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Sample records for long-term luciferase expression

  1. Computational analysis and functional expression of ancestral copepod luciferase.

    Science.gov (United States)

    Takenaka, Yasuhiro; Noda-Ogura, Akiko; Imanishi, Tadashi; Yamaguchi, Atsushi; Gojobori, Takashi; Shigeri, Yasushi

    2013-10-10

    We recently reported the cDNA sequences of 11 copepod luciferases from the superfamily Augaptiloidea in the order Calanoida. They were classified into two groups, Metridinidae and Heterorhabdidae/Lucicutiidae families, by phylogenetic analyses. To elucidate the evolutionary processes, we have now further isolated 12 copepod luciferases from Augaptiloidea species (Metridia asymmetrica, Metridia curticauda, Pleuromamma scutullata, Pleuromamma xiphias, Lucicutia ovaliformis and Heterorhabdus tanneri). Codon-based synonymous/nonsynonymous tests of positive selection for 25 identified copepod luciferases suggested that positive Darwinian selection operated in the evolution of Heterorhabdidae luciferases, whereas two types of Metridinidae luciferases had diversified via neutral mechanism. By in silico analysis of the decoded amino acid sequences of 25 copepod luciferases, we inferred two protein sequences as ancestral copepod luciferases. They were expressed in HEK293 cells where they exhibited notable luciferase activity both in intracellular lysates and cultured media, indicating that the luciferase activity was established before evolutionary diversification of these copepod species. © 2013.

  2. Memory effect in expressed emotions during long term group interactions

    NARCIS (Netherlands)

    Gorbunov, R.; Barakova, E.I.; Rauterberg, M.; Ferrández Vicente, J.M.; Álvarez-Sánchez, J.R.; de la Paz López, F.; Toledo Moreo, J.; Adeli, H.

    2017-01-01

    Long-term interactions in groups can be monitored through games in which the participants need to show their social preferences by making choice to help or to use egoistic game strategy. In this paper we analyse the facial expressions of a group of isolated individuals (astronauts) during repeated

  3. Long-term expression of glomerular genes in diabetic nephropathy.

    Science.gov (United States)

    Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

    2018-01-11

    Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney

  4. Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

    Energy Technology Data Exchange (ETDEWEB)

    Dumpala, Pradeep R., E-mail: pdumpala@rixd.org [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States); Holdcraft, Robert W.; Martis, Prithy C.; Laramore, Melissa A. [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States); Parker, Thomas S.; Levine, Daniel M. [The Rogosin Institute, 505 East 70th Street, New York, NY 10021 (United States); Smith, Barry H. [The Rogosin Institute, 505 East 70th Street, New York, NY 10021 (United States); NewYork-Presbyterian Hospital, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021 (United States); Gazda, Lawrence S. [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States)

    2016-08-05

    Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.

  5. Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

    International Nuclear Information System (INIS)

    Dumpala, Pradeep R.; Holdcraft, Robert W.; Martis, Prithy C.; Laramore, Melissa A.; Parker, Thomas S.; Levine, Daniel M.; Smith, Barry H.; Gazda, Lawrence S.

    2016-01-01

    Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.

  6. Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

    Science.gov (United States)

    Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

    2007-01-01

    The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

  7. Ways how to express the Value of Long-term Assets

    OpenAIRE

    Tomášková, Pavlína

    2008-01-01

    The goal of this study is to analyze the current methods of expression the Value of Long-term Assets. The captures are in such order that after the explanation of basic terms there is application of the Measurment methods to different types of Assets, like tangible or intangible assets.

  8. Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.

    Science.gov (United States)

    Costa, Rui Ponte; Padamsey, Zahid; D'Amour, James A; Emptage, Nigel J; Froemke, Robert C; Vogels, Tim P

    2017-09-27

    Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.

    Science.gov (United States)

    Larrosa, Pablo Nicolás Fernández; Ojea, Alejandro; Ojea, Ignacio; Molina, Victor Alejandro; Zorrilla-Zubilete, María Aurelia; Delorenzi, Alejandro

    2017-07-01

    Acute stress impairs memory retrieval of several types of memories. An increase in glucocorticoids, several minutes after stressful events, is described as essential to the impairing retrieval-effects of stressors. Moreover, memory retrieval under stress can have long-term consequences. Through what process does the reactivated memory under stress, despite the disrupting retrieval effects, modify long-term memories? The reconsolidation hypothesis proposes that a previously consolidated memory reactivated by a reminder enters a vulnerability phase (labilization) during which it is transiently sensitive to modulation, followed by a re-stabilization phase. However, previous studies show that the expression of memories during reminder sessions is not a condition to trigger the reconsolidation process since unexpressed memories can be reactivated and labilized. Here we evaluate whether it is possible to reactivate-labilize a memory under the impairing-effects of a mild stressor. We used a paradigm of human declarative memory whose reminder structure allows us to differentiate between a reactivated-labile memory state and a reactivated but non-labile state. Subjects memorized a list of five cue-syllables associated with their respective response-syllables. Seventy-two hours later, results showed that the retrieval of the paired-associate memory was impaired when tested 20min after a mild stressor (cold pressor stress (CPS)) administration, coincident with cortisol levels increase. Then, we investigated the long-term effects of CPS administration prior to the reminder session. Under conditions where the reminder initiates the reconsolidation process, CPS impaired the long-term memory expression tested 24h later. In contrast, CPS did not show effects when administered before a reminder session that does not trigger reconsolidation. Results showed that memory reactivation-labilization occurs even when retrieval was impaired. Memory reactivation under stress could hinder

  10. Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture

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    Sabine Conrad

    2014-01-01

    Full Text Available This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks and long-term culture (up to more than 14 months in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.

  11. The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

    Science.gov (United States)

    Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

    2011-01-01

    Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

  12. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

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    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

    2016-01-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  13. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.

    Science.gov (United States)

    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert; Michaelevski, Izhak

    2016-02-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  14. Intrathecal injection of naked plasmid DNA provides long-term expression of secreted proteins.

    Science.gov (United States)

    Hughes, Travis S; Langer, Stephen J; Johnson, Kirk W; Chavez, Raymond A; Watkins, Linda R; Milligan, Erin D; Leinwand, Leslie A

    2009-01-01

    Therapeutic benefit has been reported to result from intrathecal (i.t.) injection of transgene vectors, including naked DNA. However, most studies using naked DNA have measured only the transgene expression of intracellular proteins. Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing either secreted alkaline phosphatase (SEAP) or human interleukin-10 (hIL-10) were injected into the i.t. space in rats, and transgene products were repeatedly measured in the cerebrospinal fluid (CSF). Both SEAP and hIL-10 were maximal at 1 and 2 days after the injection and still detectable at 4 months. The utilization of a plasmid having two features that are hypothesized to increase gene expression (matrix attachment regions (MARs) and lack of CpG dinucleotides) resulted in a significant increase in gene expression. Reinjection of SEAP or hIL-10 plasmids after 4 months significantly increased protein levels at 1 and 14 days after the reinjection. SEAP was uniformly distributed between the DNA delivery site (approximately vertebral level T13) and the lumbar puncture site (L5/L6 inter-vertebral space), was reduced at the cisterna magna, and was detectable, though at much lower levels, in serum. These data suggest that naked DNA has the potential to be used as a therapeutic tool for applications that require long-term release of transgenes into the CSF.

