, we propose a platform technology of implantable and programmable cellular systems, namely Integrated Biocircuits, which use only cells as the functional components of the device. Approach. We envision the foundational principles for this concept begins with novel in vitro platforms used for the study and reconstruction of cellular circuitry. Additionally, recent advancements in organoid and 3D culture systems account for microenvironment factors of cytoarchitecture to construct multicellular circuits as they are normally formed in the brain. We explore the current state of the art of these platforms to provide knowledge of their advancements in circuit fabrication and identify the current biological principles that could be applied in designing integrated biocircuit devices. Main results. We have highlighted the exemplary methodologies and techniques of in vitro circuit fabrication and propose the integration of selected controllable parameters, which would be required in creating suitable biodevices. Significance. We provide our perspective and propose new insights into the future of neuromodulaion devices within the scope of living cellular systems that can be applied in designing more reliable and biocompatible stimulation-based neuroprosthetics.

A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis

Science.gov (United States)

de Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos-Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Hölscher, Theresa; Kuipers, Oscar P.

2015-01-01

ABSTRACT Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor Spo0A~Pi (phosphorylated Spo0A) governs the flagellum-independent mechanism of social sliding motility. A Spo0A-deficient strain was totally unable to slide and colonize plant roots, evidencing the important role that sliding might play in natural settings. Microarray experiments plus subsequent genetic characterization showed that the machineries of sliding and biofilm formation share the same main components (i.e., surfactin, the hydrophobin BslA, exopolysaccharide, and de novo-formed fatty acids). Sliding proficiency was transduced by the Spo0A-phosphorelay histidine kinases KinB and KinC. We discovered that potassium, a previously known inhibitor of KinC-dependent biofilm formation, is the specific sliding-activating signal through a thus-far-unnoticed cytosolic domain of KinB, which resembles the selectivity filter sequence of potassium channels. The differential expression of the Spo0A~Pi reporter abrB gene and the different levels of the constitutively active form of Spo0A, Sad67, in Δspo0A cells grown in optimized media that simultaneously stimulate motile and sessile behaviors uncover the spatiotemporal response of KinB and KinC to potassium and the gradual increase in Spo0A~Pi that orchestrates the sequential activation of sliding, followed by sessile biofilm formation and finally sporulation in the same population. Overall, these results provide insights into how multicellular behaviors formerly believed to be antagonistic are coordinately activated in benefit of the bacterium and its interaction with the host. PMID:26152584

Development of Three-Dimensional Multicellular Tissue-Like Constructs for Mutational Analysis Using Macroporous Microcarriers

Science.gov (United States)

Jordan, Jacqueline A.; Fraga, Denise N.; Gonda, Steve R.

2002-01-01

A three-dimensional (3-D), tissue-like model was developed for the genotoxic assessment of space environment. In previous experiments, we found that culturing mammalian cells in a NASA-designed bioreactor, using Cytodex-3 beads as a scaffold, generated 3-D multicellular spheroids. In an effort to generate scaffold-free spheroids, we developed a new 3-D tissue-like model by coculturing fibroblast and epithelial cell in a NASA bioreactor using macroporous Cultispher-S(TradeMark) microcarriers. Big Blue(Registered Trademark) Rat 2(Lambda) fibroblasts, genetically engineered to contain multiple copies (>60 copies/cell) of the Lac I target gene, were cocultured with radio-sensitive human epithelial cells, H184F5. Over an 8-day period, samples were periodically examined by microscopy and histology to confirm cell attachment, growth, and viability. Immunohistochemistry and western analysis were used to evaluate the expression of specific cytoskeletal and adhesion proteins. Key cell culture parameters (glucose, pH, and lactate concentrations) were monitored daily. Controls were two-dimensional mono layers of fibroblast or epithelial cells cultured in T-flasks. Analysis of 3-D spheroids from the bioreactor suggests fibroblast cells attached to and completely covered the bead surface and inner channels by day 3 in the bioreactor. Treatment of the 3-day spheroids with dispase II dissolved the Cultisphers(TradeMark) and produced multicellular, bead-less constructs. Immunohistochemistry confirmed the presence of vi.mentin, cytokeratin and E-cadherin in treated spheroids. Examination of the dispase II treated spheroids with transmission electron microscopy (TEM) also showed the presence of desmosomes. These results suggest that the controlled enzymatic degradation of an artificial matrix in the low shear environment of the NASA-designed bioreactor can produce 3-D tissue-like spheroids. 2

Molecular and functional assessment of multicellular cancer spheroids produced in double emulsions enabled by efficient airway resistance based selective surface treatment

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Ma, Xiao; Leth Jepsen, Morten; Ivarsen, Anne Kathrine R.; Knudsen, Birgitta R.; Ho, Yi-Ping

2017-09-01

Multicellular spheroids have garnered significant attention as an in vitro three-dimensional cancer model which can mimick the in vivo microenvironmental features. While microfluidics generated double emulsions have become a potential method to generate spheroids, challenges remain on the tedious procedures. Enabled by a novel ‘airway resistance’ based selective surface treatment, this study presents an easy and facile generation of double emulsions for the initiation and cultivation of multicellular spheroids in a scaffold-free format. Combining with our previously developed DNA nanosensors, intestinal spheroids produced in the double emulsions have shown an elevated activities of an essential DNA modifying enzyme, the topoisomerase I. The observed molecular and functional characteristics of spheroids produced in double emulsions are similar to the counterparts produced by the commercially available ultra-low attachment plates. However, the double emulsions excel for their improved uniformity, and the consistency of the results obtained by subsequent analysis of the spheroids. The presented technique is expected to ease the burden of producing spheroids and to promote the spheroids model for cancer or stem cell study.

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

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Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako

2014-02-28

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

Asymmetric segregation of damaged cellular components in spatially structured multicellular organisms.

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Charlotte Strandkvist

Full Text Available The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.

Principles of cooperation across systems: from human sharing to multicellularity and cancer.

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Aktipis, Athena

2016-01-01

From cells to societies, several general principles arise again and again that facilitate cooperation and suppress conflict. In this study, I describe three general principles of cooperation and how they operate across systems including human sharing, cooperation in animal and insect societies and the massively large-scale cooperation that occurs in our multicellular bodies. The first principle is that of Walk Away: that cooperation is enhanced when individuals can leave uncooperative partners. The second principle is that resource sharing is often based on the need of the recipient (i.e., need-based transfers) rather than on strict account-keeping. And the last principle is that effective scaling up of cooperation requires increasingly sophisticated and costly cheater suppression mechanisms. By comparing how these principles operate across systems, we can better understand the constraints on cooperation. This can facilitate the discovery of novel ways to enhance cooperation and suppress cheating in its many forms, from social exploitation to cancer.

On the surviving fraction in irradiated multicellular tumour spheroids: calculation of overall radiosensitivity parameters, influence of hypoxia and volume effects

International Nuclear Information System (INIS)

Horas, Jorge A; Olguin, Osvaldo R; Rizzotto, Marcos G

2005-01-01

We model the heterogeneous response to radiation of multicellular tumour spheroids assuming position- and volume-dependent radiosensitivity. We propose a method to calculate the overall radiosensitivity parameters to obtain the surviving fraction of tumours. A mathematical model of a spherical tumour with a hypoxic core and a viable rim which is a caricature of a real tumour is constructed. The model is embedded in a two-compartment linear-quadratic (LQ) model, assuming a mixed bivariated Gaussian distribution to attain the radiosensitivity parameters. Ergodicity, i.e., the equivalence between ensemble and volumetric averages is used to obtain the overall radiosensitivities for the two compartments. We obtain expressions for the overall radiosensitivity parameters resulting from the use of both a linear and a nonlinear dependence of the local radiosensitivity with position. The model's results are compared with experimental data of surviving fraction (SF) for multicellular spheroids of different sizes. We make one fit using only the smallest spheroid data and we are able to predict the SF for the larger spheroids. These predictions are acceptable particularly using bounded sensitivities. We conclude with the importance of taking into account the contribution of clonogenic hypoxic cells to radiosensitivity and with the convenience of using bounded local sensitivities to predict overall radiosensitivity parameters

Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.

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Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

2016-05-01

In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. Copyright © 2016 Elsevier B.V. All rights reserved.

Time-lapse 3-D measurements of a glucose biosensor in multicellular spheroids by light sheet fluorescence microscopy in commercial 96-well plates.

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Maioli, Vincent; Chennell, George; Sparks, Hugh; Lana, Tobia; Kumar, Sunil; Carling, David; Sardini, Alessandro; Dunsby, Chris

2016-11-25

Light sheet fluorescence microscopy has previously been demonstrated on a commercially available inverted fluorescence microscope frame using the method of oblique plane microscopy (OPM). In this paper, OPM is adapted to allow time-lapse 3-D imaging of 3-D biological cultures in commercially available glass-bottomed 96-well plates using a stage-scanning OPM approach (ssOPM). Time-lapse 3-D imaging of multicellular spheroids expressing a glucose Förster resonance energy transfer (FRET) biosensor is demonstrated in 16 fields of view with image acquisition at 10 minute intervals. As a proof-of-principle, the ssOPM system is also used to acquire a dose response curve with the concentration of glucose in the culture medium being varied across 42 wells of a 96-well plate with the whole acquisition taking 9 min. The 3-D image data enable the FRET ratio to be measured as a function of distance from the surface of the spheroid. Overall, the results demonstrate the capability of the OPM system to measure spatio-temporal changes in FRET ratio in 3-D in multicellular spheroids over time in a multi-well plate format.

Low-temperature plasma-induced antiproliferative effects on multi-cellular tumor spheroids

International Nuclear Information System (INIS)

Plewa, Joseph-Marie; Yousfi, Mohammed; Eichwald, Olivier; Merbahi, Nofel; Frongia, Céline; Ducommun, Bernard; Lobjois, Valérie

2014-01-01

Biomedical applications of low-temperature plasmas are of growing interest, especially in the field of plasma-induced anti-tumor effects. The present work is aimed at investigating the regionalized antiproliferative effects of low-temperature plasmas on a multicellular tumor spheroid (MCTS), a model that mimics the 3D organization and regionalization of a microtumor region. We report that a low-temperature plasma jet, using helium flow in open air, inhibits HCT116 colon carcinoma MCTS growth in a dose-dependent manner. This growth inhibition is associated with the loss of Ki67, and the regionalized accumulation of DNA damage detected by histone H2AX phosphorylation. This regionalized genotoxic effect leads to massive cell death and loss of the MCTS proliferative region. The use of reactive oxygen species (ROS), scavenger N-acetyl cysteine (NAC) and plasma-conditioned media demonstrate that the ROS generated in the media after exposure to low-temperature plasma play a major role in these observed effects. These findings strengthen the interest in the use of MCTS for the evaluation of antiproliferative strategies, and open new perspectives for studies dedicated to demonstrate the potential of low-temperature plasma in cancer therapy

Low-temperature plasma-induced antiproliferative effects on multi-cellular tumor spheroids

Science.gov (United States)

Plewa, Joseph-Marie; Yousfi, Mohammed; Frongia, Céline; Eichwald, Olivier; Ducommun, Bernard; Merbahi, Nofel; Lobjois, Valérie

2014-04-01

Biomedical applications of low-temperature plasmas are of growing interest, especially in the field of plasma-induced anti-tumor effects. The present work is aimed at investigating the regionalized antiproliferative effects of low-temperature plasmas on a multicellular tumor spheroid (MCTS), a model that mimics the 3D organization and regionalization of a microtumor region. We report that a low-temperature plasma jet, using helium flow in open air, inhibits HCT116 colon carcinoma MCTS growth in a dose-dependent manner. This growth inhibition is associated with the loss of Ki67, and the regionalized accumulation of DNA damage detected by histone H2AX phosphorylation. This regionalized genotoxic effect leads to massive cell death and loss of the MCTS proliferative region. The use of reactive oxygen species (ROS), scavenger N-acetyl cysteine (NAC) and plasma-conditioned media demonstrate that the ROS generated in the media after exposure to low-temperature plasma play a major role in these observed effects. These findings strengthen the interest in the use of MCTS for the evaluation of antiproliferative strategies, and open new perspectives for studies dedicated to demonstrate the potential of low-temperature plasma in cancer therapy.

Respiration control of multicellularity in Bacillus subtilis by a complex of the cytochrome chain with a membrane-embedded histidine kinase

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Kolodkin-Gal, I; Elsholz, AKW; Muth, C; Girguis, PR; Kolter, R; Losick, R

2013-04-29

Bacillus subtilis forms organized multicellular communities known as biofilms wherein the individual cells are held together by a self-produced extracellular matrix. The environmental signals that promote matrix synthesis remain largely unknown. We discovered that one such signal is impaired respiration. Specifically, high oxygen levels suppressed synthesis of the extracellular matrix. In contrast, low oxygen levels, in the absence of an alternative electron acceptor, led to increased matrix production. The response to impaired respiration was blocked in a mutant lacking cytochromes caa(3) and bc and markedly reduced in a mutant lacking kinase KinB. Mass spectrometry of proteins associated with KinB showed that the kinase was in a complex with multiple components of the aerobic respiratory chain. We propose that KinB is activated via a redox switch involving interaction of its second transmembrane segment with one or more cytochromes under conditions of reduced electron transport. In addition, a second kinase (KinA) contributes to the response to impaired respiration. Evidence suggests that KinA is activated by a decrease in the nicotinamide adenine dinucleotide (NAD(+))/NADH ratio via binding of NAD(+) to the kinase in a PAS domain A-dependent manner. Thus, B. subtilis switches from a unicellular to a multicellular state by two pathways that independently respond to conditions of impaired respiration.

Respiration control of multicellularity in Bacillus subtilis by a complex of the cytochrome chain with a membrane-embedded histidine kinase

Science.gov (United States)

Kolodkin-Gal, Ilana; Elsholz, Alexander K.W.; Muth, Christine; Girguis, Peter R.; Kolter, Roberto; Losick, Richard

2013-01-01

Bacillus subtilis forms organized multicellular communities known as biofilms wherein the individual cells are held together by a self-produced extracellular matrix. The environmental signals that promote matrix synthesis remain largely unknown. We discovered that one such signal is impaired respiration. Specifically, high oxygen levels suppressed synthesis of the extracellular matrix. In contrast, low oxygen levels, in the absence of an alternative electron acceptor, led to increased matrix production. The response to impaired respiration was blocked in a mutant lacking cytochromes caa3 and bc and markedly reduced in a mutant lacking kinase KinB. Mass spectrometry of proteins associated with KinB showed that the kinase was in a complex with multiple components of the aerobic respiratory chain. We propose that KinB is activated via a redox switch involving interaction of its second transmembrane segment with one or more cytochromes under conditions of reduced electron transport. In addition, a second kinase (KinA) contributes to the response to impaired respiration. Evidence suggests that KinA is activated by a decrease in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio via binding of NAD+ to the kinase in a PAS domain A-dependent manner. Thus, B. subtilis switches from a unicellular to a multicellular state by two pathways that independently respond to conditions of impaired respiration. PMID:23599347

Biocellion: accelerating computer simulation of multicellular biological system models.

Science.gov (United States)

Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

2014-11-01

Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The diversification of the LIM superclass at the base of the metazoa increased subcellular complexity and promoted multicellular specialization.

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Bernard J Koch

Full Text Available Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass.We have identified and characterized all known LIM domain-containing proteins in six metazoans and three non-metazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineage-specific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study.Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity.

Radiobiological investigations of multicellular spheroids as an in vitro tumor model. 4

International Nuclear Information System (INIS)

Kopp, J.

1978-01-01

Multicellular spheroids of various size were irradiated with a single dose of X-rays or fast neutrons, incubated after irradiation in roller tubes for long time, and observed light-microscopically. The observed effects were found independent of the radiation used and dependent on dose (considering the RBE) and size of spheroids. After irradiation the spheroid surface showed a loosening phenomenon and the spheroid structure changed depending on dose in three various types. Up to the 10% survival fraction the spheroids recovered within some days to the structure of non-irradiated spheroids by the growth of the surviving cells. After higher doses single surviving cells inside the dead spheroid material seemed to migrate from the inner hypoxic into the rim zone. They can start proliferation many days after irradiation leading to repopulation of irradiated spheroids. The volume changes of irradiated spheroids were also dose-dependent, but the measurement of spheroid volume seems to be of limited value for predicting the effectiveness of irradiation because the spheroid volume of irradiated spheroids is not proportional to the number of cells per spheroid. (author)

Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma.

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Sminia, Peter; Acker, Helmut; Eikesdal, Hans Petter; Kaaijk, Patricia; Enger, Per øvind; Slotman, Ben; Bjerkvig, Rolf

2003-01-01

Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation. Tumour specimens of glioblastoma multiforme patients (n = 16) were initiated as OMS. Following 20 Gy gamma-irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by micro-electrode pO2 measurements and pimonidazole immunostaining. Spheroids prepared from established human glioma cell lines were used as a reference. Irradiation inhibited spheroid outgrowth by 12 to 88% relative to the non-irradiated controls. A large interpatient variation was noticed. Oxygen measurements revealed a gradual decrease in pO2 level from the periphery to the core of the spheroids, but the pO2 values remained within an oxygenated range. However, in the cell line spheroids an intermediate layer of hypoxia surrounding the central core was observed. Cell line spheroids with a hypoxic cell fraction and well-oxygenated OMS both show high resistance to irradiation, indicating that hypoxia may not be the biological factor determining the radioresistance of glioma spheroids in vitro.

Drosophila melanogaster--the model organism of choice for the complex biology of multi-cellular organisms

Science.gov (United States)

Beckingham, Kathleen M.; Armstrong, J. Douglas; Texada, Michael J.; Munjaal, Ravi; Baker, Dean A.

2005-01-01

Drosophila melanogaster has been intensely studied for almost 100 years. The sophisticated array of genetic and molecular tools that have evolved for analysis of gene function in this organism are unique. Further, Drosophila is a complex multi-cellular organism in which many aspects of development and behavior parallel those in human beings. These combined advantages have permitted research in Drosophila to make seminal contributions to the understanding of fundamental biological processes and ensure that Drosophila will continue to provide unique insights in the genomic era. An overview of the genetic methodologies available in Drosophila is given here, together with examples of outstanding recent contributions of Drosophila to our understanding of cell and organismal biology. The growing contribution of Drosophila to our knowledge of gravity-related responses is addressed.

A molecular timescale of eukaryote evolution and the rise of complex multicellular life

Science.gov (United States)

Hedges, S. Blair; Blair, Jaime E.; Venturi, Maria L.; Shoe, Jason L.

2004-01-01

BACKGROUND: The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. RESULTS: Our phylogenetic analyses revealed that (i) animals are more closely related to fungi than to plants, (ii) red algae are closer to plants than to animals or fungi, (iii) choanoflagellates are closer to animals than to fungi or plants, (iv) diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v) diplomonads are basal to other eukaryotes (including alveolates and euglenozoans). Divergence times were estimated from global and local clock methods using 20-188 proteins per node, with data treated separately (multigene) and concatenated (supergene). Different time estimation methods yielded similar results (within 5%): vertebrate-arthropod (964 million years ago, Ma), Cnidaria-Bilateria (1,298 Ma), Porifera-Eumetozoa (1,351 Ma), Pyrenomycetes-Plectomycetes (551 Ma), Candida-Saccharomyces (723 Ma), Hemiascomycetes-filamentous Ascomycota (982 Ma), Basidiomycota-Ascomycota (968 Ma), Mucorales-Basidiomycota (947 Ma), Fungi-Animalia (1,513 Ma), mosses-vascular plants (707 Ma), Chlorophyta-Tracheophyta (968 Ma), Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma), Plantae-Animalia (1,609 Ma), Alveolata-plants+animals+fungi (1,973 Ma), Euglenozoa-plants+animals+fungi (1,961 Ma), and Giardia-plants+animals+fungi (2,309 Ma). By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to

A molecular timescale of eukaryote evolution and the rise of complex multicellular life

Directory of Open Access Journals (Sweden)

Venturi Maria L

2004-01-01

Full Text Available Abstract Background The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. Results Our phylogenetic analyses revealed that (i animals are more closely related to fungi than to plants, (ii red algae are closer to plants than to animals or fungi, (iii choanoflagellates are closer to animals than to fungi or plants, (iv diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v diplomonads are basal to other eukaryotes (including alveolates and euglenozoans. Divergence times were estimated from global and local clock methods using 20–188 proteins per node, with data treated separately (multigene and concatenated (supergene. Different time estimation methods yielded similar results (within 5%: vertebrate-arthropod (964 million years ago, Ma, Cnidaria-Bilateria (1,298 Ma, Porifera-Eumetozoa (1,351 Ma, Pyrenomycetes-Plectomycetes (551 Ma, Candida-Saccharomyces (723 Ma, Hemiascomycetes-filamentous Ascomycota (982 Ma, Basidiomycota-Ascomycota (968 Ma, Mucorales-Basidiomycota (947 Ma, Fungi-Animalia (1,513 Ma, mosses-vascular plants (707 Ma, Chlorophyta-Tracheophyta (968 Ma, Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma, Plantae-Animalia (1,609 Ma, Alveolata-plants+animals+fungi (1,973 Ma, Euglenozoa-plants+animals+fungi (1,961 Ma, and Giardia-plants+animals+fungi (2,309 Ma. By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to ~10

A Novel Multiparametric Drug-Scoring Method for High-Throughput Screening of 3D Multicellular Tumor Spheroids Using the Celigo Image Cytometer.

Science.gov (United States)

Cribbes, Scott; Kessel, Sarah; McMenemy, Scott; Qiu, Jean; Chan, Leo Li-Ying

2017-06-01

Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates. Using parameters such as MCTS diameter and invasion area, growth and invasion were monitored for 9 and 3 d, respectively. Furthermore, fluorescent staining with calcein AM, propidium iodide, Hoechst 33342, and caspase 3/7 was performed at day 9 posttreatment to measure viability and apoptosis. Using the kinetic and endpoint data generated, we created a novel multiparametric drug-scoring system for 3D MCTS that can be used to identify and classify potential drug candidates earlier in the drug discovery process. Furthermore, the combination of quantitative and qualitative image data can be used to delineate differences between drugs that induce cytotoxic and cytostatic effects. The 3D MCTS-based multiparametric scoring method described here can provide an alternative screening method to better qualify tested drug compounds.

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks.

Science.gov (United States)

Walpole, J; Chappell, J C; Cluceru, J G; Mac Gabhann, F; Bautch, V L; Peirce, S M

2015-09-01

Many biological processes are controlled by both deterministic and stochastic influences. However, efforts to model these systems often rely on either purely stochastic or purely rule-based methods. To better understand the balance between stochasticity and determinism in biological processes a computational approach that incorporates both influences may afford additional insight into underlying biological mechanisms that give rise to emergent system properties. We apply a combined approach to the simulation and study of angiogenesis, the growth of new blood vessels from existing networks. This complex multicellular process begins with selection of an initiating endothelial cell, or tip cell, which sprouts from the parent vessels in response to stimulation by exogenous cues. We have constructed an agent-based model of sprouting angiogenesis to evaluate endothelial cell sprout initiation frequency and location, and we have experimentally validated it using high-resolution time-lapse confocal microscopy. ABM simulations were then compared to a Monte Carlo model, revealing that purely stochastic simulations could not generate sprout locations as accurately as the rule-informed agent-based model. These findings support the use of rule-based approaches for modeling the complex mechanisms underlying sprouting angiogenesis over purely stochastic methods.

Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: a study of human melanoma multicellular spheroids.

Science.gov (United States)

Rofstad, E K; Eide, K; Skøyum, R; Hystad, M E; Lyng, H

1996-09-01

The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia- induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WIX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-microM spheroids were 32 +/- 12% (BEX-c) and 2.5 +/- 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 +/- 6% (BEX-c) and 1.4 +/- 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c showed lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of

Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids

Directory of Open Access Journals (Sweden)

Cui J

2014-02-01

Full Text Available Jie Cui,1,2 Ya-Huan Guo,3 Hong-Yi Zhang,4 Li-Li Jiang,1 Jie-Qun Ma,1 Wen-Juan Wang,1 Min-Cong Wang,1 Cheng-Cheng Yang,1 Ke-Jun Nan,1 Li-Ping Song5 1Department of Oncology, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, 2Department of Oncology, Yan'an University Affiliated Hospital, Yan'an, 3Department of Oncology, Shaanxi Province Cancer Hospital, Xi'an, 4Department of Urology, Yan'an University Affiliated Hospital, Yan'an, 5Department of Radiotherapy, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, People's Republic of China Purpose: Celecoxib, an inhibitor of cyclooxygenase-2 (COX2, was investigated for enhancement of chemotherapeutic efficacy in cancer clinical trials. This study aimed to determine whether celecoxib combined with 5-fluorouracil or sorafenib or gefitinib is beneficial in HepG2 multicellular spheroids (MCSs, as well as elucidate the underlying mechanisms. Methods: The human hepatocellular carcinoma cell line HepG2 MCSs were used as in vitro models to investigate the effects of celecoxib combined with 5-fluorouracil or sorafenib or gefitinib treatment on cell growth, apoptosis, and signaling pathway. Results: MCSs showed resistance to drugs compared with monolayer cells. Celecoxib combined with 5-fluorouracil or sorafenib exhibited a synergistic action. Exposure to celecoxib (21.8 µmol/L plus 5-fluorouracil (8.1 × 10-3 g/L or sorafenib (4.4 µmol/L increased apoptosis but exerted no effect on COX2, phosphorylated epidermal growth-factor receptor (p-EGFR and phosphorylated (p-AKT expression. Gefitinib (5 µmol/L, which exhibits no growth-inhibition activity as a single agent, increased the inhibitory effect of celecoxib. Gefitinib (5 µmol/L plus celecoxib (21.8 µmol/L increased apoptosis. COX2, p-EGFR, and p-AKT were inhibited. Conclusion: Celecoxib combined with 5-fluorouracil or sorafenib or gefitinib may be superior to single-agent therapy in HepG2

Realisation and qualification of a tissue equivalent proportional counter with a multi-cellular geometry for the individual neutron dosimetry

International Nuclear Information System (INIS)

Hoflack, Ch.

1999-01-01

The present day dosimetry means for radiations with a strong ionization density cannot fulfill the future radioprotection regulations which will require an individual dosimetry with active dosemeters. The aim of this work is the study and development of an individual dosemeter based on a tissue equivalent proportional counter and with a multi-cellular geometry allowing to reach a sensibility equivalent to environmental dosemeters. A pressure regulation bench has been added to the detector in order to reduce the degassing of the detector parts and to reach a sufficient service life for the implementation of the characterization tests. The hole counter system has been adopted for the first prototypes in order to reduce the sensibility of the wires multiplication system with respect to mechanical vibrations. Tests performed with an internal alpha source have shown that a better electrical efficiency can be reached when more severe mechanical limits are adopted during the construction. The dose equivalent response of the prototype for mono-energy neutrons of 144 keV to 2.5 MeV is analyzed experimentally and by simulation. During experiments with normal incidence neutrons, the prototype fulfills the requirements of the CEI N O 1323 standard for energies comprised between 400 keV and 2.5 MeV, while the simulation indicates a satisfactory response up to 200 keV. A preliminary study of the behaviour of the detector with respect to the neutrons incidence indicates that the multi-cellular geometry is efficient for large angles (the sensibility of the prototype is increased by a factor 3). Finally, simulation studies have to be made to optimize the electrical operation and the geometry of the next prototype. (J.S.)

Characterization of variants isolated from BCNU-treated 9L multicellular spheroids

International Nuclear Information System (INIS)

Hoff, M.H.B.; Deen, D.F.

1984-01-01

Multicellular spheroids of the 9L rat brain tumor cell line were treated with a single high-dose to produce cells of varying sensitivity. Treatment of 350-450 μm diameter 9L spheroids with 45 μM BCNU for 1 hr at 37 0 C produced 5 log cell kill. Some of the treated spheroids were dissociated immediately after treatment; others were dissociated after 1 wk. From these populations, twenty clones were selected and passaged as monolayers. Each clone was assayed at passage 2 for BCNU-induced damage using colony forming efficiency and sister chromatid exchange. 60% of the clones were resistant to BCNU, 15% were unchanged, and 15% appeared hypersensitive as compared with the control, which were uncloned 9L cells. All of the hypersensitive clones originated from the spheroids that remained in suspension after treatment. Three clones were studied during subsequent passage in monolayer. Two resistant clones maintained their resistance to BCNU over -- 25 passages, while one hypersensitive clone appeared to become progressively more resistant during passage. Thus, as with monolayer and in vivo 9L cells, a single high-dose treatment with BCNU produces a spectrum of sensitivities to BCNU. Some of these phenotypes are stable over many passages and have been used to initiate 9L spheroids having varying sensitivity to BCNU. These spheroids will be used to investigate drug-radiation interactions

Use of cartography in historical seismicity analysis: a reliable tool to better apprehend the contextualization of the historical documents

Science.gov (United States)

Thibault, Fradet; Grégory, Quenet; Kevin, Manchuel

2014-05-01

hypothesis. The location of the recently explored documentary sources evidence that there was no notarial activity in this particular area at that time. The importance of the economic and political dominance of Bordeaux during the XVIIth-XVIIIth centuries has to be taken into account in order to apprehend the way the earthquake was reported by the population at the regional scale. Elements related to chimneys forms or construction techniques could in turn help in identifying regional peculiarities allowing better quantifying the vulnerability aspects of the region.

Radiation cell survival and growth delay studies in multicellular spheroids of small-cell lung carcinoma

International Nuclear Information System (INIS)

Duchesne, G.M.; Peacock, J.H.

1987-01-01

The radiation sensitivity of two small-cell lung carcinoma cell lines growing as multicellular spheroids in static culture was determined using clonogenic cell survival and growth delay as endpoints. Growth delay determination suggested that clonogenic cell kill was less than was obtained by direct assay of cell survival. Recovery from potentially lethal damage was assayed in one line (HC12) but was not demonstrable, and clonogenic cell survival decreased with time in treated spheroids with diameters greater than 300 μm which contained a hypoxic cell population. Microscopic examination of the treated spheroids showed the emergence of an abnormal giant-cell population, and the progressive clonogenic cell loss that occurred after treatment was thought to be due to oxygen and nutrient deprivation of the remaining viable cells by this doomed cell population. Correction of the growth delay measurements for changes in cell size and clonogenic cell population allowed correlation of the growth delay and cell survival data. (author)

Symbiotic Cell Differentiation and Cooperative Growth in Multicellular Aggregates.

Directory of Open Access Journals (Sweden)

Jumpei F Yamagishi

2016-10-01

Full Text Available As cells grow and divide under a given environment, they become crowded and resources are limited, as seen in bacterial biofilms and multicellular aggregates. These cells often show strong interactions through exchanging chemicals, as evident in quorum sensing, to achieve mutualism and division of labor. Here, to achieve stable division of labor, three characteristics are required. First, isogenous cells differentiate into several types. Second, this aggregate of distinct cell types shows better growth than that of isolated cells without interaction and differentiation, by achieving division of labor. Third, this cell aggregate is robust with respect to the number distribution of differentiated cell types. Indeed, theoretical studies have thus far considered how such cooperation is achieved when the ability of cell differentiation is presumed. Here, we address how cells acquire the ability of cell differentiation and division of labor simultaneously, which is also connected with the robustness of a cell society. For this purpose, we developed a dynamical-systems model of cells consisting of chemical components with intracellular catalytic reaction dynamics. The reactions convert external nutrients into internal components for cellular growth, and the divided cells interact through chemical diffusion. We found that cells sharing an identical catalytic network spontaneously differentiate via induction from cell-cell interactions, and then achieve division of labor, enabling a higher growth rate than that in the unicellular case. This symbiotic differentiation emerged for a class of reaction networks under the condition of nutrient limitation and strong cell-cell interactions. Then, robustness in the cell type distribution was achieved, while instability of collective growth could emerge even among the cooperative cells when the internal reserves of products were dominant. The present mechanism is simple and general as a natural consequence of

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

Minimal resin embedding of multicellular specimens for targeted FIB-SEM imaging.

Science.gov (United States)

Schieber, Nicole L; Machado, Pedro; Markert, Sebastian M; Stigloher, Christian; Schwab, Yannick; Steyer, Anna M

2017-01-01

Correlative light and electron microscopy (CLEM) is a powerful tool to perform ultrastructural analysis of targeted tissues or cells. The large field of view of the light microscope (LM) enables quick and efficient surveys of the whole specimen. It is also compatible with live imaging, giving access to functional assays. CLEM protocols take advantage of the features to efficiently retrace the position of targeted sites when switching from one modality to the other. They more often rely on anatomical cues that are visible both by light and electron microscopy. We present here a simple workflow where multicellular specimens are embedded in minimal amounts of resin, exposing their surface topology that can be imaged by scanning electron microscopy (SEM). LM and SEM both benefit from a large field of view that can cover whole model organisms. As a result, targeting specific anatomic locations by focused ion beam-SEM (FIB-SEM) tomography becomes straightforward. We illustrate this application on three different model organisms, used in our laboratory: the zebrafish embryo Danio rerio, the marine worm Platynereis dumerilii, and the dauer larva of the nematode Caenorhabditis elegans. Here we focus on the experimental steps to reduce the amount of resin covering the samples and to image the specimens inside an FIB-SEM. We expect this approach to have widespread applications for volume electron microscopy on multiple model organisms. Copyright © 2017 Elsevier Inc. All rights reserved.

An atlas of active enhancers across human cell types and tissues

DEFF Research Database (Denmark)

Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene

2014-01-01

Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, ...

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

The number of cell types, information content, and the evolution of complex multicellularity

Directory of Open Access Journals (Sweden)

Karl J. Niklas

2014-12-01

Full Text Available The number of different cell types (NCT characterizing an organism is often used to quantify organismic complexity. This method results in the tautology that more complex organisms have a larger number of different kinds of cells, and that organisms with more different kinds of cells are more complex. This circular reasoning can be avoided (and simultaneously tested when NCT is plotted against different measures of organismic information content (e.g., genome or proteome size. This approach is illustrated by plotting the NCT of representative diatoms, green and brown algae, land plants, invertebrates, and vertebrates against data for genome size (number of base-pairs, proteome size (number of amino acids, and proteome functional versatility (number of intrinsically disordered protein domains or residues. Statistical analyses of these data indicate that increases in NCT fail to keep pace with increases in genome size, but exceed a one-to-one scaling relationship with increasing proteome size and with increasing numbers of intrinsically disordered protein residues. We interpret these trends to indicate that comparatively small increases in proteome (and not genome size are associated with disproportionate increases in NCT, and that proteins with intrinsically disordered domains enhance cell type diversity and thus contribute to the evolution of complex multicellularity.

Study of the tensile properties of individual multicellular fibres generated by Bacillus subtilis

Science.gov (United States)

Ye, Xuan; Zhao, Liang; Liang, Jiecun; Li, Xide; Chen, Guo-Qiang

2017-04-01

Multicellular fibres formed by Bacillus subtilis (B. subtilis) are attracting interest because of their potential application as degradable biomaterials. However, mechanical properties of individual fibres remain unknown because of their small dimensions. Herein, a new approach is developed to investigate the tensile properties of individual fibres with an average diameter of 0.7 μm and a length range of 25.7-254.3 μm. Variations in the tensile strengths of fibres are found to be the result of variable interactions among pairs of microbial cells known as septa. Using Weibull weakest-link model to study this mechanical variability, we predict the length effect of the sample. Moreover, the mechanical properties of fibres are found to depend highly on relative humidity (RH), with a brittle-ductile transition occurring around RH = 45%. The elastic modulus is 5.8 GPa in the brittle state, while decreases to 62.2 MPa in the ductile state. The properties of fibres are investigated by using a spring model (RH  45%) for the time-dependent response. Loading-unloading experiments and numerical calculations demonstrate that necking instability comes from structural changes (septa) and viscoelasticity dominates the deformation of fibres at high RH.

Politically Induced Regulatory Risk and Independent Regulatory Agencies

OpenAIRE

Strausz, Roland

2015-01-01

Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

Science.gov (United States)

Arenas-Mena, Cesar; Coffman, James A.

2016-01-01

Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

Radiobiological studies of cells in multicellular spheroids using a sequential trypsinization technique

International Nuclear Information System (INIS)

Giesbrecht, J.L.; Wilson, W.R.; Hill, R.P.

1981-01-01

The radiation response of V79 Chinese hamster cells grown as multicellular spheroids has been investigated by determining survival curves for treatment under a variety of different oxygen concentrations. Spheroids were irradiated under fully oxygenated conditions in air-equilibrated medium at 37 0 C, in medium exposed to lower oxygen tension (5% O 2 ) for times varying from 1 hr to 3 days, or under anoxic conditions. For comparison with the spheroids, using identical treatment conditions, V79 cells were grown in suspension as a subconfluent monolayer attached to Sephadex (microcarrier) beads and irradiated under fully oxygenated or anoxic conditions. The radiation response of cells at different depths within the spheroid was investigated by using a sequential trypsinization technique developed to remove eight or nine shells of cells successively from the spheroid surface. When irradiation was given under fully oxygenated conditions the outer few cell layers were more sensitive than the inner cells, a finding which is not understood. As expected the inner cells in spheroids irradiated in air (at 37 0 C) or in 5% O 2 are more resistant than the outer cells. For an acute exposure to 5% O 2 (1 hr) in the inner cells displayed full radiobiological hypoxia; however, for chronic exposures to low oxygen this was not the case. These results with the sequential trypsinization procedure suggest that the radiation response of cells in spheroids is more complex than anticipted

The swimming polarity of multicellular magnetotactic prokaryotes can change during an isolation process employing magnets: evidence of a relation between swimming polarity and magnetic moment intensity.

Science.gov (United States)

de Melo, Roger Duarte; Acosta-Avalos, Daniel

2017-09-01

Magnetotactic microorganisms are characterized by swimming in the direction of an applied magnetic field. In nature, two types of swimming polarity have been observed: north-seeking microorganisms that swim in the same direction as the magnetic field, and south-seeking microorganisms that swim in the opposite direction. The present work studies the reversal in the swimming polarity of the multicellular magnetotactic prokaryote Candidatus Magnetoglobus multicellularis following an isolation process using high magnetic fields from magnets. The proportion of north- and south-seeking organisms was counted as a function of the magnetic field intensity used during the isolation of the organisms from sediment. It was observed that the proportion of north-seeking organisms increased when the magnetic field was increased. The magnetic moment for north- and south-seeking populations was estimated using the U-turn method. The average magnetic moment was higher for north- than south-seeking organisms. The results suggest that the reversal of swimming polarity must occur during the isolation process in the presence of high magnetic fields and magnetic field gradients. It is shown for the first time that the swimming polarity reversal depends on the magnetic moment intensity of multicellular magnetotactic prokaryotes, and new studies must be undertaken to understand the role of magnetic moment polarity and oxygen gradients in determination of swimming polarity.

Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression.

Science.gov (United States)

Dolega, M E; Delarue, M; Ingremeau, F; Prost, J; Delon, A; Cappello, G

2017-01-27

The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside the tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical stress distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well-defined elasticity, size and surface coating to enable internalization within the cellular environment. By isotropically compressing multicellular spheroids (MCS), which are spherical aggregates of cells mimicking a tumour, we show that the pressure is transmitted in a non-trivial manner inside the MCS, with a pressure rise towards the core. This observed pressure profile is explained by the anisotropic arrangement of cells and our results suggest that such anisotropy alone is sufficient to explain the pressure rise inside MCS composed of a single cell type. Furthermore, such pressure distribution suggests a direct link between increased mechanical stress and previously observed lack of proliferation within the spheroids core.

Differential superiority of heavy charged-particle irradiation to x-rays: Studies on biological effectivenes and side effect mechanisms in multicellular tumor and normal tissue models

Directory of Open Access Journals (Sweden)

Stefan eWalenta

2016-02-01

Full Text Available This review is focused on the radiobiology of carbon ions compared to x-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review deals with radiation-induced cell migration and mucositis.Multicellular spheroids (MCS from V79 hamster cells were irradiated with x-rays or carbon ions under ambient or restricted oxygen supply conditions. Oxygen enhancement ratios (OER were 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. A relative biological effectiveness (RBE of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M, and a dose-dependent massive induction of apoptosis. Clinically relevant doses (3 Gy of x-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in 1 integrin expression. Unlike with particles, the photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor (EGFR and AKT-ERK1/2 pathway. Comparing the gene toxicity of x-rays with that of particles using the gamma-H2AX technique in organotypic cultures of the oral mucosa, the superior effectiveness of heavy ions was confirmed by a two-fold higher number of foci per nucleus. Pro-inflammatory signs, however, were similar for both treatment modalities, e. g., the activation of NFkappaB, and the release of IL

Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

International Nuclear Information System (INIS)

Illizastigui, P.F.

2016-01-01

The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

Science.gov (United States)

Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

2014-03-01

Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

Directory of Open Access Journals (Sweden)

Betul Kul Babur

Full Text Available We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage

Safety culture as a matter of regulatory control and regulatory effectiveness

International Nuclear Information System (INIS)

Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

2002-01-01

More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

The Evolution of the Secreted Regulatory Protein Progranulin.

Science.gov (United States)

Palfree, Roger G E; Bennett, Hugh P J; Bateman, Andrew

2015-01-01

Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide

76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Science.gov (United States)

2011-04-19

... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

Regulatory inspection of nuclear facilities and enforcement by the regulatory body. Safety guide

International Nuclear Information System (INIS)

2002-01-01

The purpose of this Safety Guide is to provide recommendations for regulatory bodies on the inspection of nuclear facilities, regulatory enforcement and related matters. The objective is to provide the regulatory body with a high level of confidence that operators have the processes in place to ensure compliance and that they do comply with legal requirements, including meeting the safety objectives and requirements of the regulatory body. However, in the event of non-compliance, the regulatory body should take appropriate enforcement action. This Safety Guide covers regulatory inspection and enforcement in relation to nuclear facilities such as: enrichment and fuel manufacturing plants; nuclear power plants; other reactors such as research reactors and critical assemblies; spent fuel reprocessing plants; and facilities for radioactive waste management, such as treatment, storage and disposal facilities. This Safety Guide also covers issues relating to the decommissioning of nuclear facilities, the closure of waste disposal facilities and site rehabilitation. Section 2 sets out the objectives of regulatory inspection and enforcement. Section 3 covers the management of regulatory inspections. Section 4 covers the performance of regulatory inspections, including internal guidance, planning and preparation, methods of inspection and reports of inspections. Section 5 deals with regulatory enforcement actions. Section 6 covers the assessment of regulatory inspections and enforcement activities. The Appendix provides further details on inspection areas for nuclear facilities

The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms.

Science.gov (United States)

Barth, Emanuel; Hübler, Ron; Baniahmad, Aria; Marz, Manja

2016-05-02

The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible "mini-complexes" or COP9 complexes with independent subunits containing potentially novel and not yet identified functions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Regulatory guidance document

International Nuclear Information System (INIS)

1994-05-01

The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

Science.gov (United States)

2010-03-10

... the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold...

An integrative approach to apprehend desistance.

Science.gov (United States)

F-Dufour, Isabelle; Brassard, Renée; Martel, Joane

2015-05-01

The process underlying desistance is still a strong subject of debate. This article seeks to introduce several core concepts of Archer's morphogenic approach to study how people desist from crime. At first, it discusses the primary existing theories of desistance. Then, this article demonstrates the usefulness of this approach by presenting empirical evidence drawn from semistructured interviews collected with 29 men who desisted from crime in an eastern province of Canada. The study demonstrates how this alternative approach allows for the consolidation of existing knowledge on desistance. Then implication of these findings for both theory and practice are discussed. © The Author(s) 2013.

75 FR 63878 - Self-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate...

Science.gov (United States)

2010-10-18

...-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of...(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory...

Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

Science.gov (United States)

Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

2015-12-01

Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

International Nuclear Information System (INIS)

Kaaijk, P.; Academic Medical Center, Amsterdam; Troost, D.; Leenstra, S.; Bosch, D.A.; Sminia, P.; Hulshof, M.C.C.M..; Kracht, A.H.W. van der

1997-01-01

The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastomas patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas. (author)

Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

Energy Technology Data Exchange (ETDEWEB)

Kaaijk, P [Academic Medical Center, Amsterdam (Netherlands). Dept. of (Neuro) Pathology; [Academic Medical Center, Amsterdam (Netherlands). Dept. of Neurosurgery; Troost, D [Academic Medical Center, Amsterdam (Netherlands). Dept. of (Neuro) Pathology; Leenstra, S; Bosch, D A [Academic Medical Center, Amsterdam (Netherlands). Dept. of Neurosurgery; Sminia, P; Hulshof, M C.C.M.; Kracht, A.H.W. van der [Academic Medical Center, Amsterdam (Netherlands). Dept. of (Experimental) Radiotherapy

1997-04-01

The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastomas patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas. (author).

