WorldWideScience

Sample records for play key regulatory

  1. The Transcription Factor Interferon Regulatory Factor-1 (IRF1) Plays a Key Role in the Terminal Effector Pathways of Human Preterm Labor.

    Science.gov (United States)

    Lim, Ratana; Tran, Ha Thi; Liong, Stella; Barker, Gillian; Lappas, Martha

    2016-02-01

    Preterm birth is the largest single cause of neonatal death and morbidity. By activating cytokine- and Toll-like receptor (TLR)-signaling pathways, infection and/or inflammation are strongly associated with preterm delivery. Interferon regulatory factor-1 (IRF1) is an important regulator of the inflammatory response. The aims of this study were to establish the effect of 1) labor on IRF1 expression in human fetal membranes and myometrium, 2) prolabor mediators on IRF1 expression and activity, and 3) IRF1 small interfering RNA on the expression of prolabor mediators. IRF1 expression was higher in fetal membranes and myometrium after spontaneous term labor and in preterm fetal membranes with infection. The proinflammatory cytokine IL1B, the bacterial product fsl-1, and viral analog polyinosinic:polycytidylic acid (poly [I:C]) significantly increased IRF1 mRNA expression and transcriptional activity in human primary myometrial cells. In addition, IL1B increased IRF1 activity in primary amnion cells. IRF1 silencing in myometrial cells decreased IL1B-, fsl-1-, and poly (I:C)-induced cytokine (IL6, TNF, IL1B) and chemokine (CXCL8, CCL2) mRNA expression and IL6, CXCL8, and CCL2 release. IL1B-, fsl-1-, and poly (I:C)-induced PTGS2 mRNA expression and IL1B-induced prostaglandin release was also decreased by IRF1 silencing. In conclusion, IRF1 upregulation in fetal membranes and myometrium after term labor indicates a proinflammatory role for IRF1 in human parturition. IRF1 is involved in TLR- and cytokine-mediated signaling in human myometrium. These data provide new insights into the mechanisms associated with inflammation- and infection-associated preterm birth. IRF1 inhibitors as therapeutics for the management of spontaneous preterm birth warrants further investigation. © 2016 by the Society for the Study of Reproduction, Inc.

  2. Bioenergy has a key role to play!

    DEFF Research Database (Denmark)

    Holm-Nielsen, Jens Bo

    2010-01-01

    Key note speach - Opening seremony of the 6.th International Bioenergy Conference organized by NASU - Kiev, Ukraine; www.biomass.kiev.ua;......Key note speach - Opening seremony of the 6.th International Bioenergy Conference organized by NASU - Kiev, Ukraine; www.biomass.kiev.ua;...

  3. Bioenergy has a key role to play!

    DEFF Research Database (Denmark)

    Holm-Nielsen, Jens Bo

    2010-01-01

    Key note speach - Opening seremony of the 6.th International Bioenergy Conference organized by NASU - Kiev, Ukraine; www.biomass.kiev.ua;......Key note speach - Opening seremony of the 6.th International Bioenergy Conference organized by NASU - Kiev, Ukraine; www.biomass.kiev.ua;...

  4. Glucocorticoids play a key role in circadian cell cycle rhythms.

    Directory of Open Access Journals (Sweden)

    Thomas Dickmeis

    2007-04-01

    Full Text Available Clock output pathways play a pivotal role by relaying timing information from the circadian clock to a diversity of physiological systems. Both cell-autonomous and systemic mechanisms have been implicated as clock outputs; however, the relative importance and interplay between these mechanisms are poorly understood. The cell cycle represents a highly conserved regulatory target of the circadian timing system. Previously, we have demonstrated that in zebrafish, the circadian clock has the capacity to generate daily rhythms of S phase by a cell-autonomous mechanism in vitro. Here, by studying a panel of zebrafish mutants, we reveal that the pituitary-adrenal axis also plays an essential role in establishing these rhythms in the whole animal. Mutants with a reduction or a complete absence of corticotrope pituitary cells show attenuated cell-proliferation rhythms, whereas expression of circadian clock genes is not affected. We show that the corticotrope deficiency is associated with reduced cortisol levels, implicating glucocorticoids as a component of a systemic signaling pathway required for circadian cell cycle rhythmicity. Strikingly, high-amplitude rhythms can be rescued by exposing mutant larvae to a tonic concentration of a glucocorticoid agonist. Our work suggests that cell-autonomous clock mechanisms are not sufficient to establish circadian cell cycle rhythms at the whole-animal level. Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part.

  5. Drug lag and key regulatory barriers in the emerging markets.

    Science.gov (United States)

    Wileman, Harriet; Mishra, Arun

    2010-04-01

    There have been numerous investigations targeted at identifying whether a drug lag exists in the mature markets of the US, EU and Japan. This work focuses on the emerging markets because of the potential they hold for the future of the pharmaceutical industry as a consequence of rapid economic and political development.The aims of this work are to ascertain whether a drug lag exists in the emerging markets and how it has changed over time from the 1960s to the 2000s. It will also highlight key regulatory barriers which may contribute to drug lag.The date of the marketing authorisation (MA) approval by the US Food and Drug Administration (FDA) was used as a reference point. A comparison against the company database regarding emerging market specific approval enabled the difference in time and thus the drug lag for that particular market to be calculated.This work concludes that the overall relative drug lag in the emerging markets has decreased over time and that there are seven key regulatory barriers which need to be targeted in order to make further improvements; 'Western Approval', local clinical development (LCD), Certificate of Pharmaceutical Product (CPP), Good Manufacturing Practice (GMP), pricing approval, document authentication and harmonisation.

  6. B-type suppression: a role played by "regulatory B cells" or "regulatory plasma cells"?

    Science.gov (United States)

    Ries, Stefanie; Hilgenberg, Ellen; Lampropoulou, Vicky; Shen, Ping; Dang, Van Duc; Wilantri, Siska; Sakwa, Imme; Fillatreau, Simon

    2014-05-01

    B-cell depletion can improve disease in some patients with rheumatoid arthritis or multiple sclerosis, indicating the pathogenic contribution of B cells to autoimmunity. However, studies in mice have demonstrated that B cells have immunosuppressive functions as well, with IL-10 being a critical mediator of B-cell-mediated suppression. IL-10-secreting B cells have been shown to promote disease remission in some mouse models of autoimmune disorders. Human B cells also produce IL-10, and evidence is accumulating that human IL-10-producing B cells might inhibit immunity. There is considerable interest in identifying the phenotype of B cells providing IL-10 in a suppressive manner, which would facilitate the analysis of the molecular mechanisms controlling this B-cell property. Here, we review current knowledge on the B-cell subpopulations found to provide suppressive functions in mice, considering both the pathological context in which they were identified and the signals that control their induction. We discuss the phenotype of B cells that have IL-10-dependent regulatory activities in mice, which leads us to propose that antibody-secreting cells are, in some cases at least, the major source of B-cell-derived regulatory IL-10 in vivo. Anti-inflammatory cytokine production by antibody-secreting cells offers a novel mechanism for the coordination of innate and humoral immune responses.

  7. Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

    Science.gov (United States)

    Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

    2014-01-01

    Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

  8. KWOC (Key-Word-Out-of-Context) Index of US Nuclear Regulatory Commission Regulatory Guide Series

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Adenylyl cyclase plays a regulatory role in development, stress resistance and secondary metabolism in Fusarium fujikuroi.

    Directory of Open Access Journals (Sweden)

    Jorge García-Martínez

    Full Text Available The ascomycete fungus Fusarium fujikuroi (Gibberella fujikuroi MP-C produces secondary metabolites of biotechnological interest, such as gibberellins, bikaverin, and carotenoids. Production of these metabolites is regulated by nitrogen availability and, in a specific manner, by other environmental signals, such as light in the case of the carotenoid pathway. A complex regulatory network controlling these processes is recently emerging from the alterations of metabolite production found through the mutation of different regulatory genes. Here we show the effect of the targeted mutation of the acyA gene of F. fujikuroi, coding for adenylyl cyclase. Mutants lacking the catalytic domain of the AcyA protein showed different phenotypic alterations, including reduced growth, enhanced production of unidentified red pigments, reduced production of gibberellins and partially derepressed carotenoid biosynthesis in the dark. The phenotype differs in some aspects from that of similar mutants of the close relatives F. proliferatum and F. verticillioides: contrary to what was observed in these species, ΔacyA mutants of F. fujikuroi showed enhanced sensitivity to oxidative stress (H(2O(2, but no change in heavy metal resistance or in the ability to colonize tomato tissue, indicating a high versatility in the regulatory roles played by cAMP in this fungal group.

  10. Main regulatory pathways, key genes and microRNAs involved in flower formation and development of moso bamboo (Phyllostachys edulis).

    Science.gov (United States)

    Ge, Wei; Zhang, Ying; Cheng, Zhanchao; Hou, Dan; Li, Xueping; Gao, Jian

    2017-01-01

    Moso bamboo is characterized by infrequent sexual reproduction and erratic flowering habit; however, the molecular biology of flower formation and development is not well studied in this species. We studied the molecular regulation mechanisms of moso bamboo development and flowering by selecting three key regulatory pathways: plant-pathogen interaction, plant hormone signal transduction and protein processing in endoplasmic reticulum at different stages of flowering in moso bamboo. We selected PheDof1, PheMADS14 and six microRNAs involved in the three pathways through KEGG pathway and cluster analysis. Subcellular localization, transcriptional activation, Western blotting, in situ hybridization and qRT-PCR were used to further investigate the expression patterns and regulatory roles of pivotal genes at different flower development stages. Differential expression patterns showed that PheDof1, PheMADS14 and six miRNAs may play vital regulatory roles in flower development and floral transition in moso bamboo. Our research paves way for further studies on metabolic regulatory networks and provides insight into the molecular regulation mechanisms of moso bamboo flowering and senescence.

  11. Experimental asymmetric plug-and-play measurement-device-independent quantum key distribution

    Science.gov (United States)

    Tang, Guang-Zhao; Sun, Shi-Hai; Xu, Feihu; Chen, Huan; Li, Chun-Yan; Liang, Lin-Mei

    2016-09-01

    Measurement-device-independent quantum key distribution (MDI-QKD) is immune to all security loopholes on detection. Previous experiments on MDI-QKD required spatially separated signal lasers and complicated stabilization systems. In this paper, we perform a proof-of-principle experimental demonstration of plug-and-play MDI-QKD over an asymmetric channel setting with a single signal laser in which the whole system is automatically stabilized in spectrum, polarization, arrival time, and phase reference. Both the signal laser and the single-photon detectors are in the possession of a common server. A passive timing-calibration technique is applied to ensure the precise and stable overlap of signal pulses. The results pave the way for the realization of a quantum network in which the users only need the encoding devices.

  12. Circadian Clock Gene Plays a Key Role on Ovarian Cycle and Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Ruiwen Li

    2015-09-01

    Full Text Available Background/Aims: Circadian locomotor output cycles protein kaput (CLOCK plays a key role in maintaining circadian rhythms and activation of downstream elements. However, its function on human female reproductive system remains unknown. Methods: To investigate the potential role of CLOCK, CLOCK-shRNAs were transfected into mouse 129 ES cells or injected into the ovaries of adult female mice. Western blotting was utilized to analyze the protein interactions and flow cytometry was used to assess apoptosis. Results: The expression of CLOCK peaked at the 6th week in the healthy fetuses. However, an abnormal expression of CLOCK was detected in fetuses from spontaneous miscarriage. To determine the effect of CLOCK on female fertility, a small hairpin RNA (shRNA strategy was used to specifically knockdown the CLOCK gene expression in vitro and in vivo. Knockdown of CLOCK induced apoptosis in mouse embryonic stem (mES cells and inhibited the proliferation in mES cells in vitro. CLOCK knockdown also led to decreased release of oocytes and smaller litter size compared with control in vivo. Conclusions: Collectively, theses findings indicate that CLOCK plays an important role in fertility and that the CLOCK knockdown leads to reduction in reproduction and increased miscarriage risk.

  13. NCP1/AtMOB1A Plays Key Roles in Auxin-Mediated Arabidopsis Development.

    Science.gov (United States)

    Cui, Xiaona; Guo, Zhiai; Song, Lizhen; Wang, Yanli; Cheng, Youfa

    2016-03-01

    MOB1 protein is a core component of the Hippo signaling pathway in animals where it is involved in controlling tissue growth and tumor suppression. Plant MOB1 proteins display high sequence homology to animal MOB1 proteins, but little is known regarding their role in plant growth and development. Herein we report the critical roles of Arabidopsis MOB1 (AtMOB1A) in auxin-mediated development in Arabidopsis. We found that loss-of-function mutations in AtMOB1A completely eliminated the formation of cotyledons when combined with mutations in PINOID (PID), which encodes a Ser/Thr protein kinase that participates in auxin signaling and transport. We showed that atmob1a was fully rescued by its Drosophila counterpart, suggesting functional conservation. The atmob1a pid double mutants phenocopied several well-characterized mutant combinations that are defective in auxin biosynthesis or transport. Moreover, we demonstrated that atmob1a greatly enhanced several other known auxin mutants, suggesting that AtMOB1A plays a key role in auxin-mediated plant development. The atmob1a single mutant displayed defects in early embryogenesis and had shorter root and smaller flowers than wild type plants. AtMOB1A is uniformly expressed in embryos and suspensor cells during embryogenesis, consistent with its role in embryo development. AtMOB1A protein is localized to nucleus, cytoplasm, and associated to plasma membrane, suggesting that it plays roles in these subcellular localizations. Furthermore, we showed that disruption of AtMOB1A led to a reduced sensitivity to exogenous auxin. Our results demonstrated that AtMOB1A plays an important role in Arabidopsis development by promoting auxin signaling.

  14. NF-κB signaling dynamics play a key role in infection control in tuberculosis

    Directory of Open Access Journals (Sweden)

    Mohammad eFallahi-Sichani

    2012-06-01

    Full Text Available The NF-κB signaling pathway is central to the body’s response to many pathogens. Mathematical models based on cell culture experiments have identified important molecular mechanisms controlling the dynamics of NF-κB signaling, but the dynamics of this pathway have never been studied in the context of an infection in a host. Here, we incorporate these dynamics into a virtual infection setting. We build a multi-scale model of the immune response to the pathogen Mycobacterium tuberculosis (Mtb to explore the impact of NF-κB dynamics occurring across molecular, cellular and tissue scales in the lung. NF-κB signaling is triggered via tumor necrosis factor-α (TNF binding to receptors on macrophages; TNF has been shown to play a key role in infection dynamics in humans and multiple animal systems. Using our multi-scale model, we predict the impact of TNF-induced NF-κB-mediated responses on the outcome of infection at the level of a granuloma, an aggregate of immune cells and bacteria that forms in response to infection and is key to containment of infection and clinical latency. We show how the stability of mRNA transcripts corresponding to NF-κB-mediated responses significantly controls bacterial load in a granuloma, inflammation level in tissue, and granuloma size. Because we incorporate intracellular signaling pathways explicitly, our analysis also elucidates NF-κB associated signaling molecules and processes that may be new targets for infection control.

  15. Ring-like nucleoid does not play a key role in radioresistance of Deinococcus radiodurans

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The conclusion based on transmission electron microscopy, "the tightly packed ring-like nucleoid of the Deinococcus radiodurans R1 is a key to radioresistance", has instigated lots of debates. In this study, according to the previous research of PprI’s crucial role in radioresistance of D. radiodurans, we have attempted to examine and compare the nucleoid morphology differences among wild-type D. ra-diodurans R1 strain, pprI function-deficient mutant (YR1), and pprI function-complementary strains (YR1001, YR1002, and YR1004) before and after exposure to ionizing irradiation. Fluorescence mi-croscopy images indicate: (1) the majority of nucleoid structures in radioresistant strain R1 cells ex-hibit the tightly packed ring-like morphology, while the pprI function-deficient mutant YR1 cells carrying predominate ring-like structure represent high sensitivity to irradiation; (2) as an extreme radioresistant strain similar to wild-type R1, pprI completely function-complementary strain YR1001 almost displays the loose and irregular nucleoid morphologies. On the other hand, another radioresistant pprI partly function-complementary strain YR1002’s nucleiods exhibit about 60% ring-like structure; (3) a PprI C-terminal deletion strain YR1004 consisting of approximately 60% of ring-like nucleoid is very sensi-tive to radiation. Therefore, our present experiments do not support the conclusion that the ring-like nucleoid of D. radiodurans does play a key role in radioresistance.

  16. AF10 plays a key role in the survival of uncommitted hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Raquel Chamorro-Garcia

    Full Text Available Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells.

  17. The transcription factor NFATp plays a key role in susceptibility to TB in mice.

    Directory of Open Access Journals (Sweden)

    Laura E Via

    Full Text Available In T cells, the transcription factor nuclear factor of activated T cells p (NFATp is a key regulator of the cytokine genes tumor necrosis factor (TNF and interferon-γ (IFN-γ. Here, we show that NFATp-deficient (NFATp(-/- mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-γ transcription and protein expression in naïve or total CD4(+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC. The rapid mortality and disease severity observed in MTb-infected NFATp(-/- mice is associated with dysregulated production of TNF and IFN-γ in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp(-/- mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-γ in T cells.

  18. IFN regulatory factor 8 is a key constitutive determinant of the morphological and molecular properties of microglia in the CNS.

    Directory of Open Access Journals (Sweden)

    Carsten Minten

    Full Text Available IFN regulatory factor (IRF 8 is a transcription factor that has a key role in the cellular response to IFN-γ and is pivotal in myeloid cell differentiation. Whether IRF8 plays a role in the development and function of microglia, the tissue-resident myeloid cells of the brain, is unknown. Here, we show IRF8 is a constitutively produced nuclear factor in microglia, which suggested that IRF8 might also be a key homeostatic transcriptional determinant of the microglial cell phenotype. In support of this, in mice with a targeted disruption of the IRF8 gene, microglia were increased in number and showed gross alterations in morphology and surface area. In situ analysis of some key myeloid markers revealed that IRF8-deficient microglia had significantly reduced levels of Iba1, but increased levels of CD206 (mannose receptor and F4/80 as well as increased tomato lectin binding. Analysis of microglia ex vivo revealed IRF8-deficient microglia had significantly increased levels of CD45, CD11b and F4/80, but significantly decreased levels of the chemokine receptors CCR2, CCR5 and CX3CR1. The known involvement of some of these molecular markers in membrane dynamics and phagocytosis led us to examine the phagocytic capacity of cultured IRF8-deficient microglia, however, this was found to be similar to wild type microglia. We conclude IRF8 is a constitutively produced nuclear factor in resident microglia of the CNS being a crucial transcriptional determinant of the phenotype of these cells in the healthy brain.

  19. Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS.

    Science.gov (United States)

    Westergaard, Niels; Waagepetersen, Helle S; Belhage, Bo; Schousboe, Arne

    2017-01-05

    Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and (13)C-NMR to investigate metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles of citrate in physiological and pathophysiological processes in the CNS. An interesting feature of citrate is its ability to chelate Ca(2+), Mg(2+) and Zn(2+)and thereby playing a pivotal role as an endogenous modulator of glutamate receptors and in particular the NMDA subtypes of these receptors in the CNS. Besides its presence in cerebrospinal fluid (CSF) citrate is also found in high amounts in prostate fluid reaching concentrations as high as 180 mM and here Zn(2+) seems also to play an important role, which makes prostate cells interesting for comparison of features of citrate and Zn(2+) between these cells and cells in the CNS.

  20. Supporting Children and Families: Communities, Schools, Employers Play Key Roles. Growing Up Well. Focus on Prevention.

    Science.gov (United States)

    Barthauer, Linda; Halfon, Neal

    This report, eighth and last in a series, discusses the important role community groups and leaders, schools, and employers play in providing children and parents support and encouragement. It reports the opinions of California adults, expressed in a survey conducted by the California Center for Health Improvement (CCHI), about a variety of issues…

  1. Regulatory Innovation, Mating Disruption and 4-Play(TM) in New Zealand.

    Science.gov (United States)

    Suckling, David Maxwell; El-Sayed, Ashraf M; Walker, James T S

    2016-07-01

    Straight-chained lepidopteran pheromones are now regulated under a group standard in New Zealand, which is generic for moth pheromone products of similar low risk, under the Hazardous Substances and New Organisms Act (1996). This means that compliant new pheromone products can be developed and commercialized with low regulatory requirements. This encourages innovation and supports fruit industries interested in meeting export phytosanitary standards, while targeting low or nil residues of pesticides. Changes to pheromone blends for reasons such as technical improvements or variations in pest species composition in different crops can be made with minimal regulatory involvement. We illustrate how this system now operates with a four species mating disruption product commercialized in 2012. The odors involved in "4-Play™" consist of a range of components used by codling moth (Cydia pomonella), lightbrown apple moth (Epiphyas postvittana), green-headed leafroller (Planotortrix octo), and brown-headed leafroller (Ctenopseustis obliquana). The development of 4-Play™ illustrates how mating disruption of insects can support industry goals.

  2. Cross-phosphorylation of bacterial serine/threonine and tyrosine protein kinases on key regulatory residues

    Directory of Open Access Journals (Sweden)

    Lei eShi

    2014-09-01

    Full Text Available Bacteria possess protein serine/threonine and tyrosine kinases which resemble eukaryal kinases in their capacity to phosphorylate multiple substrates. We hypothesized that the analogy might extend further, and bacterial kinases may also undergo mutual phosphorylation and activation, which is currently considered as a hallmark of eukaryal kinase networks. In order to test this hypothesis, we explored the capacity of all members of four different classes of serine/threonine and tyrosine kinases present in the firmicute model organism Bacillus subtilis to phosphorylate each other in vitro and interact with each other in vivo. The interactomics data suggested a high degree of connectivity among all types of kinases, while phosphorylation assays revealed equally wide-spread cross-phosphorylation events. Our findings suggest that the Hanks-type kinases PrkC, PrkD and YabT exhibit the highest capacity to phosphorylate other B. subtilis kinases, while the BY-kinase PtkA and the two-component-like kinases RsbW and SpoIIAB show the highest propensity to be phosphorylated by other kinases. Analysis of phosphorylated residues on several selected recipient kinases suggests that most cross-phosphorylation events concern key regulatory residues. Therefore, cross-phosphorylation events are very likely to influence the capacity of recipient kinases to phosphorylate substrates downstream in the signal transduction cascade. We therefore conclude that bacterial serine/threonine and tyrosine kinases probably engage in a network-type behavior previously described only in eukaryal cells.

  3. Monocyte chemoattractant protein-1 plays a key role in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Dong Li; Guoliang Liu

    2005-01-01

    Type 1 diabetes is an autoimmune disease resulting from the selective destruction of β cells in the pancreatic islets.In both human and rodent models of type 1 diabetes, the clinical disease is preceded by a progressive mononuclear cell invasion of the pancreatic islets (insulitis). In the early stage of insulitis, the major components are monocyte/macrophages, and the recruitment of mononuclear cells is a critical step in the pathogenesis of the type 1 diabetes. Studies have revealed that Monocyte chemoattractant protein-1(MCP-1)specifically recruits monocytes/macrophages into pancreas and plays an important role in the development of insulitis and diabetes.

  4. The PICALM protein plays a key role in iron homeostasis and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Paula B Scotland

    Full Text Available The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM's function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation, all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases.

  5. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis

    Science.gov (United States)

    Xie, Wanqing; Zhou, Lijiang; Li, Shan; Hui, Tianqian; Chen, Di

    2015-01-01

    Spondyloarthritis (SpA) is a group of diseases consisting of psoriatic arthritis (PsA), reactive arthritis, arthritis related to inflammatory bowel disease (a subgroup of juvenile idiopathic arthritis), and ankylosing spondylitis (the prototype of SpA). Axial bone formation and the combination of concurrent erosion and new bone formation are specific characteristics of SpA disease. The use of anti-proinflammatory cytokines, such as inhibitors of tumor necrosis factor α (TNF-α), appears to be the greatest advance in the treatment of SpA over the past 20 years. However, TNF-α blockers do not halt new bone formation. Recent clinical observations and animal studies demonstrate that Wnt signaling proteins and natural Wnt inhibitors, such as DKK1 and sclerostin, are likely to play important roles in the process of ankylosis in SpA, and could potentially serve as therapeutic targets for the treatment of SpA. PMID:26629686

  6. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis.

    Science.gov (United States)

    Xie, Wanqing; Zhou, Lijiang; Li, Shan; Hui, Tianqian; Chen, Di

    2016-01-01

    Spondyloarthritis (SpA) is a group of diseases consisting of psoriatic arthritis (PsA), reactive arthritis, arthritis related to inflammatory bowel disease (a subgroup of juvenile idiopathic arthritis), and ankylosing spondylitis (the prototype of SpA). Axial bone formation and the combination of concurrent erosion and new bone formation are specific characteristics of SpA disease. The use of antiproinflammatory cytokines, such as inhibitors of tumor necrosis factor α (TNF-α), appears to be the greatest advance in the treatment of SpA over the past 20 years. However, TNF-α blockers do not halt new bone formation. Recent clinical observations and animal studies demonstrate that Wnt signaling proteins and natural Wnt inhibitors, such as DKK1 and sclerostin, are likely to play important roles in the process of ankylosis in SpA, and could potentially serve as therapeutic targets for the treatment of SpA.

  7. XHAPLN3 plays a key role in cardiogenesis by maintaining the hyaluronan matrix around heart anlage.

    Science.gov (United States)

    Ito, Yuzuru; Seno, Satsuki; Nakamura, Hiroaki; Fukui, Akimasa; Asashima, Makoto

    2008-07-01

    Hyaluronan matrix plays an important role during vertebrate cardiogenesis. Transcripts for the hyaluronan synthase Has2 gene are expressed in heart anlage, and disruption of either Has2 or versican, a hyaluronan matrix component, abrogates normal cardiac morphogenesis. However, the mechanisms by which hyaluronan matrix contributes to early heart development are largely unknown. Here we show that Xenopus hyaluronan and proteoglycan-binding link protein 3 (XHAPLN3) helps to maintain hyaluronan matrix around the cardiac anlage, and thereby contribute to cardiogenesis. XHAPLN3 mRNA transcript localization overlapped with the mRNA expression of both Xhas2 and Xversican at the heart anlage of early tailbud (stage 23) embryos. Furthermore, knockdown of XHAPLN3 or Xhas2 with morpholino antisense oligos caused a heart deficiency in developing tadpoles. Our results show when and how components of the hyaluronan matrix function in cardiogenesis, improving our understanding of how extracellular matrix participates in embryogenesis.

  8. Bromodomain protein Brd4 plays a key role in Merkel cell polyomavirus DNA replication.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Merkel cell polyomavirus (MCV or MCPyV is the first human polyomavirus to be definitively linked to cancer. The mechanisms of MCV-induced oncogenesis and much of MCV biology are largely unexplored. In this study, we demonstrate that bromodomain protein 4 (Brd4 interacts with MCV large T antigen (LT and plays a critical role in viral DNA replication. Brd4 knockdown inhibits MCV replication, which can be rescued by recombinant Brd4. Brd4 colocalizes with the MCV LT/replication origin complex in the nucleus and recruits replication factor C (RFC to the viral replication sites. A dominant negative inhibitor of the Brd4-MCV LT interaction can dissociate Brd4 and RFC from the viral replication complex and abrogate MCV replication. Furthermore, obstructing the physiologic interaction between Brd4 and host chromatin with the chemical compound JQ1(+ leads to enhanced MCV DNA replication, demonstrating that the role of Brd4 in MCV replication is distinct from its role in chromatin-associated transcriptional regulation. Our findings demonstrate mechanistic details of the MCV replication machinery; providing novel insight to elucidate the life cycle of this newly discovered oncogenic DNA virus.

  9. The Nicotinic Acetylcholine Receptor α5 Subunit Plays a Key Role in Attention Circuitry and Accuracy

    Science.gov (United States)

    Bailey, Craig D. C.; De Biasi, Mariella; Fletcher, Paul J.; Lambe, Evelyn K.

    2010-01-01

    Stimulation of the prefrontal cortex by acetylcholine is critical for attention; however, the cellular mechanisms underlying its influence on attention pathways within the brain are not well understood. Pyramidal neurons in layer VI of the prefrontal cortex are believed to play an important role in this process because they are excited by acetylcholine and provide a major source of feedback projections to the thalamus. Here, we show using whole-cell electrophysiology that the relatively rare α5 subunit of the nicotinic acetylcholine receptor powerfully enhances nicotinic currents in layer VI pyramidal neurons in prefrontal cortical brain slices from adult mice. In addition, behavioral experiments using the five-choice serial reaction time test show that the presence of the nicotinic receptor α5 subunit also increases the accuracy of adult mice on this visual attention task under highly demanding conditions. Together, these findings demonstrate a novel and important role for the nicotinic receptor α5 subunit in adult brain circuitry required for attentional performance. PMID:20610759

  10. Autocrine abscisic acid plays a key role in quartz-induced macrophage activation.

    Science.gov (United States)

    Magnone, Mirko; Sturla, Laura; Jacchetti, Emanuela; Scarfì, Sonia; Bruzzone, Santina; Usai, Cesare; Guida, Lucrezia; Salis, Annalisa; Damonte, Gianluca; De Flora, Antonio; Zocchi, Elena

    2012-03-01

    Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E(2) (PGE(2)) and tumor necrosis factor α (TNF-α). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca(2+) influx resulting in NFκ B nuclear translocation and PGE(2) and TNF-α release (3-, 2-, and 3.5-fold increase, respectively, compared to control, unstimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NFκ B nuclear translocation and PGE(2) and TNF-α release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy.

  11. Parental provisioning behaviour plays a key role in linking personality with reproductive success.

    Science.gov (United States)

    Mutzel, A; Dingemanse, N J; Araya-Ajoy, Y G; Kempenaers, B

    2013-08-07

    Repeatable behavioural traits ('personality') have been shown to covary with fitness, but it remains poorly understood how such behaviour-fitness relationships come about. We applied a multivariate approach to reveal the mechanistic pathways by which variation in exploratory and aggressive behaviour is translated into variation in reproductive success in a natural population of blue tits, Cyanistes caeruleus. Using path analysis, we demonstrate a key role for provisioning behaviour in mediating the link between personality and reproductive success (number of fledged offspring). Aggressive males fed their nestlings at lower rates than less aggressive individuals. At the same time, their low parental investment was associated with increased female effort, thereby positively affecting fledgling production. Whereas male exploratory behaviour was unrelated to provisioning behaviour and reproductive success, fast-exploring females fed their offspring at higher rates and initiated breeding earlier, thus increasing reproductive success. Our findings provide strong support for specific mechanistic pathways linking components of behavioural syndromes to reproductive success. Importantly, relationships between behavioural phenotypes and reproductive success were obscured when considering simple bivariate relationships, underlining the importance of adopting multivariate views and statistical tools as path analysis to the study of behavioural evolution.

  12. The Aquilegia FRUITFULL-like genes play key roles in leaf morphogenesis and inflorescence development.

    Science.gov (United States)

    Pabón-Mora, Natalia; Sharma, Bharti; Holappa, Lynn D; Kramer, Elena M; Litt, Amy

    2013-04-01

    The APETALA1/FRUITFULL (AP1/FUL) MADS box transcription factors are best known for the role of AP1 in Arabidopsis sepal and petal identity, the canonical A function of the ABC model of flower development. However, this gene lineage underwent multiple duplication events during angiosperm evolution, providing different taxa with unique gene complements. One such duplication correlates with the origin of the core eudicots, and produced the euAP1 and euFUL clades. Together, euAP1 and euFUL genes function in proper floral meristem identity and repression of axillary meristem growth. Independently, euAP1 genes function in floral meristem and sepal identity, whereas euFUL genes control phase transition, cauline leaf growth and fruit development. To investigate the impact of the core eudicot duplication on the functional diversification of this gene lineage, we studied the role of pre-duplication FUL-like genes in columbine (Aquilegia coerulea). Our results show that AqcFL1 genes are broadly expressed in vegetative and reproductive meristems, leaves and flowers. Virus-induced gene silencing of the loci results in plants with increased branching, shorter inflorescences with fewer flowers, and dramatic changes in leaf shape and complexity. However, aqcfl1 plants have normal flowers and fruits. Our results show that, in contrast to characterized AP1/FUL genes, the AqcFL1 loci are either genetically redundant or have been decoupled from the floral genetic program, and play a major role in leaf morphogenesis. We analyze the results in the context of the core eudicot duplication, and discuss the implications of our findings in terms of the genetic regulation of leaf morphogenesis in Aquilegia and other flowering plants.

  13. Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

    Directory of Open Access Journals (Sweden)

    Facciolo Rosa

    2011-01-01

    Full Text Available Abstract Background Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB and hibernating (HIB hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR, 3-(+-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators. Results From the behavioral results it appears that the two glutamatergic compounds exerted distinct effects. In the first case local infusion of basolateral complexes (BLA with NMDAR antagonist caused very great (p Conclusion We conclude that predominant drinking events evoked by glutamatergic mechanisms, in the presence of prevalently down regulated levels of NR1/2A of some telencephalic and hypothalamic areas appear to constitute an important neuronal switch at least during arousal stage of hibernation. The establishment of the type of glutamatergic subtypes that are linked to successful hibernating states, via drinking stimuli, may have useful bearings toward sleeping disorders.

  14. Regulatory Lymphocytes Are Key Factors in MHC-Independent Resistance to EAE

    Directory of Open Access Journals (Sweden)

    Nieves Marín

    2014-01-01

    Full Text Available Background and Objectives. Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE, an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE. Methods. For EAE induction, female C57BL/6 (susceptible strain and CD1 (resistant outbred strain showing heterogeneous MHC antigens mice were immunized with the 35–55 peptide of myelin oligodendrocyte glycoprotein (MOG35−55. We studied T cell proliferation, regulatory and effector cell subpopulations, intracellular and serum cytokine patterns, and titers of anti-MOG serum antibodies. Results. Upon immunization with MOG35−55, T lymphocytes from susceptible mice but not that of resistant strain were capable of proliferating when stimulated with MOG35−55. Accordingly, resistant mice experienced a rise in regulatory B cells (P=0.001 and, to a lower extent, in regulatory T cells (P=0.02 compared with C57BL/6 susceptible mice. As a consequence, MOG35−55-immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both IFN-gamma (P=0.02 and IL-17 (P=0.009 and higher serum levels of IL-17 (P=0.04 than resistant mice. Conclusions. Expansion of regulatory B and T cells contributes to the induction of resistance to EAE by an MHC-independent mechanism.

  15. Regulatory Lymphocytes Are Key Factors in MHC-Independent Resistance to EAE

    Science.gov (United States)

    Marín, Nieves; Mecha, Miriam; Espejo, Carmen; Mestre, Leyre; Eixarch, Herena; Montalban, Xavier; Álvarez-Cermeño, José C.; Guaza, Carmen; Villar, Luisa M.

    2014-01-01

    Background and Objectives. Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE), an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE. Methods. For EAE induction, female C57BL/6 (susceptible strain) and CD1 (resistant outbred strain showing heterogeneous MHC antigens) mice were immunized with the 35–55 peptide of myelin oligodendrocyte glycoprotein (MOG35−55). We studied T cell proliferation, regulatory and effector cell subpopulations, intracellular and serum cytokine patterns, and titers of anti-MOG serum antibodies. Results. Upon immunization with MOG35−55, T lymphocytes from susceptible mice but not that of resistant strain were capable of proliferating when stimulated with MOG35−55. Accordingly, resistant mice experienced a rise in regulatory B cells (P = 0.001) and, to a lower extent, in regulatory T cells (P = 0.02) compared with C57BL/6 susceptible mice. As a consequence, MOG35−55-immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both IFN-gamma (P = 0.02) and IL-17 (P = 0.009) and higher serum levels of IL-17 (P = 0.04) than resistant mice. Conclusions. Expansion of regulatory B and T cells contributes to the induction of resistance to EAE by an MHC-independent mechanism. PMID:24868560

  16. Informatic analysis for hidden pulse attack exploiting spectral characteristics of optics in plug-and-play quantum key distribution system

    Science.gov (United States)

    Ko, Heasin; Lim, Kyongchun; Oh, Junsang; Rhee, June-Koo Kevin

    2016-10-01

    Quantum channel loopholes due to imperfect implementations of practical devices expose quantum key distribution (QKD) systems to potential eavesdropping attacks. Even though QKD systems are implemented with optical devices that are highly selective on spectral characteristics, information theory-based analysis about a pertinent attack strategy built with a reasonable framework exploiting it has never been clarified. This paper proposes a new type of trojan horse attack called hidden pulse attack that can be applied in a plug-and-play QKD system, using general and optimal attack strategies that can extract quantum information from phase-disturbed quantum states of eavesdropper's hidden pulses. It exploits spectral characteristics of a photodiode used in a plug-and-play QKD system in order to probe modulation states of photon qubits. We analyze the security performance of the decoy-state BB84 QKD system under the optimal hidden pulse attack model that shows enormous performance degradation in terms of both secret key rate and transmission distance.

  17. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

    Directory of Open Access Journals (Sweden)

    Logan Richard M

    2010-03-01

    Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

  18. The mitochondrial PPR protein LOVASTATIN INSENSITIVE 1 plays regulatory roles in cytosolic and plastidial isoprenoid biosynthesis through RNA editing.

    Science.gov (United States)

    Tang, Jianwei; Kobayashi, Keiko; Suzuki, Masashi; Matsumoto, Shogo; Muranaka, Toshiya

    2010-02-01

    Unlike animals, plants synthesize isoprenoids via two pathways, the cytosolic mevalonate (MVA) pathway and the plastidial 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway. Little information is known about the mechanisms that regulate these complex biosynthetic networks over multiple organelles. To understand such regulatory mechanisms of the biosynthesis of isoprenoids in plants, we previously characterized the Arabidopsis mutant, lovastatin insensitive 1 (loi1), which is resistant to lovastatin and clomazone, specific inhibitors of the MVA and MEP pathways, respectively. LOI1 encodes a pentatricopeptide repeat (PPR) protein localized in mitochondria that is thought to have RNA binding ability and function in post-transcriptional regulation of mitochondrial gene expression. LOI1 belongs to the DYW subclass of PPR proteins, which is hypothesized to be correlated with RNA editing. As a result of analysis of RNA editing of mitochondrial genes in loi1, a defect in RNA editing of three genes, nad4, ccb203 and cox3, was identified in loi1. These genes are related to the respiratory chain. Wild type (WT) treated with some respiration inhibitors mimicked the loi1 phenotype. Interestingly, HMG-CoA reductase activity of WT treated with lovastatin combined with antimycin A, an inhibitor of complex III in the respiratory chain, was higher than that of WT treated with only lovastatin, despite the lack of alteration of transcript or protein levels of HMGR. These results suggest that HMGR enzyme activity is regulated through the respiratory cytochrome pathway. Although various mechanisms exist for isoprenoid biosynthesis, our studies demonstrate the novel possibility that mitochondrial respiration plays potentially regulatory roles in isoprenoid biosynthesis.

  19. mRNA translation during oocyte maturation plays a key role in development of primordial germ cells in Xenopus embryos

    Indian Academy of Sciences (India)

    Bahman Zeynali; Keith E Dixon

    2004-09-01

    It is believed that cytoplasmic localization in the egg is necessary for development of primordial germ cells (PGCs) in Xenopus embryos. In this study, we sought to determine if translation of maternal mRNA during oocyte maturation is involved in the development of PGCs. Donor oocytes were collected from both stimulated (those who receive gonadotropin) and unstimulated females, artificially matured and fertilized using a host transfer technique. Using chloramphenicol (50 M and 500 M RNA), RNA translation was inhibited during oocyte maturation. Our results showed that in unstimulated embryos treated with 50 M chloramphenicol, there was a significant reduction in the number of PGCs reaching genital ridges. In stimulated embryos, however, the number of PGCs was unchanged unless a higher concentration (500 M) of chloramphenicol was used. From these results it is suggested that maternal mRNA translation during oocyte maturation plays a key role in development of PGCs.

  20. gga-miR-375 plays a key role in tumorigenesis post subgroup J avian leukosis virus infection.

    Directory of Open Access Journals (Sweden)

    Hongxin Li

    Full Text Available Avian leukosis is a neoplastic disease caused in part by subgroup J avian leukosis virus J (ALV-J. Micro ribonucleic acids (miRNAs play pivotal oncogenic and tumour-suppressor roles in tumour development and progression. However, little is known about the potential role of miRNAs in avian leukosis tumours. We have found a novel tumour-suppressor miRNA, gga-miR-375, associated with avian leukosis tumorigenesis by miRNA microarray in a previous report. We have also previously studied the biological function of gga-miR-375; Overexpression of gga-miR-375 significantly inhibited DF-1 cell proliferation, and significantly reduced the expression of yes-associated protein 1 (YAP1 by repressing the activity of a luciferase reporter carrying the 3'-untranslated region of YAP1. This indicates that gga-miR-375 is frequently downregulated in avian leukosis by inhibiting cell proliferation through YAP1 oncogene targeting. Overexpression of gga-miR-375 markedly promoted serum starvation induced apoptosis, and there may be the reason why the tumour cycle is so long in the infected chickens. In vivo assays, gga-miR-375 was significantly downregulated in chicken livers 20 days after infection with ALV-J, and YAP1 was significantly upregulated 20 days after ALV-J infection (P<0.05. We also found that expression of cyclin E, an important regulator of cell cycle progression, was significantly upregulated (P<0.05. Drosophila inhibitor of apoptosis protein 1 (DIAP1, which is related to caspase-dependent apoptosis, was also significantly upregulated after infection. Our data suggests that gga-miR-375 may function as a tumour suppressor thereby regulating cancer cell proliferation and it plays a key role in avian leukosis tumorigenesis.

  1. Clusterin in the protein corona plays a key role in the stealth effect of nanoparticles against phagocytes.

    Science.gov (United States)

    Aoyama, Michihiko; Hata, Katsutomo; Higashisaka, Kazuma; Nagano, Kazuya; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2016-10-28

    In biological fluids, nanoparticles interact with biological components such as proteins, and a layer called the "protein corona" forms around the nanoparticles. It is believed that the composition of the protein corona affects the cellular uptake and in vivo biodistribution of nanoparticles; however, the key proteins of the protein corona that control the biological fate of nanoparticles remain unclear. Recently, it was reported that clusterin binding to pegylated nanoparticles is important for the stealth effect of pegylated nanoparticles in phagocytes. However, the effect of clusterin on non-pegylated nanoparticles is unknown, although it is known that clusterin is present in the protein corona of non-pegylated nanoparticles. Here, we assessed the stealth effect of clusterin in the corona of non-pegylated silver nanoparticles and silica nanoparticles. We found that serum- and plasma-protein corona inhibited the cellular uptake of silver nanoparticles and silica nanoparticles in phagocytes and that the plasma-protein corona showed a greater stealth effect compared with the serum-protein corona. Clusterin was present in both the serum- and plasma-protein corona, but was present at a higher level in the plasma-protein corona than in the serum-protein corona. Clusterin binding to silver nanoparticles and silica nanoparticles suppressed the cellular uptake of nanoparticles in human macrophage-like cells (THP-1 cells). Although further studies are required to determine how clusterin suppresses non-specific cellular uptake in phagocytes, our data suggest that clusterin plays a key role in the stealth effect of not only pegylated nanoparticles but also non-pegylated nanoparticles.

  2. Regulatory Shifts in Plastid Transcription Play a Key Role in Morphological Conversions of Plastids during Plant Development

    Science.gov (United States)

    Liebers, Monique; Grübler, Björn; Chevalier, Fabien; Lerbs-Mache, Silva; Merendino, Livia; Blanvillain, Robert; Pfannschmidt, Thomas

    2017-01-01

    Plastids display a high morphological and functional diversity. Starting from an undifferentiated small proplastid, these plant cell organelles can develop into four major forms: etioplasts in the dark, chloroplasts in green tissues, chromoplasts in colored flowers and fruits and amyloplasts in roots. The various forms are interconvertible into each other depending on tissue context and respective environmental condition. Research of the last two decades uncovered that each plastid type contains its own specific proteome that can be highly different from that of the other types. Composition of these proteomes largely defines the enzymatic functionality of the respective plastid. The vast majority of plastid proteins is encoded in the nucleus and must be imported from the cytosol. However, a subset of proteins of the photosynthetic and gene expression machineries are encoded on the plastid genome and are transcribed by a complex transcriptional apparatus consisting of phage-type nuclear-encoded RNA polymerases and a bacterial-type plastid-encoded RNA polymerase. Both types recognize specific sets of promoters and transcribe partly over-lapping as well as specific sets of genes. Here we summarize the current knowledge about the sequential activity of these plastid RNA polymerases and their relative activities in different types of plastids. Based on published plastid gene expression profiles we hypothesize that each conversion from one plastid type into another is either accompanied or even preceded by significant changes in plastid transcription suggesting that these changes represent important determinants of plastid morphology and protein composition and, hence, the plastid type. PMID:28154576

  3. Metabolomic Analysis of Key Regulatory Metabolites in Hepatitis C Virus–infected Tree Shrews*

    Science.gov (United States)

    Sun, Hui; Zhang, Aihua; Yan, Guangli; Piao, Chengyu; Li, Weiyun; Sun, Chang; Wu, Xiuhong; Li, Xinghua; Chen, Yun; Wang, Xijun

    2013-01-01

    Metabolomics is a powerful new technology that allows the assessment of global low-molecular-weight metabolites in a biological system and which shows great potential in biomarker discovery. Analysis of the key metabolites in body fluids has become an important part of improving the diagnosis, prognosis, and therapy of diseases. Hepatitis C virus (HCV) is a major leading cause of liver disease worldwide and a serious burden on public health. However, the lack of a small-animal model has hampered the analysis of HCV pathogenesis. We hypothesize that an animal model (Tupaia belangeri chinensis) of HCV would produce a unique characterization of metabolic phenotypes. Ultra-performance liquid-chromatography/electrospray ionization-SYNAPT-high-definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) coupled with pattern recognition methods and system analysis was carried out to obtain comprehensive metabolomics profiling and pathways of large biological data sets. Taurine, hypotaurine, ether lipid, glycerophospholipid, arachidonic acid, tryptophan, and primary bile acid metabolism pathways were acutely perturbed, and 38 differential metabolites were identified. More important, five metabolite markers were selected via the “significance analysis for microarrays” method as the most discriminant and interesting biomarkers that were effective for the diagnosis of HCV. Network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Integrated network analysis of the key metabolites yields highly related signaling pathways associated with the differentially expressed proteins, which suggests that the creation of new treatment paradigms targeting and activating these networks in their entirety, rather than single proteins, might be necessary for controlling and treating HCV efficiently. PMID:23264353

  4. Metabolomic analysis of key regulatory metabolites in hepatitis C virus-infected tree shrews.

    Science.gov (United States)

    Sun, Hui; Zhang, Aihua; Yan, Guangli; Piao, Chengyu; Li, Weiyun; Sun, Chang; Wu, Xiuhong; Li, Xinghua; Chen, Yun; Wang, Xijun

    2013-03-01

    Metabolomics is a powerful new technology that allows the assessment of global low-molecular-weight metabolites in a biological system and which shows great potential in biomarker discovery. Analysis of the key metabolites in body fluids has become an important part of improving the diagnosis, prognosis, and therapy of diseases. Hepatitis C virus (HCV) is a major leading cause of liver disease worldwide and a serious burden on public health. However, the lack of a small-animal model has hampered the analysis of HCV pathogenesis. We hypothesize that an animal model (Tupaia belangeri chinensis) of HCV would produce a unique characterization of metabolic phenotypes. Ultra-performance liquid-chromatography/electrospray ionization-SYNAPT-high-definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) coupled with pattern recognition methods and system analysis was carried out to obtain comprehensive metabolomics profiling and pathways of large biological data sets. Taurine, hypotaurine, ether lipid, glycerophospholipid, arachidonic acid, tryptophan, and primary bile acid metabolism pathways were acutely perturbed, and 38 differential metabolites were identified. More important, five metabolite markers were selected via the "significance analysis for microarrays" method as the most discriminant and interesting biomarkers that were effective for the diagnosis of HCV. Network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Integrated network analysis of the key metabolites yields highly related signaling pathways associated with the differentially expressed proteins, which suggests that the creation of new treatment paradigms targeting and activating these networks in their entirety, rather than single proteins, might be necessary for controlling and treating HCV efficiently.