  15. Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.

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    Yoshimura, Natsue; Horiuchi, Daisuke; Shibata, Masao; Saitoe, Minoru; Qi, Mei-Ling; Okazawa, Hitoshi

    2006-04-17

    Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to total or partial truncation of the C-terminal domain (CTD) and cause mental retardation in human patients. Interestingly, normal Drosophila homologue of PQBP-1 lacks CTD. As a model to analyze the molecular network of PQBP-1 affecting intelligence, we generated transgenic flies expressing human PQBP-1 with CTD. Pavlovian olfactory conditioning revealed that the transgenic flies showed disturbance of long-term memory. In addition, they showed abnormal courtship that male flies follow male flies. Abnormal functions of PQBP-1 or its binding partner might be linked to these symptoms.

  16. c-Fos expression predicts long-term social memory retrieval in mice.

    Science.gov (United States)

    Lüscher Dias, Thomaz; Fernandes Golino, Hudson; Moura de Oliveira, Vinícius Elias; Dutra Moraes, Márcio Flávio; Schenatto Pereira, Grace

    2016-10-15

    The way the rodent brain generally processes socially relevant information is rather well understood. How social information is stored into long-term social memory, however, is still under debate. Here, brain c-Fos expression was measured after adult mice were exposed to familiar or novel juveniles and expression was compared in several memory and socially relevant brain areas. Machine Learning algorithm Random Forest was then used to predict the social interaction category of adult mice based on c-Fos expression in these areas. Interaction with a familiar co-specific altered brain activation in the olfactory bulb, amygdala, hippocampus, lateral septum and medial prefrontal cortex. Remarkably, Random Forest was able to predict interaction with a familiar juvenile with 100% accuracy. Activity in the olfactory bulb, amygdala, hippocampus and the medial prefrontal cortex were crucial to this prediction. From our results, we suggest long-term social memory depends on initial social olfactory processing in the medial amygdala and its output connections synergistically with non-social contextual integration by the hippocampus and medial prefrontal cortex top-down modulation of primary olfactory structures. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. A time-course study of long term over-expression of ARR19 in mice

    Science.gov (United States)

    Qamar, Imteyaz; Ahmad, Mohammad Faiz; Narayanasamy, Arul

    2015-01-01

    A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID:26260329

  18. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852

  19. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.

  20. Long-term in vitro, cell-type-specific genome-wide reprogramming of gene expression

    International Nuclear Information System (INIS)

    Hakelien, Anne-Mari; Gaustad, Kristine G.; Taranger, Christel K.; Skalhegg, Bjorn S.; Kuentziger, Thomas; Collas, Philippe

    2005-01-01

    We demonstrate a cell extract-based, genome-wide and heritable reprogramming of gene expression in vitro. Kidney epithelial 293T cells have previously been shown to take on T cell properties following a brief treatment with an extract of Jurkat T cells. We show here that 293T cells exposed for 1 h to a Jurkat cell extract undergo genome-wide, target cell-type-specific and long-lasting transcriptional changes. Microarray analyses indicate that on any given week after extract treatment, ∼2500 genes are upregulated >3-fold, of which ∼900 are also expressed in Jurkat cells. Concomitantly, ∼1500 genes are downregulated or repressed, of which ∼500 are also downregulated in Jurkat cells. Gene expression changes persist for over 30 passages (∼80 population doublings) in culture. Target cell-type specificity of these changes is shown by the lack of activation or repression of Jurkat-specific genes by extracts of 293T cells or carcinoma cells. Quantitative RT-PCR analysis confirms the long-term transcriptional activation of genes involved in key T cell functions. Additionally, growth of cells in suspended aggregates, expression of CD3 and CD28 T cell surface markers, and interleukin-2 secretion by 293T cells treated with extract of adult peripheral blood T cells illustrate a functional nuclear reprogramming. Therefore, target cell-type-specific and heritable changes in gene expression, and alterations in cell function, can be promoted by extracts derived from transformed cells as well as from adult primary cells

  1. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  2. Long-term erythropoietin gene expression from transduced cells in bioisolator devices.

    Science.gov (United States)

    Yanay, Ofer; Barry, Simon C; Flint, Lisa Y; Brzezinski, Margaret; Barton, Randall W; Osborne, William R A

    2003-11-20

    Recombinant erythropoietin (EPO) is widely administered for long-term treatment of anemia associated with renal failure and other chronic diseases. The ability to deliver EPO by gene therapy would have clinical and economic benefit. We compared autologous and allogeneic transduced primary vascular smooth muscle cells for their ability to provide sustained EPO gene expression when encapsulated in TheraCyte devices implanted subcutaneously (SQ) or intraperitoneally (IP) in rats. Cells were transduced with retrovirus vector LrEpSN encoding rat EPO cDNA. Rats that received either autologous or allogeneic transduced cells showed elevated hematocrits (HCTs) ranging from 50 to 79% that were sustained for more than 12 months. The HCT of control rats remained at baseline (45.8%). Rats that received second SQ implants of either autologous or allogeneic cells showed elevations in hematocrit that were sustained for up to 12 months, suggesting the absence of immunological responses to transduced cells or implant material. All experimental groups had statistically significant elevated HCT (p TheraCyte devices was well tolerated and histological evaluation of the devices up to 12 months after surgery revealed a high degree of vascularization and no evidence of host immune response. TheraCyte devices offer a simple and safe gene delivery system that provides sustained therapeutic gene expression, permit removal and implantation of new devices, and do not require immunosuppression of the host.

  3. Sleeping Beauty-baculovirus hybrid vectors for long-term gene expression in the eye.

    Science.gov (United States)

    Turunen, Tytteli Anni Kaarina; Laakkonen, Johanna Päivikki; Alasaarela, Laura; Airenne, Kari Juhani; Ylä-Herttuala, Seppo

    2014-01-01

    A baculovirus vector is capable of efficiently transducing many nondiving and diving cell types. However, the potential of baculovirus is restricted for many gene delivery applications as a result of the transient gene expression that it mediates. The plasmid-based Sleeping Beauty (SB) transposon system integrates transgenes into target cell genome efficiently with a genomic integration pattern that is generally considered safer than the integration of many other integrating vectors; yet efficient delivery of therapeutic genes into cells of target tissues in vivo is a major challenge for nonviral gene therapy. In the present study, SB was introduced into baculovirus to obtain novel hybrid vectors that would combine the best features of the two vector systems (i.e. effective gene delivery and efficient integration into the genome), thus circumventing the major limitations of these vectors. We constructed and optimized SB-baculovirus hybrid vectors that bear either SB100x transposase or SB transposon in the forward or reverse orientations with respect to the viral backbone The functionality of the novel hybrid vectors was investigated in cell cultures and in a proof-of-concept study in the mouse eye. The hybrid vectors showed high and sustained transgene expression that remained stable and demonstrated no signs of decline during the 2 months follow-up in vitro. These results were verified in the mouse eye where persistent transgene expression was detected two months after intravitreal injection. Our results confirm that (i) SB-baculovirus hybrid vectors mediate long-term gene expression in vitro and in vivo, and (ii) the hybrid vectors are potential new tools for the treatment of ocular diseases. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Long-term effects of ionizing radiation on gene expression in a zebrafish model.