Regulatory activities; Actividades regulatorias

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

Chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma

International Nuclear Information System (INIS)

Shi Degang; Shi Genming; Huang Gang

2006-01-01

Objective: To investigate the chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma. Methods: The A549 irradiated resistant cells were the 10th regrowth generations after irradiated with 2.5 Gy of 6 MV X-ray, the control groups were A549 parent cells and MCFY/VCR resistant cells. The 6 kinds of chemotherapeutic drugs were DDP, VDS, 5-FU, HCP, MMC and ADM respectively, with verapamil (VPL) as reverse agent. The treatment effect was compared with MTT assay, and the multidrug resistant gene expressions of mdrl and MRP were measured with RT-PCR method. Results: A549 cells and irradiated resistant cells were resistant to DDP, but sensitivity to VDS,5-FU, HCP, MMC and ADM. The inhibitory rates of VPL to the above two cells were 98% and 25% respectively(P 2 -MG and MRP/β 2 -MG of all A549 cells were about 0 and 0.7 respectively, and those of MCFT/VCR cells were 35 and 4.36. Conclusion: The chemosensitivity of A549 irradiated resistant cells had not changed markedly, the decreased sensitivity to VPL could not be explained by the gene expression of mdrl and MRP. It is conferred that some kinds of changes in the cell membrane and decreased regrowth ability to result in resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to irradiated resistant cells. The new kinds of biological preparation should be sought to combine chemotherapy to treat recurring tumor with irradiated resistance. (authors)

The core to regulatory reform

International Nuclear Information System (INIS)

Partridge, J.W. Jr.

1993-01-01

Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2011-10-26

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2010-04-06

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

78 FR 62784 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2013-10-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer... 5210 (Publication of Transactions and Quotations) October 4, 2013. I. Introduction On August 15, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

75 FR 21686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2010-04-26

... to pay arbitration awards to remain in the securities industry presents regulatory risks and is...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or...

Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

Science.gov (United States)

Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

2012-03-01

We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Science.gov (United States)

2010-02-01

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Consolidated FINRA Rulebook January 25, 2010. On December 2, 2009, the Financial Industry Regulatory Authority... later in the rulebook consolidation process. It is therefore ordered, pursuant to Section 19(b)(2) of...

77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2012-08-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal of Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

76 FR 21084 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Science.gov (United States)

2011-04-14

... Securities April 8, 2011. I. Introduction On March 3, 2011, the Financial Industry Regulatory Authority, Inc... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64283; File No. SR-FINRA-2011-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer...

Managing Regulatory Body Competence

International Nuclear Information System (INIS)

2013-01-01

In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

Croatian energy regulatory council - independent Croatian regulatory body

International Nuclear Information System (INIS)

Klepo, M.

2002-01-01

By means of approving five energy laws, the Republic of Croatia established an appropriate legislative framework for energy sector regulation. A series of sub-law acts is presently being elaborated as well as some additional documents in order to bring about transparent and non-discriminatory provisions for the establishment of electric energy, gas, oil/oil derivatives and thermal energy markets, i.e. for the introduction and management of market activities and public services. A considerable share of these activities relates to the definition of transparent regulatory mechanisms that would guarantee the implementation of regulation rules based on the law, and be carried out by the independent regulatory body - Croatian Energy Regulatory Council. The Council's rights and obligations include firm executive functions, which present obligations to every energy entity. A dissatisfied party may set in motion a settlement of dispute, if it maintains that the decisions are not based on the law or reveal a flaw in the procedure. Therefore, it is the Council's priority to always make careful and law-abiding decisions. This paper gives insight into the regulatory framework elements based on the laws including the Council's organisational structure and non-profit entities that will prepare act proposals for the Council and perform other professional activities. (author)

Response of the MG-63 human osteosarcoma cell line grown as multicellular spheroids to neutron irradiation

International Nuclear Information System (INIS)

Kubota, Nobuo; Kakehi, Masae; Matsubara, Shou; Koike, Sachiko; Ando, Koichi.

1993-01-01

Multicellular tumor spheroids are composed of the mixed populations of cells with regard to cell proliferation, nutrition, oxygenation and radiosensitivity. Human osteogenic sarcoma is generally considered clinically radioresistant. However, the in vitro cell survival curves for human osteogenic sarcoma cell lines do not differ from those of other tumor cell lines. In this study, the responses of human osteogenic sarcoma cell line to gamma ray and neutrons were investigated by using spheroid system. The spheroids of the osteogenic sarcoma cell line are considered to be a good in vitro model of radioresistant tumors. The purpose of this study is to measure the response of the spheroids to fast neutron irradiation. MG-63 human osteogenic sarcoma cell line was used for this study. The cell line was cultured in alpha-MEM with supplement. Cell survival was estimated after the trypsinization of spheroids 24 hours after irradiation. The method of measuring spheroid cure is explained. The mean number of surviving cells per spheroid can be obtained from the mean clonogenic number and cell survival curve. The cell survival of MG-63 spheroids exposed to gamma ray and neutrons and the dose effect curves for spheroid cure after irradiation are shown. (K.I.)

Anti-regulatory T cells

DEFF Research Database (Denmark)

Andersen, Mads Hald

2017-01-01

responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells......Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...

12 CFR 562.2 - Regulatory reports.

Science.gov (United States)

2010-01-01

... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-09-29

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-04-13

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-07-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

75 FR 71164 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-11-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

Science.gov (United States)

2012-06-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold a joint meeting...

76 FR 60106 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-09-28

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... 14, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Science.gov (United States)

2010-07-15

... registered capacity, may work in other investment-related industries, such as financial planning, or may seek...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule..., 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...

Quality management of the nuclear regulatory body. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

2001-09-01

This report is the outcome of the ninth series of peer discussions on regulatory practices entitled Nuclear Regulatory Body Quality Management, held in March and May 2001, and which involved the participation of senior nuclear regulators from 23 IAEA Member States. This report conveys the essence of two peer group discussions and highlights some good practices identified by the participating senior regulators. The objective of the discussions was to share experiences of regulatory bodies in implementing QM systems in their own work so as to ensure that the regulatory control over the licensees is effective and efficient and is commensurate with the mandate assigned by their governments. The shared experiences and good practices presented in the report, however, do not necessarily reflect the views of and good practices endorsed by the governments of the nominating Member States, the organizations to which the regulators belong, or the IAEA. The report sets down the peer group's experience in developing, implementing and evaluating QM within their regulatory bodies and identifies points to bear in mind when introducing such a system. This report is structured so that it covers the subject matter under the main headings of: application of quality management to regulatory work; development and implementation of quality management; assessment and improvement of performance; and good practices

Hazard identification of exhausts from gasoline-ethanol fuel blends using a multi-cellular human lung model.

Science.gov (United States)

Bisig, Christoph; Roth, Michèle; Müller, Loretta; Comte, Pierre; Heeb, Norbert; Mayer, Andreas; Czerwinski, Jan; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

2016-11-01

Ethanol can be produced from biomass and as such is renewable, unlike petroleum-based fuel. Almost all gasoline cars can drive with fuel containing 10% ethanol (E10), flex-fuel cars can even use 85% ethanol (E85). Brazil and the USA already include 10-27% ethanol in their standard fuel by law. Most health effect studies on car emissions are however performed with diesel exhausts, and only few data exists for other fuels. In this work we investigated possible toxic effects of exhaust aerosols from ethanol-gasoline blends using a multi-cellular model of the human lung. A flex-fuel passenger car was driven on a chassis dynamometer and fueled with E10, E85, or pure gasoline (E0). Exhausts obtained from a steady state cycle were directly applied for 6h at a dilution of 1:10 onto a multi-cellular human lung model mimicking the bronchial compartment composed of human bronchial cells (16HBE14o-), supplemented with human monocyte-derived dendritic cells and monocyte-derived macrophages, cultured at the air-liquid interface. Biological endpoints were assessed after 6h post incubation and included cytotoxicity, pro-inflammation, oxidative stress, and DNA damage. Filtered air was applied to control cells in parallel to the different exhausts; for comparison an exposure to diesel exhaust was also included in the study. No differences were measured for the volatile compounds, i.e. CO, NO x , and T.HC for the different ethanol supplemented exhausts. Average particle number were 6×10 2 #/cm 3 (E0), 1×10 5 #/cm 3 (E10), 3×10 3 #/cm 3 (E85), and 2.8×10 6 #/cm 3 (diesel). In ethanol-gasoline exposure conditions no cytotoxicity and no morphological changes were observed in the lung cell cultures, in addition no oxidative stress - as analyzed with the glutathione assay - was measured. Gene expression analysis also shows no induction in any of the tested genes, including mRNA levels of genes related to oxidative stress and pro-inflammation, as well as indoleamine 2,3-dioxygenase 1

Future nuclear regulatory challenges

International Nuclear Information System (INIS)

Royen, J.

1998-01-01

In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2012-02-10

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

75 FR 59771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

Science.gov (United States)

2010-09-28

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the Proposed Rule.... I. Introduction On July 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k... pertinent distribution-related information from its members in a timely fashion to facilitate its Regulation...

76 FR 50796 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-08-16

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Increase the Position Limit for Options on the Standard and Poor's... Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

Regulatory difficulties in a developing country

International Nuclear Information System (INIS)

Jacobs, W.R. Jr.

1978-01-01

The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

Regulatory control of nuclear power plants

International Nuclear Information System (INIS)

2002-01-01

The purpose of this book is to support IAEA training courses and workshops in the field of regulatory control of nuclear power plants as well as to support the regulatory bodies of Member States in their own training activities. The target group is the professional staff members of nuclear safety regulatory bodies supervising nuclear power plants and having duties and responsibilities in the following regulatory fields: regulatory framework; regulatory organization; regulatory guidance; licensing and licensing documents; assessment of safety; and regulatory inspection and enforcement. Important topics such as regulatory competence and quality of regulatory work as well as emergency preparedness and public communication are also covered. The book also presents the key issues of nuclear safety such as 'defence-in-depth' and safety culture and explains how these should be taken into account in regulatory work, e.g. during safety assessment and regulatory inspection. The book also reflects how nuclear safety has been developed during the years on the basis of operating experience feedback and results of safety research by giving topical examples. The examples cover development of operating procedures and accident management to cope with complicated incidents and severe accidents to stress the importance of regulatory role in nuclear safety research. The main target group is new staff members of regulatory bodies, but the book also offers good examples for more experienced inspectors to be used as comparison and discussion basis in internal workshops organized by the regulatory bodies for refreshing and continuing training. The book was originally compiled on the basis of presentations provided during the two regulatory control training courses in 1997 and 1998. The textbook was reviewed at the beginning of the years 2000 and 2002 by IAEA staff members and consistency with the latest revisions of safety standards have been ensured. The textbook was completed in the

The Evolution of the Secreted Regulatory Protein Progranulin.

Directory of Open Access Journals (Sweden)

Roger G E Palfree

Full Text Available Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i: the origins of metazoan progranulins (ii: the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii: the evolution of granulin module architectures of vertebrate progranulins (iv: the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl

Improving nuclear regulatory effectiveness

International Nuclear Information System (INIS)

2001-01-01

Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-05-17

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry... restated following the formation of FINRA through the consolidation of NASD and the member regulatory...

Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

Science.gov (United States)

Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

2004-01-01

A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

Combined exposure of diesel exhaust particles and respirable Soufrière Hills volcanic ash causes a (pro-)inflammatory response in an in vitro multicellular epithelial tissue barrier model

Science.gov (United States)

Tomašek, Ines; Horwell, Claire J.; Damby, David; Barošová, Hana; Geers, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara; Clift, Martin J. D.

2016-01-01

BackgroundThere are justifiable health concerns regarding the potential adverse effects associated with human exposure to volcanic ash (VA) particles, especially when considering communities living in urban areas already exposed to heightened air pollution. The aim of this study was, therefore, to gain an imperative, first understanding of the biological impacts of respirable VA when exposed concomitantly with diesel particles.MethodsA sophisticated in vitro 3D triple cell co-culture model of the human alveolar epithelial tissue barrier was exposed to either a single or repeated dose of dry respirable VA (deposited dose of 0.26 ± 0.09 or 0.89 ± 0.29 μg/cm2, respectively) from Soufrière Hills volcano, Montserrat for a period of 24 h at the air-liquid interface (ALI). Subsequently, co-cultures were exposed to co-exposures of single or repeated VA and diesel exhaust particles (DEP; NIST SRM 2975; 0.02 mg/mL), a model urban pollutant, at the pseudo-ALI. The biological impact of each individual particle type was also analysed under these precise scenarios. The cytotoxic (LDH release), oxidative stress (depletion of intracellular GSH) and (pro-)inflammatory (TNF-α, IL-8 and IL-1β) responses were assessed after the particulate exposures. The impact of VA exposure upon cell morphology, as well as its interaction with the multicellular model, was visualised via confocal laser scanning microscopy (LSM) and scanning electron microscopy (SEM), respectively.ResultsThe combination of respirable VA and DEP, in all scenarios, incited an heightened release of TNF-α and IL-8 as well as significant increases in IL-1β, when applied at sub-lethal doses to the co-culture compared to VA exposure alone. Notably, the augmented (pro-)inflammatory responses observed were not mediated by oxidative stress. LSM supported the quantitative assessment of cytotoxicity, with no changes in cell morphology within the barrier model evident. A direct interaction of the VA with all

Nuclear Regulatory legislation

International Nuclear Information System (INIS)

1984-06-01

This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-09-02

... characteristics and risks of security futures. \\6\\ 15 U.S.C. 78o-3(b)(6). B. Self-Regulatory Organization's...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend the Security Futures Risk Disclosure Statement August 27, 2010...

NRC regulatory agenda

International Nuclear Information System (INIS)

1990-01-01

The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.

Directory of Open Access Journals (Sweden)

Remy Froissart

2005-03-01

Full Text Available Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5 to 4 x 10(-5. This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.

Nuclear Regulatory Commission information digest

International Nuclear Information System (INIS)

1990-03-01

The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide

Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models.

Science.gov (United States)

Walenta, Stefan; Mueller-Klieser, Wolfgang

2016-01-01

This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, (12)C(+6) in the plateau region, and (12)C(+6) in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during (12)C(+6) irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral

Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

Science.gov (United States)

Walenta, Stefan; Mueller-Klieser, Wolfgang

2016-01-01

This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the

Research and regulatory review

International Nuclear Information System (INIS)

Macleod, J.S.; Fryer, D.R.H.

1979-01-01

To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

76 FR 12380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2011-03-07

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1..., the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

Isolation of microRNA targets using biotinylated synthetic microRNAs

DEFF Research Database (Denmark)

Ørom, Ulf Andersson; Lund, Anders H

2007-01-01

MicroRNAs are small regulatory RNAs found in multicellular organisms where they post-transcriptionally regulate gene expression. In animals, microRNAs bind mRNAs via incomplete base pairings making the identification of microRNA targets inherently difficult. Here, we present a detailed method...... for experimental identification of microRNA targets based on affinity purification of tagged microRNAs associated with their targets. Udgivelsesdato: 2007-Oct...

The connection between splicing and cancer

OpenAIRE

Srebrow, Anabella; Kornblihtt, Alberto Rodolfo

2017-01-01

Alternative splicing is a crucial mechanism for generating protein diversity. Different splice variants of a given protein can display different and even antagonistic biological functions. Therefore, appropriate control of their synthesis is required to assure the complex orchestration of cellular processes within multicellular organisms. Mutations in cisacting splicing elements or changes in the activity of regulatory proteins that compromise the accuracy of either constitutive or alternativ...

A microfluidic chip with a U-shaped microstructure array for multicellular spheroid formation, culturing and analysis

International Nuclear Information System (INIS)

Fu, Chien-Yu; Chang, Hwan-You; Tseng, Sheng-Yang; Yang, Shih-Mo; Hsu, Long; Liu, Cheng-Hsien

2014-01-01

Multicellular spheroids (MCS), formed by self-assembly of single cells, are commonly used as a three-dimensional cell culture model to bridge the gap between in vitro monolayer culture and in vivo tissues. However, current methods for MCS generation and analysis still suffer drawbacks such as being labor-intensive and of poor controllability, and are not suitable for high-throughput applications. This study demonstrates a novel microfluidic chip to facilitate MCS formation, culturing and analysis. The chip contains an array of U-shaped microstructures fabricated by photopolymerizing the poly(ethylene glycol) diacrylate hydrogel through defining the ultraviolet light exposure pattern with a photomask. The geometry of the U-shaped microstructures allowed trapping cells into the pocket through the actions of fluid flow and the force of gravity. The hydrogel is non-adherent for cells, promoting the formation of MCS. Its permselective property also facilitates exchange of nutrients and waste for MCS, while providing protection of MCS from shearing stress during the medium perfusion. Heterotypic MCS can be formed easily by manipulating the cell trapping steps. Subsequent drug susceptibility analysis and long-term culture could also be achieved within the same chip. This MCS formation and culture platform can be used as a micro-scale bioreactor and applied in many cell biology and drug testing studies. (paper)

Doxorubicin delivery to 3D multicellular spheroids and tumors based on boronic acid-rich chitosan nanoparticles.

Science.gov (United States)

Wang, Xin; Zhen, Xu; Wang, Jing; Zhang, Jialiang; Wu, Wei; Jiang, Xiqun

2013-06-01

Boronic acid-rich chitosan-poly(N-3-acrylamidophenylboronic acid) nanoparticles (CS-PAPBA NPs) with the tunable size were successfully prepared by polymerizing N-3-acrylamidophenylboronic acid in the presence of chitosan in an aqueous solution. The CS-PAPBA NPs were then functionalized by a tumor-penetrating peptide iRGD and loading doxorubicin (DOX). The interaction between boronic acid groups of hydrophobic PAPBA and the amino groups of hydrophilic chitosan inside the nanoparticles was examined by solid-state NMR measurement. The size and morphology of nanoparticles were characterized by dynamic light scattering and electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using three-dimensional (3-D) multicellular spheroids (MCs) as the in vitro model and H22 tumor-bearing mice as the in vivo model. It was found that the iRGD-conjugated nanoparticles significantly improved the efficiency of DOX penetration in MCs, compared with free DOX and non-conjugated nanoparticles, resulting in the efficient cell killing in the MCs. In vivo antitumor activity examination indicated that iRGD-conjugated CS-PAPBA nanoparticles promoted the accumulation of nanoparticles in tumor tissue and enhanced their penetration in tumor areas, both of which improved the efficiency of DOX-loaded nanoparticles in restraining tumor growth and prolonging the life time of H22 tumor-bearing mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids

Science.gov (United States)

Judée, Florian; Fongia, Céline; Ducommun, Bernard; Yousfi, Mohammed; Lobjois, Valérie; Merbahi, Nofel

2016-02-01

This work investigates the regionalized antiproliferative effects of plasma-activated medium (PAM) on colon adenocarcinoma multicellular tumor spheroid (MCTS), a model that mimics 3D organization and regionalization of a microtumor region. PAM was generated by dielectric barrier plasma jet setup crossed by helium carrier gas. MCTS were transferred in PAM at various times after plasma exposure up to 48 hours and effect on MCTS growth and DNA damage were evaluated. We report the impact of plasma exposure duration and delay before transfer on MCTS growth and DNA damage. Local accumulation of DNA damage revealed by histone H2AX phosphorylation is observed on outermost layers and is dependent on plasma exposure. DNA damage is completely reverted by catalase addition indicating that H2O2 plays major role in observed genotoxic effect while growth inhibitory effect is maintained suggesting that it is due to others reactive species. SOD and D-mannitol scavengers also reduced DNA damage by 30% indicating that and OH* are involved in H2O2 formation. Finally, PAM is able to retain its cytotoxic and genotoxic activity upon storage at +4 °C or -80 °C. These results suggest that plasma activated media may be a promising new antitumor strategy for colorectal cancer tumors.

NRC regulatory agenda

International Nuclear Information System (INIS)

1991-04-01

The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

NRC Regulatory Agenda

International Nuclear Information System (INIS)

1991-08-01

The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

75 FR 2897 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2010-01-19

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... hereby given that on December 23, 2009, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). NASD Rule 2450...

Through the regulatory hoop

International Nuclear Information System (INIS)

Kirner, N.P.

1985-01-01

There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

Regulatory Control of Radiation Sources. Safety Guide

International Nuclear Information System (INIS)

2009-01-01

This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

NRC Regulatory Agenda

International Nuclear Information System (INIS)

1991-10-01

The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

NRC regulatory agenda

International Nuclear Information System (INIS)

1993-04-01

The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

Nuclear regulatory decision making

International Nuclear Information System (INIS)

Wieland, Patricia; Almeida, Ivan Pedro Salati de

2011-01-01

The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

Nuclear regulatory decision making

International Nuclear Information System (INIS)

2005-01-01

The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants at all times in an acceptably safe manner. In meeting this objective, the regulatory body should strive to ensure that its regulatory decisions are technically sound, consistent from case to case, and timely. In addition, the regulator must be aware that its decisions and the circumstances surrounding those decisions can affect how its stakeholders, such as government policy makers, the industry it regulates, and the public, view it as an effective and credible regulator. In order to maintain the confidence of those stakeholders, the regulator should make sure that its decisions are transparent, have a clear basis in law and regulations, and are seen by impartial observers to be fair to all parties. Based on the work of a Nuclear Energy Agency (NEA) expert group, this report discusses some of the basic principles and criteria that a regulatory body should consider in making decisions and describes the elements of an integrated framework for regulatory decision making. (author)

Virginia Power's regulatory reduction program

International Nuclear Information System (INIS)

Miller, G.D.

1996-01-01

Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

75 FR 7526 - Withdrawal of Regulatory Guide

Science.gov (United States)

2010-02-19

...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

KWOC [Key-Word-Out-of-Context] Index of US Nuclear Regulatory Commission Regulatory Guide Series

International Nuclear Information System (INIS)

Jennings, S.D.

1990-04-01

To meet the objectives of the program funded by the Department of Energy (DOE)-Nuclear Energy (NE) Technology Support Programs, the Performance Assurance Project Office (PAPO) administers a Performance Assurance Information Program that collects, compiles, and distributes program-related information, reports, and publications for the benefit of the DOE-NE program participants. THE ''KWOC Index of US Nuclear Regulatory Commission Regulatory Guide Series'' is prepared as an aid in searching for specific topics in the US Nuclear Regulatory Commission, Regulatory Guide Series

Professional and Regulatory Search

Science.gov (United States)

Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

Perceptions of regulatory approaches

International Nuclear Information System (INIS)

Halin, Magnus; Leinonen, Ruusaliisa

2012-01-01

Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2012-02-28

... 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule... FINRA and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

Generation model of positional values as cell operation during the development of multicellular organisms.

Science.gov (United States)

Ogawa, Ken-ichiro; Miyake, Yoshihiro

2011-03-01

Many conventional models have used the positional information hypothesis to explain each elementary process of morphogenesis during the development of multicellular organisms. Their models assume that the steady concentration patterns of morphogens formed in an extracellular environment have an important property of positional information, so-called "robustness". However, recent experiments reported that a steady morphogen pattern, the concentration gradient of the Bicoid protein, during early Drosophila embryonic development is not robust for embryo-to-embryo variability. These reports encourage a reconsideration of a long-standing problem in systematic cell differentiation: what is the entity of positional information for cells? And, what is the origin of the robust boundary of gene expression? To address these problems at a cellular level, in this article we pay attention to the re-generative phenomena that show another important property of positional information, "size invariance". In view of regenerative phenomena, we propose a new mathematical model to describe the generation mechanism of a spatial pattern of positional values. In this model, the positional values are defined as the values into which differentiable cells transform a spatial pattern providing positional information. The model is mathematically described as an associative algebra composed of various terms, each of which is the multiplication of some fundamental operators under the assumption that the operators are derived from the remarkable properties of cell differentiation on an amputation surface in regenerative phenomena. We apply this model to the concentration pattern of the Bicoid protein during the anterior-posterior axis formation in Drosophila, and consider the conditions needed to establish the robust boundary of the expression of the hunchback gene. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Anaerobic Respiration Using a Complete Oxidative TCA Cycle Drives Multicellular Swarming in Proteus mirabilis

Science.gov (United States)

Alteri, Christopher J.; Himpsl, Stephanie D.; Engstrom, Michael D.; Mobley, Harry L. T.