  5. CodY orchestrates the expression of virulence determinants in emetic Bacillus cereus by impacting key regulatory circuits.

    Science.gov (United States)

    Frenzel, Elrike; Doll, Viktoria; Pauthner, Matthias; Lücking, Genia; Scherer, Siegfried; Ehling-Schulz, Monika

    2012-07-01

    Bacillus cereus causes gastrointestinal diseases and local and systemic infections elicited by the depsipeptide cereulide, enterotoxins, phospholipases, cytolysins and proteases. The PlcR-PapR quorum sensing system activates the expression of several virulence factors, whereas the Spo0A-AbrB regulatory circuit partially controls the plasmid-borne cereulide synthetase (ces) operon. Here, we show that CodY, a nutrient-responsive regulator of Gram-positive bacteria, has a profound effect on both regulatory systems, which have been assumed to operate independently of each other. Deletion of codY resulted in downregulation of virulence genes belonging to the PlcR regulon and a concomitant upregulation of the ces genes. CodY was found to be a repressor of the ces operon, but did not interact with the promoter regions of PlcR-dependent virulence genes in vitro, suggesting an indirect regulation of the latter. Furthermore, CodY binds to the promoter of the immune inhibitor metalloprotease InhA1, demonstrating that CodY directly links B. cereus metabolism to virulence. In vivo studies using a Galleria mellonella infection model, showed that the codY mutant was substantially attenuated, highlighting the importance of CodY as a key regulator of pathogenicity. Our results demonstrate that CodY profoundly modulates the virulence of B. cereus, possibly controlling the development of pathogenic traits in suitable host environments.

  6. Global profiling of rice and poplar transcriptomes highlights key conserved circadian-controlled pathways and cis-regulatory modules.

    Directory of Open Access Journals (Sweden)

    Sergei A Filichkin

    Full Text Available BACKGROUND: Circadian clocks provide an adaptive advantage through anticipation of daily and seasonal environmental changes. In plants, the central clock oscillator is regulated by several interlocking feedback loops. It was shown that a substantial proportion of the Arabidopsis genome cycles with phases of peak expression covering the entire day. Synchronized transcriptome cycling is driven through an extensive network of diurnal and clock-regulated transcription factors and their target cis-regulatory elements. Study of the cycling transcriptome in other plant species could thus help elucidate the similarities and differences and identify hubs of regulation common to monocot and dicot plants. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of oligonucleotide microarrays and data mining pipelines, we examined daily rhythms in gene expression in one monocotyledonous and one dicotyledonous plant, rice and poplar, respectively. Cycling transcriptomes were interrogated under different diurnal (driven and circadian (free running light and temperature conditions. Collectively, photocycles and thermocycles regulated about 60% of the expressed nuclear genes in rice and poplar. Depending on the condition tested, up to one third of oscillating Arabidopsis-poplar-rice orthologs were phased within three hours of each other suggesting a high degree of conservation in terms of rhythmic gene expression. We identified clusters of rhythmically co-expressed genes and searched their promoter sequences to identify phase-specific cis-elements, including elements that were conserved in the promoters of Arabidopsis, poplar, and rice. CONCLUSIONS/SIGNIFICANCE: Our results show that the cycling patterns of many circadian clock genes are highly conserved across poplar, rice, and Arabidopsis. The expression of many orthologous genes in key metabolic and regulatory pathways is diurnal and/or circadian regulated and phased to similar times of day. Our results confirm

  7. Upregulation of NOXA by 10-Hydroxycamptothecin plays a key role in inducing fibroblasts apoptosis and reducing epidural fibrosis

    Directory of Open Access Journals (Sweden)

    Jihang Dai

    2017-01-01

    the first to demonstrate that upregulation of NOXA by HCPT plays a key role in inducing fibroblast apoptosis and in reducing epidural fibrosis. These findings might provide a potential therapeutic target for preventing epidural fibrosis following laminectomy.

  8. Early Childhood Curriculum Development: The Role of Play in Building Self-Regulatory Capacity in Young Children

    Science.gov (United States)

    Kroll, Linda R.

    2017-01-01

    This case study examines the development of self-regulation, socially, cognitively and emotionally, through the use of play in the curriculum in five preschool classrooms for children ages 2-5 years old at a university laboratory school. Five teachers were interviewed about their deliberate use of play to support the development of self-regulation…

  9. A Single Host-Derived Glycan Impacts Key Regulatory Nodes of Symbiont Metabolism in a Coevolved Mutualism.

    Science.gov (United States)

    Pan, Min; Schwartzman, Julia A; Dunn, Anne K; Lu, Zuhong; Ruby, Edward G

    2015-07-14

    Most animal-microbe mutualistic associations are characterized by nutrient exchange between the partners. When the host provides the nutrients, it can gain the capacity to shape its microbial community, control the stability of the interaction, and promote its health and fitness. Using the bioluminescent squid-vibrio model, we demonstrate how a single host-derived glycan, chitin, regulates the metabolism of Vibrio fischeri at key points in the development and maintenance of the symbiosis. We first characterized the pathways for catabolism of chitin sugars by V. fischeri, demonstrating that the Ccr-dependent phosphoenolpyruvate-pyruvate phosphotransferase system (PTS) prioritizes transport of these sugars in V. fischeri by blocking the uptake of non-PTS carbohydrates, such as glycerol. Next, we found that PTS transport of chitin sugars into the bacterium shifted acetate homeostasis toward a net excretion of acetate and was sufficient to override an activation of the acetate switch by AinS-dependent quorum sensing. Finally, we showed that catabolism of chitin sugars decreases the rate of cell-specific oxygen consumption. Collectively, these three metabolic functions define a physiological shift that favors fermentative growth on chitin sugars and may support optimal symbiont luminescence, the functional basis of the squid-vibrio mutualism. Host-derived glycans have recently emerged as a link between symbiont nutrition and innate immune function. Unfortunately, the locations at which microbes typically access host-derived glycans are inaccessible to experimentation and imaging, and they take place in the context of diverse microbe-microbe interactions, creating a complex symbiotic ecology. Here we describe the metabolic state of a single microbial symbiont in a natural association with its coevolved host and, by doing so, infer key points at which a host-controlled tissue environment might regulate the physiological state of its symbionts. We show that the presence of

  10. First Chinese public hospital wins Joint Commission International accreditation: the Health Information Department played a key role in the process.

    Science.gov (United States)

    Shaffer, Audrey; Jun, Cheng Li

    2008-07-01

    Sir Run Run Shaw Hospital in Hangzhou, China spent five years preparing for a Joint Commission International accreditation survey. In March 2007 it became the first public hospital on the Chinese mainland to attain international accreditation. The Health Information Department, managed according to Western standards, played an integral role in preparing the hospital for the survey.

  11. Novel two-component regulatory systems play a role in biofilm formation of Lactobacillus reuteri rodent isolate 100-23.

    Science.gov (United States)

    Su, Marcia Shu-Wei; Gänzle, Michael G

    2014-04-01

    This study characterized the two-component regulatory systems encoded by bfrKRT and cemAKR, and assessed their influence on biofilm formation by Lactobacillus reuteri 100-23. A method for deletion of multiple genes was employed to disrupt the genetic loci of two-component systems. The operons bfrKRT and cemAKR showed complementary organization. Genes bfrKRT encode a histidine kinase, a response regulator and an ATP-binding cassette-type transporter with a bacteriocin-processing peptidase domain, respectively. Genes cemAKR code for a signal peptide, a histidine kinase and a response regulator, respectively. Deletion of single or multiple genes in the operons bfrKRT and cemAKR did not affect cell morphology, growth or the sensitivity to various stressors. However, gene disruption affected biofilm formation; this effect was dependent on the carbon source. Deletion of bfrK or cemA increased sucrose-dependent biofilm formation in vitro. Glucose-dependent biofilm formation was particularly increased by deletion of cemK. The expression of cemK and cemR was altered by deletion of bfrK, indicating cross-talk between these two regulatory systems. These results may contribute to our understanding of the genetic factors related to the biofilm formation and competitiveness of L. reuteri in intestinal ecosystems.

  12. The mitochondrial Na+/Ca2+ exchanger plays a key role in the control of cytosolic Ca2+ oscillations

    OpenAIRE

    Hernández-San Miguel, Esther; Vay, Laura; Santo Domingo, Jaime; Domínguez Lobatón, María Carmen; Moreno, Alfredo; Montero, Mayte; Álvarez, Javier

    2006-01-01

    Producción Científica There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that the main mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in nonexcitable cells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillations induced by histamine from a high-frequency irregular one t...

  13. IL-10-Producing CD1dhiCD5+ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients

    Science.gov (United States)

    Chen, Ying; Li, Chao; Lu, Yiping; Zhuang, Huiying; Gu, Weijia; Liu, Bo; Liu, Fangwei; Sun, Jinkai; Yan, Bo; Weng, Dong; Chen, Jie

    2017-01-01

    Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells were involved in the development of silica-induced lung inflammation and fibrosis of mice. However, little is known about the role of Bregs in silicosis patients (SP). In this study, we found that serum concentrations of IL-10 were significantly increased in SP by using protein array screening. We further determined that the frequency of IL-10-producing CD1dhiCD5+ Bregs, not IL-10-producing non-B lymphocytes, was significantly higher in SP compared to subjects under surveillance (SS) and healthy workers (HW) by flow cytometry. We also found that regulatory T cells (Tregs) and Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in SP. Th1 cytokines (IFN-γ, IL-2, and IL-12) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were not significantly different between SP, SS, and HW. Our study indicated that IL-10-producing CD1dhiCD5+ Bregs might maintain Tregs and regulate Th1/Th2 polarization in SP, suggesting that IL-10-producing Bregs may play a critical role in modulating immune homeostasis in SP.

  14. Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60 cells.

    Science.gov (United States)

    Ma, Wei; Wang, Di-Di; Li, Li; Feng, Yu-Kuan; Gu, Hong-Mei; Zhu, Gui-Ming; Piao, Jin-Hua; Yang, Yu; Gao, Xu; Zhang, Peng-Xia

    2014-07-01

    Our previous study found that caveolin-1 (CAV-1) protein expression is upregulated during oleanolic acid (OA)-induced inhibition of proliferation and promotion of apoptosis in HL-60 cells. CAV-1 is the main structural protein component of caveolae, playing important roles in tumorigenesis and tumor development. It has been shown that cav-1 expression is lower in leukemia cancer cell lines SUP-B15, HL-60, THP-1 and K562 and in chronic lymphocytic leukemia primary (CLP) cells when compared with normal white blood cells, with the lowest cav-1 expression level found in HL-60 cells. To study the effects of cav-1 in HL-60 cells and the effects of cav-1 overexpression on OA drug efficacy, cav-1 was overexpressed in HL-60 cells using lentiviral-mediated transfection combined with OA treatment. The results showed that cav-1 overexpression inhibited HL-60 cell proliferation, promoted apoptosis, arrested the cell cycle in the G1 phase and inhibited activation of the PI3K/AKT/mTOR signaling pathway. Overexpression of CAV-1 also increased HL-60 cell sensitivity to OA. To further verify whether OA affects HL-60 cells via the activation of downstream signaling pathways by CAV-1, cav-1 gene expression was silenced using RNAi, and the cells were treated with OA to examine its efficacy. The results showed that after cav-1 silencing, OA had little effect on cell activity, apoptosis, the cell cycle and phosphorylation of HL-60 cells. This study is the first to show that CAV-1 plays a crucial role in the effects of OA on HL-60 cells.

  15. gga-miR-375 plays a key role in tumorigenesis post subgroup J avian leukosis virus infection.

    Science.gov (United States)

    Li, Hongxin; Shang, Huiqing; Shu, Dingming; Zhang, Huanmin; Ji, Jun; Sun, Baoli; Li, Hongmei; Xie, Qingmei

    2014-01-01

    Avian leukosis is a neoplastic disease caused in part by subgroup J avian leukosis virus J (ALV-J). Micro ribonucleic acids (miRNAs) play pivotal oncogenic and tumour-suppressor roles in tumour development and progression. However, little is known about the potential role of miRNAs in avian leukosis tumours. We have found a novel tumour-suppressor miRNA, gga-miR-375, associated with avian leukosis tumorigenesis by miRNA microarray in a previous report. We have also previously studied the biological function of gga-miR-375; Overexpression of gga-miR-375 significantly inhibited DF-1 cell proliferation, and significantly reduced the expression of yes-associated protein 1 (YAP1) by repressing the activity of a luciferase reporter carrying the 3'-untranslated region of YAP1. This indicates that gga-miR-375 is frequently downregulated in avian leukosis by inhibiting cell proliferation through YAP1 oncogene targeting. Overexpression of gga-miR-375 markedly promoted serum starvation induced apoptosis, and there may be the reason why the tumour cycle is so long in the infected chickens. In vivo assays, gga-miR-375 was significantly downregulated in chicken livers 20 days after infection with ALV-J, and YAP1 was significantly upregulated 20 days after ALV-J infection (Pleukosis tumorigenesis.

  16. T cell–mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis

    Science.gov (United States)

    Trautmann, Axel; Akdis, Mübeccel; Kleemann, Daniela; Altznauer, Frank; Simon, Hans-Uwe; Graeve, Thomas; Noll, Michaela; Bröcker, Eva-B.; Blaser, Kurt; Akdis, Cezmi A.

    2000-01-01

    Clinical and histologic similarities between various eczematous disorders point to a common efferent pathway. We demonstrate here that activated T cells infiltrating the skin in atopic dermatitis (AD) and allergic contact dermatitis (ACD) induce keratinocyte (KC) apoptosis. KCs normally express low levels of Fas receptor (FasR) that can be substantially enhanced by the presence of IFN-γ. KCs are rendered susceptible to apoptosis by IFN-γ when FasR numbers reach a threshold of approximately 40,000 per KC. Subsequently, KCs undergo apoptosis induced by anti-FasR mAb’s, soluble Fas ligand, supernatants from activated T cells, or direct contact between T cells and KCs. Apoptotic KCs show typical DNA fragmentation and membrane phosphatidylserine expression. KC apoptosis was demonstrated in situ in lesional skin affected by AD, ACD, and patch tests. Using numerous cytokines and anti-cytokine neutralizing mAb’s, we found no evidence that cytokines other than IFN-γ participate in this process. In addition, apoptosis-inducing pathways other than FasR triggering were ruled out by blocking T cell–induced KC apoptosis by caspase inhibitors and soluble Fas-Fc protein. Responses of normal human skin and cultured skin equivalents to activated T cells demonstrated that KC apoptosis caused by skin-infiltrating T cells is a key event in the pathogenesis of eczematous dermatitis. PMID:10880045

  17. The TvLEGU-1, a Legumain-Like Cysteine Proteinase, Plays a Key Role in Trichomonas vaginalis Cytoadherence

    Directory of Open Access Journals (Sweden)

    Francisco Javier Rendón-Gandarilla

    2013-01-01

    Full Text Available The goal of this paper was to characterize a Trichomonas vaginalis cysteine proteinase (CP legumain-1 (TvLEGU-1 and determine its potential role as a virulence factor during T. vaginalis infection. A 30-kDa band, which migrates in three protein spots (pI~6.3, ~6.5, and ~6.7 with a different type and level of phosphorylation, was identified as TvLEGU-1 by one- and two-dimensional Western blot (WB assays, using a protease-rich trichomonad extract and polyclonal antibodies produced against the recombinant TvLEGU-1 (anti-TvLEGU-1r. Its identification was confirmed by mass spectrometry. Immunofluorescence, cell binding, and WB assays showed that TvLEGU-1 is upregulated by iron at the protein level, localized on the trichomonad surface and in lysosomes and Golgi complex, bound to the surface of HeLa cells, and was found in vaginal secretions. Additionally, the IgG and Fab fractions of the anti-TvLEGU-1r antibody inhibited trichomonal cytoadherence up to 45%. Moreover, the Aza-Peptidyl Michael Acceptor that inhibited legumain proteolytic activity in live parasites also reduced levels of trichomonal cytoadherence up to 80%. In conclusion, our data show that the proteolytic activity of TvLEGU-1 is necessary for trichomonal adherence. Thus, TvLEGU-1 is a novel virulence factor upregulated by iron. This is the first report that a legumain-like CP plays a role in a pathogen cytoadherence.

  18. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    Science.gov (United States)

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. © 2014 American Heart Association, Inc.

  19. Phospho-Bcl-x(L)(Ser62) plays a key role at DNA damage-induced G(2) checkpoint.

    Science.gov (United States)

    Wang, Jianfang; Beauchemin, Myriam; Bertrand, Richard

    2012-06-01

    Accumulating evidence suggests that Bcl-xL, an anti-apoptotic member of the Bcl-2 family, also functions in cell cycle progression and cell cycle checkpoints. Analysis of a series of phosphorylation site mutants reveals that cells expressing Bcl-xL(Ser62Ala) mutant are less stable at the G 2 checkpoint and enter mitosis more rapidly than cells expressing wild-type Bcl-xL or Bcl-xL phosphorylation site mutants, including Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala and Thr115Ala. Analysis of the dynamic phosphorylation and location of phospho-Bcl-xL(Ser62) in unperturbed, synchronized cells and during DNA damage-induced G 2 arrest discloses that a pool of phospho-Bcl-xL(Ser62) accumulates into nucleolar structures in etoposide-exposed cells during G 2 arrest. In a series of in vitro kinase assays, pharmacological inhibitors and specific siRNAs experiments, we found that Polo kinase 1 and MAPK9/JNK2 are major protein kinases involved in Bcl-xL(Ser62) phosphorylation and accumulation into nucleolar structures during the G 2 checkpoint. In nucleoli, phospho-Bcl-xL(Ser62) binds to and co-localizes with Cdk1(cdc2), the key cyclin-dependent kinase required for entry into mitosis. These data indicate that during G 2 checkpoint, phospho-Bcl-xL(Ser62) stabilizes G 2 arrest by timely trapping of Cdk1(cdc2) in nucleolar structures to slow mitotic entry. It also highlights that DNA damage affects the dynamic composition of the nucleolus, which now emerges as a piece of the DNA damage response.

  20. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures.

    Science.gov (United States)

    Kusters, Elske; Della Pina, Serena; Castel, Rob; Souer, Erik; Koes, Ronald

    2015-08-15

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than changes in the encoded proteins. Here, we report a functional comparison of the promoters of homologous FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter-reporter constructs in petunia and Arabidopsis, as well as complementation experiments, showed that the divergent expression of leafy (LFY) and the petunia homolog aberrant leaf and flower (ALF) results from alterations in the upstream regulatory network rather than cis-regulatory changes. The divergent expression of unusual floral organs (UFO) from Arabidopsis, and the petunia homolog double top (DOT), however, is caused by the loss or gain of cis-regulatory promoter elements, which respond to trans-acting factors that are expressed in similar patterns in both species. Introduction of pUFO:UFO causes no obvious defects in Arabidopsis, but in petunia it causes the precocious and ectopic formation of flowers. This provides an example of how a change in a cis-regulatory region can account for a change in the plant body plan.

  1. Role played by CD4+FOXP3+ regulatory T Cells in suppression of host responses to Haemophilus ducreyi during experimental infection of human volunteers.

    Science.gov (United States)

    Li, Wei; Tenner-Racz, Klara; Racz, Paul; Janowicz, Diane M; Fortney, Kate R; Katz, Barry P; Spinola, Stanley M

    2010-06-15

    Haemophilus ducreyi causes chancroid, a genital ulcer disease. Among human volunteers, the majority of experimentally infected individuals fail to clear the infection and form pustules. Here, we investigated the role played by CD4(+)FOXP3(+) regulatory T (T(reg)) cells in the formation of pustules. In pustules, there was a significant enrichment of CD4(+)FOXP3(+) T cells, compared with that in peripheral blood. The majority of lesional FOXP3(+) T cells were CD4(+), CD25(+), CD127(lo/-), and CTLA-4(+). FOXP3(+) T cells were found throughout pustules but were most abundant at their base. Significantly fewer lesional CD4(+)FOXP3(+) T cells expressed interferon gamma, compared with lesional CD4(+)FOXP3(-) effector T cells. Depletion of CD4(+)CD25(+) T cells from the peripheral blood of infected and uninfected volunteers significantly enhanced proliferation of H. ducreyi-reactive CD4(+) T cells. Our results indicate that the population of CD4(+)CD25(+)CD127(lo/-)FOXP3(+) T(reg) cells are expanded at H. ducreyi-infected sites and that these cells may play a role in suppressing the host immune response to the bacterium.

  2. Android系统立体视频播放关键技术研究%Key Technology Research on Playing Stereoscopic Video in Android System

    Institute of Scientific and Technical Information of China (English)

    马建设; 赵雪江; 苏萍

    2013-01-01

    为了解决立体视频在Android系统上的播放问题,对在Android系统进行立体视频播放的关键技术进行了研究.与传统2D视频播放器相比,立体视频播放器的关键技术是立体视频解码和立体视频显示.文中对这两种关键技术的实现方法进行了详细阐述,并据此开发了一款立体视频播放器.该立体视频播放器,支持常见的左/右、上/下格式立体视频,有7种视频显示方式可供选择.该视频播放器在Android 2.3系统的平板电脑上进行了测试,测试结果表明在Android系统上播放立体视频的基本功能均已实现,可以供用户使用.%In order to play stereoscopic videos on Android system, the key technology of playing stereoscopic videos on Android system is researched. Compared to 2D video player, the key technologies of stereoscopic video player are stereoscopic video decoding and stereoscopic video display. In this paper, the implementation methods of the two key technologies are presented in detail. A stereoscopic video player is developed according to the implementation methods presented. The stereoscopic video player supports two kinds of common stereoscopic video formats, including left-and-right format and top-and-bottom format. Seven kinds of video display modes are available. The stereoscopic video player is tested on a Mobile Internet Device(MID) with an operating system of Android 2.3. Test results show that basic functions of playing stereoscopic video on Android system have been realized, and the stereoscopic video player is available for commercial use.

  3. CD55 is a key complement regulatory protein that counteracts complement-mediated inactivation of Newcastle Disease Virus.

    Science.gov (United States)

    Rangaswamy, Udaya S; Cotter, Christopher R; Cheng, Xing; Jin, Hong; Chen, Zhongying

    2016-08-01

    Newcastle disease virus (NDV) is being developed as an oncolytic virus for virotherapy. In this study we analysed the regulation of complement-mediated inactivation of a recombinant NDV in different host cells. NDV grown in human cells was less sensitive to complement-mediated virus inactivation than NDV grown in embryonated chicken eggs. Additionally, NDV produced from HeLa-S3 cells is more resistant to complement than NDV from 293F cells, which correlated with higher expression and incorporation of complement regulatory proteins (CD46, CD55 and CD59) into virions from HeLa-S3 cells. Further analysis of the recombinant NDVs individually expressing the three CD molecules showed that CD55 is the most potent in counteracting complement-mediated virus inactivation. The results provide important information on selecting NDV manufacture substrate to mitigate complement-mediated virus inactivation.

  4. Healthcare regulatory concepts in Brazil.

    Science.gov (United States)

    Oliveira, Robson Rocha de; Elias, Paulo Eduardo Mangeon

    2012-06-01

    The healthcare regulatory concepts used in Brazilian scientific publications on healthcare management were reviewed. A typo-logical classification for regulatory concepts was developed from the most current ideas in five disciplines: life sciences, law, economics, sociology and political science. Four ideas stood out: control, balance, adaptation and direction, with greatest emphasis on the technical nature of regulation. The political nature of regulation was secondary. It was considered that dis-cussion of healthcare regulatory concepts was connected with comprehension of the role that the state plays in this sector. De-finition of the forms of state intervention is the key convergence point between the different ways of conceptualizing healthcare regulation.

  5. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    Science.gov (United States)

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation.

  6. Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role in progression and metastasis of colorectal cancer.

    Science.gov (United States)

    Zheng, Ping; Liu, Yong-Xia; Chen, Lin; Liu, Xun-Hua; Xiao, Zheng-Quan; Zhao, Liang; Li, Guang-Qiu; Zhou, Jun; Ding, Yan-Qing; Li, Jian-Ming

    2010-10-01

    To better understand the role of PRL-3 in progression and metastasis of colorectal cancer (CRC), we searched for PRL-3 associated proteins using proteomic methods. We identified 39 PRL-3 associated proteins based on proteomic strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines and CRC tissues indicated that PRL-3 could interact with stathmin. And, both stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells. Moreover, gain-of-function and loss-of-function analyses revealed that stathmin promoted proliferation, cell adhesion, and migration of human CRC cells. Immunohistochemical analysis of 149 colorectal tumor samples showed that overexpression of stathmin was strongly correlated with tumor differentiation (P = 0.035), tumor invasion (P = 0.024), lymph node status (P PRL-3 associated proteins for the first time. The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC.

  7. CLMP is essential for intestinal development, but does not play a key role in cellular processes involved in intestinal epithelial development.

    Directory of Open Access Journals (Sweden)

    Christine S van der Werf

    Full Text Available Loss-of-function mutations in CLMP have been found in patients with Congenital Short Bowel Syndrome (CSBS, suggesting that its encoded protein plays a major role in intestinal development. CLMP is a membrane protein that co-localizes with tight junction proteins, but its function is largely unknown. We expressed wild-type (WT-CLMP and a mutant-CLMP (associated with CSBS in human intestinal epithelial T84 cells that, as we show here, do not produce endogenous CLMP. We investigated the effects of WT-CLMP and mutant-CLMP proteins on key cellular processes that are important for intestinal epithelial development, including migration, proliferation, viability and transepithelial resistance. Our data showed that expression of WT-CLMP or mutant-CLMP does not affect any of these processes. Moreover, our aggregation assays in CHO cells show that CLMP does not act as a strong adhesion molecule. Thus, our data suggest that, in the in vitro model systems we used, the key processes involved in intestinal epithelial development appear to be unaffected by WT-CLMP or mutant-CLMP. Further research is needed to determine the role of CLMP in the development of the intestine.

  8. Comparative study between transcriptionally- and translationally-acting adenine riboswitches reveals key differences in riboswitch regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Jean-François Lemay

    2011-01-01

    Full Text Available Many bacterial mRNAs are regulated at the transcriptional or translational level by ligand-binding elements called riboswitches. Although they both bind adenine, the adenine riboswitches of Bacillus subtilis and Vibrio vulnificus differ by controlling transcription and translation, respectively. Here, we demonstrate that, beyond the obvious difference in transcriptional and translational modulation, both adenine riboswitches exhibit different ligand binding properties and appear to operate under different regulation regimes (kinetic versus thermodynamic. While the B. subtilis pbuE riboswitch fully depends on co-transcriptional binding of adenine to function, the V. vulnificus add riboswitch can bind to adenine after transcription is completed and still perform translation regulation. Further investigation demonstrates that the rate of transcription is critical for the B. subtilis pbuE riboswitch to perform efficiently, which is in agreement with a co-transcriptional regulation. Our results suggest that the nature of gene regulation control, that is transcription or translation, may have a high importance in riboswitch regulatory mechanisms.

  9. Transcriptomics profiling of Indian mustard (Brassica juncea) under arsenate stress identifies key candidate genes and regulatory pathways.

    Science.gov (United States)

    Srivastava, Sudhakar; Srivastava, Ashish K; Sablok, Gaurav; Deshpande, Tejaswini U; Suprasanna, Penna

    2015-01-01

    Arsenic (As) is a non-essential element, a groundwater pollutant, whose uptake by plants produces toxic effects. The use of As-contaminated groundwater for irrigation can affect the crop productivity. Realizing the importance of the Brassica juncea as a crop plant in terms of oil-yield, there is a need to unravel mechanistic details of response to As stress and identify key functional genes and pathways. In this research, we studied time-dependent (4-96 h) transcriptome changes in roots and shoots of B. juncea under arsenate [As(V)] stress using Agilent platform. Among the whole transcriptome profiled genes, a total of 1,285 genes showed significant change in expression pattern upon As(V) exposure. The differentially expressed genes were categorized to various signaling pathways including hormones (jasmonate, abscisic acid, auxin, and ethylene) and kinases. Significant effects were also noticed on genes related to sulfur, nitrogen, CHO, and lipid metabolisms along with photosynthesis. Biochemical assays were conducted using specific inhibitors of glutathione and jasmonate biosynthesis, and kinases. The inhibitor studies revealed interconnection among sulfur metabolism, jasmonate, and kinase signaling pathways. In addition, various transposons also constituted a part of the altered transcriptome. Lastly, we profiled a set of key functional up- and down-regulated genes using real-time RT-PCR, which could act as an early indicators of the As stress.

  10. The ζ isoform of diacylglycerol kinase plays a predominant role in regulatory T cell development and TCR-mediated ras signaling.

    Science.gov (United States)

    Joshi, Rohan P; Schmidt, Amanda M; Das, Jayajit; Pytel, Dariusz; Riese, Matthew J; Lester, Melissa; Diehl, J Alan; Behrens, Edward M; Kambayashi, Taku; Koretzky, Gary A

    2013-11-26

    Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA) and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms are DGKα and DGKζ, and deletion of the genes encoding either isoform enhances DAG-mediated signaling. We found that DGKζ, but not DGKα, suppressed the development of natural regulatory T (T(reg)) cells and predominantly mediated Ras and Akt signaling downstream of the TCR. The differential functions of DGKα and DGKζ were not attributable to differences in protein abundance in T cells or in their localization to the contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG-mediated activator of Ras signaling, associated to a greater extent with DGKζ than with DGKα; however, in silico modeling of TCR-stimulated Ras activation suggested that a difference in RasGRP1 binding affinity was not sufficient to cause differences in the functions of each DGK isoform. Rather, the model suggested that a greater catalytic rate for DGKζ than for DGKα might lead to DGKζ exhibiting increased suppression of Ras-mediated signals compared to DGKα. Consistent with this notion, experimental studies demonstrated that DGKζ was more effective than DGKα at catalyzing the metabolism of DAG to PA after TCR stimulation. The enhanced effective enzymatic production of PA by DGKζ is therefore one possible mechanism underlying the dominant functions of DGKζ in modulating T(reg) cell development.

  11. CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1 p24 production in patients on long-term treatment: HIV-1 p24-producing cells and suppression of anti-HIV immunity

    Directory of Open Access Journals (Sweden)

    Yan-Mei Jiao

    2015-08-01

    Conclusions: CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1 p24 production in long-term ART patients. Treg cells may be a target for eliminating the latent HIV reservoir after effective long-term ART.

  12. Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α.

    Science.gov (United States)

    Chai, Ok Hee; Han, Eui-Hyeog; Lee, Hern-Ku; Song, Chang Ho

    2011-01-31

    Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-α on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-Kitw/Kitw-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-α directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-α, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-α resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-α.

  13. Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.

    Science.gov (United States)

    Plouhinec, Jean-Louis; Roche, Daniel D; Pegoraro, Caterina; Figueiredo, Ana Leonor; Maczkowiak, Frédérique; Brunet, Lisa J; Milet, Cécile; Vert, Jean-Philippe; Pollet, Nicolas; Harland, Richard M; Monsoro-Burq, Anne H

    2014-02-15

    Neural crest development is orchestrated by a complex and still poorly understood gene regulatory network. Premigratory neural crest is induced at the lateral border of the neural plate by the combined action of signaling molecules and transcription factors such as AP2, Gbx2, Pax3 and Zic1. Among them, Pax3 and Zic1 are both necessary and sufficient to trigger a complete neural crest developmental program. However, their gene targets in the neural crest regulatory network remain unknown. Here, through a transcriptome analysis of frog microdissected neural border, we identified an extended gene signature for the premigratory neural crest, and we defined novel potential members of the regulatory network. This signature includes 34 novel genes, as well as 44 known genes expressed at the neural border. Using another microarray analysis which combined Pax3 and Zic1 gain-of-function and protein translation blockade, we uncovered 25 Pax3 and Zic1 direct targets within this signature. We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b. In addition, they may modulate the transcriptional output of multiple signaling pathways involved in neural crest development (Wnt, Retinoic Acid) through the induction of key pathway regulators (Axin2 and Cyp26c1). We also found that Pax3 could maintain its own expression through a positive autoregulatory feedback loop. These hierarchical inductions, feedback loops, and pathway modulations provide novel tools to understand the neural crest induction network.

  14. Retinoic acid is a key regulatory switch determining the difference between lung and thyroid fates in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Wang Jean H

    2011-12-01

    Full Text Available Abstract Background The lung and thyroid are derived from the anterior endoderm. Retinoic acid and Fgf signalling are known to be essential for development of the lung in mouse but little is known on how the lung and thyroid are specified in Xenopus. Results If either retinoic acid or Fgf signalling is inhibited, there is no differentiation of the lung as assayed by expression of sftpb. There is no change in expression of thyroid gland markers when retinoic acid signalling is blocked after gastrulation and when Fgf signalling is inhibited there is a short window of time where pax2 expression is inhibited but expression of other markers is unaffected. If exogenous retinoic acid is given to the embryo between embryonic stages 20 and 26, the presumptive thyroid expresses sftpb and sftpc, specific markers of lung differentiation and expression of key thyroid transcription factors is lost. When the presumptive thyroid is transplanted into the posterior embryo, it also expresses sftpb, although pax2 expression is not blocked. Conclusions After gastrulation, retinoic acid is required for lung but not thyroid differentiation in Xenopus while Fgf signalling is needed for lung but only for early expression of pax2 in the thyroid. Exposure to retinoic acid can cause the presumptive thyroid to switch to a lung developmental program.

  15. Crystal structure of NblA from Anabaena sp. PCC 7120, a small protein playing a key role in phycobilisome degradation.

    Science.gov (United States)

    Bienert, Ralf; Baier, Kerstin; Volkmer, Rudolf; Lockau, Wolfgang; Heinemann, Udo

    2006-02-24

    Cyanobacterial light-harvesting complexes, the phycobilisomes, are proteolytically degraded when the organisms are starved for combined nitrogen, a process referred to as chlorosis or bleaching. Gene nblA, present in all phycobilisome-containing organisms, encodes a protein of about 7 kDa that plays a key role in phycobilisome degradation. The mode of action of NblA in this degradation process is poorly understood. Here we presented the 1.8-A crystal structure of NblA from Anabaena sp. PCC 7120. In the crystal, NblA is present as a four-helix bundle formed by dimers, the basic structural units. By using pull-down assays with immobilized NblA and peptide scanning, we showed that NblA specifically binds to the alpha-subunits of phycocyanin and phycoerythrocyanin, the main building blocks of the phycobilisome rod structure. By site-directed mutagenesis, we identified amino acid residues in NblA that are involved in phycobilisome binding. The results provided evidence that NblA is directly involved in phycobilisome degradation, and the results allowed us to present a model that gives insight into the interaction of this small protein with the phycobilisomes.

  16. Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation

    Science.gov (United States)

    Barría, María Inés; González, Angel; Vera-Otarola, Jorge; León, Ursula; Vollrath, Valeska; Marsac, Delphine; Monasterio, Octavio; Pérez-Acle, Tomás; Soza, Alejandro; López-Lastra, Marcelo

    2009-01-01

    The HCV internal ribosome entry site (IRES) spans a region of ∼340 nt that encompasses most of the 5′ untranslated region (5′UTR) of the viral mRNA and the first 24–40 nt of the core-coding region. To investigate the implication of altering the primary sequence of the 5′UTR on IRES activity, naturally occurring variants of the 5′UTR were isolated from clinical samples and analyzed. The impact of the identified mutations on translation was evaluated in the context of RLuc/FLuc bicistronic RNAs. Results show that depending on their location within the RNA structure, these naturally occurring mutations cause a range of effects on IRES activity. However, mutations within subdomain IIId hinder HCV IRES-mediated translation. In an attempt to explain these data, the dynamic behavior of the subdomain IIId was analyzed by means of molecular dynamics (MD) simulations. Despite the loss of function, MD simulations predicted that mutant G266A/G268U possesses a structure similar to the wt-RNA. This prediction was validated by analyzing the secondary structure of the isolated IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg2+ ions. These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation. PMID:19106142

  17. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-01-01

    Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

  18. CBF2A-CBF4B genomic region copy numbers alongside the circadian clock play key regulatory mechanisms driving expression of FR-H2 CBFs.

    Science.gov (United States)

    Dhillon, Taniya; Morohashi, Kengo; Stockinger, Eric J

    2017-06-01

    The C-Repeat Binding Factors (CBFs) are DNA-binding transcriptional activators that were identified using Arabidopsis thaliana. In barley, Hordeum vulgare, a cluster of CBF genes reside at FROST RESISTANCE-H2, one of two loci having major effects on winter-hardiness. FR-H2 was revealed in a population derived from the winter barley 'Nure' and the spring barley 'Trèmois'. 'Nure' harbors two to three copies of CBF2A and CBF4B as a consequence of tandem iteration of the genomic region encompassing these genes whereas 'Trèmois' harbors single copies, and these copy number differences are associated with their transcript level differences. Here we explore further the relationship between FR-H2 CBF gene copy number and transcript levels using 'Admire', a winter barley accumulating FR-H2 CBF gene transcripts to very high levels, and a group of lines related to 'Admire' through descent. DNA blot hybridization indicated the CBF2A-CBF4B genomic region is present in 7-8 copies in 'Admire' and is highly variable in copy number across the lines related to 'Admire'. At normal growth temperatures transcript levels of CBF12, CBF14, and CBF16 were higher in lines having greater CBF2A-CBF4B genomic region copy numbers than in lines having fewer copy numbers at peak expression level time points controlled by the circadian clock. Chromatin immunoprecipitation indicated CBF2 was at the CBF12 and CBF16 promoters at normal growth temperatures. These data support a scenario in which CBF2A-CBF4B genomic region copy numbers affect expression of other FR-H2 CBFs through a mechansim in which these other FR-H2 CBFs are activated by those in the copy number variable unit.

  19. RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

    Directory of Open Access Journals (Sweden)

    Elias Abdou

    2017-05-01

    Full Text Available For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL, were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work

  20. Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation

    OpenAIRE

    Read, Simon; Malmström, Vivianne; Powrie, Fiona

    2000-01-01

    It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25+CD45RBlowCD4+) as those that control autoimmunity. Previous studies have failed to identify how CD25+ Treg cells function in vivo. Our studies reveal that the immune-suppressive func...

  1. Arabidopsis DAYU/ABERRANT PEROXISOME MORPHOLOGY9 is a key regulator of peroxisome biogenesis and plays critical roles during pollen maturation and germination in planta.

    Science.gov (United States)

    Li, Xin-Ran; Li, Hong-Ju; Yuan, Li; Liu, Man; Shi, Dong-Qiao; Liu, Jie; Yang, Wei-Cai

    2014-02-01

    Pollen undergo a maturation process to sustain pollen viability and prepare them for germination. Molecular mechanisms controlling these processes remain largely unknown. Here, we report an Arabidopsis thaliana mutant, dayu (dau), which impairs pollen maturation and in vivo germination. Molecular analysis indicated that DAU encodes the peroxisomal membrane protein ABERRANT PEROXISOME MORPHOLOGY9 (APEM9). DAU is transiently expressed from bicellular pollen to mature pollen during male gametogenesis. DAU interacts with peroxisomal membrane proteins PEROXIN13 (PEX13) and PEX16 in planta. Consistently, both peroxisome biogenesis and peroxisome protein import are impaired in dau pollen. In addition, the jasmonic acid (JA) level is significantly decreased in dau pollen, and the dau mutant phenotype is partially rescued by exogenous application of JA, indicating that the male sterility is mainly due to JA deficiency. In addition, the phenotypic survey of peroxin mutants indicates that the PEXs most likely play different roles in pollen germination. Taken together, these data indicate that DAU/APEM9 plays critical roles in peroxisome biogenesis and function, which is essential for JA production and pollen maturation and germination.

  2. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.

    Science.gov (United States)

    Read, S; Malmström, V; Powrie, F

    2000-07-17

    It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies have failed to identify how CD25(+) Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor beta. Strikingly, constitutive expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.

  3. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    Science.gov (United States)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  4. OsLEA3-2, an abiotic stress induced gene of rice plays a key role in salt and drought tolerance.

    Directory of Open Access Journals (Sweden)

    Jianli Duan

    Full Text Available Late embryogenesis abundant (LEA proteins are involved in tolerance to drought, cold and high salinity in many different organisms. In this report, a LEA protein producing full-length gene OsLEA3-2 was identified in rice (Oryza sativa using the Rapid Amplification of cDNA Ends (RACE method. OsLEA3-2 was found to be only expressed in the embryo and can be induced by abiotic stresses. The coding protein localizes to the nucleus and overexpression of OsLEA3-2 in yeast improved growth performance compared with control under salt- and osmotic-stress conditions. OsLEA3-2 was also inserted into pHB vector and overexpressed in Arabidopsis and rice. The transgenic Arabidopsis seedlings showed better growth on MS media supplemented with 150 mM mannitol or 100 mM NaCl as compared with wild type plants. The transgenic rice also showed significantly stronger growth performance than control under salinity or osmotic stress conditions and were able to recover after 20 days of drought stress. In vitro analysis showed that OsLEA3-2 was able to protect LDH from aggregation on freezing and inactivation on desiccation. These results indicated that OsLEA3-2 plays an important role in tolerance to abiotic stresses.

  5. Endocytic Trafficking towards the Vacuole Plays a Key Role in the Auxin Receptor SCFTIR-Independent Mechanism of Lateral Root Formation in A.thaliana

    Institute of Scientific and Technical Information of China (English)

    Patricio Pérez-Henríquez; Natasha V.Raikhel; Lorena Norambuena

    2012-01-01

    Plants' developmental plasticity plays a pivotal role in responding to environmental conditions.One of the most plastic plant organs is the root system.Different environmental stimuli such as nutrients and water deficiency may induce lateral root formation to compensate for a low level of water and/or nutrients.It has been shown that the hormone auxin tunes lateral root development and components for its signaling pathway have been identified.Using chemical biology,we discovered an Arabidopsis thaliana lateral root formation mechanism that is independent of the auxin receptor SCFTIR.The bioactive compound Sortin2 increased lateral root occurrence by acting upstream from the morphological marker of lateral root primordium formation,the mitotic activity.The compound did not display auxin activity.At the cellular level,Sortin2 accelerated endosomal trafficking,resulting in increased trafficking of plasma membrane recycling proteins to the vacuole.Sortin2 affected Late endosome/PVC/MVB trafficking and morphology.Combining Sortin2 with well-known drugs showed that endocytic trafficking of Late E/PVC/MVB towards the vacuole is pivotal for Sortin2induced SCFTIR-independent lateral root initiation.Our results revealed a distinctive role for endosomal trafficking in the promotion of lateral root formation via a process that does not rely on the auxin receptor complex SCFTIR.

  6. The ZntA-like NpunR4017 plays a key role in maintaining homeostatic levels of zinc in Nostoc punctiforme.

    Science.gov (United States)

    Hudek, L; Bräu, L; Michalczyk, A A; Neilan, B A; Meeks, J C; Ackland, M L

    2015-12-01

    Analysis of cellular response to zinc exposure provides insights into how organisms maintain homeostatic levels of zinc that are essential, while avoiding potentially toxic cytosolic levels. Using the cyanobacterium Nostoc punctiforme as a model, qRT-PCR analyses established a profile of the changes in relative mRNA levels of the ZntA-like zinc efflux transporter NpunR4017 in response to extracellular zinc. In cells treated with 18 μM of zinc for 1 h, NpunR4017 mRNA levels increased by up to 1300 % above basal levels. The accumulation and retention of radiolabelled (65)Zn by NpunR4107-deficient and overexpressing strains were compared to wild-type levels. Disruption of NpunR4017 resulted in a significant increase in zinc accumulation up to 24 % greater than the wild type, while cells overexpressing NpunR4107 accumulated 22 % less than the wild type. Accumulation of (65)Zn in ZntA(-) Escherichia coli overexpressing NpunR4017 was reduced by up to 21 %, indicating the capacity for NpunR4017 to compensate for the loss of ZntA. These findings establish the newly identified NpunR4017 as a zinc efflux transporter and a key transporter for maintaining zinc homeostasis in N. punctiforme.

  7. Tomato Glutamate Decarboxylase Genes SlGAD2 and SlGAD3 Play Key Roles in Regulating γ-Aminobutyric Acid Levels in Tomato (Solanum lycopersicum).

    Science.gov (United States)

    Takayama, Mariko; Koike, Satoshi; Kusano, Miyako; Matsukura, Chiaki; Saito, Kazuki; Ariizumi, Tohru; Ezura, Hiroshi

    2015-08-01

    Tomato (Solanum lycopersicum) can accumulate relatively high levels of γ-aminobutyric acid (GABA) during fruit development. However, the molecular mechanism underlying GABA accumulation and its physiological function in tomato fruits remain elusive. We previously identified three tomato genes (SlGAD1, SlGAD2 and SlGAD3) encoding glutamate decarboxylase (GAD), likely the key enzyme for GABA biosynthesis in tomato fruits. In this study, we generated transgenic tomato plants in which each SlGAD was suppressed and those in which all three SlGADs were simultaneously suppressed. A significant decrease in GABA levels, i.e. 50-81% compared with wild-type (WT) levels, was observed in mature green (MG) fruits of the SlGAD2-suppressed lines, while a more drastic reduction (up to tomato fruits. The importance of SlGAD3 expression was also confirmed by generating transgenic tomato plants that over-expressed SlGAD3. The MG and red fruits of the over-expressing transgenic lines contained higher levels of GABA (2.7- to 5.2-fold) than those of the WT. We also determined that strong down-regulation of the SlGADs had little effect on overall plant growth, fruit development or primary fruit metabolism under normal growth conditions.