    Directory of Open Access Journals (Sweden)

    Lahcen Jaafar

    Full Text Available Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose or 1.0 Gy (moderate dose of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.

  5. Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia

    OpenAIRE

    Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

    2014-01-01

    eLife digest Cells called neurons allow information to travel quickly around the body so that we can rapidly respond to any changes that we sense in our environment. This includes non-conscious reactions, such as the knee-jerk reflex in humans. Reflexes and other behaviors can be influenced by long-term memory, and it is thought that long-term memory is stored by changes in the synapses that connect neurons to each other. The reflexes of a sea slug known as Aplysia are often used to study mem...

  6. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    NARCIS (Netherlands)

    D. Chadha; T.D. Pache; F.J. Huikeshoven (Frans); A.O. Brinkmann (Albert); Th.H. van der Kwast (Theo)

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated

  7. Long-Term Protective Immune Response Elicited by Vaccination with an Expression Genomic Library of Toxoplasma gondii

    OpenAIRE

    Fachado, Alberto; Rodriguez, Alexandro; Molina, Judith; Silvério, Jaline C.; Marino, Ana P. M. P.; Pinto, Luzia M. O.; Angel, Sergio O.; Infante, Juan F.; Traub-Cseko, Yara; Amendoeira, Regina R.; Lannes-Vieira, Joseli

    2003-01-01

    Immunization of BALB/c mice with an expression genomic library of Toxoplasma gondii induces a Th1-type immune response, with recognition of several T. gondii proteins (21 to 117 kDa) and long-term protective immunity against a lethal challenge. These results support further investigations to achieve a multicomponent anti-T. gondii DNA vaccine.

  8. p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

    Science.gov (United States)

    Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

    1996-12-20

    In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

  9. Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

    Science.gov (United States)

    Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

    2014-11-17

    Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.

  10. Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

    Science.gov (United States)

    Zanin, M P; Hellström, M; Shepherd, R K; Harvey, A R; Gillespie, L N

    2014-09-26

    Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    OpenAIRE

    Chadha, D.; Pache, T.D.; Huikeshoven, Frans; Brinkmann, Albert; Kwast, Theo

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycy...

  12. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    OpenAIRE

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS...

  13. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

  14. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

    DEFF Research Database (Denmark)

    Alfieri, A; Martone, D; Randers, Morten Bredsgaard

    2015-01-01

    and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM...... to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males....... are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool...

  15. A transgenic Plasmodium falciparum NF54 strain that expresses GFP-luciferase throughout the parasite life cycle.

    Science.gov (United States)

    Vaughan, Ashley M; Mikolajczak, Sebastian A; Camargo, Nelly; Lakshmanan, Viswanathan; Kennedy, Mark; Lindner, Scott E; Miller, Jessica L; Hume, Jen C C; Kappe, Stefan H I

    2012-12-01

    Plasmodium falciparum is the pathogenic agent of the most lethal of human malarias. Transgenic P. falciparum parasites expressing luciferase have been created to study drug interventions of both asexual and sexual blood stages but luciferase-expressing mosquito stage and liver stage parasites have not been created which has prevented the easy quantification of mosquito stage development (e.g. for transmission blocking interventions) and liver stage development (for interventions that prevent infection). To overcome this obstacle, we have created a transgenic P. falciparum NF54 parasite that expresses a GFP-luciferase transgene throughout the life cycle. Luciferase expression is robust and measurable at all life cycle stages, including midgut oocyst, salivary gland sporozoites and liver stages, where in vivo development is easily measurable using humanized mouse infections in conjunction with an in vivo imaging system. This parasite reporter strain will accelerate testing of interventions against pre-erythrocytic life cycle stages. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

    Science.gov (United States)

    Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

    2015-03-15

    Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Noradrenergic control of gene expression and long-term neuronal adaptation evoked by learned vocalizations in songbirds.

    Directory of Open Access Journals (Sweden)

    Tarciso A F Velho

    Full Text Available Norepinephrine (NE is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM, an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.

  18. Long-term transfer and expression of the human beta-globin gene in a mouse transplant model.

    Science.gov (United States)

    Raftopoulos, H; Ward, M; Leboulch, P; Bank, A

    1997-11-01

    Somatic gene therapy of hemoglobinopathies depends initially on the demonstration of safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models. We have used a beta-globin gene/beta-locus control region retroviral vector containing several modifications to optimize gene transfer and expression in a mouse transplant model. In this report we show that transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice leads to the continued presence of the gene up to 8 months posttransplantation. The transferred human beta-globin gene is detected in 3 of 5 mice surviving long term (>4 months) transplanted with bone marrow cells transduced with high-titer virus. Southern blotting confirms the presence of the unrearranged 5.1-kb human beta-globin gene-containing provirus in 2 of these mice. In addition, long-term expression of the transferred gene is seen in 2 mice at levels of 5% and 20% that of endogenous murine beta-globin at 6 and 8 months posttransplantation. We further document stem cell transduction by the successful transfer and high-level expression of the human beta-globin gene from mice transduced 9 months earlier into irradiated secondary recipient mice. These results demonstrate high-level, long-term somatic human beta-globin gene transfer into the hematopoietic stem cells of an animal for the first time, and suggest the potential feasibility of a retroviral gene therapy approach to sickle cell disease and the beta thalassemias.

  19. Long-term expression of human adenosine deaminase in mice transplanted with retrovirus-infected hematopoietic stem cells

    International Nuclear Information System (INIS)

    Lim, B.; Apperley, J.F.; Orkin, S.H.; Williams, D.A.