2012-01-01

ABSTRACT Proteus mirabilis rapidly migrates across surfaces using a periodic developmental process of differentiation alternating between short swimmer cells and elongated hyperflagellated swarmer cells. To undergo this vigorous flagellum-mediated motility, bacteria must generate a substantial proton gradient across their cytoplasmic membranes by using available energy pathways. We sought to identify the link between energy pathways and swarming differentiation by examining the behavior of defined central metabolism mutants. Mutations in the tricarboxylic acid (TCA) cycle (fumC and sdhB mutants) caused altered patterns of swarming periodicity, suggesting an aerobic pathway. Surprisingly, the wild-type strain swarmed on agar containing sodium azide, which poisons aerobic respiration; the fumC TCA cycle mutant, however, was unable to swarm on azide. To identify other contributing energy pathways, we screened transposon mutants for loss of swarming on sodium azide and found insertions in the following genes that involved fumarate metabolism or respiration: hybB, encoding hydrogenase; fumC, encoding fumarase; argH, encoding argininosuccinate lyase (generates fumarate); and a quinone hydroxylase gene. These findings validated the screen and suggested involvement of anaerobic electron transport chain components. Abnormal swarming periodicity of fumC and sdhB mutants was associated with the excretion of reduced acidic fermentation end products. Bacteria lacking SdhB were rescued to wild-type pH and periodicity by providing fumarate, independent of carbon source but dependent on oxygen, while fumC mutants were rescued by glycerol, independent of fumarate only under anaerobic conditions. These findings link multicellular swarming patterns with fumarate metabolism and membrane electron transport using a previously unappreciated configuration of both aerobic and anaerobic respiratory chain components. PMID:23111869

76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2011-02-22

.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

Nuclear Regulatory Legislation

International Nuclear Information System (INIS)

1989-08-01

This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel, US Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document. Persons using this document are placed on notice that it may not be used as an authoritative citation in lieu of the primary legislative sources. Furthermore, while every effort has been made to ensure the completeness and accuracy of this material, neither the United States Government, the Nuclear Regulatory Commission, nor any of their employees makes any expressed or implied warranty or assumes liability for the accuracy or completeness of the material presented in this compilation

Risk-based Regulatory Evaluation Program methodology

International Nuclear Information System (INIS)

DuCharme, A.R.; Sanders, G.A.; Carlson, D.D.; Asselin, S.V.

1987-01-01

The objectives of this DOE-supported Regulatory Evaluation Progrwam are to analyze and evaluate the safety importance and economic significance of existing regulatory guidance in order to assist in the improvement of the regulatory process for current generation and future design reactors. A risk-based cost-benefit methodology was developed to evaluate the safety benefit and cost of specific regulations or Standard Review Plan sections. Risk-based methods can be used in lieu of or in combination with deterministic methods in developing regulatory requirements and reaching regulatory decisions

Methodology for the Systematic Assessment of the Regulatory Competence Needs (SARCoN) for Regulatory Bodies of Nuclear Installations

International Nuclear Information System (INIS)

2015-03-01

A regulatory body’s competence is dependent, among other things, on the competence of its staff. A necessary, but not sufficient, condition for a regulatory body to be competent is that its staff can perform the tasks related to the functions of the regulatory body. In 2001, the IAEA published TECDOC 1254, Training the Staff of the Regulatory Body for Nuclear Facilities: A Competency Framework, which examines the manner in which the recognized regulatory functions of a nuclear regulatory body results in competence needs. Using the internationally recognized systematic approach to training, TECDOC 1254 provides a framework for regulatory bodies for managing training and developing, and maintaining the competence of its staff. It has been successfully used by many regulatory bodies all over the world, including States embarking on a nuclear power programme. The IAEA has also introduced a methodology and an assessment tool — Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) — which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2013, the IAEA published Safety Reports Series No. 79, Managing Regulatory Body Competence, which provides generic guidance based on IAEA safety requirements in the development of a competence management system within a regulatory body’s integrated management system. An appendix in the Safety Report deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an embarking State’s regulatory system. This publication provides guidance for the analysis of required and existing competences to identify those required by the regulatory body to perform its functions and therefore associated needs for acquiring competences. Hence, it is equally applicable to the needs of States embarking on nuclear power

76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2011-02-22

.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance..., and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the... in sections A, B, and C below, of the most significant aspects of such statements. A. Self-Regulatory...

First update to the US Nuclear Regulatory Commission's regulatory strategy for the high-level waste repository program

International Nuclear Information System (INIS)

Johnson, R.L.; Linehan, J.J.

1991-01-01

The US Nuclear Regulatory Commission (NRC) staff has updated its initial regulatory strategy for the High-Level Waste Repository Licensing Program. The update describes changes to the initial strategy and summarizes progress and future activities. This paper summarizes the first update of the regulatory strategy. In general the overall strategy of identifying and reducing uncertainties is unchanged. Identifying regulatory and institutional uncertainties is essentially complete, and therefore, the current and future emphasis is on reducing those regulatory and institutional uncertainties identified to date. The NRC staff has improved the methods of reducing regulatory uncertainties by (1) enhancing the technical basis preparation process for potential rulemakings and guidance and (2) designing a new guidance document, called a staff position, for clarifying regulatory uncertainties. For guiding the US DOE's reduction of technical uncertainties, the NRC staff will give more emphasis to prelicense application reviews and less emphasis on preparing staff technical positions

National legislative and regulatory activities

International Nuclear Information System (INIS)

2012-01-01

This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

Developing regulatory approaches

International Nuclear Information System (INIS)

Axelsson, Lars

2012-01-01

Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

Trust in regulatory regimes

NARCIS (Netherlands)

Six, Frédérique; Verhoest, Koen

2017-01-01

Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

Directory of Open Access Journals (Sweden)

Vipin Narang

Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

Strengthening Regulatory Competence in Pakistan

International Nuclear Information System (INIS)

Sadiq, M.

2016-01-01

Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

The Political Economy of Regulatory Risk

OpenAIRE

Strausz, Roland

2009-01-01

I investigate the argument that, in a two–party system with different regulatory objectives, political uncertainty generates regulatory risk. I show that this risk has a fluctuation effect that hurts both parties and an output–expansion effect that benefits one party. Consequently, at least one party dislikes regulatory risk. Moreover, both political parties gain from eliminating regulatory risk when political divergence is small or the winning probability of the regulatory–risk–averse party ...

Reduction of regulatory risk: a network economic approach

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2007-01-01

Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

Radioactive waste below regulatory concern

International Nuclear Information System (INIS)

Neuder, S.M.

1987-01-01

The U.S. Nuclear Regulatory Commission (NRC) published two notices in the Federal Register concerning radioactive waste below regulatory concern. The first, a Commission Policy Statement and Implementation Plan published August 29, 1986, concerns petition to exempt specific radioactive waste streams from the regulations. The second, an Advanced Notice of Proposed Rulemaking published Decemger 2, 1986, addresses the concept of generic rulemaking by the NRC on radioactive wastes that are below regulatory concern. Radioactive waste determined to be below regulatory concern would not be subject to regulatory control and would not need to go to a licensed low-level radioactive waste disposal site. The Policy Statement and Implementation Plan describe (1) the information a petitioner should file in support of a petition to exempt a specific waste stream, (2) the decision criteria the Commission intends to use for judging the petition, and (3) the internal administrative procedures to use be followed in order to permit the Commission to act upon the petition in an expedited manner

75 FR 22868 - Withdrawal of Regulatory Guide

Science.gov (United States)

2010-04-30

...'s public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0167] Withdrawal of Regulatory Guide AGENCY: Nuclear...

National legislative and regulatory activities

International Nuclear Information System (INIS)

2016-01-01

This section treats of the following National legislative and regulatory activities: 1 - France: General legislation, regulations and instruments; Nuclear trade (including non-proliferation); International co-operation; 2 - India: Licensing and regulatory infrastructure; Liability and compensation; 3 - Ireland: Nuclear safety and radiological protection (including nuclear emergency planning); Transport of radioactive material; Nuclear trade (including non-proliferation); 4 - Lithuania: Licensing and regulatory infrastructure; Nuclear safety and radiological protection (including nuclear emergency planning); Radioactive waste management; 5 - Luxembourg: Nuclear safety and radiological protection (including nuclear emergency planning); 6 - Slovak Republic: International co-operation; General legislation, regulations and instruments; 7 - Spain: Radioactive materials (including physical protection); Radioactive waste management; 8 - United States: Licensing and regulatory infrastructure

76 FR 24539 - Final Regulatory Guide: Issuance, Availability

Science.gov (United States)

2011-05-02

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . Electronic copies... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

A global regulatory science agenda for vaccines.

Science.gov (United States)

Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

2013-04-18

The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

75 FR 42170 - Final Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-07-20

... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0425] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

75 FR 48381 - Final Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-08-10

... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0274] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Regulatory Guide...

Regulatory and licensee surveys

International Nuclear Information System (INIS)

2009-01-01

Prior to the workshop two CSNI/WGHOF surveys were distributed. One survey was directed at regulatory bodies and the other was directed at plant licensees. The surveys were: 1 - Regulatory Expectations of Licensees' Arrangements to Ensure Suitable Organisational Structure, Resources and Competencies to Manage Safety (sent to WGHOF regulatory members). The survey requested that the respondents provide a brief overview of the situation related to plant organisations in their country, their regulatory expectations and their formal requirements. The survey addressed three subjects: the demonstration and documentation of organisational structures, resources and competencies, organisational changes, issues for improvement (for both current and new plants). Responses were received from eleven regulatory bodies. 2 - Approaches to Justify Organisational Suitability (sent to selected licensees). The purpose of the survey to was to gain an understanding of how licensees ensure organisational suitability, resources and competencies. This information was used to assist in the development of the issues and subjects that were addressed at the group discussion sessions. Responses were received from over fifteen licensees from nine countries. The survey requested that the licensees provide information on how they ensure effective organisational structures at their plants. The survey grouped the questions into the following four categories: organisational safety functions, resource and competence, decision-making and communication, good examples and improvement needs. The findings from these surveys were used in conjunction with other factors to identify the key issues for the workshop discussion sessions. The responses from these two surveys are discussed briefly in Sections 4 and 5 of this report. More extensive reviews of the regulatory and licensee responses are provided in Appendix 1

12 CFR 914.1 - Regulatory Report defined.

Science.gov (United States)

2010-01-01

... Bank. (b) Examples. Regulatory Report includes: (1) Call reports and reports of instrument-level risk... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Regulatory Report defined. 914.1 Section 914.1... DATA AVAILABILITY AND REPORTING § 914.1 Regulatory Report defined. (a) Definition. Regulatory Report...

Nuclear Regulatory Commission 1989 Information Digest

International Nuclear Information System (INIS)

1989-03-01

The Nuclear Regulatory Commission 1989 Information Digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the Commission. This is the first of an annual publication for the general use of the NRC staff and is available to the public. The Digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide

Regulatory pathways for vaccines for developing countries.

Science.gov (United States)

Milstien, Julie; Belgharbi, Lahouari

2004-01-01

Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235

The development of AECB regulatory documents

International Nuclear Information System (INIS)

Joyce, M.

1981-01-01

This document describes the Atomic Energy Control Board's (AECB) approach to the development and preparation of regulatory documents. The principal factors that have shaped the AECB'a regulatory approach are identified as background to the evolution of regulatory documents as are a number of current influences that affect the present and future development of these documents. Also described are the process by which regulatory documents are prepared and published and the points of contact between this process and the Canadian Standards Association program for nuclear standards. (author)

Regulatory inspection of BARC facilities

International Nuclear Information System (INIS)

Rajdeep; Jayarajan, K.

2017-01-01

Nuclear and radiation facilities are sited, constructed, commissioned, operated and decommissioned, in conformity with the current safety standards and codes. Regulatory bodies follow different means to ensure compliance of the standards for the safety of the personnel, the public and the environment. Regulatory Inspection (RI) is one of the important measures employed by regulatory bodies to obtain the safety status of a facility or project and to verify the fulfilment of the conditions stipulated in the consent

Environment, safety, and health regulatory implementation plan

International Nuclear Information System (INIS)

1993-01-01

To identify, document, and maintain the Uranium Mill Tailings Remedial Action (UMTRA) Project's environment, safety, and health (ES ampersand H) regulatory requirements, the US Department of Energy (DOE) UMTRA Project Office tasked the Technical Assistance Contractor (TAC) to develop a regulatory operating envelope for the UMTRA Project. The system selected for managing the UMTRA regulatory operating envelope data bass is based on the Integrated Project Control/Regulatory Compliance System (IPC/RCS) developed by WASTREN, Inc. (WASTREN, 1993). The IPC/RCS is a tool used for identifying regulatory and institutional requirements and indexing them to hardware, personnel, and program systems on a project. The IPC/RCS will be customized for the UMTRA Project surface remedial action and groundwater restoration programs. The purpose of this plan is to establish the process for implementing and maintaining the UMTRA Project's regulatory operating envelope, which involves identifying all applicable regulatory and institutional requirements and determining compliance status. The plan describes how the Project will identify ES ampersand H regulatory requirements, analyze applicability to the UMTRA Project, and evaluate UMTRA Project compliance status

40 CFR 92.6 - Regulatory structure.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 92.6 Section 92... Regulations for Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides an overview of the regulatory structure of this part. (a) The regulations of this part 92 are intended to...

40 CFR 94.6 - Regulatory structure.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 94.6 Section 94... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an overview of the regulatory structure of this part. (a) The regulations of this Part 94 are intended to control...

An integrated in vitro imaging platform for characterizing filarial parasite behavior within a multicellular microenvironment.

Directory of Open Access Journals (Sweden)

Timothy Kassis

2014-11-01

Full Text Available Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele. The mechanisms driving worm migration and retention within the lymphatics are currently unknown. We have developed an integrated in vitro imaging platform capable of quantifying B. malayi migration and behavior in a multicellular microenvironment relevant to the initial site of worm injection by incorporating the worm in a Polydimethylsiloxane (PDMS microchannel in the presence of human dermal lymphatic endothelial cells (LECs and human dermal fibroblasts (HDFs. The platform utilizes a motorized controllable microscope with CO2 and temperature regulation to allow for worm tracking experiments with high resolution over large length and time scales. Using post-acquisition algorithms, we quantified four parameters: 1 speed, 2 thrashing intensity, 3 percentage of time spent in a given cell region and 4 persistence ratio. We demonstrated the utility of our system by quantifying these parameters for L3 B. malayi in the presence of LECs and HDFs. Speed and thrashing increased in the presence of both cell types and were altered within minutes upon exposure to the anthelmintic drug, tetramisole. The worms displayed no targeted migration towards either cell type for the time course of this study (3 hours. When cells were not present in the chamber, worm thrashing correlated directly with worm speed. However, this correlation was lost in the presence of cells. The described platform provides the ability to further study B. malayi migration and behavior.

ENSI’s regulatory framework strategy

International Nuclear Information System (INIS)

2015-03-01

This short brochure issued by the Swiss Federal Nuclear Safety Inspectorate ENSI defines the organisation’s regulatory framework strategy. Six guiding principles are declared and discussed: Comprehensive harmonisation with relevant international requirements, basing the regulatory framework on existing, tried-and-tested regulations, issuing of its own guidelines only when it is necessary to do so, guidelines to be drawn up transparently and with the involvement of all stakeholders and basing the level of detail of its regulatory framework on hazard potential and risk

75 FR 80556 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-12-22

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 13, 2010, Financial Industry... application by their terms. For more information about the rulebook consolidation process, see Information...

75 FR 43588 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Science.gov (United States)

2010-07-26

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule... FINRA Rule 4320 in the Consolidated FINRA Rulebook July 20, 2010. On May 21, 2010, the Financial... application by their terms. For more information about the rulebook consolidation process, see Information...

75 FR 79049 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-12-17

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2008-0427] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.12...

75 FR 45173 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-08-02

... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2008-0638] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.151...

76 FR 18262 - Notice of issuance of Regulatory Guide

Science.gov (United States)

2011-04-01

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0277] Notice of issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.44...

76 FR 14107 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-03-15

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0276] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.43...

76 FR 14108 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-03-15

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0275] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.50...

Delay-independent stability of genetic regulatory networks.

Science.gov (United States)

Wu, Fang-Xiang

2011-11-01

Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

76 FR 67236 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2011-10-31

... a foreign financial institution, and as part of the corporate control transaction, the foreign... subsidiaries, both of which are U.S. non-broker-dealer financial institutions, and as part of the corporate...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...

75 FR 29793 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-05-27

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on May 4, 2010, Financial.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

Development of three-dimensional lung multicellular spheroids in air- and liquid-interface culture for the evaluation of anticancer therapeutics.

Science.gov (United States)

Meenach, Samantha A; Tsoras, Alexandra N; McGarry, Ronald C; Mansour, Heidi M; Hilt, J Zach; Anderson, Kimberly W

2016-04-01

Three-dimensional (3D) lung multicellular spheroids (MCS) in liquid-covered culture (LCC) and air-interface culture (AIC) conditions have both been developed for the evaluation of aerosol anticancer therapeutics in solution and aerosols, respectively. The MCS were formed by seeding lung cancer cells on top of collagen where they formed spheroids due to the prevalence of cell-to-cell interactions. LCC MCS were exposed to paclitaxel (PTX) in media whereas AIC MCS were exposed to dry powder PEGylated phospholipid aerosol microparticles containing paclitaxel. The difference in viability for 2D versus 3D culture for both LCC and AIC was evaluated along with the effects of the particles on lung epithelium via transepithelial electrical resistance (TEER) measurements. For LCC and AIC conditions, the 3D spheroids were more resistant to treatment with higher IC50 values for A549 and H358 cell lines. TEER results initially indicated a decrease in resistance upon drug or particle exposure, however, these values increased over the course of several days indicating the ability of the cells to recover. Overall, these studies offer a comprehensive in vitro evaluation of aerosol particles used in the treatment of lung cancer while introducing a new method for culturing lung cancer MCS in both LCC and AIC conditions.

Annual Report 2008. Nuclear Regulatory Authority

International Nuclear Information System (INIS)

2009-01-01

The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across four parts and seven annexes the activities developed by the organism during 2008. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational and budgetary developments. Also, this publication have annexes with the following content: regulatory documents; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

Annual Report 2007. Nuclear Regulatory Authority

International Nuclear Information System (INIS)

2008-01-01

The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across tree parts and seven annexes the activities developed by the organism during 2007. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

A BABCOCK–LEIGHTON SOLAR DYNAMO MODEL WITH MULTI-CELLULAR MERIDIONAL CIRCULATION IN ADVECTION- AND DIFFUSION-DOMINATED REGIMES

Energy Technology Data Exchange (ETDEWEB)

Belucz, Bernadett; Forgács-Dajka, Emese [Eötvös University, Department of Astronomy, 1518 Budapest, Pf. 32 (Hungary); Dikpati, Mausumi, E-mail: bbelucz@astro.elte.hu, E-mail: dikpati@ucar.edu [High Altitude Observatory, National Center for Atmospheric Research, 3080 Center Green, Boulder, CO 80307-3000 (United States)

2015-06-20

Babcock–Leighton type-solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock–Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that the presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in the butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of the butterfly wing to an antisolar type. A butterfly diagram constructed from the middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in latitude behaves distinctly differently in the two regimes, producing solar-like butterfly diagrams with fast cycles in the higher diffusivity regime, and complex branches in butterfly diagrams in the lower diffusivity regime. We also find that dynamo solutions for a four-celled pattern, two in radius and two in latitude, prefer to quickly relax to quadrupolar parity if the bottom flow speed is strong enough, of similar order of magnitude as the surface flow speed.

A BABCOCK–LEIGHTON SOLAR DYNAMO MODEL WITH MULTI-CELLULAR MERIDIONAL CIRCULATION IN ADVECTION- AND DIFFUSION-DOMINATED REGIMES

International Nuclear Information System (INIS)

Belucz, Bernadett; Forgács-Dajka, Emese; Dikpati, Mausumi

2015-01-01

Babcock–Leighton type-solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock–Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that the presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in the butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of the butterfly wing to an antisolar type. A butterfly diagram constructed from the middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in latitude behaves distinctly differently in the two regimes, producing solar-like butterfly diagrams with fast cycles in the higher diffusivity regime, and complex branches in butterfly diagrams in the lower diffusivity regime. We also find that dynamo solutions for a four-celled pattern, two in radius and two in latitude, prefer to quickly relax to quadrupolar parity if the bottom flow speed is strong enough, of similar order of magnitude as the surface flow speed

77 FR 38694 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2012-06-28

... matrix will be an effective means of assessing related fees. For instance, the proposed fee structure...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... Organization's Statement of the Terms of the Substance of the Proposed Rule Change FINRA is proposing to amend...

Risk literacy for scientists. Invitation to regulatory science

International Nuclear Information System (INIS)

Ono, Kyoko

2012-01-01

This paper discusses a regulatory science, which fills a gap between scientific knowledge and regulatory actions. The author provides examples of the regulatory science employed in chemical risk assessment, such as the linear non-threshold theory. In the regulatory science, scientific data as well as scientific reasoning based on scientific knowledge - or regulatory rules - should play an important role. It is important to recognize that the rules facilitate transparent decision making under conditions of uncertainty and time constraints. Furthermore, the development of traditional or pure science results in the validation of regulatory rules, and subsequently, the regulatory science procedure develops more systematically. The concept of this science should be understood by those engaged in governmental decision making. (author)

78 FR 44165 - Nuclear Regulatory Commission Enforcement Policy

Science.gov (United States)

2013-07-23

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0159] Nuclear Regulatory Commission Enforcement Policy AGENCY: Nuclear Regulatory Commission. ACTION: Enforcement policy; request for comment. SUMMARY: The U.S... Policy. In SRM-SECY-12-0047, ``Revisions to the Nuclear Regulatory Commission Enforcement Policy,'' dated...

78 FR 68893 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2013-11-15

... that the size of the BBO equals the minimum quote size. Number of market makers actively quoting...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Extend the Tier Size Pilot of FINRA Rule 6433 (Minimum Quotation Size...

75 FR 5630 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-02-03

... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0031] Draft Regulatory Guide: Issuance, Availability... Guide, DG-4017. FOR FURTHER INFORMATION CONTACT: Gregory Chapman, U.S. Nuclear Regulatory Commission...