  8. Mechanisms of Mitochondrial Holocytochrome c Synthase and the Key Roles Played by Cysteines and Histidine of the Heme Attachment Site, Cys-XX-Cys-His*

    Science.gov (United States)

    Babbitt, Shalon E.; San Francisco, Brian; Mendez, Deanna L.; Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.; Bretsnyder, Eric C.; Kranz, Robert G.

    2014-01-01

    Mitochondrial cytochrome c assembly requires the covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1. The enzyme holocytochrome c synthase (HCCS) binds heme and apocytochrome c substrate to catalyze this attachment, subsequently releasing holocytochrome c for proper folding to its native structure. We address mechanisms of assembly using a functional Escherichia coli recombinant system expressing human HCCS. Human cytochrome c variants with individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions (of CXXCH) were co-purified with HCCS. Single and double mutants form a complex with HCCS but not the triple mutant. Resonance Raman and UV-visible spectroscopy support the proposal that heme puckering induced by both thioether bonds facilitate release of holocytochrome c from the complex. His-19 (of CXXCH) supplies the second axial ligand to heme in the complex, the first axial ligand was previously shown to be from HCCS residue His-154. Substitutions of His-19 in cytochrome c to seven other residues (Gly, Ala, Met, Arg, Lys, Cys, and Tyr) were used with various approaches to establish other roles played by His-19. Three roles for His-19 in HCCS-mediated assembly are suggested: (i) to provide the second axial ligand to the heme iron in preparation for covalent attachment; (ii) to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation; and (iii) to aid in release of the holocytochrome c from the HCCS active site. Only H19M is able to carry out these three roles, albeit at lower efficiencies than the natural His-19. PMID:25170082

  9. Hydathode trichomes actively secreting water from leaves play a key role in the physiology and evolution of root-parasitic rhinanthoid Orobanchaceae

    Science.gov (United States)

    Světlíková, Petra; Hájek, Tomáš; Těšitel, Jakub

    2015-01-01

    Background and Aims Root hemiparasites from the rhinanthoid clade of Orobanchaceae possess metabolically active glandular trichomes that have been suggested to function as hydathode trichomes actively secreting water, a process that may facilitate resource acquisition from the host plant’s root xylem. However, no direct evidence relating the trichomes to water secretion exists, and carbon budgets associated with this energy-demanding process have not been determined. Methods Macro- and microscopic observations of the leaves of hemiparasitic Rhinanthus alectorolophus were conducted and night-time gas exchange was measured. Correlations were examined among the intensity of guttation, respiration and transpiration, and analysis of these correlations allowed the carbon budget of the trichome activity to be quantified. We examined the intensity of guttation, respiration and transpiration, correlations among which indicate active water secretion. Key Results Guttation was observed on the leaves of 50 % of the young, non-flowering plants that were examined, and microscopic observations revealed water secretion from the glandular trichomes present on the abaxial leaf side. Night-time rates of respiration and transpiration and the presence of guttation drops were positively correlated, which is a clear indicator of hydathode trichome activity. Subsequent physiological measurements on older, flowering plants indicated neither intense guttation nor the presence of correlations, which suggests that the peak activity of hydathodes is in the juvenile stage. Conclusions This study provides the first unequivocal evidence for the physiological role of the hydathode trichomes in active water secretion in the rhinanthoid Orobanchaceae. Depending on the concentration of organic elements calculated to be in the host xylem sap, the direct effect of water secretion on carbon balance ranges from close to neutral to positive. However, it is likely to be positive in the xylem-only feeding

  10. The unique prodomain of T-cadherin plays a key role in adiponectin binding with the essential extracellular cadherin repeats 1 and 2.

    Science.gov (United States)

    Fukuda, Shiro; Kita, Shunbun; Obata, Yoshinari; Fujishima, Yuya; Nagao, Hirofumi; Masuda, Shigeki; Tanaka, Yoshimitsu; Nishizawa, Hitoshi; Funahashi, Tohru; Takagi, Junichi; Maeda, Norikazu; Shimomura, Iichiro

    2017-05-12

    Adiponectin, an adipocyte-derived circulating protein, accumulates in the heart, vascular endothelium, and skeletal muscles through an interaction with T-cadherin (T-cad), a unique glycosylphosphatidylinositol-anchored cadherin. Recent studies have suggested that this interaction is essential for adiponectin-mediated cardiovascular protection. However, the precise protein-protein interaction between adiponectin and T-cad remains poorly characterized. Using ELISA-based and surface plasmon analyses, we report here that T-cad fused with IgG Fc as a fusion tag by replacing its glycosylphosphatidylinositol-anchor specifically bound both hexameric and larger multimeric adiponectin with a dissociation constant of ∼1.0 nm and without any contribution from other cellular or serum factors. The extracellular T-cad repeats 1 and 2 were critical for the observed adiponectin binding, which is required for classical cadherin-mediated cell-to-cell adhesion. Moreover, the 130-kDa prodomain-bearing T-cad, uniquely expressed on the cell surface among members of the cadherin family and predominantly increased by adiponectin, contributed significantly to adiponectin binding. Inhibition of prodomain-processing by a prohormone convertase inhibitor increased 130-kDa T-cad levels and also enhanced adiponectin binding to endothelial cells both by more preferential cell-surface localization and by higher adiponectin-binding affinity of 130-kDa T-cad relative to 100-kDa T-cad. The preferential cell-surface localization of 130-kDa T-cad relative to 100-kDa T-cad was also observed in normal mice aorta in vivo In conclusion, our study shows that a unique key feature of the T-cad prodomain is its involvement in binding of the T-cad repeats 1 and 2 to adiponectin and also demonstrates that adiponectin positively regulates T-cad abundance. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Play Matters

    DEFF Research Database (Denmark)

    Sicart (Vila), Miguel Angel

    , but not necessarily fun. Play can be dangerous, addictive, and destructive. Along the way, Sicart considers playfulness, the capacity to use play outside the context of play; toys, the materialization of play--instruments but also play pals; playgrounds, play spaces that enable all kinds of play; beauty......, the aesthetics of play through action; political play -- from Maradona's goal against England in the 1986 World Cup to the hactivist activities of Anonymous; the political, aesthetic, and moral activity of game design; and why play and computers get along so well....

  12. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 1: Key ethical requirements and progress toward the definition of an international regulatory framework.

    Science.gov (United States)

    Cozzi, Emanuele; Tallacchini, Mariachiara; Flanagan, Enda B; Pierson, Richard N; Sykes, Megan; Vanderpool, Harold Y

    2009-01-01

    The outstanding results recently obtained in islet xenotransplantation suggest that porcine islet clinical trials may soon be scientifically appropriate. Before the initiation of such clinical studies, however, it is essential that a series of key ethical and regulatory conditions are satisfied. As far as ethics is concerned, the fundamental requirements have been previously reported in a position paper of the Ethics Committee of the International Xenotransplantation Association. These include aspects related to the selection of adequately informed, appropriate recipients; animal breeding and welfare; safety issues and the need for a favorable risk/benefit assessment based on strong efficacy data in relevant xenotransplantation studies in the primate. As most diabetic patients are not at risk of short-term mortality without islet transplantation, only a small subset of patients could currently be considered for any type of islet transplant. However, there are potential advantages to xenotransplantation that could result in a favorable benefit-over-harm determination for islet xenotransplantation in this subpopulation and ultimately in a broader population of diabetic patients. With regard to regulatory aspects, the key concepts underlying the development of the regulatory models in existence in the United States, Europe and New Zealand are discussed. Each of these models provides an example of a well-defined regulatory approach to ensure the initiation of well-regulated and ethically acceptable clinical islet xenotransplantation trials. At this stage, it becomes apparent that only a well-coordinated international effort such as that initiated by the World Health Organization, aimed at harmonizing xenotransplantation procedures according to the highest ethical and regulatory standards on a global scale, will enable the initiation of clinical xenotransplantation trials under the best auspices for its success and minimize any risk of failure.

  13. Playful Gaming.

    Science.gov (United States)

    Makedon, Alexander

    A philosophical analysis of play and games is undertaken in this paper. Playful gaming, which is shown to be a synthesis of play and games, is utilized as a category for undertaking the examination of play and games. The significance of playful gaming to education is demonstrated through analyses of Plato's, Dewey's, Sartre's, and Marcuse's…

  14. Aesthetic Play

    DEFF Research Database (Denmark)

    Bang, Jytte Susanne

    2012-01-01

    to the children’s complex life-worlds. Further, this leads to an analysis of music-play activities as play with an art-form (music), which includes aesthetic dimensions and gives the music-play activities its character of being aesthetic play. Following Lev Vygotsky’s insight that art is a way of building life...

  15. Reactive oxygen species and PI3K/Akt signaling play key roles in the induction of Nrf2-driven heme oxygenase-1 expression in sulforaphane-treated human mesothelioma MSTO-211H cells.

    Science.gov (United States)

    Lee, Yoon-Jin; Jeong, Hyang-Yun; Kim, Yong-Bae; Lee, Yong-Jin; Won, Seong Youn; Shim, Jung-Hyun; Cho, Moon-Kyun; Nam, Hae-Seon; Lee, Sang-Han

    2012-02-01

    The nuclear factor erythroid-derived 2 related factor 2 (Nrf2)/heme oxygenase (HO)-1 induction plays cytoprotective roles against oxidative injury, apoptosis, and anticancer therapy; however, little is known about its regulation in human mesothelioma MSTO-211H cells. In this study, we investigated Nrf2/HO-1 induction in response to sulforaphane and determined the signaling pathways involved in this process. Sulforaphane treatment decreased cell viability and triggered a rapid and transient increase in the intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) prevented sulforaphane-induced cytotoxicity. Erk1/2 was activated within 1h of sulforaphane addition, whereas Akt phosphorylation was suppressed until the first 8h, and was then maintained at an elevated level until 72h, displaying a biphasic regulatory feature. Nrf2 protein levels in both nuclear and whole cell lysates were increased after sulforaphane treatment and were decreased by pretreatment with NAC, actinomycin D and cycloheximide. Activation of the Nrf2/HO-1 system after sulforaphane treatment was suppressed by pretreatment with NAC or Ly294002, a PI3K inhibitor. Knockdown of Nrf2 with siRNA decreased cell viability and attenuated sulforaphane-induced HO-1 up-regulation. Overall, our results indicate that ROS generation and/or activation of PI3K/Akt signaling regulate cell survival and Nrf2-driven HO-1 expression in sulforaphane-treated MSTO-211H cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Aesthetic Play

    DEFF Research Database (Denmark)

    Bang, Jytte Susanne

    2012-01-01

    The present article explores the role of music-related artefacts and technologies in children’s lives. More specifically, it analyzes how four 10- to 11-year old girls use CDs and DVD games in their music-play activities and which developmental themes and potentials may accrue from such activities...... to the children’s complex life-worlds. Further, this leads to an analysis of music-play activities as play with an art-form (music), which includes aesthetic dimensions and gives the music-play activities its character of being aesthetic play. Following Lev Vygotsky’s insight that art is a way of building life...

  17. Playful Membership

    DEFF Research Database (Denmark)

    Åkerstrøm Andersen, Niels; Pors, Justine Grønbæk

    2014-01-01

    This article studies the implications of current attempts by organizations to adapt to a world of constant change by introducing the notion of playful organizational membership. To this end we conduct a brief semantic history of organizational play and argue that when organizations play, employees...... are expected to engage in playful exploration of alternative selves. Drawing on Niklas Luhmann's theory of time and decision-making and Gregory Bateson's theory of play, the article analyses three empirical examples of how games play with conceptions of time. We explore how games represent an organizational...... desire to reach out - not just to the future - but to futures beyond the future presently imaginable. The article concludes that playful membership is membership through which employees are expected to develop a surplus of potential identities and continuously cross boundaries between real and virtual...

  18. Art of Play

    DEFF Research Database (Denmark)

    Froes, Isabel Cristina G.; Walker, Kevin

    2011-01-01

    Play is a key element in cultural development, according to the Dutch historian Johan Huizinga. Nowadays many of us interact with other people in online games and social networks, through multiple digital devices. But harnessing playful activities for museum learning is mostly undeveloped. In thi...

  19. Art of Play

    DEFF Research Database (Denmark)

    Froes, Isabel Cristina G.; Walker, Kevin

    2011-01-01

    Play is a key element in cultural development, according to the Dutch historian Johan Huizinga. Nowadays many of us interact with other people in online games and social networks, through multiple digital devices. But harnessing playful activities for museum learning is mostly undeveloped. In thi...

  20. Magnolol causes alterations in the cell cycle in androgen insensitive human prostate cancer cells in vitro by affecting expression of key cell cycle regulatory proteins.

    Science.gov (United States)

    McKeown, Brendan T; McDougall, Luke; Catalli, Adriana; Hurta, Robert A R

    2014-01-01

    Prostate cancer, one of the most common cancers in the Western world, affects many men worldwide. This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on the behavior of 2 androgen insensitive human prostate cancer cell lines, DU145 and PC3, in vitro. Magnolol, in a 24-h exposure at 40 and 80 μM, was found to be cytotoxic to cells. Magnolol also affected cell cycle progression of DU145 and PC3 cells, resulting in alterations to the cell cycle and subsequently decreasing the proportion of cells entering the G2/M-phase of the cell cycle. Magnolol inhibited the expression of cell cycle regulatory proteins including cyclins A, B1, D1, and E, as well as CDK2 and CDK4. Protein expression levels of pRBp107 decreased and pRBp130 protein expression levels increased in response to magnolol exposure, whereas p16(INK4a), p21, and p27 protein expression levels were apparently unchanged post 24-h exposure. Magnolol exposure at 6 h did increase p27 protein expression levels. This study has demonstrated that magnolol can alter the behavior of androgen insensitive human prostate cancer cells in vitro and suggests that magnolol may have potential as a novel anti-prostate cancer agent.

  1. Structure, variation and expression analysis of glutenin gene promoters from Triticum aestivum cultivar Chinese Spring shows the distal region of promoter 1Bx7 is key regulatory sequence.

    Science.gov (United States)

    Wang, Kai; Zhang, Xue; Zhao, Ying; Chen, Fanguo; Xia, Guangmin

    2013-09-25

    In this study, ten glutenin gene promoters were isolated from model wheat (Triticum aestivum L. cv. Chinese Spring) using a genomic PCR strategy with gene-specific primers. Six belonged to high-molecular-weight glutenin subunit (HMW-GS) gene promoters, and four to low-molecular-weight glutenin subunit (LMW-GS). Sequence lengths varied from 1361 to 2,554 bp. We show that the glutenin gene promoter motifs are conserved in diverse sequences in this study, with HMW-GS and LMW-GS gene promoters characterized by distinct conserved motif combinations. Our findings show that HMW-GS promoters contain more functional motifs in the distal region of the glutenin gene promoter (> -700 bp) compared with LMW-GS. The y-type HMW-GS gene promoters possess unique motifs including RY repeat and as-2 box compared to the x-type. We also identified important motifs in the distal region of HMW-GS gene promoters including the 5'-UTR Py-rich stretch motif and the as-2 box motif. We found that cis-acting elements in the distal region of promoter 1Bx7 enhanced the expression of HMW-GS gene 1Bx7. Taken together, these data support efforts in designing molecular breeding strategies aiming to improve wheat quality. Our results offer insight into the regulatory mechanisms of glutenin gene expression.

  2. Playful Literacy

    DEFF Research Database (Denmark)

    Froes, Isabel

    2017-01-01

    these practices, which compose the taxonomy of tablet play. My contribution lies in identifying and proposing a series of theoretical concepts that complement recent theories related to play and digital literacy studies. The data collected through observations informed some noteworthy aspects, including how...... with tablets’ physical and digital affordances shape children’s digital play. This thesis presents how young children’s current practices when playing with tablets inform digital experiences in Denmark and Japan. Through an interdisciplinary lens and a grounded theory approach, I have identified and mapped...... vocabulary in children’s digital play experiences. These early digital experiences set the rules for the playgrounds and assert digital tablets as twenty-first-century toys, shaping young children’s playful literacy....

  3. Pretend play.

    Science.gov (United States)

    Weisberg, Deena Skolnick

    2015-01-01

    Pretend play is a form of playful behavior that involves nonliteral action. Although on the surface this activity appears to be merely for fun, recent research has discovered that children's pretend play has connections to important cognitive and social skills, such as symbolic thinking, theory of mind, and counterfactual reasoning. The current article first defines pretend play and then reviews the arguments and evidence for these three connections. Pretend play has a nonliteral correspondence to reality, hence pretending may provide children with practice with navigating symbolic relationships, which may strengthen their language skills. Pretend play and theory of mind reasoning share a focus on others' mental states in order to correctly interpret their behavior, hence pretending and theory of mind may be mutually supportive in development. Pretend play and counterfactual reasoning both involve representing nonreal states of affairs, hence pretending may facilitate children's counterfactual abilities. These connections make pretend play an important phenomenon in cognitive science: Studying children's pretend play can provide insight into these other abilities and their developmental trajectories, and thereby into human cognitive architecture and its development.

  4. Playful Interaction

    DEFF Research Database (Denmark)

    2003-01-01

    The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs...... as well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...

  5. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts....... In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  6. Play practices and play moods

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg

    2013-01-01

    The aim of this article is to develop a view of play as a relation between play practices and play moods based on an empirical study of children's everyday life and by using Bateson's term of ‘framing’ [(1955/2001). In Steps to an ecology of mind (pp. 75–80). Chicago: University of Chicago Press......], Schmidt's notion of ‘commonness’ [(2005). Om respekten. København: Danmarks Pædagogiske Universitets Forlag; (2011). On respect. Copenhagen: Danish School of Education University Press] and Heidegger's term ‘mood’ [(1938/1996). Time and being. Cornwall: Wiley-Blackwell.]. Play mood is a state of being...... in which we are open and ready, both to others and their production of meaning and to new opportunities for producing meaning. This play mood is created when we engage with the world during play practices. The article points out four types of play moods – devotion, intensity, tension and euphorica – which...

  7. Role of GnRH Neurons and Their Neuronal Afferents as Key Integrators between Food Intake Regulatory Signals and the Control of Reproduction

    Directory of Open Access Journals (Sweden)

    Juan Roa

    2013-01-01

    Full Text Available Reproductive function is regulated by a plethora of signals that integrate physiological and environmental information. Among others, metabolic factors are key components of this circuit since they inform about the propitious timing for reproduction depending on energy availability. This information is processed mainly at the hypothalamus that, in turn, modulates gonadotropin release from the pituitary and, thereby, gonadal activity. Metabolic hormones, such as leptin, insulin, and ghrelin, act as indicators of the energy status and convey this information to the reproductive axis regulating its activity. In this review, we will analyse the central mechanisms involved in the integration of this metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of GnRH, Kiss1, NPY, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction.

  8. Playful Organizations

    DEFF Research Database (Denmark)

    Pors, Justine Grønbæk; Åkerstrøm Andersen, Niels

    2015-01-01

    and undecidability. With an empirical point of departure in Danish public school policy and two concrete examples of games utilised in school development, the article analyses how play is a way for organisations to simultaneously decide and also avoid making a decision, thus keeping flexibility and possibilities...... intact. In its final sections, the article discusses what happens to conditions of decision-making when organisations do not just see undecidability as a given condition, but as a limited resource indispensable for change and renewal. The article advances discussions of organisational play by exploring......This article explores how organisational play becomes a managerial tool to increase and benefit from undecidability. The article draws on Niklas Luhmann's concept of decision and on Gregory Bateson's theory of play to create a conceptual framework for analysing the relation between decision...

  9. Conformational transitions of the catalytic domain of heme-regulated eukaryotic initiation factor 2α kinase, a key translational regulatory molecule.

    Science.gov (United States)

    Sreejith, R K; Suresh, C G; Bhosale, Siddharth H; Bhavnani, Varsha; Kumar, Avinash; Gaikwad, Sushama M; Pal, Jayanta K

    2012-01-01

    In mammalian cells, the heme-regulated inhibitor (HRI) plays a critical role in the regulation of protein synthesis at the initiation step through phosphorylation of α-subunit of the eukaryotic initiation factor 2 (eIF2). In this study we have cloned and performed biophysical characterization of the kinase catalytic domain (KD) of rabbit HRI. The KD described here comprises kinase 1, the kinase insertion domain (KI) and kinase 2. We report here the existence of an active and stable monomer of HRI (KD). The HRI (KD) containing three tryptophan residues was examined for its conformational transitions occurring under various denaturing conditions using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The parameter A and phase diagram analysis revealed multi-state unfolding and existence of three stable intermediates during guanidine hydrochloride (Gdn-HCl) induced unfolding of HRI (KD). The protein treated with 6 M Gdn-HCl showed collisional and static mechanism of acrylamide quenching and the constants (K(sv) = 3.08 M(-1) and K(s)= 5.62 M(-1)) were resolved using time resolved fluorescence titration. Based on pH, guanidine hydrochloride and temperature mediated transitions, HRI (KD) appears to exemplify a rigid molten globule-like intermediate with compact secondary structure, altered tertiary structure and exposed hydrophobic patches at pH 3.0. The results indicate the inherent structural stability of HRI (KD), a member of the class of stress response proteins.

  10. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    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...

  11. Group play

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    of group dynamics, the influence of the fictional game characters and the comparative play experience between the two formats. The results indicate that group dynamics and the relationship between the players and their digital characters, are integral to the quality of the gaming experience in multiplayer......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...

  12. Postphenomenological Play

    DEFF Research Database (Denmark)

    Hammar, Emil

    This paper aims to identify an understanding of digital games in virtual environments by using Don Ihde’s (1990) postphenomenological approach to how technology mediates the world to human beings in conjunction with Hans-Georg Gadamer’s (1993) notion of play . Through this tentatively proposed...... amalgamation of theories I point towards an alternative understanding of the relationship between play and game as not only dialectic, but also as socially and ethically relevant qua the design and implementation of the game as technology....

  13. The E3 Ubiquitin Ligase SCFTIR1/AFB and Membrane Sterols Play Key Roles in Auxin Regulation of Endocytosis, Recycling, and Plasma Membrane Accumulation of the Auxin Efflux Transporter PIN2 in Arabidopsis thaliana[C][W][OA

    Science.gov (United States)

    Pan, Jianwei; Fujioka, Shozo; Peng, Jianling; Chen, Jianghua; Li, Guangming; Chen, Rujin

    2009-01-01

    The PIN family of auxin efflux transporters exhibit polar plasma membrane (PM) localization and play a key role in auxin gradient-mediated developmental processes. Auxin inhibits PIN2 endocytosis and promotes its PM localization. However, the underlying mechanisms remain elusive. Here, we show that the inhibitory effect of auxin on PIN2 endocytosis was impaired in SCFTIR1/AFB auxin signaling mutants. Similarly, reducing membrane sterols impaired auxin inhibition of PIN2 endocytosis. Gas chromatography–mass spectrometry analyses indicate that membrane sterols were significantly reduced in SCFTIR1/AFB mutants, supporting a link between membrane sterols and auxin signaling in regulating PIN2 endocytosis. We show that auxin promoted PIN2 recycling from endosomes to the PM and increased PIN2 steady state levels in the PM fraction. Furthermore, we show that the positive effect of auxin on PIN2 levels in the PM was impaired by inhibiting membrane sterols or auxin signaling. Consistent with this, the sterol biosynthetic mutant fk-J79 exhibited pronounced defects in primary root elongation and gravitropic response. Our data collectively indicate that, although there are distinct processes involved in endocytic regulation of specific PM-resident proteins, the SCFTIR1/AFB-dependent processes are required for auxin regulation of endocytosis, recycling, and PM accumulation of the auxin efflux transporter PIN2 in Arabidopsis thaliana. PMID:19218398

  14. Clay Play

    Science.gov (United States)

    Rogers, Liz; Steffan, Dana

    2009-01-01

    This article describes how to use clay as a potential material for young children to explore. As teachers, the authors find that their dialogue about the potential of clay as a learning medium raises many questions: (1) What makes clay so enticing? (2) Why are teachers noticing different play and conversation around the clay table as compared to…

  15. Group play

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects of the v......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...... RPGs, with the first being of greater importance to digital games and the latter to the tabletop version....

  16. Regulatory T Cells: Molecular Actions on Effector Cells in Immune Regulation

    Directory of Open Access Journals (Sweden)

    Asiel Arce-Sillas

    2016-01-01

    Full Text Available T regulatory cells play a key role in the control of the immune response, both in health and during illness. While the mechanisms through which T regulatory cells exert their function have been extensively described, their molecular effects on effector cells have received little attention. Thus, this revision is aimed at summarizing our current knowledge on those regulation mechanisms on the target cells from a molecular perspective.

  17. Playing Possum

    Directory of Open Access Journals (Sweden)

    Enrico Euli

    2016-07-01

    Full Text Available Our society is drenched in the catastrophe; where the growth of financial crisis, environmental cataclysm and militarization represents its gaudiest and mortifying phenomena. Humans struggle with depression, sense of impotence, anguish towards a future considered a threat.  A possibility to keep us alive can be represented by the enhancement of our ability in ‘playing Possum’, an exercise of desisting and renitence: to firmly say ‘no’. To say no to a world that proposes just one way of being and living free, that imposes as the only unavoidable possible destiny.

  18. Playful Technology

    DEFF Research Database (Denmark)

    Johansen, Stine Liv; Eriksson, Eva

    2013-01-01

    In this paper, the design of future services for children in Danish public libraries is discussed, in the light of new challenges and opportunities in relation to new media and technologies. The Danish government has over the last few years initiated and described a range of initiatives regarding...... in the library, the changing role of the librarians and the library space. We argue that intertwining traditional library services with new media forms and engaging play is the core challenge for future design in physical public libraries, but also that it is through new media and technology that new...

  19. Playful Technology

    DEFF Research Database (Denmark)

    Johansen, Stine Liv; Eriksson, Eva

    2013-01-01

    in the library, the changing role of the librarians and the library space. We argue that intertwining traditional library services with new media forms and engaging play is the core challenge for future design in physical public libraries, but also that it is through new media and technology that new......In this paper, the design of future services for children in Danish public libraries is discussed, in the light of new challenges and opportunities in relation to new media and technologies. The Danish government has over the last few years initiated and described a range of initiatives regarding...

  20. Playing cards.

    Science.gov (United States)

    1977-01-01

    Mrs. Zahia Marzouk, vice-president of the Alexandria Family Planning Association and a living legend of Egyptian family planning, does not believe in talking about problems. She is far too busy learning from people and teaching them. Her latest brainstorm is a set of playing cards designed to help girls and women to read and learn about family planning at the same time. The 5 packs of cards, representing familiar words and sounds, and each with a family planning joker, took Mrs. Marzouk 6 months to design and paint by hand. They have now been printed, packed into packets provided by UNICEF, and distributed to some 2000 literacy groups in factories and family planning clinics. Each woman who succeeds in learning to read is encouraged to teach 4 others. They then go to the family planning clinic to be examined and gain a certificate. For the teacher who has made them proficient there is a special prize. Girls at El Brinth village outside Alexandria are pictured playing cards at the family planning center where they are learning various skills including how to read.

  1. Regulatory T cell memory

    Science.gov (United States)

    Rosenblum, Michael D.; Way, Sing Sing; Abbas, Abul K.

    2016-01-01

    Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime challenge models of infection. However, recent work has also identified persistently expanded populations of antigen-specific regulatory T cells that protect against aberrant immune responses. In this Review, we consider the parallels between memory effector T cells and memory regulatory T cells, along with the functional implications of regulatory memory in autoimmunity, antimicrobial host defence and maternal fetal tolerance. In addition, we discuss emerging evidence for regulatory T cell memory in humans and key unanswered questions in this rapidly evolving field. PMID:26688349

  2. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  3. PlayFit: Designing playful activity interventions for teenagers

    NARCIS (Netherlands)

    M. M. Deen; Rob Tieben; Dr. Tilde Bekker; Dr. Janienke Sturm; B.A.M. Ben Schouten

    2011-01-01

    Young people spend a large part of their day sedentary, both at school and at home. The aim of the PlayFit project is to persuade teenagers to lead a more active lifestyle by using digital as well as non-digital games and play. In this position paper, we describe in detail the three key principles o

  4. Functional interaction of hepatic nuclear factor-4 and peroxisome proliferator-activated receptor-gamma coactivator 1alpha in CYP7A1 regulation is inhibited by a key lipogenic activator, sterol regulatory element-binding protein-1c.

    Science.gov (United States)

    Ponugoti, Bhaskar; Fang, Sungsoon; Kemper, Jongsook Kim

    2007-11-01

    Insulin inhibits transcription of cholesterol 7alpha-hydroxylase (Cyp7a1), a key gene in bile acid synthesis, and the hepatic nuclear factor-4 (HNF-4) site in the promoter was identified as a negative insulin response sequence. Using a fasting/feeding protocol in mice and insulin treatment in HepG2 cells, we explored the inhibition mechanisms. Expression of sterol regulatory element-binding protein-1c (SREBP-1c), an insulin-induced lipogenic factor, inversely correlated with Cyp7a1 expression in mouse liver. Interaction of HNF-4 with its coactivator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), was observed in livers of fasted mice and was reduced after feeding. Conversely, HNF-4 interaction with SREBP-1c was increased after feeding. In vitro studies suggested that SREBP-1c competed with PGC-1alpha for direct interaction with the AF2 domain of HNF-4. Reporter assays showed that SREBP-1c, but not of a SREBP-1c mutant lacking the HNF-4 interacting domain, inhibited HNF-4/PGC-1alpha transactivation of Cyp7a1. SREBP-1c also inhibited PGC-1alpha-coactivation of estrogen receptor, constitutive androstane receptor, pregnane X receptor, and farnesoid X receptor, implying inhibition of HNF-4 by SREBP-1c could extend to other nuclear receptors. In chromatin immunoprecipitation studies, HNF-4 binding to the promoter was not altered, but PGC-1alpha was dissociated, SREBP-1c and histone deacetylase-2 (HDAC2) were recruited, and acetylation of histone H3 was decreased upon feeding. Adenovirus-mediated expression of a SREBP-1c dominant-negative mutant, which blocks the interaction of SREBP-1c and HNF-4, partially but significantly reversed the inhibition of Cyp7a1 after feeding. Our data show that SREBP-1c functions as a non-DNA-binding inhibitor and mediates, in part, suppression of Cyp7a1 by blocking functional interaction of HNF-4 and PGC-1alpha. This mechanism may be relevant to known repression of many other HNF-4 target genes upon

  5. The theory of the regulatory bodies and the CSN; La teoria de las entidades reguladoras y el CSN

    Energy Technology Data Exchange (ETDEWEB)

    Gamir Casares, L.

    2011-07-01

    In this article the vice president of the Nuclear Safety Council and professor of Economics and Politics, Luis Gamir, analyses the theoretical nature of the role played by regulatory organisations in democratic societies and the keys of their credibility, with special reference to the Council and the Strategic Plan recently approved for the period 2011-2016. (Author)

  6. Glucokinase regulatory proten genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

    Science.gov (United States)

    Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3...

  7. Human CD45RA(-) FoxP3(hi) Memory-Type Regulatory T Cells Show Distinct TCR Repertoires With Conventional T Cells and Play an Important Role in Controlling Early Immune Activation.

    Science.gov (United States)

    Lei, H; Kuchenbecker, L; Streitz, M; Sawitzki, B; Vogt, K; Landwehr-Kenzel, S; Millward, J; Juelke, K; Babel, N; Neumann, A; Reinke, P; Volk, H-D

    2015-10-01

    Adoptive immunotherapy with regulatory T cells (Treg) is a new option to promote immune tolerance following solid organ transplantation (SOT). However, Treg from elderly patients awaiting transplantation are dominated by the CD45RA(-) CD62L(+) central memory type Treg subset (TregCM), and the yield of well-characterized and stable naïve Treg (TregN) is low. It is, therefore, important to determine whether these TregCM are derived from the thymus and express high stability, suppressive capacity and a broad antigen repertoire like TregN. In this study, we showed that TregCM use a different T cell receptor (TCR) repertoire from conventional T cells (Tconv), using next-generation sequencing of all 24 Vβ families, with an average depth of 534 677 sequences. This showed almost no contamination with induced Treg. Furthermore, TregCM showed enhanced suppressive activity on Tconv at early checkpoints of immune activation controlling activation markers expression and cytokine secretion, but comparable inhibition of proliferation. Following in vitro expansion under mTOR inhibition, TregCM expanded equally as well as TregN without losing their function. Despite relatively limited TCR repertoire, TregCM also showed specific alloresponse, although slightly reduced compared to TregN. These results support the therapeutic usefulness of manufacturing Treg products from CD45RA(-) CD62L(+) Treg-enriched starting material to be applied for adoptive Treg therapy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. Se14, encoding a JmjC domain-containing protein, plays key roles in long-day suppression of rice flowering through the demethylation of H3K4me3 of RFT1.

    Directory of Open Access Journals (Sweden)

    Takayuki Yokoo

    Full Text Available Floral transition from the vegetative to the reproductive growth phase is a major change in the plant life cycle and a key factor in reproductive success. In rice (Oryza sativa L., a facultative short-day plant, numerous flowering time and flower formation genes that control floral transition have been identified and their physiological effects and biochemical functions have been clarified. In the present study, we used a Se14-deficient mutant line (HS112 and other flowering mutant lines to investigate the photoperiodic response, chromosomal location and function in the photoperiod sensitivity of the Se14 gene. We also studied the interactive effects of this locus with other crucial flowering time genes. We found that Se14 is independent of the known photoperiod-sensitive genes, such as Hd1 and Ghd7, and is identical to Os03g0151300, which encodes a Jumonji C (JmjC domain-containing protein. Expression analysis revealed that the expressions of RFT1, a floral initiator known as a "florigen-like gene", and Ehd1 were up-regulated in HS112, whereas this up-regulation was not observed in the original variety of 'Gimbozu'. ChIP assays of the methylation states of histone H3 at lysine 4 (H3K4 revealed that the trimethylated H3K4 in the promoter region of the RFT1 chromatin was significantly increased in HS112. We conclude that Se14 is a novel photoperiod-sensitivity gene that has a suppressive effect on floral transition (flowering time under long day-length conditions through the modification of chromatin structure by H3K4me3 demethylation in the promoter region of RFT1.

  9. 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....

  10. HMGB1-TLR4 Axis Plays a Regulatory Role in the Pathogenesis of Mesial Temporal Lobe Epilepsy in Immature Rat Model and Children via the p38MAPK Signaling Pathway.

    Science.gov (United States)

    Yang, Weihong; Li, Jing; Shang, Yun; Zhao, Li; Wang, Mingying; Shi, Jipeng; Li, Shujun

    2017-02-07

    The HMGB1-TLR4 axis is activated in adult mouse models of acute and chronic seizure. Nevertheless, whether HMGB1 was involved in the pathogenesis of mesial temporal lobe epilepsy (MTLE) remains unknown. In this study, we first measured the dynamic expression patterns of HMGB1 and TLR4 in the hippocampi of a rat model and in children with MTLE, as well as the levels of TNF-α and IL-1β. In addition, HMGB1 was added to mimic the process of inflammatory response in neurons. Neuronal somatic size and dendritic length were measured by immunohistochemistry and digital imaging. The results showed that the expression of HMGB1 and TLR4 as well as the levels of TNF-α and IL-1β were higher in the three stages of MTLE development in the rat model and in the children with MTLE. HMGB1 increased the levels of TNF-α and IL-1β, upregulated the protein level of p-p38MAPK and promoted the growth of cell somatic size and dendritic length in neurons. Pre-treatment with p38MAPK inhibitor SB203580 decreased the levels of TNF-α and IL-1β, while downregulation of TLR4 significantly reduced HMGB1-induced p38MAPK signaling pathway activation. These data demonstrated that the HMGB1-TLR4 axis may play an important role in the pathogenesis of MTLE via the p38MAPK signaling pathway.

  11. 磷酸酶STEP的Q-loop中T541参与催化反应的机制%T541 in Q-loop of STEP plays a key role in the catalytical activity

    Institute of Scientific and Technical Information of China (English)

    谢迪东; 龚正; 李容; 李慧; 刘宏达; 孙金鹏; 庞琦

    2013-01-01

    Objective To explore the essential role of Threonine at position 541 and 330 (T541,T330)in the intrinsic phosphatase activity of striatal-enriched protein tyrosine phosphatase (STEP).Methods STEP wild type (STEP-WT) and its mutants STEP-T330D/T541A were sub-cloned into the PET15b vector.Expression and purification of STEP-WT and its mutants were performed by affinity column and liquid chromatography.The phosphatase activity was measured in vitro with 4-nitrophenyl phosphate (pNPP) as substrate.The inhibition by NaVO3 was measured to monitor the effects of mutants on protein folding.The pH-dependence and leaving-group pKa dependence of STEP catalysis were carded out to dissect the underlying molecular mechanism.Results STEP-WT and STEP-T330D displayed similar catalytic ability toward pNPP at pH 7.0.The kcat of STEP-T541 A decreased 3 folds compared to STEP-WT.STEP-WT and the two mutants had similar Ki for NaVO3.Examination of the kcat versus pH curve revealed that pK2app of STEP-T541A significantly increased and the (kcat) lim dropped by at least 10 folds.In consisitent with these observations,βlg (kcat) of STEP-T541A increased significantly.Conclusion T541 plays an important role in STEP catalysis,by participating the processes from product formation to phosphate release.Future drugs targeting to STEP for therapeutic usage could be developed through modulating T541 conformations.%目的 研究纹状体蛋白质酪氨酸磷酸酶(STEP) pY-loop结构上第330位的苏氨酸(T330)和Q-loop结构上第541位的苏氨酸(T541)参与催化反应的作用机制.方法 构建STEP野生型(STEP-WT)及其突变体(STEP-T330D/T541A)的表达质粒;表达并纯化STEP-WT及其突变体蛋白,体外检测这些蛋白对小分子底物4-硝基苯磷酸二钠(pNPP)的催化活力,分析NaVO3对STEP-WT及其突变体酶活性的抑制作用;检测STEP-WT及其突变体催化反应的pH依赖性和对解离基团pKa的依赖性.结果 体外催

  12. Local neurons play key roles in the mammalian olfactory bulb.

    Science.gov (United States)

    Saghatelyan, Armen; Carleton, Alan; Lagier, Samuel; de Chevigny, Antoine; Lledo, Pierre-Marie

    2003-01-01

    Over the past few decades, research exploring how the brain perceives, discriminates, and recognizes odorant molecules has received a growing interest. Today, olfaction is no longer considered a matter of poetry. Chemical senses entered the biological era when an increasing number of scientists started to elucidate the early stages of the olfactory pathway. A combination of genetic, biochemical, cellular, electrophysiological and behavioral methods has provided a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. Our group is exploring the physiology of the main olfactory bulb, the first processing relay in the mammalian brain. From different electrophysiological approaches, we are attempting to understand the cellular rules that contribute to the synaptic transmission and plasticity at this central relay. How olfactory sensory inputs, originating from the olfactory epithelium located in the nasal cavity, are encoded in the main olfactory bulb remains a crucial question for understanding odor processing. More importantly, the persistence of a high level of neurogenesis continuously supplying the adult olfactory bulb with newborn local neurons provides an attractive model to investigate how basic olfactory functions are maintained when a large proportion of local neurons are continuously renewed. For this purpose, we summarize the current ideas concerning the molecular mechanisms and organizational strategies used by the olfactory system to encode and process information in the main olfactory bulb. We discuss the degree of sensitivity of the bulbar neuronal network activity to the persistence of this high level of neurogenesis that is modulated by sensory experience. Finally, it is worth mentioning that analyzing the molecular mechanisms and organizational strategies used by the olfactory system to transduce, encode, and process odorant information in the olfactory bulb should aid in understanding the general neural mechanisms involved in both sensory perception and memory. Due to space constraints, this review focuses exclusively on the olfactory systems of vertebrates and primarily those of mammals.

  13. Landsat plays a key role in reducing hunger on earth

    Science.gov (United States)

    ,

    2016-08-24

    The United Nations’ Department of Economic and Social Affairs predicts 9.7 billion people will sit down every day to the global dinner table by 2050. If this prediction is correct, the world is going to need more crops, more livestock, and more efficient agricultural practices.

  14. Parliamentarians play key role in linking population and social development.

    Science.gov (United States)

    1995-01-01

    Mr. Hirofunti Ando, Deputy Executive Director of the UNFPA, delivered the statement of Dr. Nafis Sadik, Executive Director of the UNFPA at the International Meeting of Parliamentarians on Population and Social Development. The International Conference of Parliamentarians on Population and Development (ICPPD) in Cairo in September 1994 made a significant impact on the attitudes and support of parliamentarians regarding population issues. The Asian Forum of Parliamentarians on Population and Development (AFPPD) brought together a group of parliamentarians from all over the world to discuss population issues and social development. The World Summit included in its deliberations the accumulated experiences of earlier international conferences dealing with social economic issues. The ICPD Program of Action addressed concerns relevant to the agenda of the Social Summit: the crucial contribution that early population stabilization will make towards the attainment of sustainable development; the significant role of integrated policies on population and development in creating employment; the importance of population policies and programs in alleviating poverty; the contributions of reproductive health policies, including high-quality family planning services, to the enhancement of the status of women and to the achievement of gender equality; the synergy between education, family planning, and the general improvement of the human condition; and the relationship between population pressures, poverty, and environmental degradation. The ICPD Program of Action also identified critically important population and development objectives, such as ensuring access to education, especially of girls; reducing infant, child, and maternal mortality; and providing universal access to reproductive health and family planning services. Now the challenge is to mobilize the necessary resources for the Social Summit.

  15. Focal osteoporosis defects play a key role in hip fracture.

    Science.gov (United States)

    Poole, Kenneth E S; Skingle, Linda; Gee, Andrew H; Turmezei, Thomas D; Johannesdottir, Fjola; Blesic, Karen; Rose, Collette; Vindlacheruvu, Madhavi; Donell, Simon; Vaculik, Jan; Dungl, Pavel; Horak, Martin; Stepan, Jan J; Reeve, Jonathan; Treece, Graham M

    2017-01-01

    Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. 构建重庆市食品安全监控体系的要点研究%Study on key points of food safety regulatory system construction in Chongqing

    Institute of Scientific and Technical Information of China (English)

    郑炯; 杨琳; 丁涌波; 舒开奎; 阚建全

    2015-01-01

    随着经济的发展,人们的生活水平有了很大的提高,但食品安全问题却层出不穷,各国政府和消费者对食品安全给予了前所未有的关注。食品安全问题在全世界范围内会随着食品的产业化和规模化,随着新物质和新技术的涌现而越来越复杂化。为进一步完善重庆市食品安全监控体系,提高食品安全监管水平,促进食品产业健康发展,本文从食品企业和食品安全监管部门两方面对目前重庆市食品安全监管存在的问题进行了剖析。在借鉴国内外食品安全监管成功经验的基础上,结合重庆实际,从法规标准体系、检验检测体系、过程控制体系、应急管理体系等四个方面探讨了重庆市食品安全监管体系的构建要点。%With the development of economy, people's living standards have been greatly improved, but the crisis of food safety also has been becoming worse. The governments and consumers all over the world have focused on the problems of food safety. Food safety issues will be complex with the mechanization and centralization of food products and will intricacy when food industries use more new materials and new technologies. To further improve the Chongqing food safety regulatory system and the level of food safety supervision, and to promote the healthy development of the food industry, we carried on the analysis to the existing problems of Chongqing food safety regulatory system from food companies and food safety supervision department. Based on the successful experience of domestic and international food safety supervision and the reality of Chongqing, this paper discussed the construction of Chongqing food safety regulatory system from four aspects: regulations and standards system, inspection system, process control system, and emergency management system.

  17. The Political Communication of Independent Regulatory Agencies

    National Research Council Canada - National Science Library

    Puppis, Manuel; Maggetti, Martino; Gilardi, Fabrizio; Biela, Jan; Papadopoulos, Yannis

    2014-01-01

    .... In this context, public communication plays an important role. On the one hand, regulatory agencies might try to use communication to raise their accountability and thereby to mitigate their democratic deficit...

  18. Depth keying

    Science.gov (United States)

    Gvili, Ronen; Kaplan, Amir; Ofek, Eyal; Yahav, Giora

    2003-05-01

    We present a new solution to the known problem of video keying in a natural environment. We segment foreground objects from background objects using their relative distance from the camera, which makes it possible to do away with the use of color for keying. To do so, we developed and built a novel depth video camera, capable of producing RGB and D signals, where D stands for the distance to each pixel. The new RGBD camera enables the creation of a whole new gallery of effects and applications such as multi-layer background substitutions. This new modality makes the production of real time mixed reality video possible, as well as post-production manipulation of recorded video. We address the problem of color spill -- in which the color of the foreground object is mixed, along its boundary, with the background color. This problem prevents an accurate separation of the foreground object from its background, and it is most visible when compositing the foreground objects to a new background. Most existing techniques are limited to the use of a constant background color. We offer a novel general approach to the problem with enabling the use of the natural background, based upon the D channel generated by the camera.

  19. Significant roles played by interleukin-10 in outcome of pregnancy.

    Science.gov (United States)

    Mobini, Masoud; Mortazavi, Maryam; Nadi, Somayeh; Zare-Bidaki, Mohammad; Pourtalebi, Somayeh; Arababadi, Mohammad Kazemi

    2016-02-01

    Imbalanced immune responses against fetus alloantigens can lead to abnormality in pregnancy. Interleukin-10 (IL-10) plays key roles in regulation of immune responses against self and foreign antigens to induce tolerance to these antigens. Therefore, alteration in expression of IL-10 during pregnancy may result in several pathologic conditions such as preterm labor. IL-10 leads to a normal pregnancy via several molecular mechanisms including development of tolerogenic dendritic cells, T regulatory lymphocytes and activation of the JAK1/STAT3 pathway in the target cells. This review has collected recent data regarding the status of IL-10 expression during term and preterm deliveries and also its molecular mechanisms that lead to a normal pregnancy.