    1989-01-01

    Long-term stable expression of foreign genetic sequences transferred into hematopoietic stem cells by using retroviral vectors constitutes a relevant model for somatic gene therapy. Such stability of expression may depend on vector design, including the presence or absence of specific sequences within the vector, in combination with the nature and efficiency of infection of the hematopoietic target cells. The authors have previously reported successful transfer of human DNA encoding adenosine deaminase (ADA) into CFU-S (colony-forming unit-spleen) stem cells using simplified recombinant retroviral vectors. Human ADA was expressed in CFU-S-derived spleen colonies at levels near to endogenous enzyme. However, because of the lack of an efficient dominant selectable marker and low recombinant viral titers, stability of long-term expression of human ADA was not examined. They report here the development of an efficient method of infection of hematopoietic stem cells (HSC) without reliance on in vitro selection. Peripheral blood samples of 100% of mice transplanted with HSC infected by this protocol exhibit expression of human ADA 30 days after transplantation. Some mice (6 of 13) continue to express human ADA in all lineages after complete hematopoietic reconstitution (4 months). The use of recombinant retroviral vectors that efficiently transfer human ADA cDNA into HSC leading to stable expression of functional ADA in reconstituted mice, provides an experimental framework for future development of approaches to somatic gene therapy

  20. Public Attitudes Toward Sexual Expression in Long-Term Care: Does Context Matter?

    Science.gov (United States)

    Yelland, Erin; Hosier, Amy

    2017-08-01

    The purpose of this study was to (a) examine how age and sex of long-term care (LTC) residents influence public attitudes toward sexuality in LTC and (b) understand how, in the absence of cognitive decline, residing in LTC influences the perception of sexuality as a basic human right. Attitudes were examined using a factorial vignette with a probability sample of 325 respondents from a southern state. Results indicate that attitudes were not statistically affected by a vignette character's age or sex; but respondent education level, parenthood status, and religious affiliation did have direct bearing on attitudes. The notion of sexuality as a basic human right for residents of LTC was ultimately challenged as 19% of respondents said that LTC residents should not be permitted to have sexual relations with their spouse in the facility.

  1. Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

    Science.gov (United States)

    Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

    2018-06-20

    Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

  2. Cellular Immune Response Against Firefly Luciferase After Sleeping Beauty–Mediated Gene Transfer In Vivo

    Science.gov (United States)

    Podetz-Pedersen, Kelly M.; Vezys, Vaiva; Somia, Nikunj V.; Russell, Stephen J.

    2014-01-01

    Abstract The Sleeping Beauty (SB) transposon system has been shown to mediate new gene sequence integration resulting in long-term expression. Here the effectiveness of hyperactive SB100X transposase was tested, and we found that hydrodynamic co-delivery of a firefly luciferase transposon (pT2/CaL) along with SB100X transposase (pCMV-SB100X) resulted in remarkably sustained, high levels of luciferase expression. However, after 4 weeks there was a rapid, animal-by-animal loss of luciferase expression that was not observed in immunodeficient mice. We hypothesized that this sustained, high-level luciferase expression achieved using the SB100X transposase elicits an immune response in pT2/CaL co-administered mice, which was supported by the rapid loss of luciferase expression upon challenge of previously treated animals and in naive animals adoptively transferred with splenocytes from previously treated animals. Specificity of the immune response to luciferase was demonstrated by increased cytokine expression in splenocytes after exposure to luciferase peptide in parallel with MHC I–luciferase peptide tetramer binding. This anti-luciferase immune response observed following continuous, high-level luciferase expression in vivo clearly impacts its use as an in vivo reporter. As both an immunogen and an extremely sensitive reporter, luciferase is also a useful model system for the study of immune responses following in vivo gene transfer and expression. PMID:25093708

  3. Immunohistochemical expression of platelet-derived growth factor receptors in ovarian cancer patients with long-term follow-up

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Dahl Steffensen, Karina; Waldstrøm, Marianne

    2012-01-01

    relation to histopathological parameters and long-term overall survival. Methods. The immunohistochemical expression of PDGFR-α and PDGFR-β was investigated in tumor and stromal cells in 170 patients with histologically verified epithelial ovarian cancer. Results. Almost half of the tumor specimens showed......Introduction. The well-documented role of the PDGF system in tumor growth and angiogenesis has prompted the development of new biological agents targeting the PDGF system. The aim of the present study was to analyze the expression of the PDGF-receptors in ovarian cancer and to investigate its...... high expression of PDGFR-α and PDGFR-β in tumor cells (43% and 41%) and in stromal compartments (32% and 44%). There was a significant association between high expression of PDGFR-α and high expression of PDGFR-β in both tumor and stromal cells. Coexpression of PDGFR-α and PDGFR-β in stromal cells...

  4. Luciferase NanoLuc as a reporter for gene expression and protein levels in Saccharomyces cerevisiae.

    Science.gov (United States)

    Masser, Anna E; Kandasamy, Ganapathi; Kaimal, Jayasankar Mohanakrishnan; Andréasson, Claes

    2016-05-01

    Reporter proteins are essential tools in the study of biological processes and are employed to monitor changes in gene expression and protein levels. Luciferases are reporter proteins that enable rapid and highly sensitive detection with an outstanding dynamic range. Here we evaluated the usefulness of the 19 kDa luciferase NanoLuc (Nluc), derived from the deep sea shrimp Oplophorus gracilirostris, as a reporter protein in yeast. Cassettes with codon-optimized genes expressing yeast Nluc (yNluc) or its destabilized derivative yNlucPEST have been assembled in the context of the dominant drug resistance marker kanMX. The reporter proteins do not impair the growth of yeast cells and exhibit half-lives of 40 and 5 min, respectively. The commercial substrate Nano-Glo® is compatible with detection of yNluc bioluminescence in yeast using standard commercial substrate. © 2016 The Authors. Yeast published by John Wiley & Sons Ltd. © 2016 The Authors. Yeast published by John Wiley & Sons Ltd.

  5. Long-term functional impairment of hemopoietic progenitor cells engineered to express the S1 catalytic subunit of pertussis toxin.

    Science.gov (United States)

    Bonig, Halvard; Rohmer, Laurence; Papayannopoulou, Thalia

    2005-06-01

    A large body of data suggests that pertussis toxin (PTX)-sensitive G protein signals in mature and immature hemopoietic cells control their migration patterns in vitro and in vivo. These effects were derived after treatment of cells or animals with PTX. To circumvent several inherent problems of PTX holotoxin treatment, we expressed the S1 catalytic activity of PTX, thus blocking Gi protein signaling, in 32D murine myeloid progenitor cells and in primary human CD34+ cells, and studied its functional consequences. S1 was expressed using viral vectors. Effects of Gi protein blockade on proliferation, migration, adhesion, and gene expression were tested in vitro. S1 expression was nontoxic for the cells; expression and function were stable long-term and not overridden by compensatory mechanisms. S1-transduced 32D cells and primary CD34+ cells migrated poorly and did not contract their cytoskeleton upon treatment with the chemoattractant stromal cell-derived factor -1 (SDF-1), similar to the phenotype induced by PTX treatment. Gene expression studies comparing S1-transduced and control 32D cells uncovered four genes, expression of which was regulated by Gi protein blockade. Of interest, although SDF-1 signaling was inhibited, comparison between SDF-1-treated and untreated cells suggests that SDF-1 stimulation does not depend on de novo gene expression in these cells. Furthermore, when injected into nonobese diabetic/severe combined immunodeficient mice, seeding of S1-expressing 32D cells to bone marrow was largely blocked. Expression of S1 is an effective approach for studying long-term functional consequences of Gi protein blockade in hemopoietic cells in vitro and in vivo.

  6. Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

    Science.gov (United States)

    Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

    2016-11-29

    SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

  7. Enhanced green fluorescent protein is a nearly ideal long-term expression tracer for hematopoietic stem cells, whereas DsRed-express fluorescent protein is not.