Regulatory analysis technical evaluation handbook. Final report

International Nuclear Information System (INIS)

1997-01-01

The purpose of this Handbook is to provide guidance to the regulatory analyst to promote preparation of quality regulatory analysis documents and to implement the policies of the Regulatory Analysis Guidelines of the US Nuclear Regulatory Commission (NUREG/BR-0058 Rev. 2). This Handbook expands upon policy concepts included in the NRC Guidelines and translates the six steps in preparing regulatory analyses into implementable methodologies for the analyst. It provides standardized methods of preparation and presentation of regulatory analyses, with the inclusion of input that will satisfy all backfit requirements and requirements of NRC's Committee to Review Generic Requirements. Information on the objectives of the safety goal evaluation process and potential data sources for preparing a safety goal evaluation is also included. Consistent application of the methods provided here will result in more directly comparable analyses, thus aiding decision-makers in evaluating and comparing various regulatory actions. The handbook is being issued in loose-leaf format to facilitate revisions. NRC intends to periodically revise the handbook as new and improved guidance, data, and methods become available

Communication Regulatory Science: Mapping a New Field.

Science.gov (United States)

Noar, Seth M; Cappella, Joseph N; Price, Simani

2017-12-13

Communication regulatory science is an emerging field that uses validated techniques, tools, and models to inform regulatory actions that promote optimal communication outcomes and benefit the public. In the opening article to this special issue on communication and tobacco regulatory science, we 1) describe Food and Drug Administration (FDA) regulation of tobacco products in the US; 2) introduce communication regulatory science and provide examples in the tobacco regulatory science realm; and 3) describe the special issue process and final set of articles. Communication research on tobacco regulatory science is a burgeoning area of inquiry, and this work advances communication science, informs and potentially guides the FDA, and may help to withstand legal challenges brought by the tobacco industry. This research has the potential to have a major impact on the tobacco epidemic and population health by helping implement the most effective communications to prevent tobacco initiation and increase cessation. This special issue provides an example of 10 studies that exemplify tobacco regulatory science and demonstrate how the health communication field can affect regulation and benefit public health.

Functional and topological characteristics of mammalian regulatory domains

Science.gov (United States)

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Annual Report 2010. Nuclear Regulatory Authority

International Nuclear Information System (INIS)

2010-01-01

The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2010. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

Annual Report 2011. Nuclear Regulatory Authority

International Nuclear Information System (INIS)

2011-01-01

The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2011. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

Development of regulatory policy for SMART-P

Energy Technology Data Exchange (ETDEWEB)

Lee, S. H.; Lee, Y. H.; Moo, Philip; Koh, B. J.; Son, M. K.; Han, G. H.; Kim, D. H. [Korea Association for Nuclear Technology, Daejeon (Korea, Republic of)

2004-06-15

KAERI promoted the construction of a research reactor, SMART-P, the reduced scale of SMART, with intent to demonstrate the safety and performance of SMART. According to this progress, the development of regulatory process for SMART-P became necessary. The establishment of regulatory policy, based on the current regulatory guidelines as well as technical aspect, became essential matters. Considering the on-going small and medium size reactors in near future, the selection of the appropriate measure in the existing regulatory process to SMART-P is very important. Thus the schematic study for the applicable licensing procedure and regulatory requirements suitable for SMART-P is required.

Development of regulatory policy for SMART-P

Energy Technology Data Exchange (ETDEWEB)

Lee, S. H.; Moon, S. H.; Lee, Y. H.; Son, M. K.; Han, K. H.; Kim, D. H. [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

2003-06-15

KAERI promoted the construction of a research reactor, SMART-P, the reduced scale of SMART, with intent to demonstrate the safety and performance of SMART. According to this progress, the development of regulatory process for SMART-P became necessary. The establishment of regulatory policy, based on the current regulatory guidelines as well as technical aspect, became essential matters. Considering the on-going small and medium size reactors m near future, the selection of the appropriate measure in the existing regulatory process to SMART-P is very important. Thus the schematic study for the applicable licensing procedure and regulatory requirements suitable for SMART-P is required.

Annual Report 2009. Nuclear Regulatory Authority

International Nuclear Information System (INIS)

2010-01-01

The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across four parts and seven annexes the activities developed by the organism during 2009. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the environmental monitoring; the occupational surveillance; the training and the public information; improved organizational and budgetary developments. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

Environmental Regulatory Update Table, December 1989

International Nuclear Information System (INIS)

Houlbert, L.M.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

1990-01-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

Environmental regulatory update table, March 1989

International Nuclear Information System (INIS)

Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

1989-04-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

Environmental Regulatory Update Table, April 1989

International Nuclear Information System (INIS)

Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

1989-05-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

Environmental Regulatory Update Table, December 1991

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1992-01-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, August 1990

International Nuclear Information System (INIS)

Houlberg, L.M.; Nikbakht, A.; Salk, M.S.

1990-09-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

Environmental Regulatory Update Table, October 1991

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1991-11-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, November 1991

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1991-12-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, September 1991

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1991-10-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Regulatory Control of Radiation Sources. Safety Guide (Arabic Edition)

International Nuclear Information System (INIS)

2012-01-01

This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

78 FR 54502 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2013-09-04

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of a Proposed Rule... Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or ``Commission... or manipulative motivation for the trading activity at issue.\\4\\ Specifically, proposed Supplementary...

76 FR 63969 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2011-10-14

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1 to Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated... Account Statements) in the Consolidated FINRA Rulebook (``Notice''). The Notice contained incorrect...

75 FR 52999 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-08-30

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition... NUCLEAR REGULATORY COMMISSION [NRC-2009-0556] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.35...

75 FR 45171 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-08-02

... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRC's Agencywide... NUCLEAR REGULATORY COMMISSION [NRC-2010-0072] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.13...

75 FR 37842 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-06-30

... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition... NUCLEAR REGULATORY COMMISSION [NRC-2009-0396] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 2.5...

75 FR 43207 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-07-23

... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0282] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.141...

75 FR 33361 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-06-11

....gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for inspection at the... NUCLEAR REGULATORY COMMISSION [NRC-2009-0308] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.28...

75 FR 16525 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-04-01

... http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2009-0413] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.11...

75 FR 27599 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-05-17

...'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2009-0492] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Regulatory Guide 6.7...

12 CFR 567.2 - Minimum regulatory capital requirement.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Minimum regulatory capital requirement. 567.2... Regulatory Capital Requirements § 567.2 Minimum regulatory capital requirement. (a) To meet its regulatory capital requirement a savings association must satisfy each of the following capital standards: (1) Risk...

The Regulatory Independence of FANR

International Nuclear Information System (INIS)

ALNuaimi, Fatema; Choi, Kwang Shik

2012-01-01

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

The Regulatory Independence of FANR

Energy Technology Data Exchange (ETDEWEB)

ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2012-05-15

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

75 FR 16202 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-03-31

... Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available... NUCLEAR REGULATORY COMMISSION [NRC-2008-0644] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide (RG) 1.126...

75 FR 81675 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-12-28

... through the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0031] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 4.16...

75 FR 20399 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-04-19

... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0418] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 6.9...

76 FR 31382 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-05-31

... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0287] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.2...

Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms

Directory of Open Access Journals (Sweden)

Christley Scott

2010-08-01

Full Text Available Abstract Background Simulation of sophisticated biological models requires considerable computational power. These models typically integrate together numerous biological phenomena such as spatially-explicit heterogeneous cells, cell-cell interactions, cell-environment interactions and intracellular gene networks. The recent advent of programming for graphical processing units (GPU opens up the possibility of developing more integrative, detailed and predictive biological models while at the same time decreasing the computational cost to simulate those models. Results We construct a 3D model of epidermal development and provide a set of GPU algorithms that executes significantly faster than sequential central processing unit (CPU code. We provide a parallel implementation of the subcellular element method for individual cells residing in a lattice-free spatial environment. Each cell in our epidermal model includes an internal gene network, which integrates cellular interaction of Notch signaling together with environmental interaction of basement membrane adhesion, to specify cellular state and behaviors such as growth and division. We take a pedagogical approach to describing how modeling methods are efficiently implemented on the GPU including memory layout of data structures and functional decomposition. We discuss various programmatic issues and provide a set of design guidelines for GPU programming that are instructive to avoid common pitfalls as well as to extract performance from the GPU architecture. Conclusions We demonstrate that GPU algorithms represent a significant technological advance for the simulation of complex biological models. We further demonstrate with our epidermal model that the integration of multiple complex modeling methods for heterogeneous multicellular biological processes is both feasible and computationally tractable using this new technology. We hope that the provided algorithms and source code will be a

Management of the Regulatory Authority Information

International Nuclear Information System (INIS)

Suman, H.

2003-01-01

Safe Management of the Regulatory Authority Information is one of the essential elements to ensure the effectiveness of the regulatory program as a whole. This paper briefly describes the information management basis in RNRO, which is in charge of the regulatory authority tasks in Syria. SINA-2, a computational tool prepared in RNRO for managing the information related to the inventory of radiation sources and users, is also introduced

Environmental Regulatory Update Table, August 1991

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M., Hawkins, G.T.; Salk, M.S.

1991-09-01

This Environmental Regulatory Update Table (August 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental regulatory update table, July 1991

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1991-08-01

This Environmental Regulatory Update Table (July 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Mission Risk Reduction Regulatory Change Management

Science.gov (United States)

Scroggins, Sharon

2007-01-01

NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

The Danish Regulatory Reform of Telecommunications

DEFF Research Database (Denmark)

Skouby, Knud Erik

1998-01-01

An overview of the liberalisation process and regulatory reform of telecommunications in Denmark......An overview of the liberalisation process and regulatory reform of telecommunications in Denmark...

40 CFR 73.86 - State regulatory autonomy.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State regulatory autonomy. 73.86 Section 73.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulatory autonomy. Nothing in this subpart shall preclude a State or State regulatory authority from...

75 FR 12804 - Withdrawal of Regulatory Guide 8.6

Science.gov (United States)

2010-03-17

... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

75 FR 20868 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2010-04-21

... available through the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2009-0351] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.68.2...

Compact plane illumination plugin device to enable light sheet fluorescence imaging of multi-cellular organisms on an inverted wide-field microscope.

Science.gov (United States)

Guan, Zeyi; Lee, Juhyun; Jiang, Hao; Dong, Siyan; Jen, Nelson; Hsiai, Tzung; Ho, Chih-Ming; Fei, Peng

2016-01-01

We developed a compact plane illumination plugin (PIP) device which enabled plane illumination and light sheet fluorescence imaging on a conventional inverted microscope. The PIP device allowed the integration of microscope with tunable laser sheet profile, fast image acquisition, and 3-D scanning. The device is both compact, measuring approximately 15 by 5 by 5 cm, and cost-effective, since we employed consumer electronics and an inexpensive device molding method. We demonstrated that PIP provided significant contrast and resolution enhancement to conventional microscopy through imaging different multi-cellular fluorescent structures, including 3-D branched cells in vitro and live zebrafish embryos. Imaging with the integration of PIP greatly reduced out-of-focus contamination and generated sharper contrast in acquired 2-D plane images when compared with the stand-alone inverted microscope. As a result, the dynamic fluid domain of the beating zebrafish heart was clearly segmented and the functional monitoring of the heart was achieved. Furthermore, the enhanced axial resolution established by thin plane illumination of PIP enabled the 3-D reconstruction of the branched cellular structures, which leads to the improvement on the functionality of the wide field microscopy.

Quality assurance within regulatory bodies

International Nuclear Information System (INIS)

1999-06-01

The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

47 CFR 1.1160 - Refunds of regulatory fees.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Refunds of regulatory fees. 1.1160 Section 1... Statutory Charges and Procedures for Payment § 1.1160 Refunds of regulatory fees. (a) Regulatory fees will be refunded, upon request, only in the following instances: (1) When no regulatory fee is required or...

78 FR 69732 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2013-11-20

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of a Proposed Rule Change To Amend FINRA Rule 8312 (FINRA BrokerCheck Disclosure) To Include Information About Members and Their Associated Persons of Any Registered National Securities Exchange That Uses the CRD System for...

Grand Gulf-prioritization of regulatory requirements

International Nuclear Information System (INIS)

Meisner, M.J.

1993-01-01

As cost pressures mount, Grand Gulf nuclear station (GGNS) is relying increasingly on various prioritization approaches to implement, modify, eliminate, or defer regulatory requirements. Regulatory requirements can be prioritized through the use of three measures: (1) safety (or risk) significance; (2) cost; and (3) public policy (or political) significance. This paper summarizes GGNS' efforts to implement solutions to regulatory issues using these three prioritization schemes to preserve a balance between cost and safety benefit

Regulatory foci and the big five

OpenAIRE

Bak, Waclaw

2009-01-01

The distinction between promotion and prevention focus (Higgins, 1997) have been employed by many researchers dealing with processes of self-regulation. Little is known however about relations between regulatory orientations and more general personality traits. The present paper reports results of the study in which regulatory foci are analyzed in the context of five factor model of personality. To measure personality traits the NEO-FFI was used. Promotion and prevention regulatory foci was a...

Regulatory authority infrastructure for Namibia

International Nuclear Information System (INIS)

Shangula, K.

2001-01-01

The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

Regulatory focus and the family-work interface : the role of regulatory fit between cohabiting partners

NARCIS (Netherlands)

Demerouti, E.; Bakker, A.B.; Tetrick, L.

2014-01-01

The aim of the present study was to examine the impact of regulatory focus in goal pursuit and regulatory fit between marital partners on family conditions and the family–work interface. We hypothesized that when both partners are high on promotion focus (fit) they experience higher developmental

77 FR 23770 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2012-04-20

...: The financial markets as a whole should benefit from [limit order display] because the price discovery... revised tier sizes and corresponding liquidity minimum amounts are in the best interest of the market for...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1...

77 FR 52791 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory...

Science.gov (United States)

2012-08-30

... the Basel Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for... seeking comment on the two related NPRs published elsewhere in today's Federal Register. The two related... them on Regulations.gov without change, including any business or personal information that you provide...

Oxygen consumption rate and mitochondrial density in human melanoma monolayer cultures and multicellular spheroids.

Science.gov (United States)

Hystad, M E; Rofstad, E K

1994-05-15

Rate of oxygen consumption per cell has been shown in previous studies to decrease with increasing depth in the viable rim of multicellular spheroids initiated from rodent cells, human colon-carcinoma cells, and human glioma cells, due to progressive accumulation of quiescent cells during spheroid growth. The purpose of our work was to determine oxygen-consumption profiles in human melanoma spheroids. Monolayer cultures of 4 lines (BEX-c, COX-c, SAX-c, and WIX-c) and spheroid cultures of 2 lines (BEX-c and WIX-c) were subjected to investigation. Spheroids were initiated from monolayer cell cultures and grown in spinner flasks. Rate of oxygen consumption was measured with a Clarke-type electrode. Mitochondrial density was determined by stereological analysis of transmission electron micrographs. Thickness of viable rim and cell packing density were assessed by light microscopy of central spheroid sections. Cell-cycle distribution was determined by analysis of DNA histograms measured by flow cytometry. Cell volume was measured by an electronic particle counter. Rate of oxygen consumption per cell differed by a factor of approximately 1.8 between the 4 cell lines and was positively correlated to total volume of mitochondria per cell. Rate of oxygen consumption per cell and total volume of mitochondria per cell were equal for monolayer cell cultures, 600-microns spheroids and 1,200-microns spheroids of the same line. Mitochondrial density and location in the cell did not differ between cells at the spheroid surface, in the middle of the viable rim and adjacent to the central necrosis. Cell-cycle distribution, cell volume, and cell-packing density in the outer and inner halves of the viable rim were not significantly different. Consequently, the rate of oxygen consumption per cell in inner regions of the viable rim was probably equal to that at the spheroid surface, suggesting that oxygen diffusion distances may be shorter in some melanomas than in many other tumor

Regulatory Hybridization in the Transnational Sphere

DEFF Research Database (Denmark)

Kjær, Poul Fritz; Jurcys, Paulius; Yrakami, Ren

Hybridization has become a defining feature of regulatory frameworks. The combined forces of globalization and privatization together with increased reliance on self-regulation have resulted in the emergence of a multitude of regulatory arrangements which combine elements from several legal orders....... This book offers a conceptual framework as well as numerous empirical explorations capable of increasing our understanding of regulatory hybridization. A number of central dichotomies are deconstructed: national vs. transnational law; international vs. transnational law; convergence vs. divergence; … read...... moresoft law vs. hard law; territorial vs. non-territorial, ‘top-down’ vs. ‘bottom-up’ globalization and national vs. global just as the implications of regulatory hybridization for the question of choice of court and conflict of laws are analyzed....

Regulatory focus in groupt contexts

NARCIS (Netherlands)

Faddegon, Krispijn Johannes

2009-01-01

The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the

Association of Regulatory Boards of Optometry

Science.gov (United States)

... website of the Association of Regulatory Boards of Optometry (ARBO). ARBO's web site is designed to provide resources to regulatory boards of optometry throughout the world. State/Provincial/Territorial Boards of ...

A new source of elemol rich essential oil and existence of multicellular oil glands in leaves of the Dioscorea species.

Science.gov (United States)

Odimegwu, Joy I; Odukoya, Olukemi; Yadav, Ritesh K; Chanotiya, C S; Ogbonnia, Steve; Sangwan, Neelam S

2013-01-01

Dioscorea species is a very important food and drug plant. The tubers of the plant are extensively used in food and drug purposes owing to the presence of steroidal constituent's diosgenin in the tubers. In the present study, we report for the first time that the leaves of Dioscorea composita and Dioscorea floribunda grown under the field conditions exhibited the presence of multicellular oil glands on the epidermal layers of the plants using stereomicroscopy (SM) and scanning electron microscopy (SEM). Essential oil was also isolated from the otherwise not useful herbage of the plant, and gas chromatographic-mass spectroscopy analysis revealed confirmation of the essential oil constituents. Out of the 76 compounds detected in D. floribunda and 37 from D. composita essential oil, major terpenoids which are detected and reported for Dioscorea leaf essential oil are α -terpinene, nerolidol, citronellyl acetate, farnesol, elemol, α -farnesene, valerenyl acetate, and so forth. Elemol was detected as the major constituent of both the Dioscorea species occupying 41% and 22% of D. Floribunda and D. composita essential oils, respectively. In this paper, we report for the first time Dioscorea as a possible novel bioresource for the essential oil besides its well-known importance for yielding diosgenin.

A New Source of Elemol Rich Essential Oil and Existence of Multicellular Oil Glands in Leaves of the Dioscorea Species

Directory of Open Access Journals (Sweden)

Joy I. Odimegwu

2013-01-01

Full Text Available Dioscorea species is a very important food and drug plant. The tubers of the plant are extensively used in food and drug purposes owing to the presence of steroidal constituent’s diosgenin in the tubers. In the present study, we report for the first time that the leaves of Dioscorea composita and Dioscorea floribunda grown under the field conditions exhibited the presence of multicellular oil glands on the epidermal layers of the plants using stereomicroscopy (SM and scanning electron microscopy (SEM. Essential oil was also isolated from the otherwise not useful herbage of the plant, and gas chromatographic-mass spectroscopy analysis revealed confirmation of the essential oil constituents. Out of the 76 compounds detected in D. floribunda and 37 from D. composita essential oil, major terpenoids which are detected and reported for Dioscorea leaf essential oil are α-terpinene, nerolidol, citronellyl acetate, farnesol, elemol, α-farnesene, valerenyl acetate, and so forth. Elemol was detected as the major constituent of both the Dioscorea species occupying 41% and 22% of D. Floribunda and D. composita essential oils, respectively. In this paper, we report for the first time Dioscorea as a possible novel bioresource for the essential oil besides its well-known importance for yielding diosgenin.

Regulatory point of view of SAT application

International Nuclear Information System (INIS)

Juhasz, L.

2002-01-01

I present the regulatory system for monitoring operator training and check competency of operator personnel in Hungary and the effects of SAT to the regulatory framework/practice related to recruitment, training and authorisation of operating personnel. Also I introduce an application to manage the initial and refreshing training to regulatory bodies. (author)

Small Business Administration Semiannual Regulatory Agenda

Science.gov (United States)

2010-12-20

... small business concerns owned and controlled by women, and to women wishing to start a small business... Business Administration Semiannual Regulatory Agenda] Part XVII Small Business Administration Semiannual Regulatory Agenda [[Page 79864

Assessing the effectiveness of nuclear regulatory system in India

International Nuclear Information System (INIS)

Gandhia, Sonal; Choi, Kwang Sik

2012-01-01

The Fukushima accident brought up the issue of regulatory effectiveness in the fore. One of the causes of the accident has been attributed to the problems in effectiveness of the Japanese regulatory system. Regulatory reform is underway in Japan and in other countries many efforts have also been made to improve the effectiveness and independence of the regulatory bodies. It is important that the regulatory bodies make self-assessment of their weaknesses and strengths, to achieve the ultimate regulatory goal of assuring acceptable level of nuclear safety. In this paper an assessment has been done for the effectiveness of Indian nuclear regulatory system as implemented by the Atomic Energy Regulatory board (AERB). A number of good practices of AERB have been found and some areas have been identified where improvements are necessary

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

Science.gov (United States)

Guo, Liyuan; Wang, Jing

2018-01-04

Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Development of multipurpose regulatory PSA model

International Nuclear Information System (INIS)

Lee, Chang Ju; Sung, Key Yong; Kim, Hho Jung; Yang, Joon Eon; Ha, Jae Joo

2004-01-01

Generally, risk information for nuclear facilities comes from the results of Probabilistic safety assessment (PSA). PSA is a systematic tool to ensure the safety of nuclear facilities, since it is based on thorough and consistent application of probability models. In particular, the PSA has been widely utilized for risk-informed regulation (RIR), including various licensee-initiated risk-informed applications (RIA). In any regulatory decision, the main goal is to make a sound safety decision based on technically defensible information. Also, due to the increased public requests for giving a safety guarantee, the regulator should provide the visible means of safety. The use of PSA by the regulator can give the answer on this problem. Therefore, in order to study the applicability of risk information for regulatory safety management, it is a demanding task to prepare a well-established regulatory PSA model and tool. In 2002, KINS and KAERI together made a research cooperation to form a working group to develop the regulatory PSA model - so-called MPAS model. The MPAS stands for multipurpose probabilistic analysis of safety. For instance, a role of the MPAS model is to give some risk insights in the preparation of various regulatory programs. Another role of this model is to provide an independent risk information to the regulator during regulatory decision-making, not depending on the licensee's information

Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors

Science.gov (United States)

Patsialou, Antonia; Bravo-Cordero, Jose Javier; Wang, Yarong; Entenberg, David; Liu, Huiping; Clarke, Michael; Condeelis, John S.