  20. Significant roles played by interleukin-10 in outcome of pregnancy

    Directory of Open Access Journals (Sweden)

    Masoud Mobini

    2016-02-01

    Full Text Available Imbalanced immune responses against fetus alloantigens can lead to abnormality in pregnancy. Interleukin-10(IL-10 plays key roles in regulation of immune responses against self and foreign antigens to induce tolerance to these antigens. Therefore, alteration in expression of IL-10 during pregnancy may result in several pathologic conditions such as preterm labor. IL-10 leads to a normal pregnancy via several molecular mechanisms including development of tolerogenic dendritic cells, T regulatory lymphocytes and activation of the JAK1/STAT3 pathway in the target cells. This review has collected recent data regarding the status of IL-10 expression during term and preterm deliveries and also its molecular mechanisms that lead to a normal pregnancy.

  1. Children's Empowerment in Play

    Science.gov (United States)

    Canning, Natalie

    2007-01-01

    This article examines the level of empowerment and autonomy children can create in their play experiences. It examines the play discourses that children build and maintain and considers the importance of play contexts in supporting children's emotional and social development. These aspects of play are often unseen or misunderstood by the adult…

  2. The Play of Psychotherapy

    Science.gov (United States)

    Marks-Tarlow, Terry

    2012-01-01

    The author reviews the role of play within psychotherapy. She does not discuss the formal play therapy especially popular for young children, nor play from the Jungian perspective that encourages the use of the sand tray with adults. Instead, she focuses on the informal use of play during psychotherapy as it is orchestrated intuitively. Because…

  3. Two people playing together: some thoughts on play, playing, and playfulness in psychoanalytic work.

    Science.gov (United States)

    Vliegen, Nicole

    2009-01-01

    Children's play and the playfulness of adolescents and adults are important indicators of personal growth and development. When a child is not able to play, or an adolescent/adult is not able to be playful with thoughts and ideas, psychotherapy can help to find a more playful and creative stance. Elaborating Winnicott's (1968, p. 591) statement that "psychotherapy has to do with two people playing together," three perspectives on play in psychotherapy are discussed. In the first point of view, the child gets in touch with and can work through aspects of his or her inner world, while playing in the presence of the therapist. The power of play is then rooted in the playful communication with the self In a second perspective, in play the child is communicating aspects of his or her inner world to the therapist as a significant other. In a third view, in "playing together" child and therapist are coconstructing new meanings. These three perspectives on play are valid at different moments of a therapy process or for different children, depending on the complex vicissitudes of the child's constitution, life experiences, development, and psychic structure. Concerning these three perspectives, a parallel can be drawn between the therapist's attitude toward the child's play and the way the therapist responds to the verbal play of an adolescent or adult. We illustrate this with the case of Jacob, a late adolescent hardly able to play with ideas.

  4. Applying Play to Therapy.

    Science.gov (United States)

    Ritter, Patricia S.; Fokes, Joann

    The objectives of this paper are (1) to present the relationship of play to language and cognition, (2) to describe the stages of play and discuss recent literature about the characteristics of play, and (3) to describe the use of play with the multifaceted goals of cognition, pragmatics, semantics, syntax, and morphology as an intervention…

  5. Gender differences in preschool children's play

    OpenAIRE

    Tarman Starc, Ana

    2015-01-01

    The goal of the final thesis is to shed some light on gender-based differences which can be observed in the way preschool children (aged 3 to 6) play, focusing on differences in the type of play, the size of play groups of boys and girls as well as differences in their playing behaviour with special focus on prosocial and aggressive behaviour. Moreover, the educators' attitude towards play is examined, i.e. how they intervene in the play of boy and girls. In the theoretical part the key c...

  6. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  7. The play grid

    DEFF Research Database (Denmark)

    Fogh, Rune; Johansen, Asger

    2013-01-01

    In this paper we propose The Play Grid, a model for systemizing different play types. The approach is psychological by nature and the actual Play Grid is based, therefore, on two pairs of fundamental and widely acknowledged distinguishing characteristics of the ego, namely: extraversion vs...... at the Play Grid. Thus, the model has four quadrants, each of them describing one of four play types: the Assembler, the Director, the Explorer, and the Improviser. It is our hope that the Play Grid can be a useful design tool for making entertainment products for children....

  8. An efficient approach of attractor calculation for large-scale Boolean gene regulatory networks.

    Science.gov (United States)

    He, Qinbin; Xia, Zhile; Lin, Bin

    2016-11-07

    Boolean network models provide an efficient way for studying gene regulatory networks. The main dynamics of a Boolean network is determined by its attractors. Attractor calculation plays a key role for analyzing Boolean gene regulatory networks. An approach of attractor calculation was proposed in this study, which improved the predecessor-based approach. Furthermore, the proposed approach combined with the identification of constant nodes and simplified Boolean networks to accelerate attractor calculation. The proposed algorithm is effective to calculate all attractors for large-scale Boolean gene regulatory networks. If the average degree of the network is not too large, the algorithm can get all attractors of a Boolean network with dozens or even hundreds of nodes.

  9. [Role of genes and their cis-regulatory elements during animal morphological evolution].

    Science.gov (United States)

    Sun, Boyuan; Tu, Jianbo; Li, Ying; Yang, Mingyao

    2014-06-01

    Cis-regulatory hypothesis is one of the most important theories in evolutionary developmental biology (evo-devo), which claims that evolution of cis-regulatory elements (CREs) plays a key role during evolution of morphology. However, an increasing number of experimental results show that cis-regulatory hypothesis alone is not far enough to explain the complexity of evo-devo processes. Other modifications, including mutations of protein coding, gene and genome duplications, and flexibility of homeodomains and CREs, also cause the morphological changes in animals. In this review, we retrospect the recent results of evolution of CREs and genes associated with CREs and discuss new methods and trends for research in evo-devo.

  10. Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

    Science.gov (United States)

    Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

    2006-07-01

    Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

  11. Role-Playing Mitosis.

    Science.gov (United States)

    Wyn, Mark A.; Stegink, Steven J.

    2000-01-01

    Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

  12. Play the Tuberculosis Game

    Science.gov (United States)

    ... Questionnaire Tuberculosis Play Tuberculosis Experiments & Discoveries About the game Discover and experience some of the classic methods ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  13. Play the MRI Game

    Science.gov (United States)

    ... Teachers' Questionnaire MRI Play MRI the Magnetic Miracle Game About the game In the MRI imaging technique, strong magnets and ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  14. Play the Electrocardiogram Game

    Science.gov (United States)

    ... and Work Teachers' Questionnaire Electrocardiogram Play the ECG Game About the game ECG is used for diagnosing heart conditions by ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  15. Learning Through Play

    Science.gov (United States)

    ... play, such as using play dough, LEGOs, and board games. Toys such as puzzles, pegboards, beads, and lacing ... Building sets, books, bicycles, roller skates, ice skates, board games, checkers, beginning sports • Middle Schoolers and Adolescents: Athletics, ...

  16. Children, Time, and Play

    DEFF Research Database (Denmark)

    Elkind, David; Rinaldi, Carla; Flemmert Jensen, Anne;

    Proceedings from the conference "Children, Time, and Play". Danish University of Education, January 30th 2003.......Proceedings from the conference "Children, Time, and Play". Danish University of Education, January 30th 2003....

  17. Role-Playing Mitosis.

    Science.gov (United States)

    Wyn, Mark A.; Stegink, Steven J.

    2000-01-01

    Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

  18. Play at Work

    DEFF Research Database (Denmark)

    Meier Sørensen, Bent; Spoelstra, Sverre

    2012-01-01

    for business and the other insists that work and play are largely indistinguishable in the postindustrial organization. Our field study of a design and communications company in Denmark shows that organizational play can be much more than just functional to the organization. We identify three ways in which......The interest in organizational play is growing, both in popular business discourse and organization studies. As the presumption that play is dysfunctional for organizations is increasingly discarded, the existing positions may be divided into two camps; one proposes ‘serious play’ as an engine...... workplaces engage in play: play as a (serious) continuation of work, play as a (critical) intervention into work and play as an (uninvited) usurpation of work....

  19. The core regulatory network in human cells.

    Science.gov (United States)

    Kim, Man-Sun; Kim, Dongsan; Kang, Nam Sook; Kim, Jeong-Rae

    2017-03-04

    In order to discover the common characteristics of various cell types in the human body, many researches have been conducted to find the set of genes commonly expressed in various cell types and tissues. However, the functional characteristics of a cell is determined by the complex regulatory relationships among the genes rather than by expressed genes themselves. Therefore, it is more important to identify and analyze a core regulatory network where all regulatory relationship between genes are active across all cell types to uncover the common features of various cell types. Here, based on hundreds of tissue-specific gene regulatory networks constructed by recent genome-wide experimental data, we constructed the core regulatory network. Interestingly, we found that the core regulatory network is organized by simple cascade and has few complex regulations such as feedback or feed-forward loops. Moreover, we discovered that the regulatory links from genes in the core regulatory network to genes in the peripheral regulatory network are much more abundant than the reverse direction links. These results suggest that the core regulatory network locates at the top of regulatory network and plays a role as a 'hub' in terms of information flow, and the information that is common to all cells can be modified to achieve the tissue-specific characteristics through various types of feedback and feed-forward loops in the peripheral regulatory networks. We also found that the genes in the core regulatory network are evolutionary conserved, essential and non-disease, non-druggable genes compared to the peripheral genes. Overall, our study provides an insight into how all human cells share a common function and generate tissue-specific functional traits by transmitting and processing information through regulatory network.

  20. Playing with social identities

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2013-01-01

    This chapter offers support for Vygotsky’s claim that all play involves both an imagined situation as well as rules. Synthesising Schousboe’s comprehensive model of spheres of realities in playing (see Chapter 1, this volume) with Lev Vygotskys insight that all playing involve rules as well...

  1. Toddlers: Learning by Playing

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Toddlers: Learning by Playing KidsHealth > For Parents > Toddlers: Learning by Playing Print A A A What's in ... child's play, but toddlers are hard at work learning important physical skills as they gain muscle control, ...

  2. Playing against the Game

    Science.gov (United States)

    Remmele, Bernd

    2017-01-01

    The paper first outlines a differentiation of play/game-motivations that include "negative" attitudes against the play/game itself like cheating or spoilsporting. This problem is of particular importance in concern of learning games because they are not "played" for themselves--at least in the first place--but due to an…

  3. Play the Mosquito Game

    Science.gov (United States)

    ... and Work Teachers' Questionnaire Malaria Play the Mosquito Game Play the Parasite Game About the games Malaria is one of the world's most common ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  4. (Steering) interactive play behavior

    NARCIS (Netherlands)

    Delden, van Robertus Wilhelmus

    2017-01-01

    Play is a powerful means to have an impact on the cognitive, social-emotional, and/or motor skills development. The introduction of technology brings new possibilities to provide engaging and entertaining whole-body play activities. Technology mediates the play activities and in this way changes how

  5. (Steering) interactive play behavior

    NARCIS (Netherlands)

    van Delden, Robertus Wilhelmus

    2017-01-01

    Play is a powerful means to have an impact on the cognitive, social-emotional, and/or motor skills development. The introduction of technology brings new possibilities to provide engaging and entertaining whole-body play activities. Technology mediates the play activities and in this way changes how

  6. Reviewing the regulatory barriers for nanomedicine: global questions and challenges.

    Science.gov (United States)

    Bowman, Diana M; Gatof, Jake

    2015-01-01

    Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine.

  7. Playing with social identities

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2013-01-01

    This chapter offers support for Vygotsky’s claim that all play involves both an imagined situation as well as rules. Synthesising Schousboe’s comprehensive model of spheres of realities in playing (see Chapter 1, this volume) with Lev Vygotskys insight that all playing involve rules as well...... as pretence, children’s play is understood as an activity involving rules of the social order (roles and positions) as well as identification processes (imagined situations). The theoretical argumentation builds on empirical examples obtained in two different Danish day-care centres. The chapter is informed...... by ethnographic observations and draws on illustrative examples with symbolic group play as well as game-play with rules (soccer) among 5 year old boys. Findings suggest that day-care children’s play, involves negotiation of roles, positioning and identification, and rules – and that these negotiations...

  8. Teaching about the French Revolution--A Play.

    Science.gov (United States)

    Pezone, Michael

    2002-01-01

    Presents a play about the French Revolution, discussing how the play was used within a global history course. States that students read the play, work in groups to rewrite the play, and perform their version of the play. Includes key questions that are asked of the students. (CMK)

  9. Molecular profiling of gene copy number abnormalities in key regulatory genes in high-risk B-lineage acute lymphoblastic leukemia: frequency and their association with clinicopathological findings in Indian patients.

    Science.gov (United States)

    Bhandari, Prerana; Ahmad, Firoz; Das, Bibhu Ranjan

    2017-05-01

    Genes related to key cellular pathways are frequently altered in B cell ALL and are associated with poor survival especially in high-risk (HR) subgroups. We examined gene copy number abnormalities (CNA) in 101 Indian HR B cell ALL patients and their correlation with clinicopathological features by multiplex ligation-dependent probe amplification. Overall, CNA were detected in 59 (59%) cases, with 26, 10 and 23% of cases harboring 1, 2 or +3 CNA. CNA were more prevalent in BCR-ABL1 (60%), pediatric (64%) and high WCC (WBC count) (63%) patients. Frequent genes deletions included CDNK2A/B (26%), IKZF1 (25%), PAX5 (14%), JAK2 (7%), BTG1 (6%), RB1 (5%), EBF1 (4%), ETV6 (4%), while PAR1 region genes were predominantly duplicated (20%). EBF1 deletions selectively associated with adults, IKZF1 deletions occurred frequently in high WCC and BCR-ABL1 cases, while PAR1 region gains significantly associated with MLL-AF4 cases. IKZF1 haploinsufficiency group was predominant, especially in adults (65%), high WCC (60%) patients and BCR-ABL1-negative (78%) patients. Most cases harbored multiple concurrent CNA, with IKZF1 concomitantly occurring with CDNK2A/B, PAX5 and BTG1, while JAK2 occurred with CDNK2A/B and PAX5. Mutually exclusive CNA included ETV6 and IKZF1/RB1, and EBF1 and JAK2. Our results corroborate with global reports, aggregating molecular markers in Indian HR B-ALL cases. Integration of CNA data from rapid methods like MLPA, onto background of existing gold-standard methods detecting significant chromosomal abnormalities, provides a comprehensive genetic profile in B-ALL.

  10. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  11. 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.

  12. Late Modern Play Culture

    DEFF Research Database (Denmark)

    Skovbjerg-Karoff, Helle

    2008-01-01

    Children's play and culture have changed over the recent years, and it is possible to understand the changes as a result of a more general change in society. We witness a large degree of changes connected to demographical aspects of children's lives. First of all it is a fact that large groups....... They are changing play arenas in order to find the identity, which suits them. In order to play children must know and be conscious of the cultural heritage, which contains knowledge of the way to organize in the playing session, the aesthetics, the techniques of playing, and this is something that is handed down...... from one generation to the next. Because older children are no longer present as younger children grow up, the traditional "cultural leaders" are gone. They have taken with them much of the inspiration for play as well as important knowledge about how to organise a game. In that sense we can say...

  13. Play, dreams, and creativity.

    Science.gov (United States)

    Oremland, J D

    1998-01-01

    Viewed ontogenetically, creating, dreaming, and playing are a variant of object relatedness. It is suggested that in recapitulating the ontogenetic sequence, creating, dreaming, and playing each as a process initiates by de-differentiation to primal union, evolves into transitional functioning, and consummates in tertiary cognitive discourse. The products of the triad--the created object, the dream, and play--are viewed as synergistic psychodynamic composites of topical, personal, and arche-typical imperatives. Creating, dreaming, and playing are easily overburdened by events, becoming stereotypical and repetitious. Nowhere is this more clearly seen than in the play of chronically ill, hospitalized children. It is suggested that with development generally, playing is replaced by formalized games; only dreaming continues as the vestige of early creative abilities.

  14. Play and virtuality

    Directory of Open Access Journals (Sweden)

    Svein Sando

    2010-07-01

    Full Text Available The similarities between virtuality and play are obvious, beginning with, for instance, the ubiquitous character of both. This paper deals with how insights from research on play can be used to enlighten our understanding of the ethical dimensions of activities in cyberspace, and vice versa. In particular, a central claim that play is beyond vice and virtue is debated and contested.http://dx.doi.org/10.5324/eip.v4i2.1762

  15. Why do Dolphins Play?

    Directory of Open Access Journals (Sweden)

    Stan A. Kuczaj

    2014-05-01

    Full Text Available Play is an important aspect of dolphin life, perhaps even an essential one. Play provides opportunities for dolphin calves to practice and perfect locomotor skills, including those involved in foraging and mating strategies and behaviors. Play also allows dolphin calves to learn important social skills and acquire information about the characteristics and predispositions of members of their social group, particularly their peers. In addition to helping dolphin calves learn how to behave, play also provides valuable opportunities for them to learn how to think. The ability to create and control play contexts enables dolphins to create novel experiences for themselves and their playmates under relatively safe conditions. The behavioral variability and individual creativity that characterize dolphin play yield ample opportunities for individual cognitive development as well as social learning, and sometimes result in innovations that are reproduced by other members of the group. Although adults sometimes produce innovative play, calves are the primary source of such innovations. Calves are also more likely to imitate novel play behaviors than are adults, and so calves contribute significantly to both the creation and transmission of novel play behaviors within a group. Not unexpectedly, then, the complexity of dolphin play increases with the involvement of peers. As a result, the opportunity to observe and/or interact with other dolphin calves enhances the effects of play on the acquisition and maintenance of flexible problem solving skills, the emergence and strengthening of social and communicative competencies, and the establishment of social relationships. It seems that play may have evolved to help young dolphins learn to adapt to novel situations in both their physical and social worlds, the beneficial result being a set of abilities that increases the likelihood that an individual survives and reproduces.

  16. PlayBook三人行

    Institute of Scientific and Technical Information of China (English)

    黑莓时光

    2011-01-01

    PlayBook,来自非苹果的另外一个水果——黑莓,它不是iPad,却也是平板。PBer,这个并不完美的平板——PlayBook的用户,他们开朗、认真、执着。热爱PlayBook的三人,拥有各自的人生轨迹,却挂着同样的嘴角上扬。

  17. Play your part

    CERN Document Server

    Ramsey, Gaynor

    1978-01-01

    Play your part is a collection of then situations in which students have to take on the roles of particular people and express their opinions, feelings or arguments about the situation. Play your part is intended for use with advanced students of English.

  18. Role Playing and Skits

    Science.gov (United States)

    Letwin, Robert, Ed.

    1975-01-01

    Explores non-scripted role playing, dialogue role playing, sociodrama, and skits as variations of simulation techniques. Provides step-by-step guidelines for conducting such sessions. Successful Meetings, Bill Communications, Inc., 1422 Chestnut Street, Philadelphia, Pa. 19102. Subscription Rates: yearly (US, Canada, Mexico) $14.00; elsewhere,…

  19. The Play's the Thing

    Science.gov (United States)

    Bateman, Barbara

    2005-01-01

    The modern special education theater in the United States has hosted many plays, none with a larger or more diverse cast than the learning disabilities (LD) play. During the prologue, the children with LD were waiting in the wings, not yet identified as LD but there, nonetheless. With the advent of compulsory education in this country, awareness…

  20. Playfulness and Openness

    DEFF Research Database (Denmark)

    Marchetti, Emanuela; Petersson, Eva

    2011-01-01

    What does it mean to design a playful learning tool? What is needed for a learning tool to be perceived by potential users as playful? These questions emerged reflecting on a Participatory Design process aimed at enhancing museum-learning practice from the perspective of primary school children. ...

  1. Play as Experience

    Science.gov (United States)

    Henricks, Thomas S.

    2015-01-01

    The author investigates what he believes one of the more important aspects of play--the experience it generates in its participants. He considers the quality of this experience in relation to five ways of viewing play--as action, interaction, activity, disposition, and within a context. He treats broadly the different forms of affect, including…

  2. Family Play Therapy.

    Science.gov (United States)

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  3. Return to Play

    Science.gov (United States)

    Mangan, Marianne

    2013-01-01

    Call it physical activity, call it games, or call it play. Whatever its name, it's a place we all need to return to. In the physical education, recreation, and dance professions, we need to redesign programs to address the need for and want of play that is inherent in all of us.

  4. Playful Collaboration (Or Not)

    DEFF Research Database (Denmark)

    Bogers, Marcel; Sproedt, Henrik

    2012-01-01

    This article explores how playing games can be used to teach intangible social interaction across boundaries, in particular within open collaborative innovation. We present an exploratory case study of how students learned from playing a board game in a graduate course of the international...... imply several opportunities and challenges within education and beyond....

  5. Play framework cookbook

    CERN Document Server

    Reelsen, Alexander

    2015-01-01

    This book is aimed at advanced developers who are looking to harness the power of Play 2.x. This book will also be useful for professionals looking to dive deeper into web development. Play 2 .x is an excellent framework to accelerate your learning of advanced topics.

  6. Let's Just Play

    Science.gov (United States)

    Schmidt, Janet

    2003-01-01

    Children have a right to play. The idea is so simple it seems self-evident. But a stroll through any toy superstore, or any half-hour of so-called "children's" programming on commercial TV, makes it clear that violence, not play, dominates what's being sold. In this article, the author discusses how teachers and parents share the responsibility in…

  7. Transcriptional regulatory programs underlying barley germination and regulatory functions of Gibberellin and abscisic acid

    Directory of Open Access Journals (Sweden)

    Lin Li

    2011-06-01

    Full Text Available Abstract Background Seed germination is a complex multi-stage developmental process, and mainly accomplished through concerted activities of many gene products and biological pathways that are often subjected to strict developmental regulation. Gibberellins (GA and abscisic acid (ABA are two key phytohormones regulating seed germination and seedling growth. However, transcriptional regulatory networks underlying seed germination and its associated biological pathways are largely unknown. Results The studies examined transcriptomes of barley representing six distinct and well characterized germination stages and revealed that the transcriptional regulatory program underlying barley germination was composed of early, late, and post-germination phases. Each phase was accompanied with transcriptional up-regulation of distinct biological pathways. Cell wall synthesis and regulatory components including transcription factors, signaling and post-translational modification components were specifically and transiently up-regulated in early germination phase while histone families and many metabolic pathways were up-regulated in late germination phase. Photosynthesis and seed reserve mobilization pathways were up-regulated in post-germination phase. However, stress related pathways and seed storage proteins were suppressed through the entire course of germination. A set of genes were transiently up-regulated within three hours of imbibition, and might play roles in initiating biological pathways involved in seed germination. However, highly abundant transcripts in dry barley and Arabidopsis seeds were significantly conserved. Comparison with transcriptomes of barley aleurone in response to GA and ABA identified three sets of germination responsive genes that were regulated coordinately by GA, antagonistically by ABA, and coordinately by GA but antagonistically by ABA. Major CHO metabolism, cell wall degradation and protein degradation pathways were up

  8. Play vs. Procedures

    DEFF Research Database (Denmark)

    Hammar, Emil

    Through the theories of play by Gadamer (2004) and Henricks (2006), I will show how the relationship between play and game can be understood as dialectic and disruptive, thus challenging understandings of how the procedures of games determine player activity and vice versa. As such, I posit some...... analytical consequences for understandings of digital games as procedurally fixed (Boghost, 2006; Flannagan, 2009; Bathwaite & Sharp, 2010). That is, if digital games are argued to be procedurally fixed and if play is an appropriative and dialectic activity, then it could be argued that the latter affects...

  9. The role of learning environment on high school chemistry students' motivation and self-regulatory processes

    Science.gov (United States)

    Judd, Jeffrey S.

    Changes to the global workforce and technological advancements require graduating high school students to be more autonomous, self-directed, and critical in their thinking. To reflect societal changes, current educational reform has focused on developing more problem-based, collaborative, and student-centered classrooms to promote effective self-regulatory learning strategies, with the goal of helping students adapt to future learning situations and become life-long learners. This study identifies key features that may characterize these "powerful learning environments", which I term "high self-regulating learning environments" for ease of discussion, and examine the environment's role on students' motivation and self-regulatory processes. Using direct observation, surveys, and formal and informal interviews, I identified perceptions, motivations, and self-regulatory strategies of 67 students in my high school chemistry classes as they completed academic tasks in both high and low self-regulating learning environments. With social cognitive theory as a theoretical framework, I then examined how students' beliefs and processes changed after they moved from low to a high self-regulating learning environment. Analyses revealed that key features such as task meaning, utility, complexity, and control appeared to play a role in promoting positive changes in students' motivation and self-regulation. As embedded cases, I also included four students identified as high self-regulating, and four students identified as low self-regulating to examine whether the key features of high and low self-regulating learning environments played a similar role in both groups. Analysis of findings indicates that key features did play a significant role in promoting positive changes in both groups, with high self-regulating students' motivation and self-regulatory strategies generally remaining higher than the low self-regulating students; this was the case in both environments. Findings

  10. Play and Power

    DEFF Research Database (Denmark)

    The power of play, so central to psychoanalytic theory and practice, is conjoined to the social psychological or socio-politically coloured concept of power, giving rise to many fruitful discussions of how these concepts manifest themselves in clinical work with children, groups and adults....... The inspiration for this book was the 3-section EFPP conference in Copenhagen in May 2007 with the main theme "Play and Power". At the conference and in the book, this theme is presented both inside and outside the therapeutic space. It is amply illustrated in clinical cases from individual psychotherapies....... Play and power are also explored in the broader context of the community, however. In relation to society at large, psychoanalytic psychotherapy has important contributions to offer society, and we need playful creativity and power to bring forward our knowledge about it....

  11. The identification of cis-regulatory elements: A review from a machine learning perspective.

    Science.gov (United States)

    Li, Yifeng; Chen, Chih-Yu; Kaye, Alice M; Wasserman, Wyeth W

    2015-12-01

    The majority of the human genome consists of non-coding regions that have been called junk DNA. However, recent studies have unveiled that these regions contain cis-regulatory elements, such as promoters, enhancers, silencers, insulators, etc. These regulatory elements can play crucial roles in controlling gene expressions in specific cell types, conditions, and developmental stages. Disruption to these regions could contribute to phenotype changes. Precisely identifying regulatory elements is key to deciphering the mechanisms underlying transcriptional regulation. Cis-regulatory events are complex processes that involve chromatin accessibility, transcription factor binding, DNA methylation, histone modifications, and the interactions between them. The development of next-generation sequencing techniques has allowed us to capture these genomic features in depth. Applied analysis of genome sequences for clinical genetics has increased the urgency for detecting these regions. However, the complexity of cis-regulatory events and the deluge of sequencing data require accurate and efficient computational approaches, in particular, machine learning techniques. In this review, we describe machine learning approaches for predicting transcription factor binding sites, enhancers, and promoters, primarily driven by next-generation sequencing data. Data sources are provided in order to facilitate testing of novel methods. The purpose of this review is to attract computational experts and data scientists to advance this field.

  12. The expanding regulatory universe of p53 in gastrointestinal cancer.

    Science.gov (United States)

    Fesler, Andrew; Zhang, Ning; Ju, Jingfang

    2016-01-01

    Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

  13. Variability control: key to regulatory compliance and sustainability goals.

    Science.gov (United States)

    Englande, A J; Eckenfelder, W W; Jin, G

    2006-01-01

    The focus of this paper is on variability concerns in wastewater treatment and approaches to control unacceptable fluctuations in effluent quality. Areas considered include: factors contributing to variability in both waste loads and process technology performance; variability assessment; control of variability employing the process best management practice (BMP); design/operation of biological waste treatment technologies for variability reduction; and modelling to enhance process control.

  14. [The role of T-regulatory cells in the pathogenesis of immunological disturbances accompanying obesity and atherosclerosis].

    Science.gov (United States)

    Luczyński, Włodzimierz; Bossowski, Artur; Głowińska-Olszewska, Barbara; Kos, Justyna; Stasiak-Barmuta, Anna

    2010-03-30

    Obesity and atherosclerosis, and their consequences, including cardiovascular disease, are plagues of the 21st century. Chronic inflammation, whose mechanism is not well understood, underlies the pathophysiological bases of both processes. T lymphocytes, macrophages, and the proinflammatory cytokines produced by these cells play key roles in the immunological disturbances accompanying obesity and atherosclerosis. It was recently shown that T-regulatory cells can play a role in these processes. T-regulatory cells are a small subpopulation of T cells which are responsible for inhibition of the immune response. In this review, experiments conducted in mice and human models on the role of diminished number and/or function of T-regulatory lymphocytes in the pathogenesis of immune disturbances accompanying obesity and atherosclerosis are discussed. The results of studies using T-regulatory cells to stabilize and decrease atherosclerotic lesions in blood vessel walls are also summarized. The results of experiments performed so far are encouraging and give some hope for the future use of T-regulatory cells in the therapy of obesity and atherosclerosis.

  15. The role of T-regulatory cells in the pathogenesis of immunological disturbances accompanying obesity and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Włodzimierz Łuczyński

    2010-03-01

    Full Text Available Obesity and atherosclerosis, and their consequences, including cardiovascular disease, are plagues of the 21st century. Chronic inflammation, whose mechanism is not well understood, underlies the pathophysiological bases of both processes. T lymphocytes, macrophages, and the proinflammatory cytokines produced by these cells play key roles in the immunological disturbances accompanying obesity and atherosclerosis. It was recently shown that T-regulatory cells can play a role in these processes. T-regulatory cells are a small subpopulation of T cells which are responsible for inhibition of the immune response. In this review, experiments conducted in mice and human models on the role of diminished number and/or function of T-regulatory lymphocytes in the pathogenesis of immune disturbances accompanying obesity and atherosclerosis are discussed. The results of studies using T-regulatory cells to stabilize and decrease atherosclerotic lesions in blood vessel walls are also summarized. The results of experiments performed so far are encouraging and give some hope for the future use of T-regulatory cells in the therapy of obesity and atherosclerosis.

  16. Genomics in the land of regulatory science.

    Science.gov (United States)

    Tong, Weida; Ostroff, Stephen; Blais, Burton; Silva, Primal; Dubuc, Martine; Healy, Marion; Slikker, William

    2015-06-01

    Genomics science has played a major role in the generation of new knowledge in the basic research arena, and currently question arises as to its potential to support regulatory processes. However, the integration of genomics in the regulatory decision-making process requires rigorous assessment and would benefit from consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) hosted the fourth Global Summit on Regulatory Science (GSRS2014) to discuss the role of genomics in regulatory decision making, with a specific emphasis on applications in food safety and medical product development. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the analysis, interpretation and reporting of genomics data with an emphasis on transparency, traceability and "fitness for purpose" for the intended application. It was recognized that there is a need for a global path in the establishment of a regulatory bioinformatics framework for the development of transparent, reliable, reproducible and auditable processes in the management of food and medical product safety risks. It was also recognized that training is an important mechanism in achieving internationally consistent outcomes. GSRS2014 provided an effective venue for regulators andresearchers to meet, discuss common issues, and develop collaborations to address the challenges posed by the application of genomics to regulatory science, with the ultimate goal of wisely integrating novel technical innovations into regulatory decision-making.

  17. Can play be defined?

    DEFF Research Database (Denmark)

    Eichberg, Henning

    2015-01-01

    Can play be defined? There is reason to raise critical questions about the established academic demand that at phenomenon – also in humanist studies – should first of all be defined, i.e. de-lineated and by neat lines limited to a “little box” that can be handled. The following chapter develops t....... Human beings can very well understand play – or whatever phenomenon in human life – without defining it........ The academic imperative of definition seems to be linked to the positivistic attempts – and produces sometimes monstrous definitions. Have they any philosophical value for our knowledge of what play is? Definition is not a universal instrument of knowledge-building, but a culturally specific construction...

  18. Playing and gaming

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg; Ejsing-Duun, Stine; Hanghøj, Thorkild

    2013-01-01

    The paper develops an approach of playing and gaming activities through the perspective of both activities as mood activities . The point of departure is that a game - is a tool with which we, through our practices, achieve different moods. This based on an empirical study of children's everyday...... lives, where the differences emerge through actual practices, i.e. through the creation of meaning in the specific situations. The overall argument is that it is not that important whether it is a playing or a gaming activity - it is however crucial to be aware of how moods occur and what their optimal...... dimensions: practices and moods. Practice is the concept of all the doing in the activities. Moods are the particular concept of sense and feeling of being, which is what we are drawn to when we are playing or gaming....

  19. Playing and gaming

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg; Ejsing-Duun, Stine; Hanghøj, Thorkild

    2013-01-01

    The paper develops an approach of playing and gaming activities through the perspective of both activities as mood activities . The point of departure is that a game - is a tool with which we, through our practices, achieve different moods. This based on an empirical study of children's everyday...... lives, where the differences emerge through actual practices, i.e. through the creation of meaning in the specific situations. The overall argument is that it is not that important whether it is a playing or a gaming activity - it is however crucial to be aware of how moods occur and what their optimal...... dimensions: practices and moods. Practice is the concept of all the doing in the activities. Moods are the particular concept of sense and feeling of being, which is what we are drawn to when we are playing or gaming....

  20. Key concepts in social pedagogy

    DEFF Research Database (Denmark)

    Harbo, Lotte Junker

    2011-01-01

    and activities around key social pedagogical concepts, such as the Common Third, the 3 P’s, the Zone of Proximal Development and the Learning Zone model. In the article we explore how a joint activity, for example playing soccer, can be seen as a pedagogical activity and with what intentions it is undertaken...

  1. General game playing

    CERN Document Server

    Genesereth, Michael

    2014-01-01

    General game players are computer systems able to play strategy games based solely on formal game descriptions supplied at ""runtime"" (n other words, they don't know the rules until the game starts). Unlike specialized game players, such as Deep Blue, general game players cannot rely on algorithms designed in advance for specific games; they must discover such algorithms themselves. General game playing expertise depends on intelligence on the part of the game player and not just intelligence of the programmer of the game player.GGP is an interesting application in its own right. It is intell

  2. Playful Collaboration (or Not)

    DEFF Research Database (Denmark)

    Bogers, Marcel; Sproedt, Henrik

    2011-01-01

    also be conducive to deep learning. As such, a game can engage different dimensions of learning and embed elements of active, collaborative, cooperative and problem-based learning. Building on this logic, we present an exploratory case study of the use of a particular board game in a class of a course......This paper explores how games and play, which are deeply rooted in human beings as a way to learn and interact, can be used to teach certain concepts and practices related to open collaborative innovation. We discuss how playing games can be a source of creativity, imagination and fun, while it can...

  3. Five recent play dates

    DEFF Research Database (Denmark)

    Abildgaard, Mette Simonsen; Birkbak, Andreas; Jensen, Torben Elgaard

    2017-01-01

    An advantage of the playground metaphor is that it comes with the activity of going out on ‘play dates’ and developing friendships. In such playful relationships, there is always something at stake, but the interaction is also fun and inherently exploratory. In the following, we take a tour of five...... recent collaborative projects that the TANTlab has participated in. The projects differ widely and testify to different experiences with collaboration and intervention – from a data print on obesity with other researchers to a Facebook-driven intervention in Aalborg municipality’s primary school reform...

  4. Regulatory T Cells and Parasites

    Directory of Open Access Journals (Sweden)

    TP. Velavan

    2011-01-01

    Full Text Available Human host encounters a wide array of parasites; however, the crucial aspect is the failure of the host immune system to clear these parasites despite antigen recognition. In the recent past, a new immunological concept has emerged, which provides a framework to better understand several aspects of host susceptibility to parasitic infection. It is widely believed that parasites are able to modulate the magnitude of effector responses by inducing regulatory T cell (Tregs population and several studies have investigated whether this cell population plays a role in balancing protective immunity and pathogenesis during parasite infection. This review discusses the several mechanism of Treg-mediated immunosuppression in the human host and focuses on the functional role of Tregs and regulatory gene polymorphisms in infectious diseases.

  5. The Activity of Play

    DEFF Research Database (Denmark)

    Pichlmair, Martin

    2016-01-01

    This paper presents Activity Theory as a framework for understanding the action of playing games with the intention of building a foundation for the creation of new game design tools and methods. Activity Theory, an epistemological framework rooted in Soviet psychology of the first half of the 20...

  6. Playing the Role

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The G20 London summit made history. While applauding the summit’s productive communique, Ni Xiaoling, senior financial observer with Xinhua News Agency, warns of the gap between the greater responsibilities the International Monetary Fund shoulders and its limited capabilities to play the role of coordinator in economic globalization.

  7. Abstraction through Game Play

    Science.gov (United States)

    Avraamidou, Antri; Monaghan, John; Walker, Aisha

    2012-01-01

    This paper examines the computer game play of an 11-year-old boy. In the course of building a virtual house he developed and used, without assistance, an artefact and an accompanying strategy to ensure that his house was symmetric. We argue that the creation and use of this artefact-strategy is a mathematical abstraction. The discussion…

  8. Mobilities at Play

    DEFF Research Database (Denmark)

    Ungruhe, Christian

    2017-01-01

    -level perspective there is still an analytical gap between the ambitions and experiences of migrating players and economic power relations at play on the one hand and the socio-cultural embedding of the transnational connections in football migration on the other. In order to understand why and how football...

  9. Play's Importance in School

    Science.gov (United States)

    Sandberg, Anette; Heden, Rebecca

    2011-01-01

    The purpose of this study is to contribute knowledge on and gain an understanding of elementary school teachers' perspectives on the function of play in children's learning processes. The study is qualitative with a hermeneutical approach and has George Herbert Mead as a theoretical frame of reference. Interviews have been carried out with seven…

  10. Play framework essentials

    CERN Document Server

    Richard-Foy, Julien

    2014-01-01

    This book targets Java and Scala developers who already have some experience in web development and who want to master Play framework quickly and efficiently. This book assumes you have a good level of knowledge and understanding of efficient Java and Scala code.

  11. A Significant Play

    Institute of Scientific and Technical Information of China (English)

    梁海光; 陈明

    2002-01-01

    Yesterday evening, I went to see a play. It was really significant. It was about Zheng Xiaoyue, a very clever and diligent middle school student. Unfortunately, her mother died when she and her brother were very young. Her father was out of work and,

  12. Regulatory Perspectives on Continuous Pharmaceutical Manufacturing: Moving From Theory to Practice: September 26-27, 2016, International Symposium on the Continuous Manufacturing of Pharmaceuticals.

    Science.gov (United States)

    Nasr, Moheb M; Krumme, Markus; Matsuda, Yoshihiro; Trout, Bernhardt L; Badman, Clive; Mascia, Salvatore; Cooney, Charles L; Jensen, Keith D; Florence, Alastair; Johnston, Craig; Konstantinov, Konstantin; Lee, Sau L

    2017-06-26

    Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first International Symposium on Continuous Manufacturing of Pharmaceuticals in 2014, but the regulatory landscape that exists today. Key regulatory concepts including quality risk management, batch definition, control strategy, process monitoring and control, real-time release testing, data processing and management, and process validation/verification are outlined. Support from regulatory agencies, particularly in the form of the harmonization of regulatory expectations, will be crucial to the successful implementation of continuous manufacturing. Collaborative efforts, among academia, industry, and regulatory agencies, are the optimal solution for ensuring a solid future for this promising manufacturing technology. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  13. Conserved-peptide upstream open reading frames (CPuORFs are associated with regulatory genes in angiosperms

    Directory of Open Access Journals (Sweden)

    Richard A Jorgensen

    2012-08-01

    Full Text Available Upstream open reading frames (uORFs are common in eukaryotic transcripts, but those that encode conserved peptides (CPuORFs occur in less than 1% of transcripts. The peptides encoded by three plant CPuORF families are known to control translation of the downstream ORF in response to a small signal molecule (sucrose, polyamines and phosphocholine. In flowering plants, transcription factors are statistically over-represented among genes that possess CPuORFs, and in general it appeared that many CPuORF genes also had other regulatory functions, though the significance of this suggestion was uncertain (Hayden and Jorgensen, 2007. Five years later the literature provides much more information on the functions of many CPuORF genes. Here we reassess the functions of 27 known CPuORF gene families and find that 22 of these families play a variety of different regulatory roles, from transcriptional control to protein turnover, and from small signal molecules to signal transduction kinases. Clearly then, there is indeed a strong association of CPuORFs with regulatory genes. In addition, 16 of these families play key roles in a variety of different biological processes. Most strikingly, the core sucrose response network includes three different CPuORFs, creating the potential for sophisticated balancing of the network in response to three different molecular inputs. We propose that the function of most CPuORFs is to modulate translation of a downstream major ORF (mORF in response to a signal molecule recognized by the conserved peptide and that because the mORFs of CPuORF genes generally encode regulatory proteins, many of them centrally important in the biology of plants, CPuORFs play key roles in balancing such regulatory networks.

  14. Regulatory effects of fisetin on microglial activation.

    Science.gov (United States)

    Chuang, Jing-Yuan; Chang, Pei-Chun; Shen, Yi-Chun; Lin, Chingju; Tsai, Cheng-Fang; Chen, Jia-Hong; Yeh, Wei-Lan; Wu, Ling-Hsuan; Lin, Hsiao-Yun; Liu, Yu-Shu; Lu, Dah-Yuu

    2014-06-26

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  15. Regulatory Effects of Fisetin on Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jing-Yuan Chuang

    2014-06-01

    Full Text Available Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO production, and inducible nitric oxide synthase (iNOS expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  16. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC)

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular...... by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC...

  17. Regulatory T-cells in chronic lymphocytic leukemia: actor or innocent bystander?

    Science.gov (United States)

    D’Arena, Giovanni; Simeon, Vittorio; D’Auria, Fiorella; Statuto, Teodora; Sanzo, Paola Di; Martino, Laura De; Marandino, Aurelio; Sangiorgio, Michele; Musto, Pellegrino; Feo, Vincenzo De

    2013-01-01

    Regulatory T (Treg) cells are now under extensive investigation in chronic lymphocytic leukemia (CLL). This small subset of T-cells has been, in fact, considered to be involved in the pathogenesis and progression of CLL. However, whether Treg dysregulation in CLL plays a key role or it rather represents a simple epiphenomenon is still matter of debate. In the former case, Treg cells could be appealing for targeting therapies. Finally, Treg cells have also been proposed as a prognostic indicator of the disease clinical course. PMID:23358515

  18. Play or science?

    DEFF Research Database (Denmark)

    Lieberoth, Andreas; Pedersen, Mads Kock; Sherson, Jacob

    2015-01-01

    Crowdscience games may hold unique potentials as learning opportunities compared to games made for fun or education. They are part of an actual science problem solving process: By playing, players help scientists, and thereby interact with real continuous research processes. This mixes the two...... worlds of play and science in new ways. During usability testing we discovered that users of the crowdscience game Quantum Dreams tended to answer questions in game terms, even when directed explicitly to give science explanations. We then examined these competing frames of understanding though a mixed...... correlational and grounded theory analysis. This essay presents the core ideas of crowdscience games as learning opportunities, and reports how a group of players used “game”, “science” and “conceptual” frames to interpret their experience. Our results suggest that oscillating between the frames instead...

  19. Understanding Games as Played

    DEFF Research Database (Denmark)

    Leino, Olli Tapio

    2009-01-01

    Researchers interested in player’s experience would assumedly, across disciplines, agree that the goal behind enquiries into player’s experience is to understand the how games’ features end up affecting the player’s experience. Much of the contemporary interdisciplinary research into player......’s experience leans toward the empirical-scientific, in the forms (neuro)psychology, sociology and cognitive science, to name a few. In such approaches, for example demonstrating correlation between physiological symptoms and an in-game event may amount to ‘understanding’. However, the experience of computer...... game play is a viable topic also for computer game studies within the general tradition of humanities. In such context, the idea of ‘understanding an experience’ invites an approach focusing on the experienced significance of events and objects within computer game play. This focus, in turn, suggests...

  20. Ravens at Play

    Directory of Open Access Journals (Sweden)

    Deborah Bird Rose

    2011-09-01

    Full Text Available ‘We were driving through Death Valley, an American-Australian and two Aussies, taking the scenic route from Las Vegas to Santa Cruz.’ This multi-voiced account of multispecies encounters along a highway takes up the challenge of playful and humorous writing that is as well deeply serious and theoretically provocative. Our travels brought us into what Donna Haraway calls the contact zone: a region of recognition and response. The contact zone is a place of significant questions: ‘Who are you, and so who are we? Here we are, and so what are we to become?’ Events were everything in this ecology of play, in which the movements of all the actors involved the material field in its entirety. We were brought into dances of approach and withdrawal, dances emerging directly, to paraphrase Brian Massumi, from the dynamic relation between a myriad of charged particles.

  1. Public Computation & Boundary Play

    CERN Document Server

    Sengupta, Pratim

    2016-01-01

    In this paper, we introduce 'public computation' as a genre of learning environments that can be used to radically broaden public participation in authentic, computation-enabled STEM disciplinary practices. Our paradigmatic approach utilizes open source software designed for professional scientists, engineers and digital artists, and situates them in an undiluted form, alongside live and archived expert support, in a public space. We present a case study of DigiPlay, a prototypical public computation space we designed at the University of Calgary, where users can interact directly with scientific simulations as well as the underlying open source code using an array of massive multi- touch screens. We argue that in such a space, public interactions with the code can be thought of as boundary work and play, through which public participation becomes legitimate scientific act, as the public engages in scientific creation through truly open-ended explorations with the code.

  2. Play. Learn. Innovate

    DEFF Research Database (Denmark)

    Sproedt, Henrik

    evidence that play and games could be interesting perspectives to take in order to understand complex social interaction. I come to the conclusion that – in innovation settings – the social dynamics that affect the process are essentially about transformation of knowledge across boundaries. I propose......„Play. Learn. Innovate. – Grasping the Social Dynamics of Participatory Innovation“ the title of this thesis describes how the complex interplay of unexpected events led to some burning questions and eventually to this thesis, which one could call an innovation*1*. During several years...... study were to better understand the theoretical foundations and practical implications of complex social interaction in organizational innovation settings. As I did not find any existing models or hypotheses that I was interested in testing I set out to discover how I could grasp complex social...

  3. "Playing" with our users

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2014-01-01

    was from the amazing Dr Anthony Lewis Brooks (aka Tony) who has conceived the concepts GameAbilitation, ArtAbilitation, and Ludic Engagement Designs for All. While presenting some of his work on GameAbilitation and ArtAbilitation he brought up the subject of conducting research with users with disabilities......, about what happens to our users when research is over, funds are gone and the curtain of experiments has fallen. Dr Brooks presented the case of a young user who while unable to move and communicate had to part with the test device that provided him with interactive playful experience. We’ve all been...... confined in a house. For researchers that work with people with disabilities and in my case with playful interactions and positive immersive experience, we might have to think harder when we write project proposals or sketch our methodology. Devices, software and experience should be available to the users...