    Science.gov (United States)

    Tao, Wen; Evans, Barbara-Graham; Yao, Jing; Cooper, Scott; Cornetta, Kenneth; Ballas, Christopher B; Hangoc, Giao; Broxmeyer, Hal E

    2007-03-01

    Validated gene transfer and expression tracers are essential for elucidating functions of mammalian genes. Here, we have determined the suitability and unintended side effects of enhanced green fluorescent protein (EGFP) and DsRed-Express fluorescent protein as expression tracers in long-term hematopoietic stem cells (HSCs). Retrovirally transduced mouse bone marrow cells expressing either EGFP or DsRed-Express in single or mixed dual-color cell populations were clearly discerned by flow cytometry and fluorescence microscopy. The results from in vivo competitive repopulation assays demonstrated that EGFP-expressing HSCs were maintained nearly throughout the lifespan of the transplanted mice and retained long-term multilineage repopulating potential. All mice assessed at 15 months post-transplantation were EGFP positive, and, on average, 24% total peripheral white blood cells expressed EGFP. Most EGFP-expressing recipient mice lived at least 22 months. In contrast, Discosoma sp. red fluorescent protein (DsRed)-expressing donor cells dramatically declined in transplant-recipient mice over time, particularly in the competitive setting, in which mixed EGFP- and DsRed-expressing cells were cotransplanted. Moreover, under in vitro culture condition favoring preservation of HSCs, purified EGFP-expressing cells grew robustly, whereas DsRed-expressing cells did not. Therefore, EGFP has no detectable deteriorative effects on HSCs, and is nearly an ideal long-term expression tracer for hematopoietic cells; however, DsRed-Express fluorescent protein is not suitable for these cells.

  8. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

    Directory of Open Access Journals (Sweden)

    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  9. Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice.

    Science.gov (United States)

    Gokarn, Rahul; Solon-Biet, Samantha M; Cogger, Victoria C; Cooney, Gregory J; Wahl, Devin; McMahon, Aisling C; Mitchell, James R; Mitchell, Sarah J; Hine, Christopher; de Cabo, Rafael; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

    2018-04-23

    Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and fat intake had few effects on gene expression compared with protein. Pathways and processes associated with protein intake included those involved with mitochondrial function, metabolic signaling (PI3K-Akt, AMPK, mTOR) and metabolism of protein and amino acids. Protein intake had variable effects on genes associated with regulation of longevity and influenced by caloric restriction. Among the genes of interest with expression that were significantly associated with protein intake are Cth, Gls2, Igf1, and Nnmt, which were increased with higher protein intake, and Igf2bp2, Fgf21, Prkab2, and Mtor, which were increased with lower protein intake. Dietary protein has a powerful impact on hepatic gene expression in older mice, with some overlap with genes previously reported to be involved with regulation of longevity or caloric restriction.

  10. Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

    Science.gov (United States)

    Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

    2017-07-12

    The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

  11. Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences

    Science.gov (United States)

    Dumeige, Laurence; Storey, Caroline; Decourtye, Lyvianne; Nehlich, Melanie; Lhadj, Christophe; Viengchareun, Say; Kappeler, Laurent; Lombès, Marc; Martinerie, Laetitia

    2017-01-01

    Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS) method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1) and glucocorticoid-induced leucine zipper protein (Gilz), together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology. PMID:28230786

  12. Expression of HSPs: an adaptive mechanism during long-term heat stress in goats ( Capra hircus)

    Science.gov (United States)

    Dangi, Satyaveer Singh; Gupta, Mahesh; Dangi, Saroj K.; Chouhan, Vikrant Singh; Maurya, V. P.; Kumar, Puneet; Singh, Gyanendra; Sarkar, Mihir

    2015-08-01

    Menacing global rise in surface temperature compelled more focus of research over understanding heat stress response mechanism of animals and mitigation of heat stress. Twenty-four goats divided into four groups ( n = 6) such as NHS (non-heat-stressed), HS (heat-stressed), HS + VC (heat-stressed administered with vitamin C), and HS + VE + Se (heat-stressed administered with vitamin E and selenium). Except NHS group, other groups were exposed to repeated heat stress (42 °C) for 6 h on 16 consecutive days. Blood samples were collected at the end of heat exposure on days 1, 6, 11, and 16. When groups compared between days, expression of all heat shock proteins (HSPs) showed a similar pattern as first peak on day 1, reached to basal level on the sixth day, and followed by second peak on day 16. The relative messenger RNA (mRNA) and protein expression of HSP 60, HSP70, and HSP90 was observed highest ( P < 0.05) in HS group, followed by antioxidant-administered group on days 1 and 16, which signifies that antioxidants have dampening effect on HSP expression. HSP105/110 expression was highest ( P < 0.05) on day 16. We conclude that HSP expression pattern is at least two-peak phenomenon, i.e., primary window of HSP protection on the first day followed by second window of protection on day 16. HSP60, HSP70, and HSP90 play an important role during the initial phase of heat stress acclimation whereas HSP105/110 joins this cascade at later phase. Antioxidants may possibly attenuate the HSP expression by reducing the oxidative stress.

  13. Estimation of Ship Long-term Wave-induced Bending Moment using Closed-Form Expressions

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher; Mansour, A. E.

    2002-01-01

    A semi-analytical approach is used to derive frequency response functions and standard deviations for the wave-induced bending moment amidships for mono-hull ships. The results are given as closed-form expressions and the required input information for the procedure is restricted to the main......-empirical closed-form expression for the skewness. The effect of whipping is included by assuming that whipping and wave-induced responses are conditionally independent given Hs. The procedure is simple and can be used to make quick estimates of the design wave bending moment at the conceptual design phase...

  14. Long-term neuroglobin expression of human astrocytes following brain trauma.

    Science.gov (United States)

    Chen, Xiameng; Liu, Yuan; Zhang, Lin; Zhu, Peng; Zhu, Haibiao; Yang, Yu; Guan, Peng

    2015-10-08

    Neuroglobin (Ngb), a 17 kDa monomeric protein, was initially described as a vertebrate oxygen-binding heme protein in 2000 and detected in metabolically active organs or cells, like the brain, peripheral nervous system as well as certain endocrine cells. A large array of initial experimental work reported that Ngb displayed a neuron restricted expression pattern in mammalian brains. However, growing evidence indicated astrocytes may also express Ngb under pathological conditions. To address the question whether human astrocytes express Ngb under traumatic insults, we investigated Ngb immuno-reactivity in post-mortem human brain tissues that died of acute, sub-acute and chronic brain trauma, respectively. We observed astrocytic Ngb expression in sub-acute and chronic traumatic brains rather than acute traumatic brains. Strikingly, the Ngb immuno-reactive astrocytes were still strongly detectable in groups that died 12 months after brain trauma. Our findings may imply an unexplored role of Ngb in astrocytes and the involved mechanisms were suggested to be further characterized. Also, therapeutic application of Ngb or Ngb-inducible chemical compounds in neuro-genesis or astrocytic scar forming can be expected. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Sonodelivery Facilitates Sustained Luciferase Expression from an Episomal Vector in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Manoel Figueiredo Neto

    2015-07-01

    Full Text Available Successful gene delivery to skeletal muscle is a desirable goal, not only for treating muscle diseases, but also for immunization, treatment of metabolic disorders, and/or delivering gene expression that can treat systemic conditions, such as bone metastatic cancer, for example. Although naked DNA uptake into skeletal muscle is possible, it is largely inefficient in the absence of additional chemical or physical delivery methods. We describe a system for delivery of non-viral or plasmid DNA to skeletal muscle using ultrasound-assisted sonoporation of a nanoplex combining plasmid DNA and a branched polymer based on poly(cyclooctene-graft-oligopeptide. The materials and methods described herein promise to advance the field of sonodelivery and of gene delivery to muscle for therapeutic applications since a simple system is presented that enables long-term gene expression in vivo with the promise of a minimal inflammatory gene expression profile.