2014-01-01

Metastasis is the main cause of death in breast cancer patients. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. We used xenograft tumors of MDA-MB-231 cells as well as a low passage xenograft tumor from orthotopically injected patient-derived breast tumor cells. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: a. single cells and b. multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Critically, we found that only streaming and not random migration of single cells was significantly correlated with proximity to vessels, with intravasation and with numbers of elevated circulating tumor cells in the bloodstream. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Our data are the first direct visualization and assessment of in vivo migration within a live patient-derived breast xenograft tumor. PMID:25013744

[Remedial courses for alcohol apprehended drivers are effective!].

Science.gov (United States)

Jensch, M

1990-07-01

The effectiveness of the IFT, I.R.A.K. and LEER courses for drinking drivers has been examined thoroughly in an exhaustive scientific study. Empirical tests have clearly demonstrated that all three models are successful. In a critical analysis of these results, Hundhausen questions the effectiveness of the models. Hundhausen's arguments in this analysis are based on erroneous assumptions. This reply demonstrates the incorrectness of his argumentation.

Measuring and Modeling the U.S. Regulatory Ecosystem

Science.gov (United States)

Bommarito, Michael J., II; Katz, Daniel Martin

2017-09-01

Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.

Comparison of regulatory framework among bench marking countries for improving regulatory effectiveness in Malaysia

International Nuclear Information System (INIS)

Khairuddin, Nik Mohd Faiz Bin; Choi, Kwang Sik

2010-01-01

Nowadays some of developing countries in Asian region are announcing their planning to embark the nuclear power program. This progression are rising due to four factor: increasing political instabilities in fossil-fuel exporting countries; declining domestic natural energy resources; growing concerns about greenhouse gas emissions; and increasing demand for electricity. This paper gives a study on the comparison between Canada, Republic of South Korea and Malaysia regarding to their regulatory framework as well as the licensing procedures in controlling the nuclear power plants establishment. Canada and Korea were selected to study because of both of the countries have different system in controlling the nuclear power plants in terms of its regulatory framework as well as the licensing process. The idea is to compare these countries along with the guidelines by the IAEA and to find out what Malaysia could be learn to start the nuclear power program and find out the best practice in nuclear licensing. Factors taken into consideration are the regulatory framework, especially the nature of the licensing authority, the licensing process and enforcement actions. Together, these give a way to evaluate the effectiveness of the regulatory body due to the licensing authorization of nuclear power plant

Comparison of regulatory framework among bench marking countries for improving regulatory effectiveness in Malaysia

Energy Technology Data Exchange (ETDEWEB)

Khairuddin, Nik Mohd Faiz Bin [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Choi, Kwang Sik [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2010-05-15

Nowadays some of developing countries in Asian region are announcing their planning to embark the nuclear power program. This progression are rising due to four factor: increasing political instabilities in fossil-fuel exporting countries; declining domestic natural energy resources; growing concerns about greenhouse gas emissions; and increasing demand for electricity. This paper gives a study on the comparison between Canada, Republic of South Korea and Malaysia regarding to their regulatory framework as well as the licensing procedures in controlling the nuclear power plants establishment. Canada and Korea were selected to study because of both of the countries have different system in controlling the nuclear power plants in terms of its regulatory framework as well as the licensing process. The idea is to compare these countries along with the guidelines by the IAEA and to find out what Malaysia could be learn to start the nuclear power program and find out the best practice in nuclear licensing. Factors taken into consideration are the regulatory framework, especially the nature of the licensing authority, the licensing process and enforcement actions. Together, these give a way to evaluate the effectiveness of the regulatory body due to the licensing authorization of nuclear power plant

Regulatory systems-based licensing guidance documentation

International Nuclear Information System (INIS)

Delligatti, M.S.

1991-01-01

The US Nuclear Regulatory Commission (NRC) has developed a series of licensing guidance documents based on the regulatory requirements in Part 60 of Title 10 of the Code of Federal Regulations (10 CFR Part 60). This regulatory systems-based approach to licensing guidance documentation relies on the definition of the high-level waste repository in 10 CFR Part 60. A document which is important for the frame-work it gives to other programmatic licensing guidance is the Draft Regulatory Guide open-quotes Format and Content for the License Application for the High-Level Waste Repositoryclose quotes (FCRG). The FCRG describes a format and content acceptable to NRC for a high-level waste repository license application pursuant to the requirements of 10 CFR Part 60. Other licensing guidance documents will be compatible with the FCRG

Annual Report 2013. Nuclear Regulatory Authority

International Nuclear Information System (INIS)

2010-01-01

The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across seven parts and eight annexes the activities developed by the organism during 2013. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the environmental monitoring; the occupational surveillance; the training and the public information; improved organizational and budgetary developments. Also, this publication has annexes with the following content: regulatory documents; inspections to medical; presentations of publications from ARN staff; measurement and evaluation of the drinking water of Ezeiza; international expert report on the implementation of international standards on radiation protection in the Ezeiza Atomic Center; Code of Ethics of the Nuclear Regulatory Authority.

Management systems for regulatory authorities

International Nuclear Information System (INIS)

Mpandanyama, Rujeko Lynette

2015-02-01

For a regulatory body to fulfil its statutory obligations, there is need to develop and implement a regulatory management system that has the necessary arrangements for achieving and maintaining high quality performance in regulating the safety of nuclear and radiation facilities under its authority. Hence, the regulatory management system needs to fully integrate the human resources, processes and physical resources of the organization. This study sought to provide an understanding of the concept, principles, policies and fundamentals of management systems as they relate to regulatory systems in the field of radiation protection and to make appropriate recommendations to ensure that an effective management system exists for the control of ionizing radiation and radiation sources and addresses all relevant stakeholders in Zimbabwe. A comparative analysis was done on the current management status and the ideal management system, which led to the identification of the gaps existing. The main key that was found to be of significance was lack of linkages between processes and management tools within the institution. (au)

Políticas e gestão da educação superior a distância: novos marcos regulatórios? Politics and management of the superior education in the distance: new regulatory landmarks?

Directory of Open Access Journals (Sweden)

Luiz Fernandes Dourado

2008-10-01

Full Text Available Ao problematizar as políticas e gestão atuais para a educação básica e superior, o artigo enfoca os novos marcos regulatórios do processo expansionista e analisa as políticas direcionadas à formação de professores, com especial realce para a educação a distância no setor público. Nessa direção, apresenta e analisa alguns indicadores educacionais e busca apreender, no campo das políticas propostas pelo MEC, o papel da " Nova CAPES" como espaço de regulação das políticas de formação de professores, enfatizando a expansão pública, na modalidade EaD, por meio dos desafios da consolidação da Universidade Aberta do Brasil (UAB.To evaluate the current politics and management for the basic and superior education, the article focuses new regulatory landmarks of the expansion process and analyzes the politics directed to the formation of professors, with special distinction for the education in the distance in the public sector. In this direction, it presents and it analyzes some educational pointers and it searchs to apprehend, in the field of the politics proposals for the MEC, the paper of the " New CAPES" as space of regulation of the politics of formation of professors, emphasizing the public expansion, in the EaD modality, by means of the challenges of the consolidation of the Open University of Brazil (UAB.

Regulatory and Non-regulatory Responses to Hydraulic Fracturing in Local Communities

Science.gov (United States)

Phartiyal, P.

2015-12-01

The practice of extracting oil and gas from tight rock formations using advances in technology, such as hydraulic fracturing and directional drilling, has expanded exponentially in states and localities across the country. As the scientific data collection and analysis catches up on the many potential impacts of this unconventional oil and gas development, communities are turning to their local officials to make decisions on whether and how fracking should proceed. While most regulatory authority on the issue rests with the state agencies, local officials have experimented with a wide range of regulatory, non-regulatory, and fiscal tools to manage the impacts of fracking. These impacts can occur on the local air, water, seismicity, soil, roads, schools, and affect residents, on-site workers, emergency and social services. Local officials' approaches are often influenced by their prior experience with minerals extraction in their localities. The speaker will present examples of the kinds of information sources, tools and approaches communities across the country are using, from noise barriers to setback requirements to information sharing in order to be able to balance the promise and perils of oil and gas development in their jurisdictions.

Canadian and international approaches to regulatory effectiveness

International Nuclear Information System (INIS)

Lojk, R.

2014-01-01

Regulatory effectiveness is an important attribute of any regulator, particularly nuclear regulators. As the nuclear industry has matured, and as the social landscape has changed, so have views on what constitutes regulatory effectiveness. Canada has evolved its regulatory structure and modernized its legislative framework and technical requirements and guidance over time. In addition, Canada continues to collaborate with international agencies, particularly the NEA and the IAEA, to ensure that there is a common understanding of the indicators and key attributes of regulatory effectiveness. This paper discusses Canadian and international views on the subject, including perspectives from other industries. (author)

Pleiotropy constrains the evolution of protein but not regulatory sequences in a transcription regulatory network influencing complex social behaviours

Directory of Open Access Journals (Sweden)

Daria eMolodtsova

2014-12-01

Full Text Available It is increasingly apparent that genes and networks that influence complex behaviour are evolutionary conserved, which is paradoxical considering that behaviour is labile over evolutionary timescales. How does adaptive change in behaviour arise if behaviour is controlled by conserved, pleiotropic, and likely evolutionary constrained genes? Pleiotropy and connectedness are known to constrain the general rate of protein evolution, prompting some to suggest that the evolution of complex traits, including behaviour, is fuelled by regulatory sequence evolution. However, we seldom have data on the strength of selection on mutations in coding and regulatory sequences, and this hinders our ability to study how pleiotropy influences coding and regulatory sequence evolution. Here we use population genomics to estimate the strength of selection on coding and regulatory mutations for a transcriptional regulatory network that influences complex behaviour of honey bees. We found that replacement mutations in highly connected transcription factors and target genes experience significantly stronger negative selection relative to weakly connected transcription factors and targets. Adaptively evolving proteins were significantly more likely to reside at the periphery of the regulatory network, while proteins with signs of negative selection were near the core of the network. Interestingly, connectedness and network structure had minimal influence on the strength of selection on putative regulatory sequences for both transcription factors and their targets. Our study indicates that adaptive evolution of complex behaviour can arise because of positive selection on protein-coding mutations in peripheral genes, and on regulatory sequence mutations in both transcription factors and their targets throughout the network.

Regulatory Expectations for Safety Culture

Energy Technology Data Exchange (ETDEWEB)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

Regulatory Expectations for Safety Culture

International Nuclear Information System (INIS)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

2014-01-01

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

Environmental Regulatory Update Table, January/February 1995

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

1995-03-01

The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, January/February 1995

International Nuclear Information System (INIS)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

1995-03-01

The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

75 FR 2894 - Withdrawal of Regulatory Guide 1.148

Science.gov (United States)

2010-01-19

... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0013] Withdrawal of Regulatory Guide 1.148 AGENCY: Nuclear...

75 FR 70044 - Withdrawal of Regulatory Guide 1.39

Science.gov (United States)

2010-11-16

... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doollectionsc-c . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0354] Withdrawal of Regulatory Guide 1.39 AGENCY: Nuclear...

76 FR 35922 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-06-20

.... Proposed Revision 1 of Regulatory Guide (RG) 8.4, ``Personnel Monitoring Device--Direct-Reading Pocket...'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0148] Notice of Issuance of Regulatory Guide AGENCY...

76 FR 28102 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-05-13

..., Probabilistic Risk Assessment Branch, Division of Risk Analysis, Office of Nuclear Regulatory Research, U.S... results of risk analyses are used to help justify regulatory action. As such, the principles, process, and... NUCLEAR REGULATORY COMMISSION [NRC-2009-0385] Notice of Issuance of Regulatory Guide AGENCY...

Regulatory T Cells: Potential Target in Anticancer Immunotherapy

Directory of Open Access Journals (Sweden)

Chi-Mou Juang

2007-09-01

Full Text Available The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

Regulatory focus affects physician risk tolerance.

Science.gov (United States)

Veazie, Peter J; McIntosh, Scott; Chapman, Benjamin P; Dolan, James G

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention-regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (p = 0.01). The Cohen's d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (p = 0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor.

75 FR 62893 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-10-13

... the ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov... NUCLEAR REGULATORY COMMISSION [NRC-2010-0321] Draft Regulatory Guide: Issuance, Availability... Guide, DG-1196, ``Qualification for Cement Grouting for Prestressing Tendons in Containment Structures...

Policy for setting and assessing regulatory safety goals. Peer discussions on regulatory practices

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-10-01

This publication pertains to future planning for enhancement of good practices and it describes the experience to date in developing and implementing the policy for setting and assessing regulatory safety goals for nuclear facilities in 22 Member States. Senior regulators from these 22 Member States participated in four Peer Group discussions in 1993/94 which considered the policy used for setting and assessing regulatory safety goals. This publication presents the consensus views reached by the majority of these senior regulators.

Policy for setting and assessing regulatory safety goals. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1995-10-01

This publication pertains to future planning for enhancement of good practices and it describes the experience to date in developing and implementing the policy for setting and assessing regulatory safety goals for nuclear facilities in 22 Member States. Senior regulators from these 22 Member States participated in four Peer Group discussions in 1993/94 which considered the policy used for setting and assessing regulatory safety goals. This publication presents the consensus views reached by the majority of these senior regulators

Legal principles of regulatory administration and nuclear safety regulation

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyeong Hui; Cheong, Sang Kee [Hannam Univ., Taejon (Korea, Republic of)

2000-12-15

This research presents a critical analysis and evaluation of principles of administrative laws in order to provide framework of structural reform on the nuclear safety regulation system. The focus of this analysis and evaluation is centered around the area of origin of regulatory administrative laws; authorities of regulation; procedures of regulatory actions; regulatory enforcement; and administrative relief system. In chapter 2 the concept of regulatory administration is analysed. Chapter 3 identifies the origin of regulatory administration and the principles of administration laws. It also examines legal nature of the nuclear safety standard. In relation to regulatory authorities. Chapter 4 identifies role and responsibility of administration authorities and institutions. It also examines fundamental principles of delegation of power. Then the chapter discusses the nuclear safety regulation authorities and their roles and responsibilities. Chapter 5 classifies and examines regulatory administration actions. Chapter 6 evaluates enforcement measure for effectiveness of regulation. Finally, chapter 7 discusses the administrative relief system for reviewing unreasonable regulatory acts.

NRC regulatory agenda

International Nuclear Information System (INIS)

1993-07-01

The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter. The rules on which final action has been taken since March 31, 1993 are: Repeal of NRC standards of conduct; Fitness-for-duty requirements for licensees who possess, use, or transport Category I material; Training and qualification of nuclear power plant personnel; Monitoring the effectiveness of maintenance at nuclear power plants; Licensing requirements for land disposal of radioactive wastes; and Licensees' announcements of safeguards inspections

75 FR 58444 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-09-24

... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0305] Draft Regulatory Guide: Issuance, Availability... Guide, DG-1244, ``Availability of Electric Power Sources.'' FOR FURTHER INFORMATION CONTACT: Satish...

Disclosure as a regulatory tool

DEFF Research Database (Denmark)

Sørensen, Karsten Engsig

2006-01-01

The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law.......The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law....

Prediction of regulatory elements

DEFF Research Database (Denmark)

Sandelin, Albin

2008-01-01

Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

Rationales for regulatory activity

Energy Technology Data Exchange (ETDEWEB)

Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

1997-02-01

The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

Regulatory authority information system RAIS

International Nuclear Information System (INIS)

Ortiz, P.; Mrabit, K.; Miaw, S.

2000-01-01

In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

76 FR 6587 - Pennsylvania Regulatory Program

Science.gov (United States)

2011-02-07

... [PA-159-FOR; OSM 2010-0017] Pennsylvania Regulatory Program AGENCY: Office of Surface Mining... remove a required amendment to the Pennsylvania regulatory program (the ``Pennsylvania program'') under... program amendment codified in the Federal regulations, Pennsylvania has submitted information that it...

Environmental Regulatory Update Table, January--February 1993

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1993-03-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, November--December 1993

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1994-01-01

The Environmental Regulatory Update Table provides information on regulatory of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental regulatory update table November--December 1994

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

1995-01-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, May--June 1994

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Salk, M.S.

1994-07-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, May/June 1993

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1993-07-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental regulatory update table, March--April 1994

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.; Salk, M.S. [Oak Ridge National Lab., TN (United States). Environmental Sciences Div.

1994-03-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table July/August 1993

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1993-09-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, March/April 1993

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1993-05-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, November--December 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

1993-01-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly wit information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, July--August 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

1992-09-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, September/October 1993

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1993-11-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operation and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, January--February 1994

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

1994-03-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations ad contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental regulatory update table, September--October 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

1992-11-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental regulatory update table, July/August 1994

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Salk, M.S.

1994-09-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental Regulatory Update Table, March/April 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1992-05-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

Environmental regulatory update table, July/August 1994

International Nuclear Information System (INIS)

Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Salk, M.S.

1994-09-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

Safety analysis - current and future regulatory challenges

Energy Technology Data Exchange (ETDEWEB)

Jamieson, T., E-mail: Terry.Jamieson@cnsc-ccsn.gc.ca [Canadian Nuclear Safety Commission, Ottawa, ON (Canada)

2015-07-01

'Full text:' The current and future regulatory challenges associated with deterministic safety analysis are reviewed, including: 1. The CNSC's and safety control areas. 2. Traditional safety analysis approach. 3. Experience gained and impact. 4. Current analysis and regulatory approaches. 5. Current status. 6. Complexity and challenges In particular, the technical, regulatory and strategic aspects of these challenges are discussed. (author)

Safety analysis - current and future regulatory challenges

International Nuclear Information System (INIS)

Jamieson, T.

2015-01-01

'Full text:' The current and future regulatory challenges associated with deterministic safety analysis are reviewed, including: 1. The CNSC's and safety control areas. 2. Traditional safety analysis approach. 3. Experience gained and impact. 4. Current analysis and regulatory approaches. 5. Current status. 6. Complexity and challenges In particular, the technical, regulatory and strategic aspects of these challenges are discussed. (author)

Mammalian synthetic biology for studying the cell.

Science.gov (United States)

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-05-19

... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Draft Regulatory Guide: Issuance, Availability... Guide, DG-3039, ``Standard Format and Content for Emergency Plans for Fuel Cycle and Materials...

75 FR 45166 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-08-02

... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0265] Draft Regulatory Guide: Issuance, Availability... Guide, DG-3030, ``Nuclear Criticality Safety Standards for Fuels and Material Facilities.'' [[Page 45167...

75 FR 29785 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-05-27

... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0187] Draft Regulatory Guide: Issuance, Availability... Guide, DG-1248, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License...

Hydropower Regulatory and Permitting Information Desktop (RAPID) Toolkit

Energy Technology Data Exchange (ETDEWEB)

Levine, Aaron L [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2017-12-19

Hydropower Regulatory and Permitting Information Desktop (RAPID) Toolkit presentation from the WPTO FY14-FY16 Peer Review. The toolkit is aimed at regulatory agencies, consultants, project developers, the public, and any other party interested in learning more about the hydropower regulatory process.

Quantitative inference of dynamic regulatory pathways via microarray data

Directory of Open Access Journals (Sweden)

Chen Bor-Sen

2005-03-01

Full Text Available Abstract Background The cellular signaling pathway (network is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach. Results In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network. Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data. Conclusion We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory

Regulatory dendritic cells in autoimmunity: A comprehensive review.

Science.gov (United States)

Liu, Juan; Cao, Xuetao

2015-09-01

Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

NRC regulatory information conference: Proceedings

International Nuclear Information System (INIS)

1989-09-01

This volume of the report provides the proceedings from the Nuclear Regulatory Commission (NRC) Regulatory Information Conference that was held at the Mayflower Hotel, Washington, DC, on April 18, 19, and 20, 1989. This conference was held by the NRC and chaired by Dr. Thomas E. Mosley, Director, Office of Nuclear Reactor Regulations (NRR) and coordinated by S. Singh Bajwa, Chief, Technical Assistance Management Section, NRR. There were approximately 550 participants from nine countries at the conference. The countries represented were Canada, England, Italy, Japan, Mexico, Spain, Taiwan, Yugoslavia, and the United States. The NRC staff discussed with nuclear industry its regulatory philosophy and approach and the bases on which they have been established. Furthermore, the NRC staff discussed several initiatives that have been implemented recently and their bases as well as NRC's expectations for new initiatives to further improve safety. The figures contained in Appendix A to the volume correspond to the slides that were shown during the presentations. Volume 2 of this report contains the formal papers that were distributed at the beginning of the Regulatory Information Conference and other information about the conference

5 CFR 880.102 - Regulatory structure.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 880.102 Section 880.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... Regulatory structure. (a) This part contains the following subparts: (1) Subpart A contains general...

77 FR 8082 - Regulatory Flexibility Agenda

Science.gov (United States)

2012-02-13

... Required: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities and Exchange.../01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of... Withdrawn 10/01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of...

Categorization and selection of regulatory approaches for nuclear power plants

International Nuclear Information System (INIS)

Sugaya, Junko; Harayama, Yuko

2009-01-01

Several new regulatory approaches have been introduced to Japanese nuclear safety regulations, in which a prescriptive and deterministic approach had traditionally predominated. However, the options of regulatory approaches that can possibly be applied to nuclear safety regulations as well as the methodology for selecting the options are not systematically defined. In this study, various regulatory approaches for nuclear power plants are categorized as prescriptive or nonprescriptive, outcome-based or process-based, and deterministic or risk-informed. 18 options of regulatory approaches are conceptually developed and the conditions for selecting the appropriate regulatory approaches are identified. Current issues on nuclear regulations regarding responsibilities, transparency, consensus standards and regulatory inspections are examined from the viewpoints of regulatory approaches to verify usefulness of the categorization and selection concept of regulatory approaches. Finally, some of the challenges at the transitional phase of regulatory approaches are discussed. (author)

76 FR 59066 - Notice of Regulatory Review Plan

Science.gov (United States)

2011-09-23

... [No. 2011-N-10] Notice of Regulatory Review Plan AGENCY: Federal Housing Finance Agency. ACTION... of and requesting comments on the FHFA interim regulatory review plan for review of existing... comments on all aspects of the interim regulatory review plan, including legal and policy considerations...