  4. Creativity and Playfulness

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine; Skovbjerg, Helle Marie

    2015-01-01

    Abstract: This article explores how student behavior and interactions change when teachers use “producing games” as a primary pedagogical strategy (Papert, 1980; Ejsing-Duun and Karoff, 2014). Based on student and teacher actions and responses, as well as on students' production—observed during f...... fieldwork—this paper emphasizes the importance of understanding how students explore creativity and playfulness while producing in learning situations....

  5. Creativity and Playfulness

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine; Skovbjerg, Helle Marie

    2015-01-01

    Abstract: This article explores how student behavior and interactions change when teachers use “producing games” as a primary pedagogical strategy (Papert, 1980; Ejsing-Duun and Karoff, 2014). Based on student and teacher actions and responses, as well as on students' production—observed during f...... fieldwork—this paper emphasizes the importance of understanding how students explore creativity and playfulness while producing in learning situations....

  6. Design of Piano -playing Robotic Hand

    Directory of Open Access Journals (Sweden)

    Lin Jen-Chang

    2013-09-01

    Full Text Available Unlike the market slowdown of industrial robots, service & entertainment robots have been highly regarded by most robotics reseach and market research agencies. In this study we developed a music playing robot (which can also work as a service robot for public performance. The research is mainly focused on the mechanical and electrical control of piano-playing robot, the exploration of correlations among music theory, rhythm and piano keys, and eventually the research on playing skill of keyboard instrument. The piano-playing robot is capable of control linear motor, servo-motor and pneumatic devices in accordance with the notes and rhythm in order to drive the mechanical structure to proper positions for pressing the keys and generating music. The devices used for this robot are mainly crucial components produced by HIWIN Technology Corp. The design of robotic hand is based on the direction of anthropomorphic hand such that five fingers will be used for playing piano. The finger actuations include actions of finger rotation, finger pressing, and finger lifting; time required for these 3 stages must meet the requirement of rhythm. The purpose of entertainment robot can be achieved by playing electric piano with robotic hand, and we hope this research can contribute to the development of domestic entertainment music playing robots.

  7. Roadmapping as a Tool for Renewing Regulatory Practices

    DEFF Research Database (Denmark)

    Borch, Kristian; Norus, Jesper

    2004-01-01

    The aim of this paper is to explore technological roadmaps to identify key issuesconcerning the development and utilization of stem cells. From a review of the politicaldecision making processes in three countries, Denmark, the Netherlands, and Germanywe suggest that technological roadmapping...... in this emerging and discontinuedtechnology can provide critical policy information. This type of policy intelligence canbe used to rethink the regulatory practices away from today's framework basedregulation of the emerging technologies towards a regulatory policy based on how todevelop regulatory practices based...

  8. Pre-commercial procurement : regulatory effectiveness?

    NARCIS (Netherlands)

    Apostol, Anca Ramona

    2014-01-01

    Is public procurement of research and development (‘R&D’) services the key to European Union (‘EU’)’s sustainable welfare? Is it being regulated in accordance with economic prescripts for effectiveness? Is the regulatory and policy setting clear and comprehensive in order to stimulate a widespread u

  9. Overall Effects of China's Recent Macroeconomic Regulatory Policies

    Institute of Scientific and Technical Information of China (English)

    LiJianwei,; ZhuShida; DavidKelly

    2004-01-01

    China's economic regulatory policies in the last few years have played an important role in curbing the slide of its consistent growth drive. In terms of overall effects, the macroeconomic regulatory policies of each fiscal year have attained their targets. In some years, however,

  10. Celadon Figurines Play Instruments

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    This group of figurines, each 0.15m tall, were unearthed from a Tang Dynasty tomb in Changsha in 1977. Music was very developed in the Tang Dynasty. Colorful musical instruments and dances were popular both among the people and in the palace. These vivid-looking figurines wear pleated skirts with small sleeves and open chest, a style influenced by the non-Han nationalities living in the north and west of China. Some of the musical instruments were brought from the Western Regions. The figurines are playing the xiao (a vertical bamboo flute), the konghou (an

  11. Motivation, Creativity, Play & Learning

    DEFF Research Database (Denmark)

    Petersson, Eva

    2005-01-01

    implementation of robotic physical movement synchronously manipulated from sourced data movement information of a human. SoundScapes is a concept based on non-verbal communication and stimulation through interactive play with sounds and images, which is being realised in the production of a non-wearable sensor...... groups of children, including children with severe physical/multi disabilities. The sourced capture of the human data is from enhanced virtual interactive space created from sensors. The data is constituted of the situated multimodal communication and forms of expression. The ‘VIS’ is considered...

  12. Motivation, Creativity, Play & Learning

    DEFF Research Database (Denmark)

    Petersson, Eva

    2005-01-01

    implementation of robotic physical movement synchronously manipulated from sourced data movement information of a human. SoundScapes is a concept based on non-verbal communication and stimulation through interactive play with sounds and images, which is being realised in the production of a non-wearable sensor...... groups of children, including children with severe physical/multi disabilities. The sourced capture of the human data is from enhanced virtual interactive space created from sensors. The data is constituted of the situated multimodal communication and forms of expression. The ‘VIS’ is considered...

  13. "Playing" with our users

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2014-01-01

    . Unfortunately if donated in the school they are rarely being used by the students. In the case of virtual reality or artistic installations it is extremely difficult to provide such equipment to users. Last but not least we are not sure how the software will be used and if the experience will continue...... after the conduct of the research. If not due to restrictions, user should at least continue to be part of the research’s debrief and next steps. While I was in Nottingham I realised that sometimes our research, our playful educational experience, our DIY VR helmet, our beta, glitchy, research-only game...

  14. Turning training into play

    DEFF Research Database (Denmark)

    Aarhus, Rikke; Grönvall, Erik; Larsen, Simon Bo;

    2011-01-01

    Embodied gaming has been adopted and gained credibility in the field of physical rehabilitation. In this paper, we report on findings from a six-month-long study of three groups of senior citizens, and their use of Nintendo Wii Fit in a supervised physical training context. We argue that the study...... participants generally found physical training both fun and socially engaging, and experienced improved fitness. We also argue that embodied gaming motivates seniors to do more than they think themselves capable of, and allows seniors with different mental and physical capabilities to play together. However...

  15. Play and playfulness, basic features of early childhood education

    NARCIS (Netherlands)

    Singer, E.

    2013-01-01

    This article argues that play and playfulness are basic features in early childhood education, but that play curricula can have serious drawbacks. The starting point is the play theory of the Dutch historian Johan Huizinga, a radical critic of the focus on the educational benefits of play. According

  16. Play and playfulness, basic features of early childhood education

    NARCIS (Netherlands)

    Singer, E.

    2013-01-01

    This article argues that play and playfulness are basic features in early childhood education, but that play curricula can have serious drawbacks. The starting point is the play theory of the Dutch historian Johan Huizinga, a radical critic of the focus on the educational benefits of play. According

  17. EFFECTS OF PROPYLENE GLYCOL ON SERUM HORMONE AND KEY REGULATORY ENZYMES OF GLUCONEOGENESIS IN THE LIVER DURING PERIPARTUM PERIOD IN DAIRY COWS%丙二醇对奶牛围产期血浆激素和肝脏糖异生限速酶的影响

    Institute of Scientific and Technical Information of China (English)

    王聪; 刘强; 张延利; 张拴林; 裴彩霞; 白元生; 师周戈; 刘晓妮

    2013-01-01

    The objective of this study was to investigate effects of propylene glycol on blood concentration of glucose, insulin and IGF-I, concentration of glucose and key regulatory enzymes of gluconeogenesis in the liver of dairy cows during peripartum period. Twenty-four multiparous Holstein-dairy cows with similar body weight (683. 1 ±14.9 kg) , lactation number (2. 5 ±0. 2) , corrected milk yield in last lactation (7339 ±18 kg) and expected calving date (24. 5 ± 0. 2 d) were allocated into four treatments at random. Graded levels (0, 150, 300 and 450mL·d-1) of propylene glycol were supplemented in the four treatments from day 19 of prepartum. Results showed that cows receiving 300 and 450mL ·d-1 propylene glycol had a higher plasma glucose, insulin and insulin-like growth factor-I at 7, 21 and 35 d of postpartum. Under 300 and 450mL·d-1 propylene glycol supplementation the contents of glycogen and activities of key regulatory enzymes of gluconeogenesis in the liver increased compared to control (P < 0. 05 ). These findings in the present study indicated that propylene glycol supplementation was beneficial to peripartum cows in enhancing the gluconeogenesis and the optimum dose was about 300 ml per cow per day.%研究了丙二醇对奶牛国产期血浆胰岛素及胰岛素样生长因子和肝脏糖原含量及糖异生途径限速酶活性的影响.选用24头体重(683.1±14.9) kg、胎次(2.5±0.2)、上一泌乳期305d产奶量(7339±18)kg和预产期(24.5±0.2)d的经产奶牛,随机分为4组,从分娩前19d开始分别在基础日粮中添加丙二醇0、150、300和450mL·d-1.结果表明:与对照组相比,添加丙二醇300和450mL·d-1,显著提高了奶牛分娩后7、21和35d血糖、胰岛素和胰岛素样生长因子浓度(P<0.05).奶牛分娩后7、21和35d奶牛肝脏糖原含量及糖异生途径限速酶活性显著高于对照组(P<0.05).结果提示在日粮中添加丙二醇能够加强葡萄糖异生作用,适宜添加量为300mL·d-1.

  18. Playing The Lobby

    DEFF Research Database (Denmark)

    2014-01-01

    Playing a game can be defined as, in a fun way, to reach a goal by means of helpers and challenged by obstacles and opponents. In this workshop we will gain a new understanding of the lobby by making it into a game. The lobby of the museum can be understood as a game in which the players (the....... The object is surprisingly not to play the games, but to design them. Through the design process we are forced to discuss: What are the challenges of a particular lobby (e.g. ticketing, queueing, other visitors, guards, getting lost)? Which properties do the players have (e.g. patience, expectations, need...... of a toilet)? what boosters may they obtain in the lobby (e.g. coffee, help, souvenirs, signs)? And how can we make this an enjoyable experience? The object of the games is to understand the lobby in a new way to identify problems, and think of ways to improve the functions, flow, and services of the lobby....

  19. Genome-wide map of regulatory interactions in the human genome.

    Science.gov (United States)

    Heidari, Nastaran; Phanstiel, Douglas H; He, Chao; Grubert, Fabian; Jahanbani, Fereshteh; Kasowski, Maya; Zhang, Michael Q; Snyder, Michael P

    2014-12-01

    Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer-promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus. © 2014 Heidari et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Playing it Real

    DEFF Research Database (Denmark)

    Grubert, Jens; Morrison, Ann; Munz, Helmut

    2012-01-01

    Magic lens and static peephole interfaces are used in numerous consumer mobile phone applications such as Augmented Reality browsers, games or digital map applications in a variety of contexts including public spaces. Interface performance has been evaluated for various interaction tasks involving...... spatial relationships in a scene. However, interface usage outside laboratory conditions has not been considered in depth in the evaluation of these interfaces. We present findings about the usage of magic lens and static peephole interfaces for playing a find-and-select game in a public space and report...... on the reactions of the public audience to participants’ interactions. Contrary to our expectations participants favored the magic lens over a static peephole interface despite tracking errors, fatigue and potentially conspicuous gestures. Most passersby did not pay attention to the participants and vice versa...

  1. Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks

    Directory of Open Access Journals (Sweden)

    Nielsen Jens

    2008-02-01

    Full Text Available Abstract Background Uncovering the operating principles underlying cellular processes by using 'omics' data is often a difficult task due to the high-dimensionality of the solution space that spans all interactions among the bio-molecules under consideration. A rational way to overcome this problem is to use the topology of bio-molecular interaction networks in order to constrain the solution space. Such approaches systematically integrate the existing biological knowledge with the 'omics' data. Results Here we introduce a hypothesis-driven method that integrates bio-molecular network topology with transcriptome data, thereby allowing the identification of key biological features (Reporter Features around which transcriptional changes are significantly concentrated. We have combined transcriptome data with different biological networks in order to identify Reporter Gene Ontologies, Reporter Transcription Factors, Reporter Proteins and Reporter Complexes, and use this to decipher the logic of regulatory circuits playing a key role in yeast glucose repression and human diabetes. Conclusion Reporter Features offer the opportunity to identify regulatory hot-spots in bio-molecular interaction networks that are significantly affected between or across conditions. Results of the Reporter Feature analysis not only provide a snapshot of the transcriptional regulatory program but also are biologically easy to interpret and provide a powerful way to generate new hypotheses. Our Reporter Features analyses of yeast glucose repression and human diabetes data brings hints towards the understanding of the principles of transcriptional regulation controlling these two important and potentially closely related systems.

  2. The split personality of regulatory T cells in HIV infection.

    Science.gov (United States)

    Chevalier, Mathieu F; Weiss, Laurence

    2013-01-03

    Natural regulatory T cells (Tregs) participate in responses to various chronic infections including HIV. HIV infection is associated with a progressive CD4 lymphopenia and defective HIV-specific CD8 responses known to play a key role in the control of viral replication. Persistent immune activation is a hallmark of HIV infection and is involved in disease progression independent of viral load. The consequences of Treg expansion, observed in HIV infection, could be either beneficial, by suppressing generalized T-cell activation, or detrimental, by weakening HIV-specific responses and thus contributing to viral persistence. The resulting balance between Tregs contrasting outcomes might have critical implications in pathogenesis. Topics covered in this review include HIV-induced alterations of Tregs, Treg cell dynamics in blood and tissues, Treg-suppressive function, and the relationship between Tregs and immune activation. This review also provides a focus on the role of CD39(+) Tregs and other regulatory cell subsets. All these issues will be explored in different situations including acute and chronic infection, antiretroviral treatment-mediated viral control, and spontaneous viral control. Results must be interpreted with regard to both the Treg definition used in context and to the setting of the disease in an attempt to draw clearer conclusions from the apparently conflicting results.

  3. Key to Language Learning Success

    OpenAIRE

    2015-01-01

    This paper looks at the important elements of language learning and teaching i.e. the role of teachers as well as the attitude and motivation of learners. Teachers undoubtedly play crucial roles in students’ language learning outcome which could ignite or diminish students’ motivation. Positive attitudes and motivation – instrumental or integrative and intrinsic or extrinsic – are key to successful learning. Therefore it is paramount for language teachers as well as learners to know these rol...

  4. Playful Learning and Montessori Education

    National Research Council Canada - National Science Library

    Angeline S Lillard

    2013-01-01

      Although Montessori education is often considered a form of playful learning, Maria Montessori herself spoke negatively about a major component of playful learning-pretend play, or fantasy-for young children...

  5. Imagination, Playfulness, and Creativity in Children's Play with Different Toys

    Science.gov (United States)

    Mo????ller, Signe?? Juhl?

    2015-01-01

    Based on a four-month experimental study of preschool children's play with creative-construction and social-fantasy toys, the author examines the in?uence of both types of toys on the play of preschool children. Her comparative analysis considers the impact of transformative play on the development of imagination during play activities and…

  6. How difficult is inference of mammalian causal gene regulatory networks?

    Directory of Open Access Journals (Sweden)

    Djordje Djordjevic

    Full Text Available Gene regulatory networks (GRNs play a central role in systems biology, especially in the study of mammalian organ development. One key question remains largely unanswered: Is it possible to infer mammalian causal GRNs using observable gene co-expression patterns alone? We assembled two mouse GRN datasets (embryonic tooth and heart and matching microarray gene expression profiles to systematically investigate the difficulties of mammalian causal GRN inference. The GRNs were assembled based on > 2,000 pieces of experimental genetic perturbation evidence from manually reading > 150 primary research articles. Each piece of perturbation evidence records the qualitative change of the expression of one gene following knock-down or over-expression of another gene. Our data have thorough annotation of tissue types and embryonic stages, as well as the type of regulation (activation, inhibition and no effect, which uniquely allows us to estimate both sensitivity and specificity of the inference of tissue specific causal GRN edges. Using these unprecedented datasets, we found that gene co-expression does not reliably distinguish true positive from false positive interactions, making inference of GRN in mammalian development very difficult. Nonetheless, if we have expression profiling data from genetic or molecular perturbation experiments, such as gene knock-out or signalling stimulation, it is possible to use the set of differentially expressed genes to recover causal regulatory relationships with good sensitivity and specificity. Our result supports the importance of using perturbation experimental data in causal network reconstruction. Furthermore, we showed that causal gene regulatory relationship can be highly cell type or developmental stage specific, suggesting the importance of employing expression profiles from homogeneous cell populations. This study provides essential datasets and empirical evidence to guide the development of new GRN inference

  7. How difficult is inference of mammalian causal gene regulatory networks?

    Science.gov (United States)

    Djordjevic, Djordje; Yang, Andrian; Zadoorian, Armella; Rungrugeecharoen, Kevin; Ho, Joshua W K

    2014-01-01

    Gene regulatory networks (GRNs) play a central role in systems biology, especially in the study of mammalian organ development. One key question remains largely unanswered: Is it possible to infer mammalian causal GRNs using observable gene co-expression patterns alone? We assembled two mouse GRN datasets (embryonic tooth and heart) and matching microarray gene expression profiles to systematically investigate the difficulties of mammalian causal GRN inference. The GRNs were assembled based on > 2,000 pieces of experimental genetic perturbation evidence from manually reading > 150 primary research articles. Each piece of perturbation evidence records the qualitative change of the expression of one gene following knock-down or over-expression of another gene. Our data have thorough annotation of tissue types and embryonic stages, as well as the type of regulation (activation, inhibition and no effect), which uniquely allows us to estimate both sensitivity and specificity of the inference of tissue specific causal GRN edges. Using these unprecedented datasets, we found that gene co-expression does not reliably distinguish true positive from false positive interactions, making inference of GRN in mammalian development very difficult. Nonetheless, if we have expression profiling data from genetic or molecular perturbation experiments, such as gene knock-out or signalling stimulation, it is possible to use the set of differentially expressed genes to recover causal regulatory relationships with good sensitivity and specificity. Our result supports the importance of using perturbation experimental data in causal network reconstruction. Furthermore, we showed that causal gene regulatory relationship can be highly cell type or developmental stage specific, suggesting the importance of employing expression profiles from homogeneous cell populations. This study provides essential datasets and empirical evidence to guide the development of new GRN inference methods for

  8. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  9. IκBζ: A key protein in the pathogenesis of psoriasis.

    Science.gov (United States)

    Johansen, Claus

    2016-02-01

    Psoriasis is an immune-mediated chronic inflammatory skin disease with a complex etiology. The proinflammatory cytokine IL-17A is known to play key role in the pathogenesis of psoriasis, and recently anti-IL-17A antibodies have been approved for psoriasis treatment. Here, we discuss our recent findings demonstrating that IκBζ, a transcriptional co-activator, plays a crucial role in the development of psoriasis by mediating IL-17A-driven effects. These findings have significant implications as they uncover a novel crucial regulatory mechanism involved in psoriasis development, and identify IκBζ as a possible future target in the treatment of psoriasis and other IL-17A-driven diseases.

  10. Playful Learning and Montessori Education

    Science.gov (United States)

    Lillard, Angeline S.

    2013-01-01

    Although Montessori education is often considered a form of playful learning, Maria Montessori herself spoke negatively about a major component of playful learning--pretend play, or fantasy--for young children. In this essay, the author discusses this apparent contradiction: how and why Montessori education includes elements of playful learning…

  11. Play and Positive Group Dynamics

    Science.gov (United States)

    Thompson, Pam; White, Samantha

    2010-01-01

    Play is an important part of a child's life and essential to learning and development (Vygotsky, 1978). It is vital that students participate in play and that play be conducted in a restorative manner. Play allows a variety of group dynamics to emerge. Irvin Yalom (1995) identifies 11 curative factors of the group experience. These factors include…

  12. Play and playfulness in early childhood education and care.

    Directory of Open Access Journals (Sweden)

    Singer E.

    2015-06-01

    Full Text Available Play and playfulness are basic features in early childhood education. The elements of play are pleasure, a sense of freedom, and the co-construction of shared meaning through the use of rules or rhythms. Play and learning are closely related in early childhood. But when the focus on the educational benefits of play becomes too strong, the most essential feature of play is lost: children’s pleasure. Young children in group settings often have to adapt to the teachers’ demands related to security, hygiene, and social norms and values. But the playfulness of the teachers helps to overcome differences in power in the caregiver-child relationship and prevents young children from becoming overburdened with strict rules and group discipline. Play and playfulness are a resource of shared pleasure and creativity in learning processes.

  13. Ouroboros - Playing A Biochemical

    Directory of Open Access Journals (Sweden)

    D. T. Rodrigues

    2014-08-01

    Full Text Available Ouroboros: Playing A Biochemical RODRIGUES,D.T.1,2;GAYER, M.C.1,2; ESCOTO, D.F.1; DENARDIN, E.L.G.2, ROEHRS, R.1,2 1Interdisciplinary Research Group on Teaching Practice, Graduate Program in Biochemistry, Unipampa, RS, Brazil 2Laboratory of Physicochemical Studies and Natural Products, Post Graduate Program in Biochemistry, Unipampa, RS, Brazil Introduction: Currently, teachers seek different alternatives to enhance the teaching-learning process. Innovative teaching methodologies are increasingly common tools in educational routine. The use of games, electronic or conventional, is an effective tool to assist in learning and also to raise the social interaction between students. Objective: In this sense our work aims to evaluate the card game and "Ouroboros" board as a teaching and learning tool in biochemistry for a graduating class in Natural Sciences. Materials and methods: The class gathered 22 students of BSc in Natural Sciences. Each letter contained a question across the board that was drawn to a group to answer within the allotted time. The questions related concepts of metabolism, organic and inorganic chemical reactions, bioenergetics, etc.. Before the game application, students underwent a pre-test with four issues involving the content that was being developed. Soon after, the game was applied. Then again questions were asked. Data analysis was performed from the ratio of the number of correct pre-test and post-test answers. Results and discussion: In the pre-test 18.1% of the students knew all issues, 18.1% got 3 correct answers, 40.9% answered only 2 questions correctly and 22.7% did not hit any. In post-test 45.4% answered all the questions right, 31.8% got 3 questions and 22.7% got 2 correct answers. The results show a significant improvement of the students about the field of content taught through the game. Conclusion: Generally, traditional approaches of chemistry and biochemistry are abstract and complex. Thus, through games

  14. Quantum key management

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

    2016-11-29

    Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

  15. Quantum key management

    Science.gov (United States)

    Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

    2016-11-29

    Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

  16. Motivations for play in computer role-playing games

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    In this paper the motivations for play in the context of single-and multi-player digital Role-Playing Games (RPGs) are examined. Survey data were drawn from respondents online and participants in a related experimental study. The results indicate that motivations for play are not simple constructs......, but rather composed of multiple motivational drivers that are heavily interrelated and act in concert. Character uniqueness and Discovery & Immersion were the highest ranked motivational categories. Different levels of detail in motivations for playing single-/multi- Player RPGs were located......, with mechanistic/tactical play and character-based/social play being the two overall motivational factors. Copyright 2008 ACM....

  17. Public key cryptosystem and a key exchange protocol using tools of non-abelian group

    Directory of Open Access Journals (Sweden)

    H. K. Pathak,

    2010-07-01

    Full Text Available Public Key Cryptosystems assure privacy as well as integrity of the transactions between two parties. The sizes of the keys play an important role. The larger the key the harder is to crack a block ofencrypted data. We propose a new public key cryptosystem and a Key Exchange Protocol based on the generalization of discrete logarithm problem using Non-abelian group of block upper triangular matrices of higher order. The proposed cryptosystem is efficient in producing keys of large sizes without the need of large primes. The security of both the systems relies on the difficulty of discrete logarithms over finite fields.

  18. Group key management

    Energy Technology Data Exchange (ETDEWEB)

    Dunigan, T.; Cao, C.

    1997-08-01

    This report describes an architecture and implementation for doing group key management over a data communications network. The architecture describes a protocol for establishing a shared encryption key among an authenticated and authorized collection of network entities. Group access requires one or more authorization certificates. The implementation includes a simple public key and certificate infrastructure. Multicast is used for some of the key management messages. An application programming interface multiplexes key management and user application messages. An implementation using the new IP security protocols is postulated. The architecture is compared with other group key management proposals, and the performance and the limitations of the implementation are described.

  19. NRC regulatory initiatives

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, T.C. [Nuclear Regulatory Commission (United States)

    1989-11-01

    The US Nuclear Regulatory Commission (NRC) is addressing several low-level waste disposal issues that will be important to waste generators and to States and Compacts developing new disposal capacity. These issues include Greater-Than-Class C (GTCC) waste, mixed waste, below regulatory concern (BRC) waste, and the low-level waste data base. This paper discusses these issues and their current status.

  20. From Team Play to Squad Play: The Militarisation of Interactions in Multiplayer FPS Video Games

    Directory of Open Access Journals (Sweden)

    Adam Duell

    2014-11-01

    Full Text Available Since the onset of E-sports we have seen the development from casual players to professional players who push the boundary of game mastery to new heights via coordinated team play. In this short paper I explore how a group of video game players adopt military-style communication methods and strategies to coordinate their actions in the popular tactical First Person Shooter (FPS video game DayZ (Bohemia Interactive, 2014.  Utilising the key components of team interaction in the context of distributed and ad-hoc military teams (Pascual et al., 1997, I show how a group of players evolved their interactions from team play to squad play. I argue that squad play is an advancement of the strategic and tactical thinking embodied in team play through the adoption of real-world military interaction and communication strategies.

  1. Solar Power at Play

    Science.gov (United States)

    2007-03-01

    For the very first time, astronomers have witnessed the speeding up of an asteroid's rotation, and have shown that it is due to a theoretical effect predicted but never seen before. The international team of scientists used an armada of telescopes to discover that the asteroid's rotation period currently decreases by 1 millisecond every year, as a consequence of the heating of the asteroid's surface by the Sun. Eventually it may spin faster than any known asteroid in the solar system and even break apart. ESO PR Photo 11a/07 ESO PR Photo 11a/07 Asteroid 2000 PH5 "The Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect is believed to alter the way small bodies in the Solar System rotate," said Stephen Lowry (Queens University Belfast, UK), lead-author of one of the two companion papers in which this work is reported [1, 2]. "The warming caused by sunlight hitting the surfaces of asteroids and meteoroids leads to a gentle recoil effect as the heat is released," he added. "By analogy, if one were to shine light on a propeller over a long enough period, it would start spinning." Although this is an almost immeasurably weak force, its effect over millions of years is far from negligible. Astronomers believe the YORP effect may be responsible for spinning some asteroids up so fast that they break apart, perhaps leading to the formation of double asteroids. Others may be slowed down so that they take many days to complete a full turn. The YORP effect also plays an important role in changing the orbits of asteroids between Mars and Jupiter, including their delivery to planet-crossing orbits, such as those of near-Earth asteroids. Despite its importance, the effect has never been seen acting on a solar system body, until now. Using extensive optical and radar imaging from powerful Earth-based observatories, astronomers have directly observed the YORP effect in action on a small near-Earth asteroid, known as (54509) 2000 PH5. Shortly after its discovery in 2000, it was

  2. Quantum Key Distribution

    Science.gov (United States)

    Seshu, Ch.

    Quantum Key Distribution (QKD) uses Quantum Mechanics to guarantee secure communication. It enables two parties to produce a shared random bit string known only to them, which can be used as a key to encrypt and decrypt messages.

  3. Public Key Cryptography.

    Science.gov (United States)

    Tapson, Frank

    1996-01-01

    Describes public key cryptography, also known as RSA, which is a system using two keys, one used to put a message into cipher and another used to decipher the message. Presents examples using small prime numbers. (MKR)

  4. Key Management Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides a secure environment to research and develop advanced electronic key management and networked key distribution technologies for the Navy and DoD....

  5. Play technique in psychodynamic psychotherapy.

    Science.gov (United States)

    Yanof, Judith A

    2013-04-01

    Imaginary play is often a child's best way of communicating affects, fantasies, and internal states. In play children are freer to express their forbidden and conflicted thoughts. Consequently, one of the best ways for the therapist to enter the child's world is to do so from within the displacement of the play process. For children who cannot play, the therapist's goal is to teach the child to use play as a means of communication and to create meaning. This article present clinical examples to illustrate how the author uses play in the clinical situation.

  6. Quantum dense key distribution

    CERN Document Server

    Degiovanni, I P; Castelletto, S; Rastello, M L; Bovino, F A; Colla, A M; Castagnoli, G C

    2004-01-01

    This paper proposes a new protocol for quantum dense key distribution. This protocol embeds the benefits of a quantum dense coding and a quantum key distribution and is able to generate shared secret keys four times more efficiently than BB84 one. We hereinafter prove the security of this scheme against individual eavesdropping attacks, and we present preliminary experimental results, showing its feasibility.

  7. Regulatory Issues Surrounding Merchant Interconnection

    Energy Technology Data Exchange (ETDEWEB)

    Kuijlaars, Kees-Jan; Zwart, Gijsbert [Office for Energy Regulation (DTe), The Hague (Netherlands)

    2003-11-01

    We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections.

  8. MOVING EDUCATIONAL ROLE-PLAY BEYOND ENTERTAINMENT

    Directory of Open Access Journals (Sweden)

    Thomas Duus Henriksen

    2010-11-01

    Full Text Available Educational role-play has long proved an effective tool for consultants trying to develop the skills that employees are using for performing certain job functions. However, while educational role-play often is presented as an entertaining means for learning, such insistence on making learning games more gamish seems to have an inhibiting effect on designing and thinking games beyond mere skill acquisition. By emphasising the role-play based process as a conflictual negotiation between distinctive categories of knowledge, this paper presents the explorative application of knowledge, while framing the facilitation of reflective processes as the key for transcending knowledge from the game’s context to that of the participants. While pointing towards the compatibility issues between current conceptions of learning games and the facilitation of reflective processes, the paper emphasises the need for thinking the learning game as a part of a didactic design, rather than something beneficial in itself.

  9. Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis

    OpenAIRE

    Carter, N. A.; Rosser, E. C.; Mauri, C

    2012-01-01

    Introduction Interleukin-10 (IL-10) producing B cells, also known as regulatory B (Breg) cells, play a key role in controlling autoimmunity. Our laboratory and others have demonstrated a pivotal role for Bregs in rheumatological disorders, including experimental models of arthritis and lupus. The aim of this study was to identify the role of endogenous IL-10 secreting B cells in vivo in controlling the induction and disease progression of collagen-induced arthritis (CIA). Methods We generated...

  10. Learning, Play, and Your Newborn

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Learning, Play, and Your Newborn KidsHealth > For Parents > Learning, ... juega su recién nacido What Is My Newborn Learning? Play is the chief way that infants learn ...

  11. Problematic Game Play: The Diagnostic Value of Playing Motives, Passion, and Playing Time in Men

    Directory of Open Access Journals (Sweden)

    Julia Kneer

    2015-04-01

    Full Text Available Internet gaming disorder is currently listed in the DSM—not in order to diagnose such a disorder but to encourage research to investigate this phenomenon. Even whether it is still questionable if Internet Gaming Disorder exists and can be judged as a form of addiction, problematic game play is already very well researched to cause problems in daily life. Approaches trying to predict problematic tendencies in digital game play have mainly focused on playing time as a diagnostic criterion. However, motives to engage in digital game play and obsessive passion for game play have also been found to predict problematic game play but have not yet been investigated together. The present study aims at (1 analyzing if obsessive passion can be distinguished from problematic game play as separate concepts, and (2 testing motives of game play, passion, and playing time for their predictive values for problematic tendencies. We found (N = 99 males, Age: M = 22.80, SD = 3.81 that obsessive passion can be conceptually separated from problematic game play. In addition, the results suggest that compared to solely playing time immersion as playing motive and obsessive passion have added predictive value for problematic game play. The implications focus on broadening the criteria in order to diagnose problematic playing.

  12. LOCKS AND KEYS SERVICE

    CERN Multimedia

    Locks and Keys Service

    2002-01-01

    The Locks and Keys service (ST/FM) will move from building 55 to building 570 from the 2nd August to the 9th August 2002 included. During this period the service will be closed. Only in case of extreme urgency please call the 164550. Starting from Monday, 12th August, the Locks and Keys Service will continue to follow the activities related to office keys (keys and locks) and will provide the keys for furniture. The service is open from 8h30 to 12h00 and from 13h00 to 17h30. We remind you that your divisional correspondents can help you in the execution of the procedures. We thank you for your comprehension and we remain at your service to help you in solving all the matters related to keys for offices and furniture. Locks and Keys Service - ST Division - FM Group

  13. The Importance of Being Playful.

    Science.gov (United States)

    Bodrova, Elena; Leong, Deborah J.

    2003-01-01

    Recent research provides evidence of the strong connections between quality of play in preschool years and children's readiness for school instruction. Mature play, characterized by imaginary situations, multiple roles, clearly defined rules, flexible themes, language development, length of play, helps students' cognitive development. (Contains 12…

  14. Play in Evolution and Development

    Science.gov (United States)

    Pellegrini, Anthony D.; Dupuis, Danielle; Smith, Peter K.

    2007-01-01

    In this paper we examine the role of play in human ontogeny and phylogeny, following Surplus Resource Theory. We consider how juveniles use play to sample their environment in order to develop adaptive behaviors. We speculate about how innovative behaviors developed in play in response to environmental novelty may influence subsequent evolutionary…

  15. Pretend Play and Creative Processes

    Science.gov (United States)

    Russ, Sandra W.; Wallace, Claire E.

    2013-01-01

    The authors contend that many cognitive abilities and affective processes important in creativity also occur in pretend play and that pretend play in childhood affects the development of creativity in adulthood. They discuss a variety of theories and observations that attempt to explain the importance of pretend play to creativity. They argue that…

  16. EGF Uptake and Degradation Assay to Determine the Effect of HTLV Regulatory Proteins on the ESCRT-Dependent MVB Pathway.

    Science.gov (United States)

    Murphy, Colin; Sheehy, Noreen

    2017-01-01

    The endosomal sorting complex required for transport (ESCRT) pathway plays key roles in multivesicular bodies (MVBs) formation and lysosomal degradation of membrane receptors, viral budding, and midbody abscission during cytokinesis. The epidermal growth factor receptor (EGFR) is regarded as a prototypical cargo of the MVB/ESCRT pathway and following stimulation by epidermal growth factor (EGF) EGFR/EGF complexes are internalized, sorted into MVBs, and degraded by lysosomes or recycled back to the cell membrane. Here, we describe an assay to analyze the effect of human T-cell leukemia (HTLV) regulatory proteins on the functionality of ESCRT-dependent MVB/lysosomal trafficking of EGFR/EGF complexes. This is performed by direct visualization and quantification of the rate of EGF-Alexa595/EGFR internalization and degradation in HeLa cells expressing HTLV regulatory proteins by immunofluorescence and western blot.

  17. Autophagy gets in on the regulatory act

    Institute of Scientific and Technical Information of China (English)

    Steven K. Backues; Daniel J. Klionsky

    2011-01-01

    Autophagy down-regulates the Wnt signal transduction pathway via targeted degradation of a key signaling protein. This may provide an explanation for autophagy's role in tumor suppression.%@@ The eukaryotic cell has at its disposal two primary methods for getting rid of unwanted proteins: the proteasome and autophagy.The proteasome is a large protein complex comprising regulatory and proteolytic subunits whose core function is the degradation of damaged or misfolded proteins.

  18. Key to Language Learning Success

    Directory of Open Access Journals (Sweden)

    Oktavian Mantiri

    2015-01-01

    Full Text Available This paper looks at the important elements of language learning and teaching i.e. the role of teachers as well as the attitude and motivation of learners. Teachers undoubtedly play crucial roles in students’ language learning outcome which could ignite or diminish students’ motivation. Positive attitudes and motivation – instrumental or integrative and intrinsic or extrinsic – are key to successful learning. Therefore it is paramount for language teachers as well as learners to know these roles and nurture the best possible ways where language teaching and learning will thrive. This paper also suggested that both stake-holders should be open to holistic approach of language learning and that other factors such as the environment could play an important part in language teaching and learning success.

  19. Key drivers of airline loyalty

    Science.gov (United States)

    Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

    2011-01-01

    This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty. PMID:27064618

  20. Key drivers of airline loyalty.

    Science.gov (United States)

    Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

    2011-10-01

    This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty.

  1. 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.

  2. Motivations for play in computer role-playing games

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    In this paper the motivations for play in the context of single-and multi-player digital Role-Playing Games (RPGs) are examined. Survey data were drawn from respondents online and participants in a related experimental study. The results indicate that motivations for play are not simple constructs......, but rather composed of multiple motivational drivers that are heavily interrelated and act in concert. Character uniqueness and Discovery & Immersion were the highest ranked motivational categories. Different levels of detail in motivations for playing single-/multi- Player RPGs were located...

  3. The Homomorphic Key Agreement

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    There are various challenges that are faced in group communication, so it is necessary to ensure session key. Key agreement is the fundamental cryptographic primitive for establishing a secure communication. It is a process of computing a shared secret contributed by two or more entities such that no single node can predetermine the resulting value. An authenticated key agreement is attained by combining the key agreement protocol with digital signatures. After a brief introduction to existing key agreement in group communication, Making use of the additive-multiplicative homomorphism in the integer ring defined by Sander and Tschudin: A new protocols, called the homomorphism key agreement, was designed, which can be self-contributory, robust, scalable and applicable in group communication.

  4. Key Account Management

    OpenAIRE

    Dvořák, Dalibor

    2007-01-01

    This note tries to explain concept of key account management (KAM), factors leading to importance of this emerging concept, criteria to determine key accounts from customer base, benefits to both buyers and sellers agreeing to practice it, stages of KAM relationship, conditions under which power lies with buyer or seller, outlines risks faced by both the parties, key success factors, challenges faced in implementing this concept and relevance to infrastructure sector.

  5. Behavioral approaches to promoting play.

    Science.gov (United States)

    Stahmer, Aubyn C; Ingersoll, Brooke; Carter, Cynthia

    2003-12-01

    A variety of techniques grounded in behavioral psychology, and more specifically in applied behavior analysis, have been established to increase and improve play skills in children with autistic spectrum disorders. This article introduces a set of efficacious methods, which range from highly structured techniques to more naturalistic strategies. It focuses on object play as other authors in the issue discuss social play in greater depth. Behavioral techniques that are reviewed include: discrete trial training, use of stereotyped behaviors to increase play skills, pivotal response training, reciprocal imitation training, differential reinforcement of appropriate behavior, in vivo modeling and play scripts, and video modeling. A discussion of expanding behavior techniques to teach more complex play as well as training in varied environments is also presented. References are provided to allow the reader to obtain more in-depth information about each technique.

  6. Playing with the Multiple Intelligences: How Play Helps Them Grow

    Science.gov (United States)

    Eberle, Scott G.

    2011-01-01

    Howard Gardner first posited a list of "multiple intelligences" as a liberating alternative to the assumptions underlying traditional IQ testing in his widely read study "Frames of Mind" (1983). Play has appeared only in passing in Gardner's thinking about intelligence, however, even though play instructs and trains the verbal, interpersonal,…

  7. Let's Play: Teaching Play Skills to Young Children with Autism

    Science.gov (United States)

    Boutot, E. Amanda; Guenther, Tracee; Crozier, Shannon

    2005-01-01

    Watch any young child and you will likely see him or her engaged in some form of play. Play is an integral part of early childhood development in which typically developing children learn social and language skills, as well as appropriate behaviors, problem solving, and a variety of other cognitive skills. By its very definition, autism is a…

  8. Reverse engineering: a key component of systems biology to unravel global abiotic stress cross-talk.

    Science.gov (United States)

    Friedel, Swetlana; Usadel, Björn; von Wirén, Nicolaus; Sreenivasulu, Nese

    2012-01-01

    Understanding the global abiotic stress response is an important stepping stone for the development of universal stress tolerance in plants in the era of climate change. Although co-occurrence of several stress factors (abiotic and biotic) in nature is found to be frequent, current attempts are poor to understand the complex physiological processes impacting plant growth under combinatory factors. In this review article, we discuss the recent advances of reverse engineering approaches that led to seminal discoveries of key candidate regulatory genes involved in cross-talk of abiotic stress responses and summarized the available tools of reverse engineering and its relevant application. Among the universally induced regulators involved in various abiotic stress responses, we highlight the importance of (i) abscisic acid (ABA) and jasmonic acid (JA) hormonal cross-talks and (ii) the central role of WRKY transcription factors (TF), potentially mediating both abiotic and biotic stress responses. Such interactome networks help not only to derive hypotheses but also play a vital role in identifying key regulatory targets and interconnected hormonal responses. To explore the full potential of gene network inference in the area of abiotic stress tolerance, we need to validate hypotheses by implementing time-dependent gene expression data from genetically engineered plants with modulated expression of target genes. We further propose to combine information on gene-by-gene interactions with data from physical interaction platforms such as protein-protein or TF-gene networks.

  9. 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...

  10. Learning Transcriptional Regulatory Relationships Using Sparse Graphical Models

    OpenAIRE

    Xiang Zhang; Wei Cheng; Jennifer Listgarten; Carl Kadie; Shunping Huang; Wei Wang; David Heckerman

    2012-01-01

    Understanding the organization and function of transcriptional regulatory networks by analyzing high-throughput gene expression profiles is a key problem in computational biology. The challenges in this work are 1) the lack of complete knowledge of the regulatory relationship between the regulators and the associated genes, 2) the potential for spurious associations due to confounding factors, and 3) the number of parameters to learn is usually larger than the number of available microarray e...

  11. The Internet of Playful Things

    DEFF Research Database (Denmark)

    Wyeth, Peta; Brereton, Margot; Roe, Paul;

    2015-01-01

    This one-day workshop brings together researchers and practitioners to share knowledge and practices on how people can connect and interact with the Internet of Things in a playful way. Open to participants with a diverse range of interests and expertise, and by exploring novel ways to playfully...... will be a road map to support the development of a Model of Playful Connectedness, focusing on how best to design and make playful networks of things, identifying the challenges that need to be addressed in order to do so....

  12. Symbolic play and language development.

    Science.gov (United States)

    Orr, Edna; Geva, Ronny

    2015-02-01

    Symbolic play and language are known to be highly interrelated, but the developmental process involved in this relationship is not clear. Three hypothetical paths were postulated to explore how play and language drive each other: (1) direct paths, whereby initiation of basic forms in symbolic action or babbling, will be directly related to all later emerging language and motor outputs; (2) an indirect interactive path, whereby basic forms in symbolic action will be associated with more complex forms in symbolic play, as well as with babbling, and babbling mediates the relationship between symbolic play and speech; and (3) a dual path, whereby basic forms in symbolic play will be associated with basic forms of language, and complex forms of symbolic play will be associated with complex forms of language. We micro-coded 288 symbolic vignettes gathered during a yearlong prospective bi-weekly examination (N=14; from 6 to 18 months of age). Results showed that the age of initiation of single-object symbolic play correlates strongly with the age of initiation of later-emerging symbolic and vocal outputs; its frequency at initiation is correlated with frequency at initiation of babbling, later-emerging speech, and multi-object play in initiation. Results support the notion that a single-object play relates to the development of other symbolic forms via a direct relationship and an indirect relationship, rather than a dual-path hypothesis.

  13. Multispecies methods, technologies for play

    DEFF Research Database (Denmark)

    Jørgensen, Ida Kathrine Hammeleff; Wirman, Hanna

    2016-01-01

    reveals limitations of designers’ knowledge of prospected users. The article explores how to approach participants who cannot express themselves verbally and how to recognise play that may not look familiar to the designer. The article finally presents a participatory design method that allows for non......-human contributions in design. This method applies play as an interspecies co-creative act and can be used as a starting point for addressing questions of difference in play and designing games that allow for ambiguous play....

  14. Financial Key Ratios

    Directory of Open Access Journals (Sweden)

    Tănase Alin-Eliodor

    2014-08-01

    Full Text Available This article focuses on computing techniques starting from trial balance data regarding financial key ratios. There are presented activity, liquidity, solvency and profitability financial key ratios. It is presented a computing methodology in three steps based on a trial balance.

  15. The compact key

    NARCIS (Netherlands)

    NN,

    1966-01-01

    Here is given a sample of a new sort of identification key, recently developed by Dr. P. W. Leenhouts of the Rijksherbarium. Having to sort many specimens of Sapindaceae into genera, he became dissatisfied with the common dichotomous key, which too often does not work when the material is not comple

  16. Family play-learning through informal education: Make and play activities with traditional Thai toy activities at a science museum

    OpenAIRE

    Kanhadilok, Peeranut

    2013-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University This thesis charts the outcomes of family play-learning through make-and-play activities with traditional Thai toys activities (TTTA). Family learning is a component of inter-generational learning, and the research explores this through ‘edutainment’ activities within the informal educational system of a science museum. The thesis also identifies key factors that influence family play-learning...

  17. Data-driven integration of genome-scale regulatory and metabolic network models

    Directory of Open Access Journals (Sweden)

    Saheed eImam

    2015-05-01

    Full Text Available Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription and signaling have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert – a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or more network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. In this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.

  18. Seductive play in digital games

    DEFF Research Database (Denmark)

    Jørgensen, Ida Kathrine Hammeleff

    2015-01-01

    seduction is meaningless because it is nothing but appearances – a sign without reference. In his conceptualization of seduction Baudrillard draws heavily upon Huizinga’s (1950) and Callois’ (1961) theory of play. To Baudrillard play is the mode of the seductive. But in contrast to both Callois and Huizinga...

  19. Making Play Work for Education

    Science.gov (United States)

    Weisberg, Deena Skolnick; Kittredge, Audrey K.; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick; Klahr, David

    2015-01-01

    Children, especially in the preschool years, learn a tremendous amount through play. Research on guided play demonstrates how schools can couple a curriculum-centered preschool program with a developmentally appropriate pedagogical approach to classroom teaching. However, to fully test this claim, we need a clear definition of the term…

  20. Transmedia Play: Literacy across Media

    Science.gov (United States)

    Alper, Meryl; Herr-Stephenson, Rebecca

    2013-01-01

    Transmedia play is a new way to understand how children develop critical media literacy and new media literacies through their interactions with contemporary media that links stories and structures across platforms. This essay highlights five characteristics of transmedia play that make it particularly useful for learning:…

  1. Sand and Water Table Play

    Science.gov (United States)

    Wallace, Ann H.; White, Mary J.; Stone, Ryan

    2010-01-01

    The authors observed preschoolers engaged at the sand and water table to determine if math could be found within their play. Wanting to understand how children interact with provided materials and what kinds of math ideas they explore during these interactions, the authors offer practical examples of how such play can promote mathematical…

  2. Playful Interfaces: Introduction and History

    NARCIS (Netherlands)

    Nijholt, Anton; Nijholt, Anton

    2014-01-01

    In this short survey we have some historical notes about human-computer interface development with an emphasis on interface technology that has allowed us to design playful interactions with applications. The applications do not necessarily have to be entertainment applications. We can have playful

  3. Young Children and War Play.

    Science.gov (United States)

    Carlsson-Paige, Nancy; Levin, Diane E.