  16. Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

    Science.gov (United States)

    Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

    The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant No. 14-04-00173.

  17. Heparanase Expression in Malignant Salivary Gl, Tumors Inversely Correlates with Long-Term Survival

    Directory of Open Access Journals (Sweden)

    Ofer Ben-Izhak

    2006-10-01

    Full Text Available BACKGROUND: Upregulation of the endo-b-Dglucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local, distant metastatic spread, increased vascular density, reduced postoperative survival. PATIENTS, METHODS: We analyzed heparanase expression in 60 patients (aged 59 ± 17 years with malignant salivary tumors (39 males, 21 females using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity. RESULTS: Heparanase staining was positive (> 0 in 70% of tumors (42 of 60 patients, was negative (0 in the remaining 30% (18 patients. The cumulative survival of patients diagnosed as heparanase-negative (n = 18 at 300 months was 70% (95% confidence interval = 35-88. In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42 at 300 months was 0% (statistically significant difference, P = .035. CONCLUSIONS: Heparanase expression levels inversely correlate with the survival rates of salivary gl, cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy, an attractive target for anticancer drug development.

  18. Repeated batch fermentation of immobilized E. coli expressing Vitreoscilla hemoglobin for long-term use.

    Science.gov (United States)

    Sar, Taner; Seker, Gamze; Erman, Ayse Gokce; Stark, Benjamin C; Yesilcimen Akbas, Meltem

    2017-09-03

    This study describes an efficient and reusable process for ethanol production from medium containing whey powder, using alginate immobilized ethanologenic E. coli strains either expressing (TS3) or not expressing (FBR5) Vitreoscilla hemoglobin. Reuseabilities of the FBR5 and TS3 strains were investigated regarding their ethanol production capacities over the course of 15 successive 96-h batch fermentations. The ethanol production was fairly stable over the entire duration of the experiment, with strain TS3 maintaining a substantial advantage over strain FBR5. Storage of both strains in 2 different solutions for up to 60 d resulted in only a modest loss of ethanol production, with strain TS3 consistently outperforming strain FBR5 by a substantial amount. Strains stored for 15 or 30 d maintained their abilities to produce ethanol without dimunition over the course of 8 successive batch fermentations; again strain TS3 maintained a substantial advantage over strain FBR5 throughout the entire experiment. Thus, immobilization is a useful strategy to maintain the advantage in ethanol productivity afforded by expression of Vitreoscilla hemoglobin over long periods of time and large numbers of repeated batch fermentations, including, as in this case, using media with food processing wastes as the carbon source.

  19. Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

    DEFF Research Database (Denmark)

    Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

    2014-01-01

    does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

  20. The dynamics of long-term transgene expression in engrafted neural stem cells.

    Science.gov (United States)

    Lee, Jean-Pyo; Tsai, David J; In Park, Kook; Harvey, Alan R; Snyder, Evan Y

    2009-07-01

    To assess the dynamics and confounding variables that influence transgene expression in neural stem cells (NSCs), we generated distinct NSC clones from the same pool of cells, carrying the same reporter gene transcribed from the same promoter, transduced by the same retroviral vector, and transplanted similarly at the same differentiation state, at the same time and location, into the brains of newborn mouse littermates, and monitored in parallel for over a year in vivo (without immunosuppression). Therefore, the sole variables were transgene chromosomal insertion site and copy number. We then adapted and optimized a technique that tests, at the single cell level, persistence of stem cell-mediated transgene expression in vivo based on correlating the presence of the transgene in a given NSC's nucleus (by fluorescence in situ hybridization [FISH]) with the frequency of that transgene's product within the same cell (by combined immunohistochemistry [IHC]). Under the above-stated conditions, insertion site is likely the most contributory variable dictating transgene downregulation in an NSC after 3 months in vivo. We also observed that this obstacle could be effectively and safely counteracted by simple serial infections (as few as three) inserting redundant copies of the transgene into the prospective donor NSC. (The preservation of normal growth control mechanisms and an absence of tumorigenic potential can be readily screened and ensured ex vivo prior to transplantation.) The combined FISH/IHC strategy employed here for monitoring the dynamics of transgene expression at the single cell level in vivo may be used for other types of therapeutic and housekeeping genes in endogenous and exogenous stem cells of many organs and lineages. Copyright 2009 Wiley-Liss, Inc.

  1. Chorionic villi derived mesenchymal like stem cells and expression of embryonic stem cells markers during long-term culturing.

    Science.gov (United States)

    Katsiani, E; Garas, A; Skentou, C; Tsezou, A; Messini, C I; Dafopoulos, K; Daponte, A; Messinis, I E

    2016-09-01

    Mesenchymal stem cells (MSCs) can be obtained from a variety of human tissues. MSCs derived from placental chorionic villi of the first trimester are likely to resemble, biologically, embryonic stem cells (ESC), due to the earlier development stage of placenta. In the present study long-term cultures of MSC-like cells were assessed in order to evaluate MSCs multipotent characteristics and molecular features during the period of culture. CV-cells obtained from 10 samples of chorionic villus displayed typical fibroblastoid morphology, undergone 20 passages during a period of 120 days, maintaining a stable karyotype throughout long term expansion. The cells were positive, for CD90, CD73, CD105, CD29, CD44, HLA ABC antigens and negative for CD14, CD34, AC133, and HLA DR antigens as resulted from the flow cytometry analysis. CV-cells were differentiated in adipocytes, osteoblasts, chondrocytes and neuronal cells under specific culture conditions. The expression of the ESC-gene markers POU5F1 (Oct-4) and NANOG was observed at earliest stages (4-12 passages) and not at the late stages (14-20 passages) by RT-PCR analysis. ZFP42 and SOX2 expression were not detected. Moreover, CV-cells were found to express GATA4 but not NES (Nestin). Chorionic villi-derived cells possess multipotent properties, display high proliferation rate and self-renew capacity, share common surface antigens with adult MSCs and express certain embryonics stem cells gene markers. These characteristics highlight chorionic villi as an attractive source of MSCs for the needs of regenerative medicine.