Improving nuclear regulation. NEA regulatory guidance booklets volumes 1-14

International Nuclear Information System (INIS)

2011-01-01

A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are continuously maintained and operated in an acceptably safe manner. In meeting this objective the regulator must bear in mind that it is the operator that has responsibility for safely operating the nuclear facility; the role of the regulator is to assess and to provide assurance regarding the operator's activities in terms of assuming that responsibility. The full series of these reports was brought together in one edition for the first time in 2009 and was widely found to be a useful resource. This second edition comprises 14 volumes, including the latest on The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services. The reports address various challenges that could apply throughout the lifetime of a nuclear facility, including design, siting, manufacturing, construction, commissioning, operation, maintenance and decommissioning. The compilation is intended to serve as a knowledge management tool both for current regulators and the new nuclear professionals and organisations entering the regulatory field. Contents: Executive Summary; Regulatory Challenges: 1. The Role of the Nuclear Regulator in Promoting and Evaluating Safety Culture; 2. Regulatory Response Strategies for Safety Culture Problems; 3. Nuclear Regulatory Challenges Related to Human Performance; 4. Regulatory Challenges in Using Nuclear Operating Experience; 5. Nuclear Regulatory Review of Licensee Self-assessment (LSA); 6. Nuclear Regulatory Challenges Arising from Competition in Electricity Markets; 7. The Nuclear Regulatory Challenge of Judging Safety Back-fits; 8. The Regulatory Challenges of Decommissioning Nuclear Reactors; 9. The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services

Regulatory aspects of criticality control in Australia

International Nuclear Information System (INIS)

Zimin, Sergei

2003-01-01

With the creation of Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) the Australian approach to criticality safety was revisited. Consistency with international best practices is required by the Act that created ARPANSA and this was applied to practices in criticality safety adopted in other countries. This required extensive regulatory efforts both in auditing the major Australian Nuclear Operator, Australian Nuclear Science and Technology Organisation (ANSTO), and assessing the existing in Australia criticality safety practices and implementing the required changes using the new legislative power of ARPANSA. The adopted regulatory approach is formulated through both the issued by ARPANSA licenses for nuclear installations (including reactors, fuel stores and radioactive waste stores) and the string of new regulatory documents, including the Regulatory Assessment Principles and the Regulatory Assessment Guidelines for criticality safety. The main features of the adopted regulation include the requirements of independent peer-review, ongoing refresher training coupled with annual accreditation and the reliance on the safe design rather than on an administrative control. (author)

Regulatory control of fuel design and manufacturing

International Nuclear Information System (INIS)

1994-01-01

The regulatory control of the design and manufacturing of the nuclear fuel and of the control rods aims to ensure conformance to set requirements during normal operating conditions, anticipated operational transients and postulated accident conditions. The regulatory control of design, manufacturing, receiving inspections and the start of operation of the nuclear fuel are specified in the guide. The regulatory control procedure also applies to the control rods and the shield elements

5 CFR 847.102 - Regulatory structure.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 847.102 Section 847.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... INSTRUMENTALITIES General Provisions § 847.102 Regulatory structure. (a)(1) Subpart A of this part contains...

Cost-benefit and regulatory decision making

International Nuclear Information System (INIS)

Harvie, J.

1996-01-01

The Atomic Energy Control Board is investigating the feasibility of developing methods for factoring cost-benefit considerations into its regulatory decision-making. This initiative results, in part, from the federal government policy requiring cost-benefit considerations to be taken into account in regulatory processes, and from the recommendations of an Advisory Panel on Regulatory Review in 1993, submitted to the Minister of Natural Resources Canada. One of these recommendations stated: 'that mechanisms be developed to examine cost benefit issues and work towards some consensus of opinion among stake holders: a task force on the subject could be an appropriate starting point'. (author)

Transparency of nuclear regulatory activities

International Nuclear Information System (INIS)

2007-01-01

One of the main missions of nuclear regulators is to protect the public, and this cannot be completely achieved without public confidence. The more a regulatory process is transparent, the more such confidence will grow. Despite important cultural differences across countries, a number of common features characterise media and public expectations regarding any activity with an associated risk. A common understanding of transparency and main stakeholders' expectations in the field of nuclear safety were identified during this workshop, together with a number of conditions and practices aimed at improving the transparency of nuclear regulatory activities. These conditions and practices are described herein, and will be of particular interest to all those working in the nuclear regulatory field. Their implementation may, however, differ from one country to another depending on national context. (authors)

Performance-Based (Risk-Informed) Regulation: A Regulatory Perspective

International Nuclear Information System (INIS)

Kadambi, N. Prasad

2005-01-01

Performance-based regulation (PBR) has been mandated at the national level in the United States and at the agency level, where appropriate, at the U.S. Nuclear Regulatory Commission (USNRC). Guidance has been developed that implements the USNRC's definitions of PBR and other such conceptual regulatory improvements. This paper describes why PBR is important, what constitutes PBR in the context of direction provided at the USNRC, and how PBR can be implemented using a five-step process. The process steps articulate questions to be posed by the analyst regarding various aspects of a regulatory issue so that a suitably performance-based resolution can be developed. A regulatory alternative thus developed can be included among other options to be considered as part of the regulatory decision-making process

Environmental Regulatory Update Table, January/February 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

1992-03-01

The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action. This table is for January/February 1992.

The carboxy-terminal domain of Dictyostelium C-module-binding factor is an independent gene regulatory entity.

Directory of Open Access Journals (Sweden)

Jörg Lucas

Full Text Available The C-module-binding factor (CbfA is a multidomain protein that belongs to the family of jumonji-type (JmjC transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD. An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo.

Integrated light-sheet imaging and flow-based enquiry (iLIFE) system for 3D in-vivo imaging of multicellular organism

Science.gov (United States)

Rasmi, Chelur K.; Padmanabhan, Sreedevi; Shirlekar, Kalyanee; Rajan, Kanhirodan; Manjithaya, Ravi; Singh, Varsha; Mondal, Partha Pratim

2017-12-01

We propose and demonstrate a light-sheet-based 3D interrogation system on a microfluidic platform for screening biological specimens during flow. To achieve this, a diffraction-limited light-sheet (with a large field-of-view) is employed to optically section the specimens flowing through the microfluidic channel. This necessitates optimization of the parameters for the illumination sub-system (illumination intensity, light-sheet width, and thickness), microfluidic specimen platform (channel-width and flow-rate), and detection sub-system (camera exposure time and frame rate). Once optimized, these parameters facilitate cross-sectional imaging and 3D reconstruction of biological specimens. The proposed integrated light-sheet imaging and flow-based enquiry (iLIFE) imaging technique enables single-shot sectional imaging of a range of specimens of varying dimensions, ranging from a single cell (HeLa cell) to a multicellular organism (C. elegans). 3D reconstruction of the entire C. elegans is achieved in real-time and with an exposure time of few hundred micro-seconds. A maximum likelihood technique is developed and optimized for the iLIFE imaging system. We observed an intracellular resolution for mitochondria-labeled HeLa cells, which demonstrates the dynamic resolution of the iLIFE system. The proposed technique is a step towards achieving flow-based 3D imaging. We expect potential applications in diverse fields such as structural biology and biophysics.

Visualizing the effect of tumor microenvironments on radiation-induced cell kinetics in multicellular spheroids consisting of HeLa cells

International Nuclear Information System (INIS)

Kaida, Atsushi; Miura, Masahiko

2013-01-01

Highlights: •We visualized radiation-induced cell kinetics in spheroids. •HeLa-Fucci cells were used for detection of cell-cycle changes. •Radiation-induced G2 arrest was prolonged in the spheroid. •The inner and outer cell fractions behaved differently. -- Abstract: In this study, we visualized the effect of tumor microenvironments on radiation-induced tumor cell kinetics. For this purpose, we utilized a multicellular spheroid model, with a diameter of ∼500 μm, consisting of HeLa cells expressing the fluorescent ubiquitination-based cell-cycle indicator (Fucci). In live spheroids, a confocal laser scanning microscope allowed us to clearly monitor cell kinetics at depths of up to 60 μm. Surprisingly, a remarkable prolongation of G2 arrest was observed in the outer region of the spheroid relative to monolayer-cultured cells. Scale, an aqueous reagent that renders tissues optically transparent, allowed visualization deeper inside spheroids. About 16 h after irradiation, a red fluorescent cell fraction, presumably a quiescent G0 cell fraction, became distinct from the outer fraction consisting of proliferating cells, most of which exhibited green fluorescence indicative of G2 arrest. Thereafter, the red cell fraction began to emit green fluorescence and remained in prolonged G2 arrest. Thus, for the first time, we visualized the prolongation of radiation-induced G2 arrest in spheroids and the differences in cell kinetics between the outer and inner fractions

76 FR 64043 - Iowa Regulatory Program

Science.gov (United States)

2011-10-17

...) Requirements for permits for special categories of mining. 27--40.41(207) Permanent regulatory program--small... DEPARTMENT OF THE INTERIOR Office of Surface Mining Reclamation and Enforcement 30 CFR Part 915 [Docket No. IA-016-FOR; Docket ID: OSM-2011-0014] Iowa Regulatory Program AGENCY: Office of Surface Mining...

Guidelines for IAEA International Regulatory Review Teams (IRRTs)

International Nuclear Information System (INIS)

1993-04-01

This document is intended to be used by International regulatory review teams in reviewing the activities of a regulatory body as applicable to the regulation of nuclear power plants. The mission will, however, take note of any other activities of the regulatory body when drawing up the review report. The document does not specifically deal with the functions of a regulatory body responsible for other types of nuclear facilities or related nuclear activities, but it is intended that the concepts presented in the document could be applied where appropriate. Refs

Experience Transformed into Nuclear Regulatory Improvements in Russia

International Nuclear Information System (INIS)

Sapozhnikov, A.

2016-01-01

The third International Conference on Effective Nuclear Regulatory Systems (Canada, 2013) identified the main action items that should be addressed, implemented and followed up. The key technical and organizational areas important to strengthening reactor and spent fuel safety have been determined as following: • Regulatory lessons learned and actions taken (since the accident at the Fukushima Daiichi NPP); • Waste management and spent fuel safety; • Emergency management; • Emerging programmes; • Human and organizational factors, safety and security culture. Over time many activities based on results of the IAEA Integrated Regulatory Review Service in the Russian Federation, 2019, and post-mission, 2013, have been implemented. At present there is progress for the national action plan on nuclear safety, preparation and conducting of long term spent fuel management, complementary reviews for nuclear facilities other than Nuclear Power Plants, emergency exercises with the regulatory body participation, improving communication, development of national regulations and improvement of regulatory system in the whole. The regulatory body ensures assistance in development of national regulatory infrastructure, safety culture to the countries planning to construct Russian design facilities (NPPs, RRs). The report outlines the results and future actions to improve nuclear regulation based on systematic approach to safety and particularly reflects the specificity of taking measures for the research reactors. (author)

14 CFR 313.4 - Major regulatory actions.

Science.gov (United States)

2010-01-01

...) PROCEDURAL REGULATIONS IMPLEMENTATION OF THE ENERGY POLICY AND CONSERVATION ACT § 313.4 Major regulatory... of actions shall not be deemed as major regulatory actions requiring an energy statement: (1) Tariff...

Environmental regulatory reform in Poland: lessons for industrializing economies

Energy Technology Data Exchange (ETDEWEB)

Brown, H.S.; Angel, D. [Clark University, Worcester, MA (USA). George Perkins Marsh Institute

2000-09-01

This paper examines the environmental regulatory reform in Poland during the 1990s and uses the findings to consider the extent to which elements of successful regulatory systems are transferable across national boundaries. Drawing on five case studies of privatized firms, a mailed questionnaire, and policy and institutional analysis, it investigates how Poland developed an effective system for managing industrial pollution while also achieving considerable socioeconomic progress. The fundamental legitimacy of the regulators and regulatory process, the availability of information about firms and regulatory intents, and the capacity for case-specific decision-making are among the key explanatory factors. The study also shows how in Poland a good 'fit' between regulatory institutions and policies on one hand and their social context on the other hand has evolved, and how it contributes to the effectiveness of the regulatory system. Industrializing economies can indeed simultaneously pursue environmental protection and socioeconomic welfare, but elements of a proven regulatory system cannot be automatically adopted among countries and cultures. Learning from each other's experience must be sensitive to the cultural and institutional context of each regulatory system. 42 refs., 3 figs., 1 tab.

Systematic identification of regulatory variants associated with cancer risk.

Science.gov (United States)

Liu, Song; Liu, Yuwen; Zhang, Qin; Wu, Jiayu; Liang, Junbo; Yu, Shan; Wei, Gong-Hong; White, Kevin P; Wang, Xiaoyue

2017-10-23

Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities. From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach. By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

78 FR 44275 - Semiannual Regulatory Agenda

Science.gov (United States)

2013-07-23

... Rights. National Park Service--Completed Actions Regulation Sequence No. Title Identifier No. 200 Winter.... Timetable: Action Date FR Cite NPRM 07/00/13 Final Action 05/00/14 Regulatory Flexibility Analysis Required...: Action Date FR Cite NPRM 10/00/14 Final Action 10/00/14 Regulatory Flexibility Analysis Required: Yes...

Evolution of cichlid vision via trans-regulatory divergence

Directory of Open Access Journals (Sweden)

O’Quin Kelly E

2012-12-01

Full Text Available Abstract Background Phenotypic evolution may occur through mutations that affect either the structure or expression of protein-coding genes. Although the evolution of color vision has historically been attributed to structural mutations within the opsin genes, recent research has shown that opsin regulatory mutations can also tune photoreceptor sensitivity and color vision. Visual sensitivity in African cichlid fishes varies as a result of the differential expression of seven opsin genes. We crossed cichlid species that express different opsin gene sets and scanned their genome for expression Quantitative Trait Loci (eQTL responsible for these differences. Our results shed light on the role that different structural, cis-, and trans-regulatory mutations play in the evolution of color vision. Results We identified 11 eQTL that contribute to the divergent expression of five opsin genes. On three linkage groups, several eQTL formed regulatory “hotspots” associated with the expression of multiple opsins. Importantly, however, the majority of the eQTL we identified (8/11 or 73% occur on linkage groups located trans to the opsin genes, suggesting that cichlid color vision has evolved primarily via trans-regulatory divergence. By modeling the impact of just two of these trans-regulatory eQTL, we show that opsin regulatory mutations can alter cichlid photoreceptor sensitivity and color vision at least as much as opsin structural mutations can. Conclusions Combined with previous work, we demonstrate that the evolution of cichlid color vision results from the interplay of structural, cis-, and especially trans-regulatory loci. Although there are numerous examples of structural and cis-regulatory mutations that contribute to phenotypic evolution, our results suggest that trans-regulatory mutations could contribute to phenotypic divergence more commonly than previously expected, especially in systems like color vision, where compensatory changes in the

Food safety regulatory systems in Europe and China：A study of how co-regulation can improve regulatory effectiveness

Institute of Scientific and Technical Information of China (English)

Kevin Chen; WANG Xin-xin; SONG Hai-ying

2015-01-01

Food safety has received a great deal of attention in both developed and developing countries in recent years. In China, the numerous food scandals and scares that have struck over the past decade have spurred signiifcant food safety regulatory reform, which has been increasingly oriented towards the public-private partnership model adopted by the Europe Union’s (EU) food safety regulatory system. This paper analyzes the development of both the EU’s and China’s food safety regu-latory systems, identiifes the current chalenges for China and additionaly considers the role of public-private partnership. The success of co-regulation in the food regulatory system would bring signiifcant beneifts and opportunities for China. Finaly, this paper recommends additional measures like training and grants to improve the private’s sector effectiveness in co-regulating China’s food safety issues.

T-regulatory cells in chronic rejection versus stable grafts.

Science.gov (United States)

Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

2015-04-01

Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

47 CFR 1.1163 - Adjustments to regulatory fees.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Adjustments to regulatory fees. 1.1163 Section... of Statutory Charges and Procedures for Payment § 1.1163 Adjustments to regulatory fees. (a) For Fiscal Year 1995, the amounts assessed for regulatory fees are set forth in §§ 1.1152 through 1.1156. (b...

In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana.

Science.gov (United States)

Ibraheem, Omodele; Botha, Christiaan E J; Bradley, Graeme

2010-12-01

The regulation of gene expression involves a multifarious regulatory system. Each gene contains a unique combination of cis-acting regulatory sequence elements in the 5' regulatory region that determines its temporal and spatial expression. Cis-acting regulatory elements are essential transcriptional gene regulatory units; they control many biological processes and stress responses. Thus a full understanding of the transcriptional gene regulation system will depend on successful functional analyses of cis-acting elements. Cis-acting regulatory elements present within the 5' regulatory region of the sucrose transporter gene families in rice (Oryza sativa Japonica cultivar-group) and Arabidopsis thaliana, were identified using a bioinformatics approach. The possible cis-acting regulatory elements were predicted by scanning 1.5kbp of 5' regulatory regions of the sucrose transporter genes translational start sites, using Plant CARE, PLACE and Genomatix Matinspector professional databases. Several cis-acting regulatory elements that are associated with plant development, plant hormonal regulation and stress response were identified, and were present in varying frequencies within the 1.5kbp of 5' regulatory region, among which are; A-box, RY, CAT, Pyrimidine-box, Sucrose-box, ABRE, ARF, ERE, GARE, Me-JA, ARE, DRE, GA-motif, GATA, GT-1, MYC, MYB, W-box, and I-box. This result reveals the probable cis-acting regulatory elements that possibly are involved in the expression and regulation of sucrose transporter gene families in rice and Arabidopsis thaliana during cellular development or environmental stress conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

RMOD: a tool for regulatory motif detection in signaling network.

Directory of Open Access Journals (Sweden)

Jinki Kim

Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

Scientific underpinnings of biotechnology regulatory frameworks.

Science.gov (United States)

Gleim, Savannah; Smyth, Stuart J

2018-05-25

Part of what is presently missing at domestic regulatory levels (and that is important at the international level as well) is a detailed understanding of what the rules of, and for, regulation should be, who the actors, stakeholders and major decision makers are and finally, how to get agreement about the rules. Greater insights into the system of rules that underpin regulatory frameworks for agri-food and biotechnology products in genetically modified (GM) crop- adopting nations will provide value by clarifying the evidence used to commercialize these technologies. This article examines the public documents available from Canada, the United States, the European Union and the Organisation for Economic Cooperation and Development regarding the development of regulatory risk assessment frameworks for products of biotechnology to determine what science grounds these frameworks. The documentation used to provide the initial structure to the existing regulatory frameworks identifies the linkages, connections and relationships that exist between science, risk assessment and regulatory policy. The relationship between risk and regulation has never been more critical to the commercialization of innovative agricultural products. Documenting the role of science-based risk assessment in regulations and how this has changed over the 20 years of experience in regulating GM crops will identify changes in the risk/regulation relationship. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Common market but divergent regulatory practices: exploring European regulation and the effect on regulatory uncertainty in the marketing authorization of medical products

NARCIS (Netherlands)

Chowdhury, Nupur

2013-01-01

The medical product sector is characterised by a regulatory patchwork of European and national laws and guidelines operating concurrently with each other. Each of these sectors are characterised by different levels of regulatory uncertainty that may undermine the effectiveness of the regulatory

Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

Science.gov (United States)

2010-04-26

... Regulatory Commission Federal Housing Finance Agency Federal Maritime Commission Federal Mediation and... that the Regulatory Flexibility Act may require a Regulatory Flexibility Analysis, actions selected for.... Regulatory Flexibility Analysis Required -- whether an analysis is required by the Regulatory Flexibility Act...

Argentine influence on regulatory activities in Latin America

International Nuclear Information System (INIS)

Palacios, Elias

1998-01-01

An analysis of the nuclear regulatory systems and the nuclear regulations of many Latin American countries shows a substantial influence of the Argentine regulatory structure. This influence is attributed to the early Argentine development of a regulatory and control organization, the teaching of regional training courses and the advice of Argentine experts to Latin-American governments

Regulatory control of the use of contractors by operating organizations. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

2000-09-01

This report arises from the eighth series of peer discussions on regulatory practices entitled 'Regulatory control of the use of contractors by operating organizations'. Senior regulators from 19 Member States participated in two peer group discussions in March 2000 and May 2000. This report gives an account of the outcomes of these meetings and of practical suggestions put forward by senior regulators. These suggestions do not necessarily reflect the views of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. The objective of this document is to share experience between regulatory bodies and provide practical suggestions for controlling the use of contractors and subcontractors by the operating organizations during all stages, especially operation, of a nuclear power plant, so as to ensure that the quality of work and services delivered is commensurate with the safety importance of the activities and that these are carried out in a manner that will not adversely affect the safe or reliable operation of the facility. These documented practical suggestions and experiences are the result of a series of peer discussions at the IAEA in 2000. It is considered that the manner in which control is exercised, and the various challenges connected to this control, are highly dependent upon the legislative framework, maturity of the nuclear programme, the size of the national nuclear industry and the culture in each country. The report is structured so that it covers the subject matter under the following main headings: Legal Provisions, Regulatory Strategy and Requirements; Regulatory Approaches for Controlling the Use of Contractors; Types of Contracts; Practical Suggestions

77 FR 33253 - Regulatory Guide 8.33, Quality Management Program

Science.gov (United States)

2012-06-05

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0126] Regulatory Guide 8.33, Quality Management Program... Regulatory Commission (NRC or Commission) is withdrawing Regulatory Guide (RG) 8.33, ``Quality Management... Quality Management Program was deleted from the regulations as part of an overall revision in 2002 of the...

75 FR 18202 - Notice of Indo-U.S. Regulatory Workshop

Science.gov (United States)

2010-04-09

... regulatory challenges faced by commissioners from both nations. The FERC Commissioners, along with other... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Indo-U.S. Regulatory Workshop April 1, 2010. Commissioner Philip D. Moeller will convene a workshop at the Federal Energy Regulatory...

The regulatory control of radioactive sources in Argentina

International Nuclear Information System (INIS)

Rojkind, Roberto Hector

1997-01-01

Argentina has been conducting nuclear activities for more than forty years, and as early as in 1956 established a Regulatory Authority. Procedures for compliance monitoring and enforcement have been in use in the regulatory control of radioactive sources, and regulatory standards and regulations had been set in Argentina, before the accident in Goiania. The conclusions drawn from that accident encouraged in Argentina the improvement of some regulatory procedures and helped to enhance the quality of the regulatory process. Therefore, the effectiveness of the control of spent radioactive sources has gradually increased, and enforcement actions to prevent radioactive sources ending up in the public domain improved. Some lessons learned in Argentina from the accident in Goiania and the main characteristics of an effective enforcement program helpful to prevent radiological accidents in industrial, medical, research and teaching uses of radioactive sources are presented. (author)

Statistical significance of cis-regulatory modules

Directory of Open Access Journals (Sweden)

Smith Andrew D

2007-01-01

Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

Regulatory Models and the Environment: Practice, Pitfalls, and Prospects

Energy Technology Data Exchange (ETDEWEB)

Holmes, K. John; Graham, Judith A.; McKone, Thomas; Whipple, Chris

2008-06-01

Computational models support environmental regulatory activities by providing the regulator an ability to evaluate available knowledge, assess alternative regulations, and provide a framework to assess compliance. But all models face inherent uncertainties, because human and natural systems are always more complex and heterogeneous than can be captured in a model. Here we provide a summary discussion of the activities, findings, and recommendations of the National Research Council's Committee on Regulatory Environmental Models, a committee funded by the US Environmental Protection Agency to provide guidance on the use of computational models in the regulatory process. Modeling is a difficult enterprise even outside of the potentially adversarial regulatory environment. The demands grow when the regulatory requirements for accountability, transparency, public accessibility, and technical rigor are added to the challenges. Moreover, models cannot be validated (declared true) but instead should be evaluated with regard to their suitability as tools to address a specific question. The committee concluded that these characteristics make evaluation of a regulatory model more complex than simply comparing measurement data with model results. Evaluation also must balance the need for a model to be accurate with the need for a model to be reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs requires model evaluation to be applied over the"life cycle" of a regulatory model with an approach that includes different forms of peer review, uncertainty analysis, and extrapolation methods than for non-regulatory models.