    1988-01-01

    In a recent survey of parents and early childhood professionals the prevalence of war play among children and an increase in the amount of violence in children's play was noted. Outlines how the deregulation of children's television during the Reagan administration has affected children's exposure to violence in children's television programming.…

  4. Sand and Water Table Play

    Science.gov (United States)

    Wallace, Ann H.; White, Mary J.; Stone, Ryan

    2010-01-01

    The authors observed preschoolers engaged at the sand and water table to determine if math could be found within their play. Wanting to understand how children interact with provided materials and what kinds of math ideas they explore during these interactions, the authors offer practical examples of how such play can promote mathematical…

  5. The Fractal Self at Play

    Science.gov (United States)

    Marks-Tarlow, Terry

    2010-01-01

    In this article, the author draws on contemporary science to illuminate the relationship between early play experiences, processes of self-development, and the later emergence of the fractal self. She argues that orientation within social space is a primary function of early play and developmentally a two-step process. With other people and with…

  6. The Play of Socratic Dialogue

    Science.gov (United States)

    Smith, Richard

    2011-01-01

    Proponents of philosophy for children generally see themselves as heirs to the "Socratic" tradition. They often claim too that children's aptitude for play leads them naturally to play with abstract, philosophical ideas. However in Plato's dialogues we find in the mouth of "Socrates" many warnings against philosophising with the young. Those…

  7. Empowering Groups that Enable Play

    Science.gov (United States)

    Wilson, David Sloan; Marshall, Danielle; Iserhott, Hindi

    2011-01-01

    Creating play environments for children usually requires groups of adults working together. An extensive scientific literature describes how groups function to achieve shared goals in general terms, and groups attempting to empower play may find this literature useful. Design principles for managing natural resources, identified by Elinor Ostrom…

  8. Let's Play Three on Three!

    Science.gov (United States)

    Kern, Jack; Calleja, Paul

    2008-01-01

    Over the course of nine years as a supervisor of intern teachers, the first author collected observations of game play during lessons taught by intern teachers or their mentors. In general, the observations indicated that the majority of students got limited practice opportunities during game play. A close look at the data revealed an interesting…

  9. Shale Gas Play Screening and Evaluation Criteria

    Institute of Scientific and Technical Information of China (English)

    Michael D. Burnaman; Wenwu Xia; John Shelton

    2009-01-01

    The uniqueness of shale gas plays is contrasted with conventional oil and gas exploration. Based on our ten year history in shale gas exploration, a practical 17 point list of criteria to use for screening shale gas projects and ranking that encompasses geoscience, geochemistry, reservoir engineering, drilling, completions and production operations is developed and explained. Other considerations that will impact shale gas development are identified and discussed. Some key methodologies to incorporate in the evaluation process are also proposed. The outcome of this proposed screening process, if rigorously applied,should quickly identify the projects that have the most likely chance for success for recommendation to management. Examples from active shale gas plays in the United States are used to support these criteria and references to relevant recent publications and presentations are provided.

  10. Psychodrama: group psychotherapy through role playing.

    Science.gov (United States)

    Kipper, D A

    1992-10-01

    The theory and the therapeutic procedure of classical psychodrama are described along with brief illustrations. Classical psychodrama and sociodrama stemmed from role theory, enactments, "tele," the reciprocity of choices, and the theory of spontaneity-robopathy and creativity. The discussion focuses on key concepts such as the therapeutic team, the structure of the session, transference and reality, countertransference, the here-and-now and the encounter, the group-as-a-whole, resistance and difficult clients, and affect and cognition. Also described are the neoclassical approaches of psychodrama, action methods, and clinical role playing, and the significance of the concept of behavioral simulation in group psychotherapy.

  11. Comparative Evolution of Morphological Regulatory Functions in Candida Species

    Science.gov (United States)

    Lackey, Erika; Vipulanandan, Geethanjali; Childers, Delma S.

    2013-01-01

    Morphological transitions play an important role in virulence and virulence-related processes in a wide variety of pathogenic fungi, including the most commonly isolated human fungal pathogen Candida albicans. While environmental signals, transcriptional regulators, and target genes associated with C. albicans morphogenesis are well-characterized, considerably little is known about morphological regulatory mechanisms and the extent to which they are evolutionarily conserved in less pathogenic and less filamentous non-albicans Candida species (NACS). We have identified specific optimal filament-inducing conditions for three NACS (C. tropicalis, C. parapsilosis, and C. guilliermondii), which are very limited, suggesting that these species may be adapted for niche-specific filamentation in the host. Only a subset of evolutionarily conserved C. albicans filament-specific target genes were induced upon filamentation in C. tropicalis, C. parapsilosis, and C. guilliermondii. One of the genes showing conserved expression was UME6, a key filament-specific regulator of C. albicans hyphal development. Constitutive high-level expression of UME6 was sufficient to drive increased filamentation as well as biofilm formation and partly restore conserved filament-specific gene expression in both C. tropicalis and C. parapsilosis, suggesting that evolutionary differences in filamentation ability among pathogenic Candida species may be partially attributed to alterations in the expression level of a conserved filamentous growth machinery. In contrast to UME6, NRG1, an important repressor of C. albicans filamentation, showed only a partly conserved role in controlling NACS filamentation. Overall, our results suggest that C. albicans morphological regulatory functions are partially conserved in NACS and have evolved to respond to more specific sets of host environmental cues. PMID:23913541

  12. 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.

  13. Nuclear Regulatory Commission information digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    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.

  14. On the Fair Play Spirit%论Fair Play

    Institute of Scientific and Technical Information of China (English)

    张维; 林琳

    2011-01-01

    采用文献资料法,历史分析了"Fair Play"精神的起源,并结合Fair Play精神面临的时代压力,探讨现代体育生命力延续的议题,提出"人"才是体育及其"Fair Play"精神继续生存或走向毁灭的主宰者.

  15. 破译戏剧象征艺术的一把钥匙--读《尤金·奥尼尔戏剧象征艺术研究》%A Key to Decipher Drama’s Symbolic Art---On Symbolic Art Research of Eugene O’Neill Plays

    Institute of Scientific and Technical Information of China (English)

    李冉英

    2014-01-01

    文章对詹虎、赵学斌、于立得最近出版的学术专著《尤金·奥尼尔戏剧象征艺术研究》进行评述。通过阅读这部专著,不但可窥一斑而知全豹地为欣赏戏剧艺术打开一扇窗户,而且可以推而广之地以象征艺术的视觉方法,去破译自然、社会、人生的诸多生命密码。%This article evaluates Symbolic Art Research of Eugene O’Neill Plays, a newly published monograph jointly written by Zhan Hu, Zhao Xuebin and Yu Lide. It concludes that the monograph not only opens a window to enjoy the dramatic arts, but also decipher the life codes concerning nature, society and human life by means of the symbolic art of visual methods.

  16. Playful biometrics: controversial technology through the lens of play.

    Science.gov (United States)

    Ellerbrok, Ariane

    2011-01-01

    This article considers the role of play in the context of technological emergence and expansion, particularly as it relates to recently emerging surveillance technologies. As a case study, I consider the trajectory of automated face recognition—a biometric technology of numerous applications, from its more controversial manifestations under the rubric of national security to a clearly emerging orientation toward play. This shift toward “playful” biometrics—or from a technology traditionally coded as “hard” to one now increasingly coded as “soft”—is critical insofar as it renders problematic the traditional modes of critique that have, up until this point, challenged the expansion of biometric systems into increasingly ubiquitous realms of everyday life. In response to this dynamic, I propose theorizing the expansion of face recognition specifically in relation to “play,” a step that allows us to broaden the critical space around newly emerging playful biometrics, as well as playful surveillance more generally. In addition, play may also have relevance for theorizing other forms of controversial technology, particularly given its potential role in processes of obfuscation, normalization, and marginalization.

  17. An Alternative to Keys

    Science.gov (United States)

    O'Hagan, James

    1977-01-01

    For the secondary school, the author discourages the use of dichotomous keys in favor of a punch-card system. The system is readily constructed by students for use in plant and animal classification. (CP)

  18. Keys to the City

    DEFF Research Database (Denmark)

    Monsson, Christian Kjær

    2014-01-01

    Review of: Keys to the City: How Economics, Institutions, Social Interaction, and Politics Shape Development / Michael Storper Princeton University Press, Princeton, NJ, 2013, 288 pp., $39.95/£27.95 (cloth), ISBN 9780691143118......Review of: Keys to the City: How Economics, Institutions, Social Interaction, and Politics Shape Development / Michael Storper Princeton University Press, Princeton, NJ, 2013, 288 pp., $39.95/£27.95 (cloth), ISBN 9780691143118...

  19. Key concepts in energy

    CERN Document Server

    Madureira, Nuno Luis

    2014-01-01

    Highlights how key energy concepts surfaced, tracing their evolution throughout history to encompasses four economic concepts and four technological-engineering concepts developed through their history to conclude with current economic and environmental sciences Considers the process of energy-substitutions through complementary usages, hybridization and technological mixes Combines a conceptual approach with key theoretical concepts from engineering, geological and economic sciences providing cross disciplinary overview of energy fundamentals in a short and focused reading

  20. Secret Key Crypto Implementations

    Science.gov (United States)

    Bertoni, Guido Marco; Melzani, Filippo

    This chapter presents the algorithm selected in 2001 as the Advanced Encryption Standard. This algorithm is the base for implementing security and privacy based on symmetric key solutions in almost all new applications. Secret key algorithms are used in combination with modes of operation to provide different security properties. The most used modes of operation are presented in this chapter. Finally an overview of the different techniques of software and hardware implementations is given.

  1. Hastening the regulatory process

    Energy Technology Data Exchange (ETDEWEB)

    Stringham, G. [Canadian Association of Petroleum Producers, Calgary, AB (Canada)

    2001-07-01

    The state of the Canadian oil industry was discussed during this power point presentation with particular emphasis on its production, exports, drilling, industry revenues and capital investment levels. The proposed projects in each of northern Alberta's oil sands deposits, the Athabasca, Peace River and Cold Lake were were announced, along with the inventory of major Alberta projects and the projection of oil sands capital investment. Since 1998, $9 billion has been invested and a further $33 billion has been announced for new or expanded oil sands projects. The year 2000 estimates for Canadian crude oil and natural gas production are 2.3 million barrels per day and 6.3 trillion cubic feet per year respectively. This represented a record year for production of both crude oil and natural gas. In 2000, more than 15,500 wells were drilled in Canada. A graph depicting Canadian crude oil supply forecasted a steady increase in supply from year 2000 to 2010. The Canadian Association of Petroleum Producers (CAPP) completed a review of the Alberta Energy and Utilities Board regulatory and enforcement processes. Both industry and government efforts are focusing on eliminating regulatory overlap and duplication. Some of the main areas of interest for exploration, drilling, production and pipeline facilities include the examination of regulatory processes for environmentally sensitive areas, rural municipalities with planning bylaws, aboriginal lands and additional fees. 8 figs.

  2. PKA regulatory subunit expression in tooth development.

    Science.gov (United States)

    de Sousa, Sílvia Ferreira; Kawasaki, Katsushige; Kawasaki, Maiko; Volponi, Ana Angelova; Gomez, Ricardo Santiago; Gomes, Carolina Cavaliéri; Sharpe, Paul T; Ohazama, Atsushi

    2014-05-01

    Protein kinase A (PKA) plays critical roles in many biological processes including cell proliferation, cell differentiation, cellular metabolism and gene regulation. Mutation in PKA regulatory subunit, PRKAR1A has previously been identified in odontogenic myxomas, but it is unclear whether PKA is involved in tooth development. The aim of the present study was to assess the expression of alpha isoforms of PKA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization. PRKAR1A and PRKAR2A mRNA transcription was further confirmed in a human deciduous germ by qRT-PCR. Mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis. These isoforms thus showed different expression pattern between human and mouse tooth germs. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Reconstruction and analysis of transcription factor-miRNA co-regulatory feed-forward loops in human cancers using filter-wrapper feature selection.

    Directory of Open Access Journals (Sweden)

    Chen Peng

    Full Text Available BACKGROUND: As one of the most common types of co-regulatory motifs, feed-forward loops (FFLs control many cell functions and play an important role in human cancers. Therefore, it is crucial to reconstruct and analyze cancer-related FFLs that are controlled by transcription factor (TF and microRNA (miRNA simultaneously, in order to find out how miRNAs and TFs cooperate with each other in cancer cells and how they contribute to carcinogenesis. Current FFL studies rely on predicted regulation information and therefore suffer the false positive issue in prediction results. More critically, FFLs generated by existing approaches cannot represent the dynamic and conditional regulation relationship under different experimental conditions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we proposed a novel filter-wrapper feature selection method to accurately identify co-regulatory mechanism by incorporating prior information from predicted regulatory interactions with parallel miRNA/mRNA expression datasets. By applying this method, we reconstructed 208 and 110 TF-miRNA co-regulatory FFLs from human pan-cancer and prostate datasets, respectively. Further analysis of these cancer-related FFLs showed that the top-ranking TF STAT3 and miRNA hsa-let-7e are key regulators implicated in human cancers, which have regulated targets significantly enriched in cellular process regulations and signaling pathways that are involved in carcinogenesis. CONCLUSIONS/SIGNIFICANCE: In this study, we introduced an efficient computational approach to reconstruct co-regulatory FFLs by accurately identifying gene co-regulatory interactions. The strength of the proposed feature selection method lies in the fact it can precisely filter out false positives in predicted regulatory interactions by quantitatively modeling the complex co-regulation of target genes mediated by TFs and miRNAs simultaneously. Moreover, the proposed feature selection method can be generally applied to

  4. A multiverse play divides opinion

    Science.gov (United States)

    Crease, Robert P.

    2015-03-01

    The stage lights rise. A man and woman meet in a cute way - "Do you know why it's impossible to lick the tips of your elbows?" she asks - they chat momentarily, and separate. The play is Constellations by Nick Payne.

  5. Play the Blood Typing Game

    Science.gov (United States)

    ... Nobel's Life and Work Teachers' Questionnaire The Blood Typing Game What happens if you get a blood ... learn about human blood types! Play the Blood Typing Game About this game Embed the Blood Typing ...

  6. Discussion of "interpretation and play".

    Science.gov (United States)

    Pick, Irma Brenman

    2011-01-01

    This discussion addresses the conflict in technique between play versus interpretation. It further considers how the nature of the interpretation may be affected by a consideration of what is being projected into the analyst.

  7. THE VALUE OF ROLE PLAY

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    IntroductionIn China,the English as a foreign language (EFL) class for non-English majors at college levelprovides little opportunity for oral interaction among students.One solution to this problem is toadopt a series of communicative teaching techniques.Role play is one such technique.This paperattempts to assess the value of role play by analysing our experience of using it as a communicationactivity.

  8. Digital Play: A New Classification

    Science.gov (United States)

    Marsh, Jackie; Plowman, Lydia; Yamada-Rice, Dylan; Bishop, Julia; Scott, Fiona

    2016-01-01

    This paper draws on an ESRC-funded study of play and creativity in preschool-aged children's use of apps in the UK. The main objectives of the study were to collect information about access to and use of apps in the home, establish the most popular apps and identify the features of those apps that are successful in promoting play and creativity. A…

  9. MOVING EDUCATIONAL ROLE-PLAY BEYOND ENTERTAINMENT MOVING EDUCATIONAL ROLE-PLAY BEYOND ENTERTAINMENT

    Directory of Open Access Journals (Sweden)

    Thomas Duus Henriksen

    2010-11-01

    Full Text Available Educational role-play has long proved an effective tool for consultants trying to develop the skills that employees are using for performing certain job functions. However, while educational role-play often is presented as an entertaining means for learning, such insistence on making learning games more gamish seems to have an inhibiting effect on designing and thinking games beyond mere skill acquisition. By emphasising the role-play based process as a conflictual negotiation between distinctive categories of knowledge, this paper presents the explorative application of knowledge, while framing the facilitation of reflective processes as the key for transcending knowledge from the game’s context to that of the participants. While pointing towards the compatibility issues between current conceptions of learning games and the facilitation of reflective processes, the paper emphasises the need for thinking the learning game as a part of a didactic design, rather than something beneficial in itself.Educational role-play has long proved an effective tool for consultants trying to develop the skills that employees are using for performing certain job functions. However, while educational role-play often is presented as an entertaining means for learning, such insistence on making learning games more gamish seems to have an inhibiting effect on designing and thinking games beyond mere skill acquisition. By emphasising the role-play based process as a conflictual negotiation between distinctive categories of knowledge, this paper presents the explorative application of knowledge, while framing the facilitation of reflective processes as the key for transcending knowledge from the game’s context to that of the participants. While pointing towards the compatibility issues between current conceptions of learning games and the facilitation of reflective processes, the paper emphasises the need for thinking the learning game as a part of a didactic

  10. Play and Space - Towards a Formal Definition of Play

    DEFF Research Database (Denmark)

    Larsen, Lasse Juel

    2015-01-01

    The aim of this article is to present a formal definition of the aspect of play generally known as ‘make-believe’. ‘Make-believe’ is defined in relation to theory of place and Dasein’s being- in-the-world as presented by Martin Heidegger in Being and time. From this point of view ‘make-believe’ can...... be defined as a uniform and situational spatial dyad where being is doubled, characterized by the presence of the physically absent. I will apply this definition after a survey of central and influential aspects of the history of the theory of play to demonstrate its relevance for a formal definition of play....

  11. GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells.

    Science.gov (United States)

    Niang, Bachir; Jin, Liyuan; Chen, Xixi; Guo, Xiaohan; Zhang, Hongshuo; Wu, Qiong; Padhiar, Arshad Ahmed; Xiao, Min; Fang, Deyu; Zhang, Jianing

    2016-01-01

    GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERα association. Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation.

  12. Quantum Public-Key Cryptosystem

    Science.gov (United States)

    Luo, Ming-Xing; Chen, Xiu-Bo; Yun, Deng; Yang, Yi-Xian

    2012-03-01

    Quantum one-way functions play a fundamental role in cryptography because of its necessity for the secure encryption schemes taking into account the quantum computer. In this paper our purpose is to establish a theoretical framework for a candidate of the quantum one-way functions and quantum trapdoor functions based on one-parameter unitary groups. The dynamics of parameterized unitary groups ensure the one-wayness and quantum undistinguishability in different levels, and the physical feasibility are derived from the simultaneous approximation of its infinitesimal generators. Moreover, these special functions are used to construct new cryptosystems-the quantum public-key cryptosystems for encrypting both the classical and quantum information.

  13. Keys through ARQ

    CERN Document Server

    Latif, Mohamed Abdel; Gamal, Hesham El

    2009-01-01

    This paper develops a novel framework for sharing secret keys using the well-known Automatic Repeat reQuest (ARQ) protocol. The proposed key sharing protocol does not assume any prior knowledge about the channel state information (CSI), but, harnesses the available opportunistic secrecy gains using only the one bit feedback, in the form of ACK/NACK. The distribution of key bits among multiple ARQ epochs, in our approach, allows for mitigating the secrecy outage phenomenon observed in earlier works. We characterize the information theoretic limits of the proposed scheme, under different assumptions on the channel spatial and temporal correlation function, and develop low complexity explicit implementations. Our analysis reveals a novel role of "dumb antennas" in overcoming the negative impact of spatial correlation, between the legitimate and eavesdropper channels, on the achievable secrecy rates. We further develop an adaptive rate allocation policy which achieves higher secrecy rates by exploiting the channe...

  14. Copper and angiogenesis: unravelling a relationship key to cancer progression.

    Science.gov (United States)

    Finney, Lydia; Vogt, Stefan; Fukai, Tohru; Glesne, David

    2009-01-01

    1. Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti-angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive. 2. Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron-derived X-rays from third-generation synchrotrons and the technique of high resolution X-ray fluorescence microprobe (XFM) analysis. 3. Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of

  15. Key World Energy Statistics

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    The IEA produced its first handy, pocket-sized summary of key energy data in 1997. This new edition responds to the enormously positive reaction to the book since then. Key World Energy Statistics produced by the IEA contains timely, clearly-presented data on supply, transformation and consumption of all major energy sources. The interested businessman, journalist or student will have at his or her fingertips the annual Canadian production of coal, the electricity consumption in Thailand, the price of diesel oil in Spain and thousands of other useful energy facts. It exists in different formats to suit our readers' requirements.

  16. Mechanistic Basis for Plant Responses to Drought Stress : Regulatory Mechanism of Abscisic Acid Signaling

    Science.gov (United States)

    Miyakawa, Takuya; Tanokura, Masaru

    The phytohormone abscisic acid (ABA) plays a key role in the rapid adaptation of plants to environmental stresses such as drought and high salinity. Accumulated ABA in plant cells promotes stomatal closure in guard cells and transcription of stress-tolerant genes. Our understanding of ABA responses dramatically improved by the discovery of both PYR/PYL/RCAR as a soluble ABA receptor and inhibitory complex of a protein phospatase PP2C and a protein kinase SnRK2. Moreover, several structural analyses of PYR/PYL/RCAR revealed the mechanistic basis for the regulatory mechanism of ABA signaling, which provides a rational framework for the design of alternative agonists in future.

  17. Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities.

    Science.gov (United States)

    Alijotas-Reig, Jaume; Melnychuk, Taisiia; Gris, Josep Maria

    2015-03-15

    Because maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to play a key role in altering the maternal immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal interface are necessary in situ to prevent early abortion, but only those pTregs that have been previously exposed to paternal alloantigens. It has been showed that pregnancy selectively stimulates the accumulation of maternal Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly, after delivery, foetal-specific pTregs persist at elevated levels, maintain tolerance to pre-existing foetal antigen, and rapidly re-accumulate during subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible future therapeutic strategy in humans. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Carbon Capture and Storage Legal and Regulatory Review. Edition 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    The International Energy Agency (IEA) estimates that 100 carbon capture and storage (CCS) projects must be implemented by 2020 and over 3000 by 2050 if CCS is to fully contribute to the least-cost technology portfolio for CO2 mitigation. To help countries address the many legal and regulatory issues associated with such rapid deployment, the IEA launched the Carbon Capture and Storage Legal and Regulatory Review (CCS Review) in October 2010. The CCS Review gathers contributions by national and regional governments, as well as leading organisations engaged in CCS regulatory activities, to provide a knowledge-sharing forum that supports national-level CCS regulatory development. Each contribution provides a short summary of recent and anticipated developments and highlights a particular regulatory theme (such as financial contributions to long-term stewardship). To introduce each edition, the IEA provides a brief analysis of key advances and trends. Produced bi-annually, the CCS Review provides an up-to-date snapshot of global CCS regulatory developments. The theme for the second edition of the CCS Review, released in May 2011, is long-term liability for stored CO2. Other key issues addressed include: national progress towards implementation of the EU CCS Directive; developments in marine treaties relevant to CCS; international climate change negotiations; and the development process for CCS regulation.

  19. Regulation of translesion DNA synthesis: Posttranslational modification of lysine residues in key proteins.

    Science.gov (United States)

    McIntyre, Justyna; Woodgate, Roger

    2015-05-01

    Posttranslational modification of proteins often controls various aspects of their cellular function. Indeed, over the past decade or so, it has been discovered that posttranslational modification of lysine residues plays a major role in regulating translesion DNA synthesis (TLS) and perhaps the most appreciated lysine modification is that of ubiquitination. Much of the recent interest in ubiquitination stems from the fact that proliferating cell nuclear antigen (PCNA) was previously shown to be specifically ubiquitinated at K164 and that such ubiquitination plays a key role in regulating TLS. In addition, TLS polymerases themselves are now known to be ubiquitinated. In the case of human polymerase η, ubiquitination at four lysine residues in its C-terminus appears to regulate its ability to interact with PCNA and modulate TLS. Within the past few years, advances in global proteomic research have revealed that many proteins involved in TLS are, in fact, subject to a previously underappreciated number of lysine modifications. In this review, we will summarize the known lysine modifications of several key proteins involved in TLS; PCNA and Y-family polymerases η, ι, κ and Rev1 and we will discuss the potential regulatory effects of such modification in controlling TLS in vivo.

  20. Adaptive Forgetting Factor Fictitious Play

    CERN Document Server

    Smyrnakis, Michalis

    2011-01-01

    It is now well known that decentralised optimisation can be formulated as a potential game, and game-theoretical learning algorithms can be used to find an optimum. One of the most common learning techniques in game theory is fictitious play. However fictitious play is founded on an implicit assumption that opponents' strategies are stationary. We present a novel variation of fictitious play that allows the use of a more realistic model of opponent strategy. It uses a heuristic approach, from the online streaming data literature, to adaptively update the weights assigned to recently observed actions. We compare the results of the proposed algorithm with those of stochastic and geometric fictitious play in a simple strategic form game, a vehicle target assignment game and a disaster management problem. In all the tests the rate of convergence of the proposed algorithm was similar or better than the variations of fictitious play we compared it with. The new algorithm therefore improves the performance of game-t...

  1. Why Play Outside? Problematising Outdoor Play as a Biopedagogical Task

    Science.gov (United States)

    Robinson, Daniel B.; Barrett, Joe

    2017-01-01

    Although outdoor play has been widely recognised for the many benefits it affords children, some have rationalised the need for it based on goals related to physical health. More specifically, these instrumental goals have been closely related to obesity, overweight, and/or physical (in)activity. Adhering to obesity discourses and the notion of a…

  2. Parent-Child Play across Cultures: Advancing Play Research

    Science.gov (United States)

    Roopnarine, Jaipaul L.; Davidson, Kimberly L.

    2015-01-01

    In this article, the authors argue for a greater understanding of children's play across cultures through better integration of scientific thinking about the developed and developing societies, through consideration of socialization beliefs and goals, and, finally, through the use of more complex models in research investigations. They draw on…

  3. Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

    Science.gov (United States)

    Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

    2015-01-01

    During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

  4. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages.

    Science.gov (United States)

    Clark, Kristopher; MacKenzie, Kirsty F; Petkevicius, Kasparas; Kristariyanto, Yosua; Zhang, Jiazhen; Choi, Hwan Geun; Peggie, Mark; Plater, Lorna; Pedrioli, Patrick G A; McIver, Ed; Gray, Nathanael S; Arthur, J Simon C; Cohen, Philip

    2012-10-16

    Macrophages acquire strikingly different properties that enable them to play key roles during the initiation, propagation, and resolution of inflammation. Classically activated (M1) macrophages produce proinflammatory mediators to combat invading pathogens and respond to tissue damage in the host, whereas regulatory macrophages (M2b) produce high levels of anti-inflammatory molecules, such as IL-10, and low levels of proinflammatory cytokines, like IL-12, and are important for the resolution of inflammatory responses. A central problem in this area is to understand how the formation of regulatory macrophages can be promoted at sites of inflammation to prevent and/or alleviate chronic inflammatory and autoimmune diseases. Here, we demonstrate that the salt-inducible kinases (SIKs) restrict the formation of regulatory macrophages and that their inhibition induces striking increases in many of the characteristic markers of regulatory macrophages, greatly stimulating the production of IL-10 and other anti-inflammatory molecules. We show that SIK inhibitors elevate IL-10 production by inducing the dephosphorylation of cAMP response element-binding protein (CREB)-regulated transcriptional coactivator (CRTC) 3, its dissociation from 14-3-3 proteins and its translocation to the nucleus where it enhances a gene transcription program controlled by CREB. Importantly, the effects of SIK inhibitors on IL-10 production are lost in macrophages that express a drug-resistant mutant of SIK2. These findings identify SIKs as a key molecular switch whose inhibition reprograms macrophages to an anti-inflammatory phenotype. The remarkable effects of SIK inhibitors on macrophage function suggest that drugs that target these protein kinases may have therapeutic potential for the treatment of inflammatory and autoimmune diseases.

  5. Locks and Keys Service

    CERN Multimedia

    Claude Ducastel

    The GS-LS-SEM section is pleased to inform you that as from Monday 30 November 2009, the opening hours of the Locks and Keys service will be the following: 08h30 - 12h30 / 13h30 - 16:30, Mondays to Fridays. GS-SEM-LS 73333

  6. Keyed shear joints

    DEFF Research Database (Denmark)

    Hansen, Klaus

    This report gives a summary of the present information on the behaviour of vertical keyed shear joints in large panel structures. An attemp is made to outline the implications which this information might have on the analysis and design of a complete wall. The publications also gives a short...

  7. Cryptographic Key Management System

    Energy Technology Data Exchange (ETDEWEB)

    No, author

    2014-02-21

    This report summarizes the outcome of U.S. Department of Energy (DOE) contract DE-OE0000543, requesting the design of a Cryptographic Key Management System (CKMS) for the secure management of cryptographic keys for the energy sector infrastructure. Prime contractor Sypris Electronics, in collaboration with Oak Ridge National Laboratories (ORNL), Electric Power Research Institute (EPRI), Valicore Technologies, and Purdue University's Center for Education and Research in Information Assurance and Security (CERIAS) and Smart Meter Integration Laboratory (SMIL), has designed, developed and evaluated the CKMS solution. We provide an overview of the project in Section 3, review the core contributions of all contractors in Section 4, and discuss bene ts to the DOE in Section 5. In Section 6 we describe the technical construction of the CKMS solution, and review its key contributions in Section 6.9. Section 7 describes the evaluation and demonstration of the CKMS solution in different environments. We summarize the key project objectives in Section 8, list publications resulting from the project in Section 9, and conclude with a discussion on commercialization in Section 10 and future work in Section 11.

  8. Key performance indicators

    NARCIS (Netherlands)

    Zwetsloot, G.I.J.M.

    2014-01-01

    This paper addresses how organisations can use OSH performance indicators. This is an important way to mainstream OSH into business management. Key performance indicators (KPIs) should provide objective data on the OSH situation. It is often said that ‘what gets measured gets managed’. Without

  9. Key performance indicators

    NARCIS (Netherlands)

    Zwetsloot, G.I.J.M.

    2014-01-01

    This paper addresses how organisations can use OSH performance indicators. This is an important way to mainstream OSH into business management. Key performance indicators (KPIs) should provide objective data on the OSH situation. It is often said that ‘what gets measured gets managed’. Without infor

  10. Modular robotics for playful physiotherapy

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop

    2009-01-01

    We developed modular robotic tiles to be used for playful physiotherapy, which is supposed to motivate patients to engage in and perform physical rehabilitation exercises. We tested the modular robotic tiles for an extensive period of time (3 years) in daily use in a hospital rehabilitation unit e.......g. for cardiac patients. Also, the tiles were tested for performing physical rehabilitation of stroke patients in their private home. In all pilot test cases qualitative feedback indicate that the patients find the playful use of modular robotic tiles engaging and motivating for them to perform...... the rehabilitation. Also, initial pilot test data suggest that some playful exercises on the tiles demand an average heart rate of 75% and 86% of the maximum heart rate....

  11. 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...

  12. Evolutionary algorithms in genetic regulatory networks model

    CERN Document Server

    Raza, Khalid

    2012-01-01

    Genetic Regulatory Networks (GRNs) plays a vital role in the understanding of complex biological processes. Modeling GRNs is significantly important in order to reveal fundamental cellular processes, examine gene functions and understanding their complex relationships. Understanding the interactions between genes gives rise to develop better method for drug discovery and diagnosis of the disease since many diseases are characterized by abnormal behaviour of the genes. In this paper we have reviewed various evolutionary algorithms-based approach for modeling GRNs and discussed various opportunities and challenges.

  13. Rapport. Play and Learn Innovation

    DEFF Research Database (Denmark)

    Larsen, Maria Neumann; Søgaard, Karoline

    Erfaringer og anbefalinger fra innovationsprojektet Play and Learn, hvor pædagoger har arbejdet med sprogstimulering af børn fra 3-9 år. Legende læring i daglige rutiner og pædagogiske aktiviteter har været fokuspunktet.......Erfaringer og anbefalinger fra innovationsprojektet Play and Learn, hvor pædagoger har arbejdet med sprogstimulering af børn fra 3-9 år. Legende læring i daglige rutiner og pædagogiske aktiviteter har været fokuspunktet....

  14. Impact of regulatory science on global public health.

    Science.gov (United States)

    Patel, Meghal; Miller, Margaret Ann

    2012-07-01

    Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies.

  15. Clinical research: regulatory issues.

    Science.gov (United States)

    Wermeling, D P

    1999-02-01

    The regulatory issues faced by institutions performing clinical research are described. Many institutions do not have on staff an expert who understands the regulatory issues involved in managing investigational new drug research and who knows the institution's obligations under the federal rules. Because pharmacists understand the FDA regulations that apply to the management of drugs in clinical research, institutions are asking pharmacists to expand their role and manage clinical research offices. Many authorities govern various aspects of investigational drug research. FDA has published regulations for good clinical practice (GCP), and the International Conference on Harmonisation is developing an international standard for the proper management of clinical trials. The guidelines published by the Joint Commission on Accreditation of Healthcare Organizations aim to protect patients who are in the institution to receive health care and also participate in clinical trials. The Social Security Administration Acts specifically state that only items and services that are reasonable and necessary for the diagnosis and treatment of injury or disease can be billed to the government; research-related billings are excluded from coverage. Proper management of drug research is crucial to the success of a research program that is integrated with patient care.

  16. Toxicogenomics in regulatory ecotoxicology

    Science.gov (United States)

    Ankley, Gerald T.; Daston, George P.; Degitz, Sigmund J.; Denslow, Nancy D.; Hoke, Robert A.; Kennedy, Sean W.; Miracle, Ann L.; Perkins, Edward J.; Snape, Jason; Tillitt, Donald E.; Tyler, Charles R.; Versteeg, Donald

    2006-01-01

    Recently, we have witnessed an explosion of different genomic approaches that, through a combination of advanced biological, instrumental, and bioinformatic techniques, can yield a previously unparalleled amount of data concerning the molecular and biochemical status of organisms. Fueled partially by large, well-publicized efforts such as the Human Genome Project, genomic research has become a rapidly growing topical area in multiple biological disciplines. Since 1999, when the term “toxicogenomics” was coined to describe the application of genomics to toxicology (1), a rapid increase in publications on the topic has occurred (Figure 1). The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions and, as with any new technology, has evoked a wide range of opinion (2–6). VIEWPOINT © 2006 american chemical Society july 1, 2006 / EnvironmEntal SciEncE & tEchnology n 4055 The purpose of this feature article is to consider the roles of toxicogenomics in the field of regulatory ecotoxicology, explore current limitations in the science and practice of genomics, and propose possible avenues to approach and resolve some of the major challenges. A significant amount of input to our analysis came from a workshop sponsored by the Society of Environmental Toxicology and Chemistry (SETAC) in Pellston, Mich., in September 2005. A complete list of names and affiliations of the experts participating in that workshop is provided online in Table 1 of the Supporting Information for this paper.

  17. An integer linear programming approach for finding deregulated subgraphs in regulatory networks.

    Science.gov (United States)

    Backes, Christina; Rurainski, Alexander; Klau, Gunnar W; Müller, Oliver; Stöckel, Daniel; Gerasch, Andreas; Küntzer, Jan; Maisel, Daniela; Ludwig, Nicole; Hein, Matthias; Keller, Andreas; Burtscher, Helmut; Kaufmann, Michael; Meese, Eckart; Lenhof, Hans-Peter

    2012-03-01

    Deregulation of cell signaling pathways plays a crucial role in the development of tumors. The identification of such pathways requires effective analysis tools that facilitate the interpretation of expression differences. Here, we present a novel and highly efficient method for identifying deregulated subnetworks in a regulatory network. Given a score for each node that measures the degree of deregulation of the corresponding gene or protein, the algorithm computes the heaviest connected subnetwork of a specified size reachable from a designated root node. This root node can be interpreted as a molecular key player responsible for the observed deregulation. To demonstrate the potential of our approach, we analyzed three gene expression data sets. In one scenario, we compared expression profiles of non-malignant primary mammary epithelial cells derived from BRCA1 mutation carriers and of epithelial cells without BRCA1 mutation. Our results suggest that oxidative stress plays an important role in epithelial cells of BRCA1 mutation carriers and that the activation of stress proteins may result in avoidance of apoptosis leading to an increased overall survival of cells with genetic alterations. In summary, our approach opens new avenues for the elucidation of pathogenic mechanisms and for the detection of molecular key players.

  18. Carbon Capture and Storage Legal and Regulatory Review. Edition 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    The International Energy Agency (IEA) considers carbon capture and storage (CCS) a crucial part of worldwide efforts to limit global warming by reducing greenhouse-gas emissions. The IEA estimates that emissions can be reduced to a level consistent with a 2°C global temperature increase through the broad deployment of low-carbon energy technologies – and that CCS would contribute about one-fifth of emission reductions in this scenario. Achieving this level of deployment will require that regulatory frameworks – or rather a lack thereof – do not unnecessarily impede environmentally safe demonstration and deployment of CCS, so in October 2010 the IEA launched the IEA Carbon Capture and Storage Legal and Regulatory Review. The CCS Review is a regular review of CCS regulatory progress worldwide. Produced annually, it collates contributions by national and regional governments, as well as leading organisations engaged in CCS regulatory activities, to provide a knowledge-sharing forum to support CCS framework development. Each two page contribution provides a short summary of recent and anticipated CCS regulatory developments and highlights a particular, pre-nominated regulatory theme. To introduce each edition, the IEA provides a brief analysis of key advances and trends, based on the contributions submitted. The theme for this third edition is stakeholder engagement in the development of CO2 storage projects. Other issues addressed include: regulating CO2-EOR, CCS and CO2-EOR for storage; CCS incentive policy; key, substantive issues being addressed by jurisdictions taking steps to finalise CCS regulatory framework development; and CCS legal and regulatory developments in the context of the Clean Energy Ministerial Carbon Capture, Use and Storage Action Group.

  19. Let's 'play' with molecular pharmacology.

    Science.gov (United States)

    Choudhury, Supriyo; Pradhan, Richeek; Sengupta, Gairik; Das, Manisha; Chatterjee, Manojit; Roy, Ranendra Kumar; Chatterjee, Suparna

    2015-01-01

    Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Significant improvement in knowledge (P pharmacology in undergraduate medical curricula.

  20. Playing with Protons CREATIONS Demonstrator

    CERN Document Server

    Alexopoulos, Angelos

    2017-01-01

    This document describes Playing with Protons, a CMS education initiative that seeks to enhance teachers’ pedagogical practice with creative, hands-on methodologies through which 10-12 year old students can, in turn, get engaged effectively with science, technology and innovation.

  1. For the Phenomenology of Play

    Directory of Open Access Journals (Sweden)

    Roberto Farné

    2016-10-01

    Full Text Available The success of phenomenology in contemporary culture is due above all to the new approach to knowledge that has been proposed, breaking with the traditional objectivism of scientific knowledge and placing the “phenomenon” at the centre of the relationship between the subject and the world. Everyday reality, the language of concrete things, have become fully-fledged targets of philosophical thought. While Eugen Fink, student of Husserl, elects the phenomenon of play as the “symbol of the world”, the original interpretation of man’s relation to the world, in Italy Piero Bertolini redefines the scientific basis of pedagogy according to phenomenological categories and places play among the fundamental fields of experience of education. On one hand overcoming the traditional educational instrumentalisation of play, on the other its sterile reduction to a consumer experience, Bertolini brings play back to its authentic dimension in which risk, error, adventure are constituent parts, the “active ingredients” of his pedagogy.

  2. Electronic Instruments -- Played or Used?

    Science.gov (United States)

    Ulveland, Randall Dana

    1998-01-01

    Compares the experience of playing an acoustic instrument to an electronic instrument by analyzing the constant structures and relationships between the experiences. Concludes that students' understanding of the physical experience of making music increases when experiences with acoustic instruments precede their exposure to electronic…

  3. Moral Education through Play Therapy

    Science.gov (United States)

    Mahalle, Salwa; Zakaria, Gamal Abdul Nasir; Nawi, Aliff

    2014-01-01

    This paper will discuss on how sand therapy (as one type of play therapies) can be applied as an additional technique or approach in counseling. The research questions for this study are to see what are the development, challenges faced by the therapist during the sessions given and how sand therapy can aid to the progress of the client. It is a…

  4. Obama Plays Cheerleader for STEM

    Science.gov (United States)

    Robelen, Erik W.

    2010-01-01

    Amid a struggling economy, a raft of foreign-policy headaches, and the tail end of a heated campaign season, President Barack Obama carved out time in his schedule last month to watch students in the State Dining Room demonstrate a solar-powered model car, a water-purification system, and a soccer-playing robot. The science fair was the fifth…

  5. Playing with a digital swing

    DEFF Research Database (Denmark)

    Skovbjerg, Helle Marie

    2017-01-01

    Based on a field study in a kindergarten among children in Denmark, this paper explores playing activities on a digital swing, the SON-X Octavia (SON-X) and its Applause application. SON-X is an interactive sound unit that can be attached to any swing chain. Here, I explore the relationship betwe...

  6. Relationships between regulatory temperament dimensions and self-regulatory behaviors at 4 and 6 months of age.

    Science.gov (United States)

    Aureli, Tiziana; Coppola, Gabrielle; Picconi, Laura; Grazia, Annalisa; Ponzetti, Silvia

    2015-02-01

    The present study focused on relationships between temperament and behavior in early regulation development. Unlike most studies on the topic, we observed infant behavior in a naturalistic playful situation rather than in experimental stressful procedure, and employed temperament measures uniquely reflecting regulatory dispositions rather than a global measure of reactivity. The infant's self-regulatory behaviors were observed at 4 and 6 months during face-to-face interactions and regulatory dimensions were assessed at 4 months. We found that low intensity pleasure and soothability dimensions, related to the infant physical and social experience, respectively, significantly affected regulatory behavior and their influence showed to depend on the infant's age, with the former dimension being influential at the earlier age and the latter being influential when the behavior was observed at the later age. Results are interpreted on the light of a dynamic view of regulation development.

  7. MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Guangde Zhang

    Full Text Available Myocardial infarction (MI is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs and known human transcription factors (TFs, and we then identified 1,232 feed-forward loops (FFLs among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

  8. Introduction strategies raise key questions.

    Science.gov (United States)

    Finger, W R; Keller, S

    1995-09-01

    Key issues that must be considered before a new contraceptive is introduced center on the need for a trained provider to begin or terminate the method, its side effects, duration of use, method's ability to meet users' needs and preferences, and extra training or staff requirements. Logistics and economic issues to consider are identifying a dependable way of effectively supplying commodities, planning extra services needed for the method, and cost of providing the method. Each contraceptive method presents a different side effect pattern and burdens the service delivery setting differently. The strategy developed to introduce or expand the 3-month injectable Depo-Provera (DMPA) can be used for any method. It includes a needs assessment and addresses regulatory issues, service delivery policies and procedures, information and training, evaluation, and other concerns. Viet Nam's needs assessment showed that Norplant should not be introduced until the service delivery system becomes stronger. Any needs assessment for expansion of contraceptive services should cover sexually transmitted disease/HIV issues. A World Health Organization strategy helps officials identify the best method mix for local situations. Introductory strategies must aim to improve the quality of family planning programs and expand choices. Many begin by examining existing data and conducting interviews with policymakers, users, providers, and women's health advocates. Introductory programs for Norplant focus on provider training, adequate counseling and informed consent for users, and ready access to removal. They need a well-prepared service delivery infrastructure. The first phase of the DMPA introductory strategy for the Philippines comprised a social marketing campaign and DMPA introduction at public clinics in 10 pilot areas with strong service delivery. Successful AIDS prevention programs show that people tend to use barrier methods when they are available. USAID is currently studying

  9. Physician Appraisals: Key Challenges

    Directory of Open Access Journals (Sweden)

    Klich Jacek

    2017-06-01

    Full Text Available The main purpose of the article is to identify key criteria being used for physician appraisals and to find how communication skills of physicians are valued in those appraisals. ScienceDirect and EBSCOhost databases were used for this search. The results show that a physician appraisal is underestimated both theoretically and empirically. The particular gap exists with respect to the communication skills of physicians, which are rarely present in medical training syllabi and physician assessments. The article contributes to the theoretical discourse on physician appraisals and points out at the inconsistency between the high status of physicians as a key hospital resource on the one hand and, on the other hand, at inadequate and poorly researched assessment of their performance with a special emphasis on communication skills. The article may inspire health managers to develop and implement up-to-date assessment forms for physicians and good managerial practices in this respect in hospitals and other health care units.

  10. Efficient Quantum Key Distribution

    CERN Document Server

    Ardehali, M; Chau, H F; Lo, H K

    1998-01-01

    We devise a simple modification that essentially doubles the efficiency of a well-known quantum key distribution scheme proposed by Bennett and Brassard (BB84). Our scheme assigns significantly different probabilities for the different polarization bases during both transmission and reception to reduce the fraction of discarded data. The actual probabilities used in the scheme are announced in public. As the number of transmitted signals increases, the efficiency of our scheme can be made to approach 100%. The security of our scheme (against single-photon eavesdropping strategies) is guaranteed by a refined analysis of accepted data which is employed to detect eavesdropping: Instead of lumping all the accepted data together to estimate a single error rate, we separate the accepted data into various subsets according to the basis employed and estimate an error rate for each subset individually. Our scheme is the first quantum key distribution with an efficiency greater than 50%. We remark that our idea is rath...

  11. Ancel Keys: a tribute

    Directory of Open Access Journals (Sweden)

    VanItallie Theodore B

    2005-02-01

    Full Text Available Abstract Ancel Keys, Ph.D., who died in November, 2004, at the age of 100, was among the first scientists to recognize that human atherosclerosis is not an inevitable consequence of aging, and that a high-fat diet can be a major risk factor for coronary heart disease. During World War II, he and a group of talented co-workers at the University of Minnesota conducted a large-scale study of experimentally-induced human starvation. The data generated by this study – which was immediately recognized to be a classic – continue to be of inestimable value to nutrition scientists. In his later years, Keys spent more time at his home in Naples, Italy, where he had the opportunity to continue his personal study of the beneficial effects on health and longevity of a Mediterranean diet.

  12. Ancel Keys: a tribute.

    Science.gov (United States)

    Vanitallie, Theodore B

    2005-02-14

    Ancel Keys, Ph.D., who died in November, 2004, at the age of 100, was among the first scientists to recognize that human atherosclerosis is not an inevitable consequence of aging, and that a high-fat diet can be a major risk factor for coronary heart disease. During World War II, he and a group of talented co-workers at the University of Minnesota conducted a large-scale study of experimentally-induced human starvation. The data generated by this study - which was immediately recognized to be a classic - continue to be of inestimable value to nutrition scientists. In his later years, Keys spent more time at his home in Naples, Italy, where he had the opportunity to continue his personal study of the beneficial effects on health and longevity of a Mediterranean diet.