  2. Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent.

    Science.gov (United States)

    Papeta, Natalia; Chen, Tao; Vianello, Fabrizio; Gererty, Lyle; Malik, Ashish; Mok, Ying-Ting; Tharp, William G; Bagley, Jessamyn; Zhao, Guiling; Stevceva, Liljana; Yoon, Victor; Sykes, Megan; Sachs, David; Iacomini, John; Poznansky, Mark C

    2007-01-27

    Alloantigen specific T cells have been shown to be required for allograft rejection. The chemokine, stromal cell derived factor-1 (SDF-1) at high concentration, has been shown to act as a T-cell chemorepellent and abrogate T-cell infiltration into a site of antigen challenge in vivo via a mechanism termed fugetaxis or chemorepulsion. We postulated that this mechanism could be exploited therapeutically and that allogeneic cells engineered to express a chemorepellent protein would not be rejected. Allogeneic murine insulinoma beta-TC3 cells and primary islets from BALB/C mice were engineered to constitutively secrete differential levels of SDF-1 and transplanted into allogeneic diabetic C57BL/6 mice. Rejection was defined as the permanent return of hyperglycemia and was correlated with the level of T-cell infiltration. The migratory response of T-cells to SDF-1 was also analyzed by transwell migration assay and time-lapse videomicroscopy. The cytotoxicity of cytotoxic T cell (CTLs) against beta-TC3 cells expressing high levels of SDF-1 was measured in standard and modified chromium-release assays in order to determine the effect of CTL migration on killing efficacy. Control animals rejected allogeneic cells and remained diabetic. In contrast, high level SDF-1 production by transplanted cells resulted in increased survival of the allograft and a significant reduction in blood glucose levels and T-cell infiltration into the transplanted tissue. This is the first demonstration of a novel approach that exploits T-cell chemorepulsion to induce site specific immune isolation and thereby overcomes allograft rejection without the use of systemic immunosuppression.

  3. Highly specific expression of luciferase gene in lungs of naive nude mice directed by prostate-specific antigen promoter

    International Nuclear Information System (INIS)

    Li Hongwei; Li Jinzhong; Helm, Gregory A.; Pan Dongfeng

    2005-01-01

    PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10 9 PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of the luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases

  4. Construction and characterization of a recombinant yellow fever virus stably expressing Gaussia luciferase

    Directory of Open Access Journals (Sweden)

    TELISSA C. KASSAR

    Full Text Available ABSTRACT Yellow fever is an arthropod-borne viral disease that still poses high public health concerns, despite the availability of an effective vaccine. The development of recombinant viruses is of utmost importance for several types of studies, such as those aimed to dissect virus-host interactions and to search for novel antiviral strategies. Moreover, recombinant viruses expressing reporter genes may greatly facilitate these studies. Here, we report the construction of a recombinant yellow fever virus (YFV expressing Gaussia luciferase (GLuc (YFV-GLuc. We show, through RT-PCR, sequencing and measurement of GLuc activity, that stability of the heterologous gene was maintained after six passages. Furthermore, a direct association between GLuc expression and viral replication was observed (r2=0.9967, indicating that measurement of GLuc activity may be used to assess viral replication in different applications. In addition, we evaluated the use of the recombinant virus in an antiviral assay with recombinant human alfa-2b interferon. A 60% inhibition of GLuc expression was observed in cells infected with YFV-GLuc and incubated with IFN alfa-2b. Previously tested on YFV inhibition by plaque assays indicated a similar fold-decrease in viral replication. These results are valuable as they show the stability of YFV-GLuc and one of several possible applications of this construct.

  5. Autonomous bioluminescent expression of the bacterial luciferase gene cassette (lux in a mammalian cell line.

    Directory of Open Access Journals (Sweden)

    Dan M Close

    Full Text Available The bacterial luciferase (lux gene cassette consists of five genes (luxCDABE whose protein products synergistically generate bioluminescent light signals exclusive of supplementary substrate additions or exogenous manipulations. Historically expressible only in prokaryotes, the lux operon was re-synthesized through a process of multi-bicistronic, codon-optimization to demonstrate for the first time self-directed bioluminescence emission in a mammalian HEK293 cell line in vitro and in vivo.Autonomous in vitro light production was shown to be 12-fold greater than the observable background associated with untransfected control cells. The availability of reduced riboflavin phosphate (FMNH(2 was identified as the limiting bioluminescence substrate in the mammalian cell environment even after the addition of a constitutively expressed flavin reductase gene (frp from Vibrio harveyi. FMNH(2 supplementation led to a 151-fold increase in bioluminescence in cells expressing mammalian codon-optimized luxCDE and frp genes. When injected subcutaneously into nude mice, in vivo optical imaging permitted near instantaneous light detection that persisted independently for the 60 min length of the assay with negligible background.The speed, longevity, and self-sufficiency of lux expression in the mammalian cellular environment provides a viable and powerful alternative for real-time target visualization not currently offered by existing bioluminescent and fluorescent imaging technologies.

  6. Staff's reactions towards partnered sexual expressions involving people with dementia living in long-term care facilities.

    Science.gov (United States)

    Villar, Feliciano; Celdrán, Montserrat; Serrat, Rodrigo; Fabà, Josep; Martínez, Teresa

    2018-05-01

    To explore staff responses, in terms of common practices, towards partnered sexual relationships in long-term care facilities where one or both people involved have dementia. It also tries to determine personal and institutional factors influencing these responses. Although some studies, mostly qualitative, have focused on reactions to residents' sexual expressions so far the issue has not been assessed in a study using large and diverse samples. Cross-sectional quantitative study using vignette technique. Participants were 2,295 staff members at 152 Spanish long-term care facilities. Data were collected during 2016. A vignette describing sexual situations involving people with dementia was presented to participants. After the vignette, participants had to answer the question: "What do you think most of your colleagues would do in this situation?" with nine possible responses. Results showed that relationships involving persons with dementia were perceived as potentially problematic by staff. In both conditions, discussing the case with a colleague or supervisor was the most frequently chosen reaction. More restrictive reactions were mentioned when only one person with dementia was involved in the relationship. Factors such as participants" age and years of experience, professional post and commitment to person-centred care practices were related with the frequency of common restriction practices. Results highlight the importance of providing staff with clear guidelines regarding the management of specific sexual situations to avoid stereotyped restrictive reactions. © 2017 John Wiley & Sons Ltd.

  7. Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

    Science.gov (United States)

    McCoy, Portia; Norton, Thomas T; McMahon, Lori L

    2008-07-01

    Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

  8. NMDA receptor expression and C terminus structure in the rotifer Brachionus plicatilis and long-term potentiation across the Metazoa.