Regulatory document R-104, Regulatory objectives, requirements and guidelines for the disposal of radioactive wastes - long-term aspects

International Nuclear Information System (INIS)

1987-01-01

The purpose and scope of this document is to present the regulatory basis for judging the long-term acceptability of radioactive waste disposal options. The basic objectives of radioactive waste disposal are given as are the regulatory requirements to be satisfied. (NEA)

Methodology For Evaluation Of Regulatory Effectiveness In Physical Protection

International Nuclear Information System (INIS)

Izmaylov, Alexander; Valente, John; Griggs, James R.; Rexroth, Paul; Piskarev, Alexander; Babkin, Vladimir; Sokolov, Egor; Melton, Ronald B.; Cunningham, Mitchel E.; Baker, Kathryn A.; Brothers, Alan J.

2005-01-01

Material protection, control, and accounting (MPC and A) regulatory documents play an important role in securing and protecting nuclear material by regulating a variety of activities at different hierarchical levels. The development, implementation, and practical application of these regulatory documents requires a significant investment of financial and material resources. Therefore, it is important to evaluate the effectiveness of the regulatory development process and the extent to which regulations improve the effectiveness of MPC and A at nuclear sites. The joint Russian and U.S. Regulatory Development Project has a goal of evaluating the effectiveness of regulatory documents developed for MPC and A. As part of this joint Project, a methodology for evaluating effectiveness has been developed. This methodology was developed around physical protection objectives. The developed methodology specifies physical protection objectives to be accomplished through the implementation of a regulatory system based on the physical protection goals at the nuclear sites. It includes approaches to assessing regulatory effectiveness, the hierarchical structure of physical protection objectives to be accomplished through implementing regulations, a 'mapping' of the physical protection objectives to the regulatory framework, a list of criteria for evaluating the effectiveness of physical protection regulations and effectiveness indicators, as well as means and methods for gathering information and implementation of this evaluation.

Information system fur the management of a regulatory programme

International Nuclear Information System (INIS)

Ortiz, P.; Mrabit, K.; Miaw, S.

1998-01-01

A Regulatory Programme to monitor safety of activities involving radiation sources, implies the existence of a Regulatory Authority empowered by legislation to issue radiation protection regulations and to monitor compliance with those regulations. The core element of the programme is a system of notification and authorization (registration and licensing), inspection and enforcement. The efficiency of this system is largely dependent on the availability of reliable information on the inventory of radiation sources and installations, the administrative status of the facilities (authorization), prompt processing of inspection reports and follow up of regulatory actions, including monitoring deadlines. Essential data relevant to safety, such as personal dosimetry for occupationally exposed individuals, inspection findings and incident reports would provide, in addition, an insight on the overall safety of the country. A simple but comprehensive Regulatory Authority Information System (RAIS) linked to the authorization and inspection process will largely facilitate regulatory decisions and actions. A readily available and reliable information from the various regulatory activities will facilitate planning, optimization of resources, monitoring safety related data, disseminating safety information, making decisions and follow up regulatory actions including monitoring dead lines. The implementation of the system in more than 50 countries will contribute to experience exchange and harmonization of regulatory activities. (author)

Building Nuclear Safety and Security Culture Within Regulatory Body

International Nuclear Information System (INIS)

Huda, K.

2016-01-01

To achieve a higher level of nuclear safety and security, it needs to develop the safety and security culture not only in the facility but also in the regulatory body. The regulatory body, especially needs to develop the safety and security culture within the organization, because it has a function to promote and oversee the culture in the facilities. In this sense, the regulatory body should become a role model. Development of the nuclear safety and security culture should be started by properly understanding its concept and awakening the awareness of individual and organization on the importance of nuclear safety and security. For effectiveness of the culture development in the regulatory body, the following steps are suggested to be taken: setting up of the regulatory requirements, self-assessment, independent assessment review, communication with the licensee, oversight of management system implementation, and integration with regulatory activities. The paper discusses those steps in the framework of development of nuclear safety and security culture in the regulatory body, as well as some important elements in building of the culture in the nuclear facilities. (author)

Characterization of noncoding regulatory DNA in the human genome.

Science.gov (United States)

Elkon, Ran; Agami, Reuven

2017-08-08

Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

Regulatory guidelines for biosimilars in Malaysia.

Science.gov (United States)

Abas, Arpah

2011-09-01

The biosimilars sector continues to attract huge interest and controversy. Biosimilars are new biopharmaceuticals that are "similar" but not identical to the innovator product. Characteristics of biopharmaceuticals are closely related to the manufacturing process, which implies that the products cannot be exactly duplicated. Minuscule differences in the product's structure and manufacturing process can result in different clinical outcome. This raises concerns over the safety, efficacy and even pharmacovigilance of biosimilars. Thus, biosimilars are unique - they are not a true chemical generic and are regulated via a distinct regulatory framework. This report discusses the features of Malaysian regulatory oversight of biosimilars and experience acquired in the evaluation of some products from various countries. Ensuring regulatory position adequately reflects scientific advancement, expertise/resources is key. The regulatory situation is an evolving process. Various guidance documents are being prepared with the aim of developing a uniform global framework towards assuring the dual goal of lower costs and patient safety while expediting the availability of important biosimilar products. Copyright © 2011. Published by Elsevier Ltd.

Mutational robustness of gene regulatory networks.

Directory of Open Access Journals (Sweden)

Aalt D J van Dijk

Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

Nuclear regulatory developments in Canada

International Nuclear Information System (INIS)

Binder, M.

2012-01-01

This paper from CNSC discusses nuclear regulatory developments in Canada. It starts with the Fukushima accident and the effect on the nuclear sector. It summarises what CNSC has done, what it has learned and their plans going forward. It has made recommendations to IAEA for international enhancements to regulatory procedures. It outline the activities of Canada's nuclear power plants, Canada's uranium projects, deep geological repository and waste management as well as nuclear research in Canada.

Regulatory competition in partnership law.

OpenAIRE

Siems, Mathias

2009-01-01

Regulatory competition in company law has been extensively debated in the last few decades, but it has rarely been discussed whether there could also be regulatory competition in partnership law. This article fills this gap. It addresses the partnership law of the US, the UK, Germany, and France, and presents empirical data on the different types of partnerships and companies established in these jurisdictions. The main focus is on the use of a limited liability partnership (LLP) outside its ...

Nuclear Regulatory Commission: more aggressive leadership needed

International Nuclear Information System (INIS)

Staats, E.B.

1980-01-01

The Energy Reorganization Act of 1974 which established the Nuclear Regulatory Commission required GAO to evaluate the Commission's performance by January 18, 1980. This report responds to that requirement. GAO concluded that, although improvements have been made, the Commission's nuclear regulatory performance can be characterized best as slow, indecisive, cautious - in a word, complacent. This has largely resulted from a lack of aggressive leadership as evidenced by the Commissioners' failure to establish regulatory goals, control policymaking, and most importantly, clearly define their roles in nuclear regulation

Targeting regulatory T cells in cancer.

LENUS (Irish Health Repository)

Byrne, William L

2012-01-31

Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

Regulatory aspects of radiopharmaceuticals

International Nuclear Information System (INIS)

Kristensen, K.

1985-01-01

Regulatory systems in the field of radiopharmaceuticals have two main purposes: efficacy and safety. Efficacy expresses the quality of the diagnostic and therapeutic process for the patient. Safety involves the patient, the staff, and the environment. The world situation regarding regulations for radiopharmaceuticals is reviewed on the basis of a survey in WHO Member States. The main content of such regulations is discussed. The special properties of radiopharmaceuticals compared with ordinary drugs may call for modified regulations. Several countries are preparing such regulations. Close co-operation and good understanding among scientists working in hospital research, industry and regulatory bodies will be of great importance for the fast and safe introduction of new radiopharmaceuticals for the benefit of the patient. Before introducing new legislation in this field, a radiopharmaceutical expert should analyse the situation in the country and the relationship to the existing regulations. It is expected that the most important factor in promoting the fast introduction of new, safe and effective radiopharmaceuticals will be the training of people working within the regulatory bodies. It is foreseen that the IAEA and WHO will have an important role to play by providing expert advice and training in this area. (author)

Regulatory Anatomy

DEFF Research Database (Denmark)

Hoeyer, Klaus

2015-01-01

This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

Regulatory heterochronies and loose temporal scaling between sea star and sea urchin regulatory circuits.

Science.gov (United States)

Gildor, Tsvia; Hinman, Veronica; Ben-Tabou-De-Leon, Smadar

2017-01-01

It has long been argued that heterochrony, a change in relative timing of a developmental process, is a major source of evolutionary innovation. Heterochronic changes of regulatory gene activation could be the underlying molecular mechanism driving heterochronic changes through evolution. Here, we compare the temporal expression profiles of key regulatory circuits between sea urchin and sea star, representative of two classes of Echinoderms that shared a common ancestor about 500 million years ago. The morphologies of the sea urchin and sea star embryos are largely comparable, yet, differences in certain mesodermal cell types and ectodermal patterning result in distinct larval body plans. We generated high resolution temporal profiles of 17 mesodermally-, endodermally- and ectodermally-expressed regulatory genes in the sea star, Patiria miniata, and compared these to their orthologs in the Mediterranean sea urchin, Paracentrotus lividus. We found that the maternal to zygotic transition is delayed in the sea star compared to the sea urchin, in agreement with the longer cleavage stage in the sea star. Interestingly, the order of gene activation shows the highest variation in the relatively diverged mesodermal circuit, while the correlations of expression dynamics are the highest in the strongly conserved endodermal circuit. We detected loose scaling of the developmental rates of these species and observed interspecies heterochronies within all studied regulatory circuits. Thus, after 500 million years of parallel evolution, mild heterochronies between the species are frequently observed and the tight temporal scaling observed for closely related species no longer holds.

The regulatory framework in the UK

International Nuclear Information System (INIS)

O'Sullivan, R.

1984-01-01

The subject is covered in sections, headed: basic regulatory requirements covering the transport of radioactive material in the UK; responsibility for safety (competent authority; provision of regulations; implementation of regulations (international and national); design of transport flask; safety case; testing; assessment; approval certificate; compliance assurance; administration); advice and information on the regulatory safety standards. (U.K.)

Advanced Reactor Technologies - Regulatory Technology Development Plan (RTDP)

Energy Technology Data Exchange (ETDEWEB)

Moe, Wayne L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2017-08-23

This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

Energy Technology Data Exchange (ETDEWEB)

Moe, Wayne Leland [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-05-01

This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

Regulatory system reform of occupational health and safety in China.

Science.gov (United States)

Wu, Fenghong; Chi, Yan

2015-01-01

With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

Regulatory perspectives of concept assessment

International Nuclear Information System (INIS)

Flavelle, Peter A.

1987-09-01

The Atomic Energy Control Board is the head agency for the regulatory review of the Assessment of the Canadian Concept for Nuclear Fuel Waste Disposal being done by Atomic Energy of Canada Limited and Ontario Hydro. This paper describes the regulatory perspective of how the Concept Assessment could demonstrate the feasibility of a disposal conforming to regulatory requirements. The long-term aspects of Concept Assessment encourage the use of various predictive techniques for different time scales. Each technique will have a different potential for establishing confidence in the predictions. The predicted performance of a facility during operation should have a very high confidence, as it can be based on standard engineering calculations and the predictions can be validated later by monitoring during operation. The predictions of the transient period following closure of the facility should achieve a medium level of confidence, since they can be based on extrapolations of predictions of operational performance, using models that can be calibrated with monitoring data and with averaged input data derived from natural analog studies. Predictions based on fundamental processes will have a medium level of confidence when made to intermediate times after closure. Long-term predictions using generic or typical input data or Monte Carlo calculations of simplified models will have the least confidence and yet they can still contribute to the confidence that the disposal concept will conform to regulatory requirements

Use of risk information in regulatory reviews

International Nuclear Information System (INIS)

Sagar, B.; Benke, R.; Mohanty, S.

2004-01-01

The regulatory framework for licensing any high-level waste repository at Yucca Mountain in the United States, calls for appropriate use of risk information to ensure operational safety during the pre-closure period and long-term safety during the post-closure period. This paper focuses on the post-closure period. Regulations in the Code of Federal Regulations (CFR), Title 10, Part 63, apply to any repository at Yucca Mountain and envision use of probabilistic methods to develop quantitative risk information. Accumulated engineering and scientific experience at Yucca Mountain and analog sites and quantitative risk information from studies conducted by the implementer, regulator, and others are combined to formulate 'risk insights,' which are then used to plan and execute regulatory reviews. The U.S. Nuclear Regulatory Commission (NRC) and the Center for Nuclear Waste Regulatory Analyses (CNWRA) recently consolidated the knowledge gained during several g ears and developed such risk insights for the potential repository at Yucca Mountain. This paper discusses the types of risk information used to generate risk insights and how the risk insights will be used in regulatory reviews. A companion paper presents more details on sensitivity analysis methods used to generate risk information. (authors)

The regulatory control of radioactive sources in Argentina

International Nuclear Information System (INIS)

Rojkind, R.H.

1998-01-01

Argentina has been conducting nuclear activities for more than forty years, and had established a Regulatory Authority as early as in 1956. Procedures for compliance monitoring and enforcement have been in use in the regulatory control of radioactive sources, and regulatory standards and regulations were in force in Argentina before the accident in Goiania. The conclusions drawn from the Goiania accident encouraged the Argentine authorities to improve some regulatory procedures and helped to enhance the quality of the regulatory process. As a result, the effectiveness of the control of spent radioactive sources has gradually increased, and enforcement actions to prevent radioactive sources ending up in the public domain have improved. Lessons learned in Argentina from the accident in Goiania are presented as well as the main characteristics of an effective enforcement programme to prevent radiological accidents when radioactive sources are used for industrial, medical, research and teaching purposes. (author)

The path from biomarker discovery to regulatory qualification

CERN Document Server

Goodsaid, Federico

2013-01-01

The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

Risk acceptance criteria of the Nuclear Regulatory Authority

International Nuclear Information System (INIS)

Felizia, Eduardo R.

2005-01-01

This report describes some of the regulatory and control functions legally conferred upon the Argentine Nuclear Regulatory Authority concerning radiological risks, as well as a critical analysis of the radiological risk acceptance criteria contained in the Argentine regulatory system. A summary of the application of regulatory standards AR 3.1.3. - 'Radiological criteria related to accidents in nuclear power reactors' and AR 4.1.3. - 'Radiological criteria related to accidents in research reactors' to concrete cases is made, while the favourable and unfavourable aspects of the risk acceptance criteria are discussed. The conclusion is that the Argentine regulatory system contains adequate radiological risk acceptance criteria, that the latter are consistent with the radiological protection principles applicable to man and that, for the moment, there is no need to perform any modifications that would broaden the conceptual framework on which such criteria are based. (author) [es

Safety Committees for Argentinean Research Reactor - Regulatory Issues

International Nuclear Information System (INIS)

Perrin, Carlos D.

2009-01-01

In the field of radiological and nuclear safety, the Nuclear Regulatory Authority (ARN) of Argentina controls three research reactors and three critical assemblies, by means of evaluations, audits and inspections, in order to ensure the fulfillment of the requirements established in the Licenses, in the Regulatory Standards and in the Mandatory Documentation in general. From the Nuclear Regulatory Authority's point of view, within the general process of research reactors safety management, the Operational Organization self verification of radiological and nuclear safety plays an outstanding role. In this aspect the ARN has established specific requirements in the Regulatory Standards, in the Operation Licenses and in the Operational Limits and Conditions. These requirements include the figure of different safety committees, which act as reviewers or advisers in diverse situations. This paper describes the main characteristics of the committees, their function, scope and the regulatory documents where the requirements are included. (author)

Regulatory viewpoint on nuclear fuel quality assurance

International Nuclear Information System (INIS)

Tripp, L.E.

1976-01-01

Considerations of the importance of fuel quality and performance to nuclear safety, ''as low reasonably achievable'' release of radioactive materials in reactor effluents, and past fuel performance problems demonstrate the need for strong regulatory input, review and inspection of nuclear fuel quality assurance programs at all levels. Such a regulatory program is being applied in the United States of America by the US Nuclear Regulatory Commission. Quality assurance requirements are contained within government regulations. Guidance on acceptable methods of implementing portions of the quality assurance program is contained within Regulatory Guides and other NRC documents. Fuel supplier quality assurance program descriptions are reviewed as a part of the reactor licensing process. Inspections of reactor licensee control of their fuel vendors as well as direct inspections of fuel vendor quality assurance programs are conducted on a regularly scheduled basis. (author)

Regulatory framework for nuclear power plant operation

International Nuclear Information System (INIS)

Perez Alcaniz, T.; Esteban Barriendos, M.

1995-01-01

As the framework of standards and requirements covering each phase of nuclear power plant project and operation developed, plant owners defined their licensing commitments (codes, rules and design requirements) during the project and construction phase before start-up and incorporated regulatory requirements imposed by the regulatory Body during the licensing process prior to operation. This produces a regulatory framework for operating a plant. It includes the Licensing Basis, which is the starting point for analyzing and incorporating new requirements, and for re-evaluation of existing ones. This presentation focuses on the problems of applying this regulatory framework to new operating activities, in particular to new projects, analyzing new requirements, and reconsidering existing ones. Clearly establishing a plant's licensing basis allows all organizations involved in plant operation to apply the requirements in a more rational way. (Author)

Removal of regulatory controls for materials and sites

International Nuclear Information System (INIS)

2004-01-01

Issues with the removal of regulatory controls are very important on the agenda of the regulatory authorities dealing with radioactive waste management (RWM). These issues arise prominently in decommissioning and in site remediation, and decisions can be very wide ranging having potentially important economic impacts and reaching outside the RWM area. The RWMC Regulators Forum started to address these issues by holding a topical discussion at its meeting in March 2003. Ths present document collates the national regulatory positions in the area of removal of regulatory controls. A summary of the national positions is also provided. The document is up to date to April 2004. (authors)

Regulatory Risk Management of Advanced Nuclear Power Plants

International Nuclear Information System (INIS)

George, Glenn R.

2002-01-01

Regulatory risk reflects both the likelihood of adverse outcomes during regulatory interactions and the severity of those outcomes. In the arena of advanced nuclear power plant licensing and construction, such adverse outcomes may include, for example, required design changes and construction delays. These, in turn, could significantly affect the economics of the plant and the generation portfolio in which it will operate. In this paper, the author addresses these issues through the lens of risk management. The paper considers various tools and techniques of regulatory risk management, including design diversity and hedging strategies. The effectiveness of alternate approaches is weighed and recommendations are made in several regulatory contexts. (author)

Phylogeny based discovery of regulatory elements

Directory of Open Access Journals (Sweden)

Cohen Barak A

2006-05-01

Full Text Available Abstract Background Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. Results We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. Conclusion The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.

Activities relating to PSA in the regulatory process

International Nuclear Information System (INIS)

Campbell, J.F.; Grint, G.C.

1994-01-01

In addition to the IAEA activities concerning the use of PSA in the regulatory process there are two other international initiatives in this area by the European Commission and the OECD's Committee for Nuclear Regulatory Authorities (CRNA). The paper gives a brief outline of these activities as well as introducing an update on the regulatory use of PSA in the UK. 3 refs, 3 tabs

Regulatory facility guide for Ohio

Energy Technology Data Exchange (ETDEWEB)

Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

1994-02-28

The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

Down-regulation of DNA mismatch repair enhances initiation and growth of neuroblastoma and brain tumour multicellular spheroids.

Directory of Open Access Journals (Sweden)

Samuel L Collins

Full Text Available Multicellular tumour spheroid (MCTS cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. One mechanism linked to tumourigenesis in a number of cancers is genetic instability arising from impaired DNA mismatch repair (MMR. This study aimed to determine the role of MMR in MCTS initiation and development. Using surface-associated N2a and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming cells. By using small interfering RNA (siRNA against these genes we show that silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent expansion. This effect was prolonged over several passages following siRNA transfection. Down-regulation of DNA MMR can contribute to tumour initiation and progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated MCTS differentiation may have broader applications in studying events in the initiation of cancer foci.

Regulatory and technical reports (abstract index journal)

International Nuclear Information System (INIS)

1994-06-01

This compilation consists of bibliographic data and abstracts for the formal regulatory and technical reports issued by the US Nuclear Regulatory Commission (NRC) Staff and its contractors. It is NRC's intention to publish this compilation quarterly and to cumulate it annually

76 FR 20052 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-04-11

... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0187] Notice of Issuance of Regulatory Guide AGENCY... Guide 1.149, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License...

Low-income minority fathers' control strategies and children's regulatory skills

Science.gov (United States)

Malin, Jenessa L.; Cabrera, Natasha J.; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith

2015-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24-months and children's regulatory skills at pre-kindergarten (pre-K). Using a sample of low-income minority families with 2-year-olds from the Early Head Start Evaluation Research Program (n = 71) we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24-months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at pre-kindergarten. There were three main findings. First, fathers' overwhelmingly use commands (e.g., do that) to promote compliance in their 24-month old children. Second, children's vocabulary skills predict fathers' regulatory behaviors during a father-child interaction, whereas children's gender predicts fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24-months predict children's sustained attention at pre-kindergarten whereas fathers' regulatory language at 24-months predicts children's emotion regulation at pre-kindergarten. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. PMID:25798496

NRC regulatory agenda

International Nuclear Information System (INIS)

1990-10-01

The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

NRC regulatory agenda

International Nuclear Information System (INIS)

1990-04-01

The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

Regulatory system reform of occupational health and safety in China

Science.gov (United States)

WU, Fenghong; CHI, Yan

2015-01-01

With the explosive economic growth and social development, China’s regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined. PMID:25843565

Apoptosis Gene Hunting Using Retroviral Expression Cloning: Identification of Vacuolar ATPase Subunit E

Directory of Open Access Journals (Sweden)

Claire L. Anderson

2003-01-01

Full Text Available Over the past 10-15 years there has been an explosion of interest in apoptosis. The delayed realisation that cell death is an essential part of life for any multicellular organism has meant that, despite the recent and rapid developments of the last decade, the precise biochemical pathways involved in apoptosis remain incomplete and potentially novel genes may, as yet, remain undiscovered. The hunt is therefore on to bridge the remaining gaps in our knowledge. Our contribution to this research effort utilises a functional cloning approach to isolate important regulatory genes involved in apoptosis. This mini-review focuses on the use and advantages of a retroviral expression cloning strategy and describes the isolation and identification of one such potential apoptosis regulatory gene, namely that encoding vacuolar ATPase subunit E.