  13. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem;

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

  14. Play for learning and learning for play: Children’s play in a toddler group

    Directory of Open Access Journals (Sweden)

    Anne Greve

    2013-10-01

    Full Text Available There is a concern that children’s right to play is restricted as a result of the governments’ narrow focus on school preparatory activities and learning. Play and learning are rights embodied in the United Nations convention on the rights of the child. This article discusses how play and learning are organized in the everyday life of a Norwegian toddler group. Critical voices claim that there is not enough structure and that there should be more teaching and mapping to facilitate early intervention in Norwegian kindergartens. The article suggests that the critics’ claim can be countered by asking if there are too few teachers with adequate education and too large groups of children.

  15. Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD.

    Science.gov (United States)

    Martínez, Luary C; Yakhnin, Helen; Camacho, Martha I; Georgellis, Dimitris; Babitzke, Paul; Puente, José L; Bustamante, Víctor H

    2011-06-01

    Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) play key roles in the pathogenesis of Salmonella enterica. Previously, we showed that when Salmonella grows in Luria-Bertani medium, HilD, encoded in SPI-1, first induces the expression of hilA, located in SPI-1, and subsequently of the ssrAB operon, located in SPI-2. These genes code for HilA and the SsrA/B two-component system, the positive regulators of the SPI-1 and SPI-2 regulons respectively. In this study, we demonstrate that CsrA, a global regulatory RNA binding protein, post-transcriptionally regulates hilD expression by directly binding near the Shine-Dalgarno and translation initiation codon sequences of the hilD mRNA, preventing its translation and leading to its accelerated turnover. Negative regulation is counteracted by the global SirA/BarA two-component system, which directly activates the expression of CsrB and CsrC, two non-coding regulatory RNAs that sequester CsrA, thereby preventing it from binding to its target mRNAs. Our results illustrate the integration of global and specific regulators into a multifactorial regulatory cascade controlling the expression of virulence genes acquired by horizontal transfer events.

  16. Targeted inactivation of Snail family EMT regulatory factors by a Co(III)-Ebox conjugate

    National Research Council Canada - National Science Library

    Harney, Allison S; Meade, Thomas J; LaBonne, Carole

    2012-01-01

    Snail family proteins are core EMT (epithelial-mesenchymal transition) regulatory factors that play essential roles in both development and disease processes and have been associated with metastasis in carcinomas...

  17. 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

  18. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  19. Experimental plug and play quantum coin flipping

    Science.gov (United States)

    Pappa, Anna; Jouguet, Paul; Lawson, Thomas; Chailloux, André; Legré, Matthieu; Trinkler, Patrick; Kerenidis, Iordanis; Diamanti, Eleni

    2014-04-01

    Performing complex cryptographic tasks will be an essential element in future quantum communication networks. These tasks are based on a handful of fundamental primitives, such as coin flipping, where two distrustful parties wish to agree on a randomly generated bit. Although it is known that quantum versions of these primitives can offer information-theoretic security advantages with respect to classical protocols, a demonstration of such an advantage in a practical communication scenario has remained elusive. Here we experimentally implement a quantum coin flipping protocol that performs strictly better than classically possible over a distance suitable for communication over metropolitan area optical networks. The implementation is based on a practical plug and play system, developed by significantly enhancing a commercial quantum key distribution device. Moreover, we provide combined quantum coin flipping protocols that are almost perfectly secure against bounded adversaries. Our results offer a useful toolbox for future secure quantum communications.

  20. Synthetic biology - the state of play.

    Science.gov (United States)

    Kitney, Richard; Freemont, Paul

    2012-07-16

    Just over two years ago there was an article in Nature entitled "Five Hard Truths for Synthetic Biology". Since then, the field has moved on considerably. A number of economic commentators have shown that synthetic biology very significant industrial potential. This paper addresses key issues in relation to the state of play regarding synthetic biology. It first considers the current background to synthetic biology, whether it is a legitimate field and how it relates to foundational biological sciences. The fact that synthetic biology is a translational field is discussed and placed in the context of the industrial translation process. An important aspect of synthetic biology is platform technology, this topic is also discussed in some detail. Finally, examples of application areas are described. Copyright © 2012. Published by Elsevier B.V.

  1. 75 FR 54210 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2010-09-03

    ...-2010-032] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... Transactions August 30, 2010. On June 17, 2010, the Financial Industry Regulatory Authority, Inc....

  2. Deciphering ascorbic acid regulatory pathways in ripening tomato fruit using a weighted gene correlation network analysis approach.

    Science.gov (United States)

    Gao, Chao; Ju, Zheng; Li, Shan; Zuo, Jinhua; Fu, Daqi; Tian, Huiqin; Luo, Yunbo; Zhu, Benzhong

    2013-11-01

    Genotype is generally determined by the co-expression of diverse genes and multiple regulatory pathways in plants. Gene co-expression analysis combining with physiological trait data provides very important information about the gene function and regulatory mechanism. L-Ascorbic acid (AsA), which is an essential nutrient component for human health and plant metabolism, plays key roles in diverse biological processes such as cell cycle, cell expansion, stress resistance, hormone synthesis, and signaling. Here, we applied a weighted gene correlation network analysis approach based on gene expression values and AsA content data in ripening tomato (Solanum lycopersicum L.) fruit with different AsA content levels, which leads to identification of AsA relevant modules and vital genes in AsA regulatory pathways. Twenty-four modules were compartmentalized according to gene expression profiling. Among these modules, one negatively related module containing genes involved in redox processes and one positively related module enriched with genes involved in AsA biosynthetic and recycling pathways were further analyzed. The present work herein indicates that redox pathways as well as hormone-signal pathways are closely correlated with AsA accumulation in ripening tomato fruit, and allowed us to prioritize candidate genes for follow-up studies to dissect this interplay at the biochemical and molecular level.

  3. Boolean Modelling Reveals New Regulatory Connections between Transcription Factors Orchestrating the Development of the Ventral Spinal Cord

    Science.gov (United States)

    Lovrics, Anna; Gao, Yu; Juhász, Bianka; Bock, István; Byrne, Helen M.; Dinnyés, András; Kovács, Krisztián A.

    2014-01-01

    We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks. PMID:25398016

  4. Deciphering Ascorbic Acid Regulatory Pathways in Ripening Tomato Fruit Using a Weighted Gene Correlation Network Analysis Approach

    Institute of Scientific and Technical Information of China (English)

    Chao Gao; Zheng Ju; Shan Li; Jinhua Zuo; Daqi Fu; Huiqin Tian; Yunbo Luo; Benzhong Zhu

    2013-01-01

    Genotype is generally determined by the co-expression of diverse genes and multiple regulatory pathways in plants. Gene co-expression analysis combining with physiological trait data provides very important information about the gene function and regulatory mechanism. L-Ascorbic acid (AsA), which is an essential nutrient component for human health and plant metabolism, plays key roles in diverse biological processes such as cell cycle, cell expansion, stress resistance, hormone synthesis, and signaling. Here, we applied a weighted gene correlation network analysis approach based on gene expression values and AsA content data in ripening tomato (Solanum lycopersicum L.) fruit with different AsA content levels, which leads to identification of AsA relevant modules and vital genes in AsA regulatory pathways. Twenty-four modules were compartmentalized according to gene expression profiling. Among these modules, one negatively related module containing genes involved in redox processes and one positively related module enriched with genes involved in AsA biosynthetic and recycling pathways were further analyzed. The present work herein indicates that redox pathways as well as hormone-signal pathways are closely correlated with AsA accumulation in ripening tomato fruit, and allowed us to prioritize candidate genes for follow-up studies to dissect this interplay at the biochemical and molecular level.

  5. Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

    KAUST Repository

    Lovrics, Anna

    2014-11-14

    We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.

  6. Evolutionary analysis and lateral gene transfer of two-component regulatory systems associated with heavy-metal tolerance in bacteria.

    Science.gov (United States)

    Bouzat, Juan L; Hoostal, Matthew J

    2013-05-01

    Microorganisms have adapted intricate signal transduction mechanisms to coordinate tolerance to toxic levels of metals, including two-component regulatory systems (TCRS). In particular, both cop and czc operons are regulated by TCRS; the cop operon plays a key role in bacterial tolerance to copper, whereas the czc operon is involved in the efflux of cadmium, zinc, and cobalt from the cell. Although the molecular physiology of heavy metal tolerance genes has been extensively studied, their evolutionary relationships are not well-understood. Phylogenetic relationships among heavy-metal efflux proteins and their corresponding two-component regulatory proteins revealed orthologous and paralogous relationships from species divergences and ancient gene duplications. The presence of heavy metal tolerance genes on bacterial plasmids suggests these genes may be prone to spread through horizontal gene transfer. Phylogenetic inferences revealed nine potential examples of lateral gene transfer associated with metal efflux proteins and two examples for regulatory proteins. Notably, four of the examples suggest lateral transfer across major evolutionary domains. In most cases, differences in GC content in metal tolerance genes and their corresponding host genomes confirmed lateral gene transfer events. Three-dimensional protein structures predicted for the response regulators encoded by cop and czc operons showed a high degree of structural similarity with other known proteins involved in TCRS signal transduction, which suggests common evolutionary origins of functional phenotypes and similar mechanisms of action for these response regulators.

  7. Agents Play Mix-game

    CERN Document Server

    Gou, C

    2005-01-01

    In mix-game which is an extension of minority game, there are two groups of agents; group1 plays the majority game, but the group2 plays the minority game. This paper studies the change of the average winnings of agents and volatilities vs. the change of mixture of agents in mix-game model. It finds that the correlations between the average winnings of agents and the mean of local volatilities are different with different combinations of agent memory length when the proportion of agents in group 1 increases. This study result suggests that memory length of agents in group1 be smaller than that of agent in group2 when mix-game model is used to simulate the financial markets.

  8. Playing Business "Ball" with Cuba

    Institute of Scientific and Technical Information of China (English)

    Yang Wei; Gong Liming

    2007-01-01

    @@ If you were lucky enough to have seen the World Volleyball Tournament,you must have seen the Cuban Women's volleyball team take on China in the championship game,a game of which Cuba has become the world champion for 10 times.The great determination and strong tenacity of these young Cuban girls' has been an encouragement to everyone that watches them play.

  9. Regulatory mechanism of protein metabolic pathway during the differentiation process of chicken male germ cell.

    Science.gov (United States)

    Li, Dong; Zuo, Qisheng; Lian, Chao; Zhang, Lei; Shi, Qingqing; Zhang, Zhentao; Wang, Yingjie; Ahmed, Mahmoud F; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

    2015-08-01

    We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

  10. Involvement of the CREB5 regulatory network in colorectal cancer metastasis.

    Science.gov (United States)

    Qi, Lu; Ding, Yanqing

    2014-07-01

    The signal regulatory network involved in colorectal cancer metastasis is complicated and thus the search for key control steps in the network is of great significance for unraveling colorectal cancer metastasis mechanism and finding drug-target site. Previous studies suggested that CREB5 (cAMP responsive element binding protein 5) might play key role in the metastatic signal network of colorectal cancer. Through colorectal cancer expression profile and enriching analysis of the effect of CREB5 gene expression levels on colorectal cancer molecular events, we found that these molecular events are correlated with tumor metastasis. Based on the feature that CREB5 could combine with c-Jun to form heterodimer, together with enriched binding sites for transcription factor AP-1, we identified 16 genes which were up-regulated in the CREB5 high-expression group, contained AP-1 binding sites, and participated in cancer pathway. The molecular network involving these 16 genes, in particular, CSF1R, MMP9, PDGFRB, FIGF and IL6, regulates cell migration. Therefore, CREB5 might accelerate the metastasis of colorectal cancer by regulating these five key genes.

  11. Playing Moderately Hard to Get

    Directory of Open Access Journals (Sweden)

    Stephen Reysen

    2013-12-01

    Full Text Available In two studies, we examined the effect of different degrees of attraction reciprocation on ratings of attraction toward a potential romantic partner. Undergraduate college student participants imagined a potential romantic partner who reciprocated a low (reciprocating attraction one day a week, moderate (reciprocating attraction three days a week, high (reciprocating attraction five days a week, or unspecified degree of attraction (no mention of reciprocation. Participants then rated their degree of attraction toward the potential partner. The results of Study 1 provided only partial support for Brehm’s emotion intensity theory. However, after revising the high reciprocation condition vignette in Study 2, supporting Brehm’s emotion intensity theory, results show that a potential partners’ display of reciprocation of attraction acted as a deterrent to participants’ intensity of experienced attraction to the potential partner. The results support the notion that playing moderately hard to get elicits more intense feelings of attraction from potential suitors than playing too easy or too hard to get. Discussion of previous research examining playing hard to get is also re-examined through an emotion intensity theory theoretical lens.

  12. Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter.

    Directory of Open Access Journals (Sweden)

    Vítor S Fernandes

    Full Text Available According to previous observations nitric oxide (NO, as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE and cystathionine β-synthase (CBS, measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS and the H2S donor P-(4-methoxyphenyl-P-4-morpholinylphosphinodithioic acid (GYY4137 evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS with, respectively, PPG and NG-nitro-L-arginine (L-NOARG, greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA desensitization with capsaicin and blockade of ATP-dependent K+ (KATP channels, transient receptor potential A1 (TRPA1, transient receptor potential vanilloid 1 (TRPV1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP and calcitonin gene-related peptide (CGRP receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.

  13. Beyond the brochure. Administrators play key role in positioning the practice, aligning marketing with mission.

    Science.gov (United States)

    Redling, Bob

    2007-04-01

    Marketing doesn't start and stop with a glossy brochure, a display ad in the local Yellow Pages or a Web site. Those are merely tactics that a medical group practice might use to position its physicians' services in the community. Marketing and planning support a medical group's mission and vision--and its strategic plan. The adminstrator must demonstrate this connection to physicians and educate them about what marketing really is.

  14. Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation.

    Science.gov (United States)

    Cheng, Han; Wang, Lei; Wang, Chih-chen

    2010-07-01

    alpha-Synuclein (alpha Syn) is the main component of Lewy bodies formed in midbrain dopaminergic neurons which is a pathological characteristic of Parkinson's disease. It has been recently showed to induce endoplasmic reticulum (ER) stress and impair ER functions. However, the mechanism of how ER responds to alpha Syn toxicity is poorly understood. In the present study, we found that protein disulfide isomerase (PDI), a stress protein abundant in ER, effectively inhibits alpha Syn fibril formation in vitro. In PDI molecule with a structure of abb'xa'c, domain a' was found to be essential and sufficient for PDI to inhibit alpha Syn fibril formation. PDI was further found to be more avid for binding with intermediate species formed during alpha Syn fibril formation, and the binding was more intensive in the later lag phase. Our results provide new insight into the role of PDI in protecting ER from the deleterious effects of misfolded protein accumulation in many neurodegenerative diseases.

  15. ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury.

    Science.gov (United States)

    Liao, Chia-Chih; Day, Yuan-Ji; Lee, Hung-Chen; Liou, Jiin-Tarng; Chou, An-Hsun; Liu, Fu-Chao

    2017-01-01

    Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.

  16. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    2014-04-22

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.  Created: 4/22/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

  17. AHNAK is highly expressed and plays a key role in cell migration and invasion in mesothelioma.

    Science.gov (United States)

    Sudo, Hitomi; Tsuji, Atsushi B; Sugyo, Aya; Abe, Masaaki; Hino, Okio; Saga, Tsuneo

    2014-02-01

    The worldwide incidence of the highly aggressive tumor mesothelioma is expected to increase. Mesothelioma is classified into three main histological subtypes: epithelioid, sarcomatoid and biphasic. Although the pathological diagnostic markers for epithelioid are established, to date no adequate marker for sarcomatoid mesothelioma has been found. Thus, a reliable diagnostic marker of sarcomatoid mesothelioma is necessary. In this study, to identify an unknown protein with 120 kDa expressed only in the mesothelioma cell line 211H, we conducted proteomic analysis and found five candidate proteins. One such protein, AHNAK, was highly expressed in all seven mesothelioma cell lines (211H, H28, H226, H2052, H2452, MESO1 and MESO4), but not in the mesothelial cell line MeT-5A by RT-PCR and immunofluorescence staining. Furthermore, we confirmed high AHNAK expression not only in xenografts but also in human mesothelioma specimens including sarcomatoid, epithelioid and biphasic mesothelioma using immunohistochemical staining. These findings suggest that AHNAK has the potential to be a new marker for detecting mesothelioma. Since AHNAK is involved in cell migration and invasion in other metastatic tumor cells, we conducted migration and invasion assays in mesothelioma cell lines. The number of migrating cells in six of seven mesothelioma cell lines and the number of invading cells in all seven cell lines were significantly increased compared with those in MeT-5A. Knockdown of AHNAK significantly reduced the cell migration and invasion ability in all seven mesothelioma cell lines. These results support further clinical evaluation of the association of AHNAK and metastasis in mesothelioma.

  18. GTPase activity plays a key role in the pathobiology of LRRK2.

    Directory of Open Access Journals (Sweden)

    Yulan Xiong

    2010-04-01

    Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD and also contribute to sporadic disease. The LRRK2 gene encodes a large protein with multiple domains, including functional Roc GTPase and protein kinase domains. Mutations in LRRK2 most likely cause disease through a toxic gain-of-function mechanism. The expression of human LRRK2 variants in cultured primary neurons induces toxicity that is dependent on intact GTP binding or kinase activities. However, the mechanism(s underlying LRRK2-induced neuronal toxicity is poorly understood, and the contribution of GTPase and/or kinase activity to LRRK2 pathobiology is not well defined. To explore the pathobiology of LRRK2, we have developed a model of LRRK2 cytotoxicity in the baker's yeast Saccharomyces cerevisiae. Protein domain analysis in this model reveals that expression of GTPase domain-containing fragments of human LRRK2 are toxic. LRRK2 toxicity in yeast can be modulated by altering GTPase activity and is closely associated with defects in endocytic vesicular trafficking and autophagy. These truncated LRRK2 variants induce similar toxicity in both yeast and primary neuronal models and cause similar vesicular defects in yeast as full-length LRRK2 causes in primary neurons. The toxicity induced by truncated LRRK2 variants in yeast acts through a mechanism distinct from toxicity induced by human alpha-synuclein. A genome-wide genetic screen identified modifiers of LRRK2-induced toxicity in yeast including components of vesicular trafficking pathways, which can also modulate the trafficking defects caused by expression of truncated LRRK2 variants. Our results provide insight into the basic pathobiology of LRRK2 and suggest that the GTPase domain may contribute to the toxicity of LRRK2. These findings may guide future therapeutic strategies aimed at attenuating LRRK2-mediated neurodegeneration.

  19. Ultrasound plays a key role in imaging and management of genital angiomyofibroblastoma: a case report.

    Science.gov (United States)

    Wolf, Benjamin; Horn, Lars-Christian; Handzel, Romy; Einenkel, Jens

    2015-10-28

    Angiomyofibroblastoma is a benign, rare mesenchymal tumor arising from the genital tract of both men and women and was first described by Fletcher and colleagues in 1992. The tumor needs to be distinguished from other, similar lesions, such as deep and superficial aggressive angiomyxoma and cellular angiofibroma, because aggressive angiomyxoma demands much more extensive treatment. The vast majority of angiomyofibroblastomas arise from the vulva and appear as solid cystic masses on ultrasound images. We report a case of a 35-year-old Caucasian woman with an angiomyofibroblastoma arising from the vagina. She presented with a painless mass of about 5cm in diameter that had a rather homogeneous, hypoechoic appearance on ultrasound images. The patient underwent surgical resection of the mass, which was subsequently diagnosed as angiomyofibroblastoma. We present sonographic and magnetic resonance imaging findings, intraoperative and histologic images, and a thorough review of the literature. In our opinion, ultrasonography is the most valuable tool to establish a preoperative diagnosis of this tumor entity, differentiate it from other lesions of the female genital tract, and plan surgery accordingly. Even though it is a rare tumor, gynecologists should be able to recognize it and to differentiate it from other tumor entities that demand more aggressive treatment. We describe a different sonographic appearance of this tumor than previously reported.

  20. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

    Directory of Open Access Journals (Sweden)

    Robert A Scranton

    Full Text Available BACKGROUND: The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated. METHODS AND FINDINGS: In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum. CONCLUSIONS: This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  1. Elevated Nicotianamine Levels in Arabidopsis halleri Roots Play a Key Role in Zinc Hyperaccumulation

    National Research Council Canada - National Science Library

    Ulrich Deinlein; Michael Weber; Holger Schmidt; Stefan Rensch; Aleksandra Trampczynska; Thomas H. Hansen; Søren Husted; Jan K. Schjoerring; Ina N. Talke; Ute Krämer; Stephan Clemens

    2012-01-01

    Zn deficiency is among the leading health risk factors in developing countries. Breeding of Zn-enriched crops is expected to be facilitated by molecular dissection of plant Zn hyperaccumulation (i.e...

  2. ISFET pH Sensitivity: Counter-Ions Play a Key Role

    Science.gov (United States)

    Parizi, Kokab B.; Xu, Xiaoqing; Pal, Ashish; Hu, Xiaolin; Wong, H. S. Philip

    2017-02-01

    The Field Effect sensors are broadly used for detecting various target analytes in chemical and biological solutions. We report the conditions under which the pH sensitivity of an Ion Sensitive Field Effect transistor (ISFET) sensor can be significantly enhanced. Our theory and simulations show that by using pH buffer solutions containing counter-ions that are beyond a specific size, the sensor shows significantly higher sensitivity which can exceed the Nernst limit. We validate the theory by measuring the pH response of an extended gate ISFET pH sensor. The consistency and reproducibility of the measurement results have been recorded in hysteresis free and stable operations. Different conditions have been tested to confirm the accuracy and validity of our experiment results such as using different solutions, various oxide dielectrics as the sensing layer and off-the-shelf versus IC fabricated transistors as the basis of the ISFET sensor.

  3. RE: Forests and forest management plays a key role in mitigating climate change

    DEFF Research Database (Denmark)

    Bentsen, Niclas Scott; Nord-Larsen, Thomas; Larsen, Søren

    2016-01-01

    . The authors present an analysis of net carbon emissions from forest, but omit substitution effects related to the link between forest management and the fossil carbon pool. The link between fossil and terrestrial carbon pools is however critical for modelling climate impacts. To conclude as they do...... yield forest management was developed to meet demands for energy and materials for an increasing population and prevented a complete destruction of Europe’s forest. Particularly since 1850, forest management has increased Europe’s forest area and productivity, and thus also the forest carbon pool...... as also reported by Naudts et al. By ignoring the link between forestry and fossil carbon pools and not considering development in the absence of forest management, there is no accounting for the effect on GHG emissions, and no basis for estimating the contribution of forest management to cl...

  4. Symmetry plays a key role in the erasing of patterned surface features

    Energy Technology Data Exchange (ETDEWEB)

    Benzaquen, Michael; Salez, Thomas; Raphaël, Elie [Laboratoire de Physico-Chimie Théorique, UMR CNRS Gulliver 7083, ESPCI ParisTech, PSL Research University, 75005 Paris (France); Ilton, Mark; Massa, Michael V.; Fowler, Paul [Department of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1 (Canada); Dalnoki-Veress, Kari, E-mail: dalnoki@mcmaster.ca [Department of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1 (Canada); Laboratoire de Physico-Chimie Théorique, UMR CNRS Gulliver 7083, ESPCI ParisTech, PSL Research University, 75005 Paris (France)

    2015-08-03

    We report on how the relaxation of patterns prepared on a thin film can be controlled by manipulating the symmetry of the initial shape. The validity of a lubrication theory for the capillary-driven relaxation of surface profiles is verified by atomic force microscopy measurements, performed on films that were patterned using focused laser spike annealing. In particular, we observe that the shape of the surface profile at late times is entirely determined by the initial symmetry of the perturbation, in agreement with the theory. The results have relevance in the dynamical control of topographic perturbations for nanolithography and high density memory storage.

  5. Cancer immunotherapy: how low-level ionizing radiation can play a key role.

    Science.gov (United States)

    Janiak, Marek K; Wincenciak, Marta; Cheda, Aneta; Nowosielska, Ewa M; Calabrese, Edward J

    2017-07-01

    The cancer immunoediting hypothesis assumes that the immune system guards the host against the incipient cancer, but also "edits" the immunogenicity of surviving neoplastic cells and supports remodeling of tumor microenvironment towards an immunosuppressive and pro-neoplastic state. Local irradiation of tumors during standard radiotherapy, by killing neoplastic cells and generating inflammation, stimulates anti-cancer immunity and/or partially reverses cancer-promoting immunosuppression. These effects are induced by moderate (0.1-2.0 Gy) or high (>2 Gy) doses of ionizing radiation which can also harm normal tissues, impede immune functions, and increase the risk of secondary neoplasms. In contrast, such complications do not occur with exposures to low doses (≤0.1 Gy for acute irradiation or ≤0.1 mGy/min dose rate for chronic exposures) of low-LET ionizing radiation. Furthermore, considerable evidence indicates that such low-level radiation (LLR) exposures retard the development of neoplasms in humans and experimental animals. Here, we review immunosuppressive mechanisms induced by growing tumors as well as immunomodulatory effects of LLR evidently or likely associated with cancer-inhibiting outcomes of such exposures. We also offer suggestions how LLR may restore and/or stimulate effective anti-tumor immunity during the more advanced stages of carcinogenesis. We postulate that, based on epidemiological and experimental data amassed over the last few decades, whole- or half-body irradiations with LLR should be systematically examined for its potential to be a viable immunotherapeutic treatment option for patients with systemic cancer.

  6. Elevated nicotianamine levels in Arabidopsis halleri roots play a key role in zinc hyperaccumulation.

    Science.gov (United States)

    Deinlein, Ulrich; Weber, Michael; Schmidt, Holger; Rensch, Stefan; Trampczynska, Aleksandra; Hansen, Thomas H; Husted, Søren; Schjoerring, Jan K; Talke, Ina N; Krämer, Ute; Clemens, Stephan

    2012-02-01

    Zn deficiency is among the leading health risk factors in developing countries. Breeding of Zn-enriched crops is expected to be facilitated by molecular dissection of plant Zn hyperaccumulation (i.e., the ability of certain plants to accumulate Zn to levels >100-fold higher than normal plants). The model hyperaccumulators Arabidopsis halleri and Noccaea caerulescens share elevated nicotianamine synthase (NAS) expression relative to nonaccumulators among a core of alterations in metal homeostasis. Suppression of Ah-NAS2 by RNA interference (RNAi) resulted in strongly reduced root nicotianamine (NA) accumulation and a concomitant decrease in root-to-shoot translocation of Zn. Speciation analysis by size-exclusion chromatography coupled to inductively coupled plasma mass spectrometry showed that the dominating Zn ligands in roots were NA and thiols. In NAS2-RNAi plants, a marked increase in Zn-thiol species was observed. Wild-type A. halleri plants cultivated on their native soil showed elemental profiles very similar to those found in field samples. Leaf Zn concentrations in NAS2-RNAi lines, however, did not reach the Zn hyperaccumulation threshold. Leaf Cd accumulation was also significantly reduced. These results demonstrate a role for NAS2 in Zn hyperaccumulation also under near-natural conditions. We propose that NA forms complexes with Zn(II) in root cells and facilitates symplastic passage of Zn(II) toward the xylem.

  7. Elevated Nicotianamine Levels in Arabidopsis halleri Roots Play a Key Role in Zinc Hyperaccumulation[W

    Science.gov (United States)

    Deinlein, Ulrich; Weber, Michael; Schmidt, Holger; Rensch, Stefan; Trampczynska, Aleksandra; Hansen, Thomas H.; Husted, Søren; Schjoerring, Jan K.; Talke, Ina N.; Krämer, Ute; Clemens, Stephan

    2012-01-01

    Zn deficiency is among the leading health risk factors in developing countries. Breeding of Zn-enriched crops is expected to be facilitated by molecular dissection of plant Zn hyperaccumulation (i.e., the ability of certain plants to accumulate Zn to levels >100-fold higher than normal plants). The model hyperaccumulators Arabidopsis halleri and Noccaea caerulescens share elevated nicotianamine synthase (NAS) expression relative to nonaccumulators among a core of alterations in metal homeostasis. Suppression of Ah-NAS2 by RNA interference (RNAi) resulted in strongly reduced root nicotianamine (NA) accumulation and a concomitant decrease in root-to-shoot translocation of Zn. Speciation analysis by size-exclusion chromatography coupled to inductively coupled plasma mass spectrometry showed that the dominating Zn ligands in roots were NA and thiols. In NAS2-RNAi plants, a marked increase in Zn-thiol species was observed. Wild-type A. halleri plants cultivated on their native soil showed elemental profiles very similar to those found in field samples. Leaf Zn concentrations in NAS2-RNAi lines, however, did not reach the Zn hyperaccumulation threshold. Leaf Cd accumulation was also significantly reduced. These results demonstrate a role for NAS2 in Zn hyperaccumulation also under near-natural conditions. We propose that NA forms complexes with Zn(II) in root cells and facilitates symplastic passage of Zn(II) toward the xylem. PMID:22374395

  8. Phytochelatins play a key role in arsenic accumulation and tolerance in the aquatic macrophyte Wolffia globosa.

    Science.gov (United States)

    Zhang, Xin; Uroic, M Kalle; Xie, Wan-Ying; Zhu, Yong-Guan; Chen, Bao-Dong; McGrath, Steve P; Feldmann, Jörg; Zhao, Fang-Jie

    2012-06-01

    The rootless duckweed Wolffia globosa can accumulate and tolerate relatively large amounts of arsenic (As); however, the underlying mechanisms were unknown. W. globosa was exposed to different concentrations of arsenate with or without l-buthionine sulphoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. Free thiol compounds and As(III)-thiol complexes were identified and quantified using HPLC - high resolution ICP-MS - accurate mass ESI-MS. Without BSO, 74% of the As accumulated in the duckweed was complexed with phytochelatins (PCs), with As(III)-PC(4) and As(III)-PC(3) being the main species. BSO was taken up by the duckweed and partly deaminated. The BSO treatment completely suppressed the synthesis of PCs and the formation of As(III)-PC complexes, and also inhibited the reduction of arsenate to arsenite. BSO markedly decreased both As accumulation and As tolerance in W. globosa. The results demonstrate an important role of PCs in detoxifying As and enabling As accumulation in W. globosa.

  9. RE: Forests and forest management plays a key role in mitigating climate change

    DEFF Research Database (Denmark)

    Bentsen, Niclas Scott; Nord-Larsen, Thomas; Larsen, Søren

    2016-01-01

    . The authors present an analysis of net carbon emissions from forest, but omit substitution effects related to the link between forest management and the fossil carbon pool. The link between fossil and terrestrial carbon pools is however critical for modelling climate impacts. To conclude as they do...

  10. Swimming motility plays a key role in the stochastic dynamics of cell clumping

    Science.gov (United States)

    Qi, Xianghong; Nellas, Ricky B.; Byrn, Matthew W.; Russell, Matthew H.; Bible, Amber N.; Alexandre, Gladys; Shen, Tongye

    2013-04-01

    Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell-cell or cell-surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell-cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense.

  11. Mutual Assistance Associations: Refugee Self-Help Groups Play Key Role.

    Science.gov (United States)

    Ranard, Donald A.

    1990-01-01

    The history and current status of Indochinese Mutual Assistance Programs (MAAs) is reviewed in the newsletter issue, and a description is provided of the six kinds of MAAs that are found in the United States. They include the following: (1) cultural preservation/social activities; (2) religious services; (3) special constituency groups; (4)…

  12. ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes

    Directory of Open Access Journals (Sweden)

    Hsiao P.J. Voon

    2015-04-01

    Full Text Available Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. H3.3 deposition at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to aberrant telomere lengthening in certain cancers. In this study, we show that ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin and telomeres but also occurs at heterochromatic sites throughout the genome. Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic expression. We propose a model whereby ATRX-dependent deposition of H3.3 into heterochromatin is normally required to maintain the memory of silencing at imprinted loci.

  13. ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes.

    Science.gov (United States)

    Voon, Hsiao P J; Hughes, Jim R; Rode, Christina; De La Rosa-Velázquez, Inti A; Jenuwein, Thomas; Feil, Robert; Higgs, Douglas R; Gibbons, Richard J

    2015-04-21

    Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. H3.3 deposition at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to aberrant telomere lengthening in certain cancers. In this study, we show that ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin and telomeres but also occurs at heterochromatic sites throughout the genome. Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic expression. We propose a model whereby ATRX-dependent deposition of H3.3 into heterochromatin is normally required to maintain the memory of silencing at imprinted loci.

  14. ABSTRACTS AND KEY WORDS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Establishment of a Method for Content Determination of Polysaccharide in Membranous milkveteh root Applied in Fisheries Yu Xiao-qing et al. (1) Abstract Some chemical component in the traditional Chinese medicine Membranous milkvetch root can improve the ability of disease-prevention of animal and it can be applied in fisheries. In the paper, the method about content determination of polysaccharide in the root was established based on orthogonal experimental design Key words medicine; polysaccharide in Membranous milkvetch root; method of determination

  15. Ancel Keys: a tribute

    OpenAIRE

    VanItallie Theodore B

    2005-01-01

    Abstract Ancel Keys, Ph.D., who died in November, 2004, at the age of 100, was among the first scientists to recognize that human atherosclerosis is not an inevitable consequence of aging, and that a high-fat diet can be a major risk factor for coronary heart disease. During World War II, he and a group of talented co-workers at the University of Minnesota conducted a large-scale study of experimentally-induced human starvation. The data generated by this study – which was immediately recogni...

  16. Direction of technical and tactical skill in athletes playing team sports, playing with light position

    Directory of Open Access Journals (Sweden)

    Doroshenko Eduard Iur'evich

    2011-10-01

    Full Text Available A new method for evaluating the effectiveness of technical and tactical activities in basketball. A distinctive feature of the technique is presented key components of the accounting games, length of stay in the athletes play and the specific features of the game line. Established the specific means of correction of the training process taking into account the magnitude and direction of the load. Identified ways of solving the problem of optimal evaluation of gaming activities, taking into account the length of stay player on the court and its role. Refine management training process in team sports.

  17. Scientists ID Key Fetal Cells Vulnerable to Zika

    Science.gov (United States)

    ... html Scientists ID Key Fetal Cells Vulnerable to Zika Lab study suggests possible mechanism for birth defects ... 29, 2016 (HealthDay News) -- The devastating mosquito-borne Zika virus can infect cells that play a role ...

  18. Identification key to Quivira milkweeds

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document is a key to milkweed identification at Quivira National Wildlife Refuge. It contains a dichotomous key as well as a picture key. Milkweeds found on the...

  19. 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 g

  20. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    May, Peter J.; Winter, Søren

    2000-01-01

    This study addresses enforcement styles of regulatory inspectors, based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about i...

  1. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    J. May, Peter; Winter, Søren

    2007-01-01

    This study addresses enforcement styles of regulatory inspectors based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about in...

  2. Regulatory Foci and Organizational Commitment

    Science.gov (United States)

    Markovits, Yannis; Ullrich, Johannes; van Dick, Rolf; Davis, Ann J.

    2008-01-01

    We use regulatory focus theory to derive specific predictions regarding the differential relationships between regulatory focus and commitment. We estimated a structural equation model using a sample of 520 private and public sector employees and found in line with our hypotheses that (a) promotion focus related more strongly to affective…

  3. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    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....

  4. Fiscal 1998 achievement report on regional consortium research and development project. Regional consortium of venture business fostering type--Creation of key industries (Development of technologies for manufacturing and utilizing various biological regulatory substances using Hokkaido-produced biomasses as materials); 1998 nendo Dosan biomass wo genryo to shita kakushu seitai chosetsu kino busshitsu no seisan riyo gijutsu kaihatsu seika hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The efforts aim to meet consumers' needs for products that will prevent lifestyle diseases or the like. For this purpose, substances answering the purpose are extracted from Hokkaido-produced agricultural and aquatic biomasses, and prepared for testing. Researches are conducted on how they behave in the enzyme, cell, and biological systems, and active substances are isolated and identified. In relation to the aquatic biomass, a technology is established of extracting and separating DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), taurine, etc., which are multivalent unsaturated fatty acids effective in preventing lifestyle diseases, from the unused parts of the squid. In relation to the agricultural biomass, antimicrobial active substances are extracted and separated from small fruit plants such as the chicory. Long-keeping foods are tentatively produced by the addition of dried powder of the chicory root tuber. In the elucidation of various biological regulatory substances contained in the Hokkaido-produced biomasses, they are tested for their abilities to resist microbes and active oxygen. Furthermore, verification tests are conducted by administering the substances to the senescence-accelerated mouse (SAM). (NEDO)

  5. Regulatory Impact of RNA Secondary Structure across the Arabidopsis Transcriptome[W][OA

    Science.gov (United States)

    Li, Fan; Zheng, Qi; Vandivier, Lee E.; Willmann, Matthew R.; Chen, Ying; Gregory, Brian D.

    2012-01-01

    The secondary structure of an RNA molecule plays an integral role in its maturation, regulation, and function. However, the global influence of this feature on plant gene expression is still largely unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach in conjunction with transcriptome-wide sequencing of rRNA-depleted (RNA sequencing), small RNA, and ribosome-bound RNA populations to investigate the impact of RNA secondary structure on gene expression regulation in Arabidopsis thaliana. From this analysis, we find that highly unpaired and paired RNAs are strongly correlated with euchromatic and heterochromatic epigenetic histone modifications, respectively, providing evidence that secondary structure is necessary for these RNA-mediated posttranscriptional regulatory pathways. Additionally, we uncover key structural patterns across protein-coding transcripts that indicate RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in this model plant. We further reveal that RNA folding is significantly anticorrelated with overall transcript abundance, which is often due to the increased propensity of highly structured mRNAs to be degraded and/or processed into small RNAs. Finally, we find that secondary structure affects mRNA translation, suggesting that this feature regulates plant gene expression at multiple levels. These findings provide a global assessment of RNA folding and its significant regulatory effects in a plant transcriptome. PMID:23150631

  6. A new method for discovering disease-specific MiRNA-target regulatory networks.

    Directory of Open Access Journals (Sweden)

    Miriam Baglioni

    Full Text Available Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA--targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the miRable method whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal miRable follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools and pathology specific data (gene expression data. A case study on Prostate Cancer has shown that miRable is able to: 1 find new potential miRNA-targets pairs, 2 highlight novel genes potentially involved in a disease but never or little studied before, 3 reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms.

  7. Coordination of flower maturation by a regulatory circuit of three microRNAs.

    Directory of Open Access Journals (Sweden)

    Ignacio Rubio-Somoza

    2013-03-01

    Full Text Available The development of multicellular organisms relies on interconnected genetic programs that control progression through their life cycle. MicroRNAs (miRNAs and transcription factors (TFs play key roles in such regulatory circuits. Here, we describe how three evolutionary conserved miRNA-TF pairs interact to form multiple checkpoints during reproductive development of Arabidopsis thaliana. Genetic, cellular, and physiological experiments show that miR159- and miR319-regulated MYB and TCP transcription factors pattern the expression of miR167 family members and their ARF6/8 targets. Coordinated action of these miRNA-TF pairs is crucial for the execution of consecutive hormone-dependent transitions during flower maturation. Cross-regulation includes both cis- and trans-regulatory interactions between these miRNAs and their targets. Our observations reveal how different miRNA-TF pairs can be organized into modules that coordinate successive steps in the plant life cycle.

  8. Transcriptional control by two leucine-responsive regulatory proteins in Halobacterium salinarum R1

    Directory of Open Access Journals (Sweden)

    Tarasov Valery

    2010-05-01

    Full Text Available Abstract Background Archaea combine bacterial-as well as eukaryotic-like features to regulate cellular processes. Halobacterium salinarum R1 encodes eight leucine-responsive regulatory protein (Lrp-homologues. The function of two of them, Irp (OE3923F and lrpA1 (OE2621R, were analyzed by gene deletion and overexpression, including genome scale impacts using microarrays. Results It was shown that Lrp affects the transcription of multiple target genes, including those encoding enzymes involved in amino acid synthesis, central metabolism, transport processes and other regulators of transcription. In contrast, LrpA1 regulates transcription in a more specific manner. The aspB3 gene, coding for an aspartate transaminase, was repressed by LrpA1 in the presence of L-aspartate. Analytical DNA-affinity chromatography was adapted to high salt, and demonstrated binding of LrpA1 to its own promoter, as well as L-aspartate dependent binding to the aspB3 promoter. Conclusion The gene expression profiles of two archaeal Lrp-homologues report in detail their role in H. salinarum R1. LrpA1 and Lrp show similar functions to those already described in bacteria, but in addition they play a key role in regulatory networks, such as controlling the transcription of other regulators. In a more detailed analysis ligand dependent binding of LrpA1 was demonstrated to its target gene aspB3.

  9. Role of Regulatory T-cells in Different Clinical Expressions of Helicobacter pylori Infection.

    Science.gov (United States)

    Bagheri, Nader; Azadegan-Dehkordi, Fatemeh; Rahimian, Ghorbanali; Rafieian-Kopaei, Mahmoud; Shirzad, Hedayatollah

    2016-05-01

    Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection does not disappear and a chronic active gastritis continues if left untreated. It has been shown that the topographical pattern and immune response of gastritis are the main reasons for the bacteria persistence and the clinical outcome. Gastritis due to H. pylori is caused by a complicated interaction among a variety of T cell subsets. Regulatory T (Treg) cells suppressing the immune response of antigen-specific T-cells have recently been demonstrated to play a key role in chronic inflammation by immunologic tolerance. Treg cells have been identified as the major regulatory component of the adaptive immune response and being involved in H. pylori-related inflammation and bacterial persistence. There have been many controversies over the role of Treg cells in H. pylori infection. Many studies have shown that the local Treg response protects the gastric mucosa from intensified inflammation and tissue damage, and the risk of H. pylori-associated diseases has an inverse correlation with Treg accumulation, even if the decrease in the inflammatory response is recognized by Treg it causes increase in bacterial density. This paper reviews the role of Treg in different clinical expressions of H. pylori infection.

  10. Occupational noise exposure and regulatory adherence in music venues in the United Kingdom.

    Science.gov (United States)

    Barlow, Christopher; Castilla-Sanchez, Francisco

    2012-01-01

    Noise in most working environments is an unwanted by-product of the process. In most countries, noise exposure for workers has been controlled by legislation for many years. In the music industry the "noise" is actually the "desired" product, and for a long time the UK entertainment industry was exempt from these regulations. From April 2008, however, it became regulated under the Noise at Work Regulations 2005, meaning that employers from orchestras to nightclubs are legally required to adhere to the same requirements (based on ISO 9612:2009) for controlling noise exposure for their staff that have been applied to other industries for many years. A key question is to what degree, 2 years after implementation, these employers are complying with their legal responsibilities to protect the staff from noise? This study assessed four public music venues where live and/or recorded music is regularly played. Thirty staff members in different roles in the venues were monitored using noise dosimetry to determine noise exposure. Questionnaires were used to determine work patterns, attitudes to noise and hearing loss, and levels of training about noise risk. Results showed that the majority of staff (70%) in all venues exceeded the daily noise exposure limit value in their working shift. Use of hearing protection was rare (noise was low, and implementation of the noise regulations was haphazard, with staff regularly exceeding regulatory limits. The implication is that the industry is failing to meet regulatory requirements.

  11. A new method for discovering disease-specific MiRNA-target regulatory networks.

    Science.gov (United States)

    Baglioni, Miriam; Russo, Francesco; Geraci, Filippo; Rizzo, Milena; Rainaldi, Giuseppe; Pellegrini, Marco

    2015-01-01

    Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs) are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA--targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the miRable method whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal miRable follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools) and pathology specific data (gene expression data). A case study on Prostate Cancer has shown that miRable is able to: 1) find new potential miRNA-targets pairs, 2) highlight novel genes potentially involved in a disease but never or little studied before, 3) reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms.

  12. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    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...... 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...

  13. Automated secured cost effective key refreshing technique to enhance WiMAX privacy key management

    Science.gov (United States)

    Sridevi, B.; Sivaranjani, S.; Rajaram, S.

    2013-01-01

    In all walks of life the way of communication is transformed by the rapid growth of wireless communication and its pervasive use. A wireless network which is fixed and richer in bandwidth is specified as IEEE 802.16, promoted and launched by an industrial forum is termed as Worldwide Interoperability for Microwave Access (WiMAX). This technology enables seamless delivery of wireless broadband service for fixed and/or mobile users. The obscurity is the long delay which occurs during the handoff management in every network. Mobile WiMAX employs an authenticated key management protocol as a part of handoff management in which the Base Station (BS) controls the distribution of keying material to the Mobile Station (MS). The protocol employed is Privacy Key Management Version 2- Extensible Authentication Protocol (PKMV2-EAP) which is responsible for the normal and periodical authorization of MSs, reauthorization as well as key refreshing. Authorization key (AK) and Traffic Encryption key (TEK) plays a vital role in key exchange. When the lifetime of key expires, MS has to request for a new key to BS which in turn leads to repetition of authorization, authentication as well as key exchange. To avoid service interruption during reauthorization , two active keys are transmitted at the same time by BS to MS. The consequences of existing work are hefty amount of bandwidth utilization, time consumption and large storage. It is also endured by Man in the Middle attack and Impersonation due to lack of security in key exchange. This paper designs an automatic mutual refreshing of keys to minimize bandwidth utilization, key storage and time consumption by proposing Previous key and Iteration based Key Refreshing Function (PKIBKRF). By integrating PKIBKRF in key generation, the simulation results indicate that 21.8% of the bandwidth and storage of keys are reduced and PKMV2 mutual authentication time is reduced by 66.67%. The proposed work is simulated with Qualnet model and

  14. Quantum Key Distribution Protocol with Private-Public Key

    OpenAIRE

    Serna, Eduin H.

    2009-01-01

    A quantum cryptographic protocol based in public key cryptography combinations and private key cryptography is presented. Unlike the BB84 protocol [1] and its many variants [2,3] two quantum channels are used. The present research does not make reconciliation mechanisms of information to derive the key. A three related system of key distribution are described.

  15. Jakob Kelemina on Shakespeare's plays

    Directory of Open Access Journals (Sweden)

    Mirko Jurak

    2007-12-01

    Full Text Available Among Slovene scholars in English and German studies Jakob Kelemina (19 July 1882- 14 May 1957 has a very important  place. Janez Stanonik justly places him among the founding fathers of the University of Ljubljana (Stanonik 1966: 332. From 1920 Kelemina was professor of Germanic philology and between 1920 and 1957 he was also the Chair of the Deparment ofGermanic Languages and Literatures at the Faculty of Arts of this university. The major part of Kelemina's research was devoted to German and Austrian literatures,  German  philology, German-Slovene cultural relations, and literary theory; his work in these fields has already been discussed  by severa! Slovene scholars. However, in the first two decades of the twentieth century Kelemina also wrote severa! book reviews of Slovene and Croatian translations of Shakespeare's plays as well as three introductory essays to Slovene translations  of Shakespeare's plays. They are considered  as the first serious studies on Shakespeare in Slovenia (Moravec 1974: 437, and have not been analysed yet. Therefore this topic presents the core of my study, together with an evaluation  of Kelemina's contribution  to Slovene translations  of Shakespeare's plays done by Oton Župančič (1878-1949 during the first half of the twentieth century. Župančič's translations  became the criterion  for all further translations  of Shakespeare's dramatic works in Slovene. Župančič is stili one of our most important  poets and translators of this time and Kelemina's advice and criticism undoubtedly  also helped him to achieve such a high standard in his translations. In the central part of my study I also include some new material (e.g. Kelernina's letters, which is relevant for our understanding  of his co-operation with Oton Župančič  and other Slovene authors and critics. In order to put Kelemina's work into a historical perspective I present at the beginning of my study a brief survey of the

  16. Changes of standard physiological-perceptual markers and circulating MicroRNAs in response to tennis match-play: A case report of two elite players

    Directory of Open Access Journals (Sweden)

    Hoppe Matthias Wilhelm

    2016-06-01

    Full Text Available This study aimed to describe the acute changes of both standard physiological-perceptual markers and circulating microRNAs in response to tennis match-play in a detailed case report. Two elite male baseliners with comparable tennis experience were tested for anthropometric and fitness related variables and played 2 h of match-play on a red-clay court. The changes of standard physiological-perceptual markers including the heart rate, lactate concertation, creatine kinase activity, urea concentration and rating of perceived exertion as well as circulating microRNA-133a, -486 and -126 expression rates were examined at 10 different time-points (i.e., pre, during and up to 24 h post match-play. Player 2 had lower fitness related variables, but a higher heart rate, lactate concentration, creatine kinase activity and rating of perceived exertion during play than player 1. Player 2 showed an increase in all microRNAs (≤3.83-fold, most evident post match-play, whereas player 1 demonstrated a decrease (≤0.41-fold. The time-course in the changes of all standard physiological-perceptual markers was similar in both players, whereas this of the microRNAs was different. It was concluded that the relative changes of the circulating microRNA-133a, -486 and 126 expression rates of both players differed in response to tennis match-play with respect to the experienced physiological-perceptual stress and the underlying fitness level. Therefore, circulating microRNAs can serve as additional biomarkers for tennis exercise physiology and may be assessed together with standard markers to conclude whether key cellular regulatory processes were induced in response to match-play.

  17. Is Left-Right Symmetry the Key?

    CERN Document Server

    Senjanovic, Goran

    2016-01-01

    Abdus Salam challenged the chiral gauge nature of the Standard Model by paving the road towards the Left-Right symmetric electro-weak theory. I describe here the logical and historical construction of this theory, by emphasising the pioneering and key role it played for neutrino mass. I show that it is a self-contained and predictive model with the Higgs origin of Majorana neutrino mass, in complete analogy with the SM situation regarding charged fermions.

  18. ID-based Key-insulated Authenticated Key Agreement Protocol

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yuan; CHENG Xiao-ming; CHAI Zhen-chuan

    2007-01-01

    The basic idea behind an ID-based cryptosystem is that end user's public key can be determined by his identity information. Comparing with the traditional certificate-based cryptography, identity-based cryptography can eliminate much of the overhead associated with the deployment and management of certificate. However, exposure of private keys can be the most devastating attack on a public key based cryptosystem since such that all security guarantees are lost. In this paper, an ID-based authenticated key agreement protocol was presented. For solving the problem of key exposure of the basic scheme, the technique of key insulation was applied and a key insulated version is developed.

  19. Playing Children Adorn Ancient Porcelain

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    Porcelain is one of China’s greatest achievernents. It appeared during the Eastern Han Dynasty (25-220) and developed into three types of blue porcelain, white porcelain and colored porcelain between the Tang and Song dynasties. From the time of the Ming Dynasty (1368-1644), porcelain-making evolved, glazes and colors improved and porcelain was sold overseas. The quaint shapes and colorfully deslgned porcelain of the Ming Dynasty showed the appeal of folklife, but it was mainly used in the palace. Shown here are some pieces decorated with children at play. From these artifacts we can get an idea of the hairstyles, dress and architecture of that time.

  20. How to play Reverse Hex

    DEFF Research Database (Denmark)

    Toft, Bjarne; Hayward, Ryan B.; Henderson, Philip

    2012-01-01

    We present new results on how to play Reverse Hex, also known as Rex, or Misère Hex, on n × n boards. We give new proofs – and strengthened versions – of Lagarias and Sleator’s theorem (for n × n boards, each player can prolong the game until the board is full, so the first/second player can always......, we find second-player winning replies. Finally, in response to comments by Martin Gardner, for each n ≤ 5, we give a simple winning strategy for the n × n board....

  1. Regulatory Streamlining and Improvement

    Energy Technology Data Exchange (ETDEWEB)

    Mark A. Carl

    2006-07-11

    The Interstate Oil and Gas Compact Commission (IOGCC) engaged in numerous projects outlined under the scope of work discussed in the United States Department of Energy (DOE) grant number DE-FC26-04NT15456 awarded to the IOGCC. Numerous projects were completed that were extremely valuable to state oil and gas agencies as a result of work performed utilizing resources provided by the grant. There are numerous areas in which state agencies still need assistance. This additional assistance will need to be addressed under future scopes of work submitted annually to DOE's Project Officer for this grant. This report discusses the progress of the projects outlined under the grant scope of work for the 2005-2006 areas of interest, which are as follows: Area of Interest No. 1--Regulatory Streamlining and Improvement: This area of interest continues to support IOGCC's regulatory streamlining efforts that include the identification and elimination of unnecessary duplications of efforts between and among state and federal programs dealing with exploration and production on public lands. Area of Interest No. 2--Technology: This area of interest seeks to improve efficiency in states through the identification of technologies that can reduce costs. Area of Interest No. 3--Training and Education: This area of interest is vital to upgrading the skills of regulators and industry alike. Within the National Energy Policy, there are many appropriate training and education opportunities. Education was strongly endorsed by the President's National Energy Policy Development group. Acting through the governors offices, states are very effective conduits for the dissemination of energy education information. While the IOGCC favors the development of a comprehensive, long-term energy education plan, states are also supportive of immediate action on important concerns, such as energy prices, availability and conservation. Area of Interest No. 4--Resource Assessment and

  2. Supervising the uncanny: the play within the play.

    Science.gov (United States)

    Leader, Carol

    2015-11-01

    The writer offers a combined experience in analysis and the performing arts to explore uncanny aspects of the unconscious subtext of the patient's inner drama; subtext which can remain hidden from view in supervision. Freud and Jung's understanding of uncanny experience is considered together with a painting from medieval alchemy and Matte Blanco's conceptions concerning the symmetrical nature of unconscious process. Theatre and the work of the theatre director and actor in approaching the multidimensional aspects of a play are then introduced. Finally clinical case material from group supervision demonstrates how the 'theatre of therapy' and the work of the supervisory couple and group promote the emergence of a more authentic conscious asymmetrical response to the patient's 'script' that can break the 'spell' of the transference/countertransference relationship. This in turn brings meaning to the underlying and implicit 'stage directions' that the patient has been unconsciously communicating. © 2015, The Society of Analytical Psychology.

  3. 75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-06-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers... National Association of Securities Dealers, Inc., the Financial Industry Regulatory Authority, Inc., or...

  4. 75 FR 40000 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-07-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change Relating to the Restated Certificate of Incorporation of Financial Industry Regulatory Authority, Inc. July 2, 2010. On May 21, 2010, Financial Industry Regulatory Authority, Inc....

  5. Paediatric pharmacokinetics: key considerations

    Science.gov (United States)

    Batchelor, Hannah Katharine; Marriott, John Francis

    2015-01-01

    A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials. PMID:25855821

  6. ABSTRACTS AND KEY WORDS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Determination of the Estrogen Alkylphenols and Bisphenol A in Marine Sediments by Gas Chromatography-Mass Spectrometry Deng Xu-xiu et al. (1) Abstract Octylphenol, nonylphenol and bisphenol A are recognized environmental endocrine disruptors. A quantitative method was established for the simultaneous determination of octylphenol, nonylphenol and bisphenol A in marine sediments by gas chromatography-mass spectrometry. The test sample was extracted by methanol with ultrasonic technique, purified with copper powder and carbon solid phase extraction column, and derived with heptafluorobutyric anhydride. Then the analytes were separated on HP-5ms column and determined by gas chromatography-mass. The recovery of the method was between 84.3% and 94.5%, and the LOQ of 4-N- octylphenol, nonylphenol and bisphenol A was 0.25 g/kg, 0.15 g/kg and 0.15 g/kg. Key words octylphenol; nonylphenol; bisphenol A; gas chromatography-mass spectrometry

  7. Key aspects congenital infection

    Directory of Open Access Journals (Sweden)

    Yu. V. Lobzin

    2014-01-01

    Full Text Available The key questions to solve the problem of congenital infection in the Russian Federation are: using in national practice over world accepted terminology adapted to the recommendations of the World Health Organization; representation of the modern concepts of an infectious process in the classification of congenital infections; scientific development and introducing in clinical practice the «standard case definitions», applied to different congenital infections; optimization of protocols and clinical guidelines for diagnosis, treatment and prevention of congenital infections; improvement a knowledge in the infectious disease for all  pecialists involved in the risk assessment of congenital infections, manage pregnancy and children. Based on our experience and analysis of publications, the authors suggest possible solutions.

  8. Playing Games with Quantum Mechanics

    CERN Document Server

    Phoenix, Simon J D

    2012-01-01

    We present a perspective on quantum games that focuses on the physical aspects of the quantities that are used to implement a game. If a game is to be played, it has to be played with objects and actions that have some physical existence. We call such games playable. By focusing on the notion of playability for games we can more clearly see the distinction between classical and quantum games and tackle the thorny issue of what it means to quantize a game. The approach we take can more properly be thought of as gaming the quantum rather than quantizing a game and we find that in this perspective we can think of a complete quantum game, for a given set of preferences, as representing a single family of quantum games with many different playable versions. The versions of Quantum Prisoners Dilemma presented in the literature can therefore be thought of specific instances of the single family of Quantum Prisoner's Dilemma with respect to a particular measurement. The conditions for equilibrium are given for playab...

  9. Regulating regulatory T cells.

    Science.gov (United States)

    Le, N T; Chao, N

    2007-01-01

    Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.

  10. Internationalization of regulatory requirements.

    Science.gov (United States)

    Juillet, Y

    2003-02-01

    The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

  11. [The role of regulatory T cells in allergic contact dermatitis].

    Science.gov (United States)

    Krecisz, Beata; Chomiczewska, Dorota; Kieć-Swierczyńska, Marta

    2009-01-01

    Regulatory T cells (Treg) play a crucial role in the regulatory mechanisms of immune system. They are responsible for the induction and maintenance of immune tolerance. They are also involved in the pathogenesis of autoimmune and allergic diseases and implicated in transplant rejection and immunopathology of cancers. Treg cells constitute the population of lymphocytes heterogeneous in their phenotype. CD4+CD25+Foxp3+ cells are most important among Treg subsets. Modification of Treg actvity may be useful in the therapy of different diseases, including allergic disorders.

  12. An overview of the gene regulatory network controlling trichome development in the model plant, Arabidopsis

    Directory of Open Access Journals (Sweden)

    Sitakanta ePattanaik

    2014-06-01

    Full Text Available Trichomes are specialized epidermal cells located on aerial parts of plants and are associated with a wide array of biological processes. Trichomes protect plants from adverse conditions including UV light and herbivore attack and are also an important source of a number of phytochemicals. The simple unicellular trichomes of Arabidopsis serve as an excellent model to study molecular mechanism of cell differentiation and pattern formation in plants. The emerging picture suggests that the developmental process is controlled by a transcriptional network involving three major groups of transcription factors: the R2R3 MYB, basic helix-loop-helix (bHLH and WD40 repeat (WDR protein. These regulatory proteins form a trimeric activator complex that positively regulates trichome development. The single repeat R3 MYBs act as negative regulators of trichome development. They compete with the R2R3 MYBs to bind the bHLH factor and form a repressor complex. In addition to activator-repressor mechanism, a depletion mechanism may operate in parallel during trichome development. In this mechanism, the bHLH factor traps the WDR protein which results in depletion of WDR protein in neighboring cells. Consequently, the cells with high levels of bHLH and WDR proteins are developed into trichomes. A group of C2H2 zinc finger TFs has also been implicated in trichome development. Phytohormones, including gibberellins and jasmonic acid, play significant roles in this developmental process. Recently, microRNAs have been shown to be involved in trichome development. Furthermore, it has been demonstrated that the activities of the key regulatory proteins involved in trichome development are controlled by the 26S/ubiquitin proteasome system (UPS, highlighting the complexity of the regulatory network controlling this developmental process. To complement several excellent recent relevant reviews, this review focuses on the transcriptional network and hormonal interplay

  13. Calpain and caspase-3 play required roles in immobilization-induced limb muscle atrophy.

    Science.gov (United States)

    Talbert, Erin E; Smuder, Ashley J; Min, Kisuk; Kwon, Oh Sung; Powers, Scott K

    2013-05-15

    Prolonged skeletal muscle inactivity results in a rapid decrease in fiber size, primarily due to accelerated proteolysis. Although several proteases are known to contribute to disuse muscle atrophy, the ubiquitin proteasome system is often considered the most important proteolytic system during many conditions that promote muscle wasting. Emerging evidence suggests that calpain and caspase-3 may also play key roles in inactivity-induced atrophy of respiratory muscles, but it remains unknown if these proteases are essential for disuse atrophy in limb skeletal muscles. Therefore, we tested the hypothesis that activation of both calpain and caspase-3 is required for locomotor muscle atrophy induced by hindlimb immobilization. Seven days of immobilization (i.e., limb casting) promoted significant atrophy in type I muscle fibers of the rat soleus muscle. Independent pharmacological inhibition of calpain or caspase-3 prevented this casting-induced atrophy. Interestingly, inhibition of calpain activity also prevented caspase-3 activation, and, conversely, inhibition of caspase-3 prevented calpain activation. These findings indicate that a regulatory cross talk exists between these proteases and provide the first evidence that the activation of calpain and caspase-3 is required for inactivity-induced limb muscle atrophy.

  14. Regulatory coordination of clustered microRNAs based on microRNA-transcription factor regulatory network

    Directory of Open Access Journals (Sweden)

    Wang Jin

    2011-12-01

    Full Text Available Abstract Background MicroRNA (miRNA is a class of small RNAs of ~22nt which play essential roles in many crucial biological processes and numerous human diseases at post-transcriptional level of gene expression. It has been revealed that miRNA genes tend to be clustered, and the miRNAs organized into one cluster are usually transcribed coordinately. This implies a coordinated regulation mode exerted by clustered miRNAs. However, how the clustered miRNAs coordinate their regulations on large scale gene expression is still unclear. Results We constructed the miRNA-transcription factor regulatory network that contains the interactions between transcription factors (TFs, miRNAs and non-TF protein-coding genes, and made a genome-wide study on the regulatory coordination of clustered miRNAs. We found that there are two types of miRNA clusters, i.e. homo-clusters that contain miRNAs of the same family and hetero-clusters that contain miRNAs of various families. In general, the homo-clustered as well as the hetero-clustered miRNAs both exhibit coordinated regulation since the miRNAs belonging to one cluster tend to be involved in the same network module, which performs a relatively isolated biological function. However, the homo-clustered miRNAs show a direct regulatory coordination that is realized by one-step regulation (i.e. the direct regulation of the coordinated targets, whereas the hetero-clustered miRNAs show an indirect regulatory coordination that is realized by a regulation comprising at least three steps (e.g. the regulation on the coordinated targets by a miRNA through a sequential action of two TFs. The direct and indirect regulation target different categories of genes, the former predominantly regulating genes involved in emergent responses, the latter targeting genes that imply long-term effects. Conclusion The genomic clustering of miRNAs is closely related to the coordinated regulation in the gene regulatory network. The pattern of

  15. Regulatory research / Pesquisa regulatória

    Directory of Open Access Journals (Sweden)

    Altair Souza de Assis

    2013-05-01

    Full Text Available We present in this paper the concept, importance, and scope of research into the regulatory framework of regulation and legislation, with a particular focus on legislation related to legal metrology. This study also describes a comparative analysis of the various forms of regulation and the associated regulatory research, with the ultimate goal of better defi ning the concept and to validate the need to have research groups within a country’s regulatory bodies. Based on this work, we conclude that regulatory research is a key factor in the success of any regulatory body’s activities. Such research helps to avoid the creation of absurd or impractical regulatory barriers to a country’s technological development, or worse, to permit “orphans,” that is, technologies that are outside regulatory control, as is currently the case. Indeed, for a country to have a robust technological infrastructure, especially if it is still a developing country, strong and competent regulatory control is essential. However, this must be balanced by an atmosphere that fosters continuous and consistent technological innovation, and such development must also be self-sustainable from economic, social, and environmental viewpoints. ------------------------------------------------ Apresenta-se neste trabalho o conceito, a importância e a abrangência da pesquisa regulatória no âmbito da regulação e da regulamentação, com foco particular na regulamentação relacionada à metrologia legal. Faz-se também uma análise comparativa entre as várias formas de regular e regulamentar, e as suas pesquisas regulatórias afi ns, tendo como meta principal situar melhor o conceito e validar a necessidade de se fazer pesquisa nos órgãos e agências regulatórias do país. Com base neste trabalho, concluímos que a pesquisa regulatória é um fator chave para o sucesso de qualquer plano de ação de regulação para os agentes regulatórios do país. Ela ajuda a

  16. Waste-to-Energy in China: Key Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Dongliang Zhang

    2015-12-01

    Full Text Available China—the largest developing country in the world—is experiencing both rapid economic maturation and large-scale urbanization. These situations have led to waste disposal problems, and the need to identify alternative energy sources. Waste-to-energy (WTE conversion processes, a source of renewable energy, are expected to play an increasingly important role in China’s sustainable management of municipal solid waste (MSW. The purpose of this research is to investigate the key problems and opportunities associated with WTE, to provide recommendations for the government. This paper begins by describing China’s current MSW management situation and analyzing its waste disposal problems. The major challenges associated with China’s WTE incineration are then discussed from economic, environmental and social points of view. These include the high costs associated with constructing necessary facilities, the susceptibility of facilities to corrosion, the lower heating value of China’s MSW, air pollutant emissions and especially public opposition to WTE incineration. Since discarded waste can be used to produce energy for electricity and heat—thus reducing its volume and the production of greenhouse gas (GHG emissions—with government policies and financial incentives, the use of WTE incineration as a renewable energy source and part of a sustainable waste management strategy will be of increasing importance in the future. The paper concludes by summarizing the management, economic and social benefits that could be derived from developing the country’s domestic capacity for producing the needed incineration equipment, improving source separation capabilities, standardizing regulatory and legal responsibilities and undertaking more effective public consultation processes.

  17. Play behaviours and play object preferences of young children with autistic disorder in a clinical play environment.

    Science.gov (United States)

    Dominguez, Anna; Ziviani, Jenny; Rodger, Sylvia

    2006-01-01

    Play is the primary occupation of childhood and provides a potentially powerful means of assessing and treating children with autistic disorder. This study utilized a cross-sectional comparison design to investigate the nature of play engagement in children with AD (n = 24), relative to typically developing children (n = 34) matched for chronological age. Play behaviours were recorded in a clinical play environment. Videotapes comprising 15 minutes of the children's spontaneous play behaviour were analysed using time-interval analysis. The particular play behaviours observed and play objects used were coded. Differences in play behaviours (p motivation.

  18. Hand kinematics of piano playing.

    Science.gov (United States)

    Furuya, Shinichi; Flanders, Martha; Soechting, John F

    2011-12-01

    Dexterous use of the hand represents a sophisticated sensorimotor function. In behaviors such as playing the piano, it can involve strong temporal and spatial constraints. The purpose of this study was to determine fundamental patterns of covariation of motion across joints and digits of the human hand. Joint motion was recorded while 5 expert pianists played 30 excerpts from musical pieces, which featured ∼50 different tone sequences and fingering. Principal component analysis and cluster analysis using an expectation-maximization algorithm revealed that joint velocities could be categorized into several patterns, which help to simplify the description of the movements of the multiple degrees of freedom of the hand. For the thumb keystroke, two distinct patterns of joint movement covariation emerged and they depended on the spatiotemporal patterns of the task. For example, the thumb-under maneuver was clearly separated into two clusters based on the direction of hand translation along the keyboard. While the pattern of the thumb joint velocities differed between these clusters, the motions at the metacarpo-phalangeal and proximal-phalangeal joints of the four fingers were more consistent. For a keystroke executed with one of the fingers, there were three distinct patterns of joint rotations, across which motion at the striking finger was fairly consistent, but motion of the other fingers was more variable. Furthermore, the amount of movement spillover of the striking finger to the adjacent fingers was small irrespective of the finger used for the keystroke. These findings describe an unparalleled amount of independent motion of the fingers.

  19. Games people play the psychology of human relationships

    CERN Document Server

    Berne, Eric

    2010-01-01

    The bestselling Games People Play is the book that has helped millions of people understand the dynamics of relationships, by psychiatrist Eric Berne.We all play games. In every encounter with other people we are doing so. The nature of these games depends both on the situation and on who we meet.Eric Berne's classic Games People Play is the most accessible and insightful book ever written about the games we play: those patterns of behaviour that reveal hidden feelings and emotions. Wise and witty, it shows the underlying motivations behind our relationships and explores the roles that we try to play - and are forced to play.Games People Play gives you the keys to unlock the psychology of others - and yourself. You'll become more honest, more effective, and a true team player.'A brilliant, amusing, and clear catalogue of the psychological theatricals that human beings play over and over again' Kurt VonnegutEric Berne was a prominent psychiatrist and bestselling author.After inventing his groundbreaking Transa...

  20. Regulatory Effects of Fisetin on Microglial Activation

    OpenAIRE

    Jing-Yuan Chuang; Pei-Chun Chang; Yi-Chun Shen; Chingju Lin; Cheng-Fang Tsai; Jia-Hong Chen; Wei-Lan Yeh; Ling-Hsuan Wu; Hsiao-Yun Lin; Yu-Shu Liu; Dah-Yuu Lu

    2014-01-01

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS...

  1. Regulatory Effects of Fisetin on Microglial Activation

    OpenAIRE

    Jing-Yuan Chuang; Pei-Chun Chang; Yi-Chun Shen; Chingju Lin; Cheng-Fang Tsai; Jia-Hong Chen; Wei-Lan Yeh; Ling-Hsuan Wu; Hsiao-Yun Lin; Yu-Shu Liu; Dah-Yuu Lu

    2014-01-01

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS...

  2. Nanofluids research: key issues.

    Science.gov (United States)

    Wang, Liqiu; Fan, Jing

    2010-05-22

    Nanofluids are a new class of fluids engineered by dispersing nanometer-size structures (particles, fibers, tubes, droplets) in base fluids. The very essence of nanofluids research and development is to enhance fluid macroscopic and megascale properties such as thermal conductivity through manipulating microscopic physics (structures, properties and activities). Therefore, the success of nanofluid technology depends very much on how well we can address issues like effective means of microscale manipulation, interplays among physics at different scales and optimization of microscale physics for the optimal megascale properties. In this work, we take heat-conduction nanofluids as examples to review methodologies available to effectively tackle these key but difficult problems and identify the future research needs as well. The reviewed techniques include nanofluids synthesis through liquid-phase chemical reactions in continuous-flow microfluidic microreactors, scaling-up by the volume averaging and constructal design with the constructal theory. The identified areas of future research contain microfluidic nanofluids, thermal waves and constructal nanofluids.

  3. Nanofluids Research: Key Issues

    Directory of Open Access Journals (Sweden)

    Wang Liqiu

    2010-01-01

    Full Text Available Abstract Nanofluids are a new class of fluids engineered by dispersing nanometer-size structures (particles, fibers, tubes, droplets in base fluids. The very essence of nanofluids research and development is to enhance fluid macroscopic and megascale properties such as thermal conductivity through manipulating microscopic physics (structures, properties and activities. Therefore, the success of nanofluid technology depends very much on how well we can address issues like effective means of microscale manipulation, interplays among physics at different scales and optimization of microscale physics for the optimal megascale properties. In this work, we take heat-conduction nanofluids as examples to review methodologies available to effectively tackle these key but difficult problems and identify the future research needs as well. The reviewed techniques include nanofluids synthesis through liquid-phase chemical reactions in continuous-flow microfluidic microreactors, scaling-up by the volume averaging and constructal design with the constructal theory. The identified areas of future research contain microfluidic nanofluids, thermal waves and constructal nanofluids.

  4. 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...

  5. Taking Stock of Regulatory Variation.

    Science.gov (United States)

    Maurano, Matthew T; Stamatoyannopoulos, John A

    2015-07-29

    Three recent studies measure individual variation in regulatory DNA accessibility. What do they tell us about the prospects of assessing variation in single cells and across populations? Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Current Regulations and Regulatory Actions

    Science.gov (United States)

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  7. Play your Brain (Russisk oversættelse)

    DEFF Research Database (Denmark)

    Fredens, Kjeld; Prehn, Annette

    Do you want to... Turn your brain into a co-player not an opponent? Create that crucial readiness to change in yourself and others? Build a stronger repertoire in whatever you do? Then get to know the 8 keys on your inner piano. In Play Your Brain, award-winning trainer Anette Prehn...... and neuroscience researcher Kjeld Fredens introduce a groundbreaking approach to coaching yourself: through knowledge of how your brain works, combined with a playful, flexible, musical attitude in working along with it. Here are simple yet powerful tools for achieving the goals in your life and career. Whatever...... your experience in other instruments, you can become a virtuoso at playing your brain and playing your way to success...

  8. Play your Brain (Russisk oversættelse)

    DEFF Research Database (Denmark)

    Fredens, Kjeld; Prehn, Annette

    Do you want to... Turn your brain into a co-player not an opponent? Create that crucial readiness to change in yourself and others? Build a stronger repertoire in whatever you do? Then get to know the 8 keys on your inner piano. In Play Your Brain, award-winning trainer Anette Prehn...... and neuroscience researcher Kjeld Fredens introduce a groundbreaking approach to coaching yourself: through knowledge of how your brain works, combined with a playful, flexible, musical attitude in working along with it. Here are simple yet powerful tools for achieving the goals in your life and career. Whatever...... your experience in other instruments, you can become a virtuoso at playing your brain and playing your way to success...

  9. Key Updating Methods for Combinatorial Design Based Key Management Schemes

    Directory of Open Access Journals (Sweden)

    Chonghuan Xu

    2014-01-01

    Full Text Available Wireless sensor network (WSN has become one of the most promising network technologies for many useful applications. However, for the lack of resources, it is different but important to ensure the security of the WSNs. Key management is a corner stone on which to build secure WSNs for it has a fundamental role in confidentiality, authentication, and so on. Combinatorial design theory has been used to generate good-designed key rings for each sensor node in WSNs. A large number of combinatorial design based key management schemes have been proposed but none of them have taken key updating into consideration. In this paper, we point out the essence of key updating for the unital design based key management scheme and propose two key updating methods; then, we conduct performance analysis on the two methods from three aspects; at last, we generalize the two methods to other combinatorial design based key management schemes and enhance the second method.

  10. 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.

  11. Electronic Commerce Removing Regulatory Impediments

    Science.gov (United States)

    1992-05-01

    AD-A252 691 ELECTRONIC COMMERCE Removing Regulatory Impediments ~DuiG A% ELECTE I JUL1 8 1992 0 C D Daniel J. Drake John A. Ciucci ... - ""N ST AT KE...Management Institute 6400 Goldsboro Road Bethesda, Maryland 20817-5886 92 LMI Executive Summary ELECTRONIC COMMERCE : REMOVING REGULATORY IMPEDIMENTS... Electronic Commerce techniques, such as electronic mail and electronic data interchange (EDI), enable Government agencies to conduct business without the

  12. A threshold key escrow scheme based on public key cryptosystem

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In key escrow field it is important to solve the problem thatuser's secret key completely depends on the trusted escrow agency. In 1995, some methods of solving the problem were presented. But these methods are no better than that of directly using threshold cryptography. In this paper, we present a common pattern of threshold key escrow scheme based on public key cryptosystem, and a detailed design based on the improved RSA algorithm is given. The above problem is solved by this scheme.

  13. Regulatory T cells in systemic lupus erythematosus and pregnancy.

    Science.gov (United States)

    Tower, Clare; Mathen, Stephy; Crocker, Ian; Bruce, Ian N

    2013-06-01

    Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that predominantly affects women of reproductive age. As clinical outcomes improve, pregnancy in these women is becoming more common. Although epidemiological data have documented an improvement in the prognosis of pregnancy in these women over recent years, they are still at significantly increased risk of pregnancy complications, such as miscarriage, stillbirth, pre-eclampsia and impaired foetal growth. The pathogenesis of SLE involves marked immune dysfunction, and in particular, the function of immunosuppressive elements of the immune system is impaired, including regulatory T-cell function. Because regulatory T cells are likely to be the key cell-modulating feto-maternal tolerance, this review overviews the possibility that regulatory T-cell impairments contribute to pregnancy pathology in women with SLE and contribute to the clinical challenge of managing these women during pregnancy.

  14. The US uranium industry: Regulatory and policy impediments

    Energy Technology Data Exchange (ETDEWEB)

    Drennen, T.E.; Glicken, J.

    1995-06-01

    The Energy Policy Act of 1992 required the DOE to develop recommendations and implement government programs to assist the domestic uranium industry in increasing export opportunities. In 1993, as part of that effort, the Office of Nuclear Energy identified several key factors that could (or have) significantly impact(ed) export opportunities for domestic uranium. This report addresses one of these factors: regulatory and policy impediments to the flow of uranium products between the US and other countries. It speaks primarily to the uranium market for civil nuclear power. Changes in the world political and economic order have changed US national security requirements, and the US uranium industry has found itself without the protected market it once enjoyed. An unlevel playing field for US uranium producers has resulted from a combination of geology, history, and a general US political philosophy of nonintervention that precludes the type of industrial policy practiced in other uranium-exporting countries. The US has also been hampered in its efforts to support the domestic uranium-producing industry by its own commitment to free and open global markets and by international agreements such as GATT and NAFTA. Several US policies, including the imposition of NRC fees and licensing costs and Harbor Maintenance fees, directly harm the competitiveness of the domestic uranium industry. Finally, requirements under US law, such as those in the 1979 Nuclear Nonproliferation Act, place very strict limits on the use of US-origin uranium, limitations not imposed by other uranium-producing countries. Export promotion and coordination are two areas in which the US can help the domestic uranium industry without violating existing trade agreements or other legal or policy constraints.

  15. Workers' Compensation and Collegiate Athletes: The Debate over the Pay for Play Model: A Counterpoint.

    Science.gov (United States)

    Mondello, Michael J.; Beckham, Joseph

    2002-01-01

    Counterpoint argument to article in the October 2001 issue of the "Journal of Law & Education" wherein Christopher Haden argued that college athletes with athletic scholarships should receive additional compensation of $100 per month. Provides judicial, legislative, and regulatory evidence to back argument against pay-for-play model…

  16. RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-β-catenin signaling.

    Science.gov (United States)

    Cruciat, Cristina-Maria; Dolde, Christine; de Groot, Reinoud E A; Ohkawara, Bisei; Reinhard, Carmen; Korswagen, Hendrik C; Niehrs, Christof

    2013-03-22

    Casein kinase 1 (CK1) members play key roles in numerous biological processes. They are considered "rogue" kinases, because their enzymatic activity appears unregulated. Contrary to this notion, we have identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt-β-catenin network, where it acts as a regulatory subunit of CK1ε: In a Wnt-dependent manner, DDX3 binds CK1ε and directly stimulates its kinase activity, and promotes phosphorylation of the scaffold protein dishevelled. DDX3 is required for Wnt-β-catenin signaling in mammalian cells and during Xenopus and Caenorhabditis elegans development. The results also suggest that the kinase-stimulatory function extends to other DDX and CK1 members, opening fresh perspectives for one of the longest-studied protein kinase families.

  17. Scientific and Regulatory Policy Committee (SRPC) Review: Interpretation and Use of Cell Proliferation Data in Cancer Risk Assessment.

    Science.gov (United States)

    Wood, Charles E; Hukkanen, Renee R; Sura, Radhakrishna; Jacobson-Kram, David; Nolte, Thomas; Odin, Marielle; Cohen, Samuel M

    2015-08-01

    Increased cell proliferation is a central key event in the mode of action for many non-genotoxic carcinogens, and quantitative cell proliferation data play an important role in the cancer risk assessment of many pharmaceutical and environmental compounds. Currently, there is limited unified information on assay standards, reference values, targeted applications, study design issues, and quality control considerations for proliferation data. Here, we review issues in measuring cell proliferation indices, considerations for targeted studies, and applications within current risk assessment frameworks. As the regulatory environment moves toward more prospective evaluations based on quantitative pathway-based models, standardization of proliferation assays will become an increasingly important part of cancer risk assessment. To help address this development, we also discuss the potential role for proliferation data as a component of alternative carcinogenicity testing models. This information should improve consistency of cell proliferation methods and increase efficiency of targeted testing strategies.

  18. Sets, Subsets, and Dichotomous Keys

    Science.gov (United States)

    Cole, E. James

    1973-01-01

    Discusses the procedures that should be observed in constructing a dichotomous key. The keying exercise described was used as a laboratory activity in a biology course for elementary education majors, however it could be used in other courses. (JR)

  19. Practice of Regulatory Science (Drug Development).

    Science.gov (United States)

    Kawanishi, Toru

    2017-01-01

     The practice of regulatory science (RS) for drug development is described. In the course material for education in pharmaceutical sciences drafted by the RS Division of the Pharmaceutical Society of Japan, RS for pharmaceuticals is defined as the science of predicting, assessing, and judging the quality, efficacy, and safety of pharmaceutical products throughout their lifespan. RS is also described as an integrated science based on basic and applied biomedical sciences, including analytical chemistry, biochemistry, pharmacology, toxicology, genetics, biostatistics, epidemiology, and clinical trial methodology, and social sciences such as decision science, risk assessment, and communication science. The involvement of RS in drug development generally starts after the optimization of lead compounds. RS plays important roles governing pharmaceuticals during their entire life cycle management phase as well as the drug development phase.

  20. Mechanisms of T regulatory cell function.

    Science.gov (United States)

    Askenasy, Nadir; Kaminitz, Ayelet; Yarkoni, Shai

    2008-05-01

    Regulatory T cells (Treg) play a pivotal role in tolerance to self-antigens and tissue grafts, and suppression of autoimmune reactions. These cells modulate the intensity and quality of immune reactions through attenuation of the cytolytic activities of reactive immune cells. Treg cells operate primarily at the site of inflammation where they modulate the immune reaction through three major mechanisms: a) direct killing of cytotoxic cells through cell-to-cell contact, b) inhibition of cytokine production by cytotoxic cells, in particular interleukin-2, c) direct secretion of immunomodulatory cytokines, in particular TGF-beta and interleukin-10. In addition to differential contributions of these mechanisms under variable inflammatory conditions, mechanistic complexity and diversity evolves from the diverse tasks performed by various Treg cell subsets in different stages of the immune reaction. Here we attempt to integrate the current experimental evidence to delineate the major suppressive pathways of Treg cells.

  1. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis.

    Science.gov (United States)

    Sun, Mengge; Zhou, Xiaoya; Chen, Lili; Huang, Shishu; Leung, Victor; Wu, Nan; Pan, Haobo; Zhen, Wanxin; Lu, William; Peng, Songlin

    2016-01-01

    MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  2. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

    Directory of Open Access Journals (Sweden)

    Mengge Sun

    2016-01-01

    Full Text Available MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  3. Key Concepts in Informatics: Algorithm

    Science.gov (United States)

    Szlávi, Péter; Zsakó, László

    2014-01-01

    "The system of key concepts contains the most important key concepts related to the development tasks of knowledge areas and their vertical hierarchy as well as the links of basic key concepts of different knowledge areas." (Vass 2011) One of the most important of these concepts is the algorithm. In everyday life, when learning or…

  4. Play and Community in the Classroom.

    Science.gov (United States)

    King, Nechie R.

    1997-01-01

    Children recognize two kinds of classroom play: instrumental play organized by teachers for academic purposes; and illicit play stressing surreptitious, unsanctioned activities like whispering and clowning around. Each is associated with a particular form of classroom community. This article considers how the nature of classroom play influences…

  5. Teatro! Hispanic Plays for Young People.

    Science.gov (United States)

    Vigil, Angel

    This collection of 14 folk drama scripts is drawn from the Hispanic culture and traditions of the American Southwest and designed for use in educational settings. The plays are short, simple, and easy to produce. A single play can fill a class period, while several plays grouped together would make a school assembly. Six plays, intended for grades…

  6. The development of early sociodramatic play

    NARCIS (Netherlands)

    Deunk, M.I.; Berenst, J.; de Glopper, C.M.

    2008-01-01

    In this article we study the beginnings of sociodramatic play. We examine the pretend play interactions of a Dutch girl, Peggy, and focus on her transition into sociodramatic play. Initially, Peggy interprets only some elements of her play interactions at the pretend level. At age 2;9, Peggy shows s

  7. Teatro! Hispanic Plays for Young People.

    Science.gov (United States)

    Vigil, Angel

    This collection of 14 folk drama scripts is drawn from the Hispanic culture and traditions of the American Southwest and designed for use in educational settings. The plays are short, simple, and easy to produce. A single play can fill a class period, while several plays grouped together would make a school assembly. Six plays, intended for grades…

  8. Evaluative Intervention Research in Child's Play.

    Science.gov (United States)

    Yawkey, Thomas Daniels; Fox, Franklin Daniel

    1981-01-01

    Evaluative intervention research studies in pretend play are investigations that examine the potential of imaginative play in young children to demonstrate a relationship between play and cognitive, social, and emotional growth. A review of the research indicates that children who engage in imaginative play yield higher test scores than those in…

  9. Superman Comes to Preschool: Superhero TV Play.

    Science.gov (United States)

    Ritchie, Kathleen E.; Johnson, Zita M.

    Systematic efforts at the Arizona State Child Study Laboratory were successful in replacing children's undesirable superhero play with other types of sociodramatic play. Teachers found superhero play undesirable because it was aggressive and noisy and was accompanied by an increase in random activity. Observations indicated that superhero play had…

  10. Conceptualizing the Play Policies in Preschool Curriculums

    Science.gov (United States)

    Sener, Tulin

    2013-01-01

    This research attempted to describe the play policies in preschool institutions in Ankara, Turkey. The aim of this study is to determine the approaches of the preschools to the children's play. "Play Policy Questionnaire" administered to all directors and teachers of 20 public preschools and 20 private preschools. Play policy of…

  11. Introduction to Plays, English: 5112.44.

    Science.gov (United States)

    Ozan, Ruth S.

    Several plays are studied to introduce students to theatrical terms and to the elements of a play in this quinmester course for Dade County High Schools. Several approaches to the study of the play are suggested such as individual and a large group production of a play, the use of a unified theme such as Youth vs. Tradition, or the line of…

  12. Strategies for Family Facilitation of Play Dates

    Science.gov (United States)

    Chambers, Cynthia R.; Horn, Eva M.

    2010-01-01

    Play dates can serve several functions for young children, including children with social difficulties, such as developmental delays, behavioral disorders, autism spectrum disorders, and shyness. Play dates provide children with additional opportunities to be around peers and to practice skills associated with peer play interactions. Play dates…

  13. Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

    Science.gov (United States)

    Yessoufou, Akadiri; Plé, Aude; Moutairou, Kabirou; Hichami, Aziz; Khan, Naim Akhtar

    2009-01-01

    Immunological tolerance is one of the fundamental aspects of the immune system. The CD4+CD25+ regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capacity on immune response. In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4+CD25− effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Treg cells. DHA also curtailed ERK1/2 and Akt phosphorylation and downregulated the Smad7 levels in these cells. Contradictorily, DHA upregulated the mRNA expression of Foxp3, CTLA-4, TGF-β, and IL-10; nonetheless, this fatty acid increased the expression of p27KIP1 mRNA, known to be involved in Treg cell unresponsiveness. In Foxp3-immunoprepitated nuclear proteins, DHA upregulated histone desacetylase 7 levels that would again participate in the unresposnsiveness of these cells. Finally, a DHA-enriched diet also diminished, ex vivo, the suppressive capacity of Treg cells. Altogether, these results suggest that DHA, by diminishing Treg cell functions, may play a key role in health and disease. PMID:19561360

  14. Modeling genomic regulatory networks with big data.

    Science.gov (United States)

    Bolouri, Hamid

    2014-05-01

    High-throughput sequencing, large-scale data generation projects, and web-based cloud computing are changing how computational biology is performed, who performs it, and what biological insights it can deliver. I review here the latest developments in available data, methods, and software, focusing on the modeling and analysis of the gene regulatory interactions in cells. Three key findings are: (i) although sophisticated computational resources are increasingly available to bench biologists, tailored ongoing education is necessary to avoid the erroneous use of these resources. (ii) Current models of the regulation of gene expression are far too simplistic and need updating. (iii) Integrative computational analysis of large-scale datasets is becoming a fundamental component of molecular biology. I discuss current and near-term opportunities and challenges related to these three points.

  15. MicroRNAs as regulatory elements in psoriasis

    Directory of Open Access Journals (Sweden)

    Liu Yuan

    2016-01-01

    Full Text Available Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.

  16. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    Directory of Open Access Journals (Sweden)

    Junyi Li

    2016-01-01

    Full Text Available With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA based on gene coexpression network (GCN increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

  17. Accelerating regulatory progress in multi-institutional research.

    Science.gov (United States)

    Paolino, Andrea R; Lauf, Sherry Lee; Pieper, Lisa E; Rowe, Jared; Vargas, Ileana M; Goff, Melissa A; Daley, Matthew F; Tuzzio, Leah; Steiner, John F

    2014-01-01

    Multi-institutional collaborations are necessary in order to create large and robust data sets that are needed to answer important comparative effectiveness research (CER) questions. Before scientific work can begin, a complex maze of administrative and regulatory requirements must be efficiently navigated to avoid project delays. Staff from research, regulatory, and administrative teams involved in three HMO Research Network (HMORN) multi-institutional collaborations developed and employed novel approaches: to secure and maintain Institutional Review Board (IRB) approvals; to enable data sharing, and to expedite subawards for two data-only minimal risk studies. These novel approaches accelerated required processes and approvals while maintaining regulatory, human subjects, and institutional protections. Outcomes from the processes described here are compared with processes outlined in the research and regulatory literature and with processes that have been used in previous multisite research collaborations. Research, regulatory, and administrative staff are essential contributors to the success of multi-institutional collaborations. Their flexibility, creativity, and effective communication skills can lead to the development of efficient approaches to achieving the necessary oversight for these complex projects. Elements of these specific strategies can be adapted and used by other research networks. Other efforts in these areas should be evaluated and shared. The processes that help develop a "learning research system" play an important and complementary role in sustaining multi-institutional research collaborations.

  18. Psychiatrists' Perceptions of Role-Playing Games.

    Science.gov (United States)

    Lis, Eric; Chiniara, Carl; Biskin, Robert; Montoro, Richard

    2015-09-01

    The literature has seen a surge in research on the mental health impacts of technologies such as Facebook, video games, and massively-multiplayer online role-playing games such as World of Warcraft, but little is known regarding the mental health impact of non-video role-playing games, such as Dungeons & Dragons. The present study examines how psychiatrists' perceive role-playing games and whether they play them. Psychiatrists at a tertiary care centre in Canada completed a questionnaire assessing history of playing role-playing games and whether they associate them with psychopathology. Forty-eight psychiatrists responded. Twenty-three percent have played a role-playing game over their lifetimes. Twenty-two percent believed there was an association between psychopathology and role-playing games. A majority of psychiatrists who responded do not associate role-playing games with psychopathology. Implications for clinical practice and future research are discussed.

  19. A Framework for Integrating Environmental Justice in Regulatory Analysis

    Directory of Open Access Journals (Sweden)

    Onyemaechi C. Nweke

    2011-06-01

    Full Text Available With increased interest in integrating environmental justice into the process for developing environmental regulations in the United States, analysts and decision makers are confronted with the question of what methods and data can be used to assess disproportionate environmental health impacts. However, as a first step to identifying data and methods, it is important that analysts understand what information on equity impacts is needed for decision making. Such knowledge originates from clearly stated equity objectives and the reflection of those objectives throughout the analytical activities that characterize Regulatory Impact Analysis (RIA, a process that is traditionally used to inform decision making. The framework proposed in this paper advocates structuring analyses to explicitly provide pre-defined output on equity impacts. Specifically, the proposed framework emphasizes: (a defining equity objectives for the proposed regulatory action at the onset of the regulatory process, (b identifying specific and related sub-objectives for key analytical steps in the RIA process, and (c developing explicit analytical/research questions to assure that stated sub-objectives and objectives are met. In proposing this framework, it is envisioned that information on equity impacts informs decision-making in regulatory development, and that this is achieved through a systematic and consistent approach that assures linkages between stated equity objectives, regulatory analyses, selection of policy options, and the design of compliance and enforcement activities.

  20. Finger Forces in Clarinet Playing

    Directory of Open Access Journals (Sweden)

    Alex Hofmann

    2016-08-01

    Full Text Available Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17 and professional clarinettists (N = 6 were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 x 2 x 2 design (register: low--high; tempo: slow--fast, dynamics: soft--loud. There was an additional condition controlled by the experimenter, which determined the expression levels (low--high of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions. The melody was performed in three tempo conditions (slow, medium, fast in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (Fmean and peak force (Fmax were calculated. The overall finger forces were low (Fmean = 1.17 N, Fmax = 3.05 N compared to those on other musical instruments (e.g. guitar. Participants applied the largest finger forces during the high expression level performance conditions (Fmean = 1.21 N.For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (Fmean = 0.54 N. Such sensor instruments provide useful insights into player