    Science.gov (United States)

    Kenny, Nathan J; Dearden, Peter K

    2013-12-01

    The C termini of N-methyl-D-aspartate (NMDA) receptor NR2 subunits are thought to play a major role in the molecular establishment of memory across the Bilateria, via the phenomenon known as long-term potentiation (LTP). Despite their long history of use as models in the study of memory, the expression and structure of the NR2 subunit in the Lophotrochozoa has remained uncategorized. Here, we report the phylogenic relationships of NR subunits across the Bilateria, and the cloning and in situ analysis of expression of NMDA NR1 and NR2 subunits in the monogont rotifer Brachionus plicatilis. RNA in situ hybridization suggests expression of NMDA receptor subunits in B. plicatilis is neural, consistent with expression observed in other species, and ours is the first report confirming NR2 expression in the lophotrochozoan clade. However, the single NR2 subunit identified in B. plicatilis was found to lack the long C terminal domain found in vertebrates, which is believed to modulate LTP. Further investigation revealed that mollusc and annelid NR2 subunits possess long intracellular C terminal domains. As data from molluscs (and particularly Aplysia californica) are the basis for much of our understanding of LTP, understanding how these diverse lophotrochozoan C termini function in vivo will have many implications for how we consider the evolution of the molecular control of learning and memory across the Metazoa as a whole and interpret the results of experiments into this vital component of cognition.

  9. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Geun Young Lee

    2017-09-01

    Full Text Available AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG. METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS: The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038. A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810. The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05. CONCLUSION: ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

  10. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma.

    Science.gov (United States)

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group ( P =0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups ( P =0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group ( P =0.05). ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

  11. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    Science.gov (United States)

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    AIM To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05). CONCLUSION ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density. PMID:28944196

  12. Short- and long-term changes in sugarbeet (Beta vulgaris L. gene expression due to postharvest jasmonic acid treatment - Data

    Directory of Open Access Journals (Sweden)

    Lucilene Silva de Oliveira

    2017-04-01

    Full Text Available Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L. root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr, Swiss-Prot, Clusters of Orthologous Groups (COG, and Kyoto Encyclopedia of Genes and Genomes (KEGG protein databases, and unigene annotations with Gene Ontology (GO terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, “Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots” (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017 [1]. Public dissemination of this dataset will allow further analyses of the data.

  13. Long-term effects of di-octyl phthalate on the expression of immune-related genes in Tegillarca granosa

    Science.gov (United States)

    Wang, Ji; Li, Ye; Dai, Juan; Su, Xiurong; Li, Chenghua; Shen, Lingling

    2016-05-01

    Di-octyl phthalate (DOP) is widely used as a plasticizer in the plastics industry. As a result, DOP is often found in marine water ecosystems where many species are exposed to it. Our objective was to evaluate the effect of long-term (14 d) DOP exposure (2.6, 7.8, or 31.2 mg/L) on the expression of immunerelated genes in Tegillarca granosa. The expression of small heat shock protein (sHSPs) and tissue inhibitor of metalloproteinase (TIMP) were highest in clams exposed to 31.2 mg/L DOP on days 7 and 14. The relative expression of Tg-ferritin, superoxide dismutase (SOD), and metallothionein (MT) increased initially then decreased as the concentration of DOP increased. The hemoglobin of T. granosa (Tg-HbI) exhibited two distinct expression patterns at two time points. Our results suggest that the immune response of T. granosa against DOP pollution varies depending on the dose. Additionally, we identified some immune-related genes that are promising candidates for biomarkers of DOP.

  14. Variations in gene and protein expression in canine chondrodystrophic nucleus pulposus cells following long-term three-dimensional culture.

    Directory of Open Access Journals (Sweden)

    Munetaka Iwata

    Full Text Available Intervertebral disc (IVD degeneration greatly affects quality of life. The nucleus pulposus (NP of chondrodystrophic dog breeds (CDBs is similar to the human NP, because the cells disappear with age and are replaced by fibrochondrocyte-like cells. However, because IVD develops as early as within the first year of life, we used canines as a model to investigate in vitro the mechanisms underlying IVD degeneration. Specifically, we evaluated the potential of a three-dimensional (3D culture of healthy NP as an in vitro model system to investigate the mechanisms of IVD degeneration. Agarose hydrogels were populated with healthy NP cells from beagles after performing magnetic resonance imaging, and mRNA expression profiles and pericellular extracellular matrix (ECM protein distribution were determined. After 25 days of 3D culture, there was a tendency for redifferentiation into the native NP phenotype, and mRNA levels of Col2A1, COMP, and CK18 were not significantly different from those of freshly isolated cells. Our findings suggest that long-term 3D culture promoted chondrodystrophic NP redifferentiation through reconstruction of the pericellular microenvironment. Further, lipopolysaccharide (LPS induced expression of TNF-α, MMP3, MMP13, VEGF, and PGES mRNA in the 3D cultures, creating a molecular milieu that mimics that of degenerated NP. These results suggest that this in vitro model represents a reliable and cost-effective tool for evaluating new therapies for disc degeneration.

  15. Long-term dietary restriction up-regulates activity and expression of renal arginase II in aging mice.

    Science.gov (United States)

    Majaw, T; Sharma, R

    2017-06-01

    Arginase II is a mitochondrial enzyme that catalyses the hydrolysis of L-arginine into urea and ornithine. It is present in other extra-hepatic tissues that lack urea cycle. Therefore, it is plausible that arginase II has a physiological role other than urea cycle which includes polyamine, proline, glutamate synthesis and regulation of nitric oxide production. The high expression of arginase II in kidney, among extrahepatic tissues, might have an important role associated with kidney functions. The present study is aimed to determine the age-associated alteration in the activity and expression of arginase II in the kidney of mice of different ages. The effect of dietary restriction to modulate the agedependent changes of arginase II was also studied. Results showed that renal arginase II activity declines significantly with the progression of age (p less than 0.01 and p less than 0.001 in 6- and 18-month-old mice, respectively as compared to 2-month old mice) and is due to the reduction in its protein as well as the mRNA level (p less than 0.001 in both 6- and 18-month-old mice as compared to 2-month-old mice). Long-term dietary restriction for three months has significantly up-regulated arginase II activity and expression level in both 2- and 18-month-old mice (p less than 0.01 and p less than 0.001, respectively as compared to AL group). These findings clearly indicate that the reducing level of arginase II during aging might have an impact on the declining renal functions. This age-dependent down-regulation of arginase II in the kidney can be attenuated by dietary restriction which may help in the maintenance of such functions.

  16. Microarray analysis of gene expression patterns of high lycopene tomato generated from seeds after long-term space flight

    Science.gov (United States)

    Lu, Jinying; Ren, Chunxiao; Pan, Yi; Nechitailo, Galina S.; Liu, Min

    Lycopene content is a most vital trait of tomatoes due to the role of lycopene in reducing the risk of some kinds of cancers. In this experiment, we gained a high lycopene (hl) tomato (named HY-2), after seven generations of self-cross selection, from seeds Russian MNP-1 carried in Russia MIR space station for six years. HPLC result showed that the lycopene content was 1.6 times more than that in Russian MNP-1 (the wild type). Microarray analysis presented the general profile of differential expressed genes at the tomato developmental stage of 7DPB (days post breaker). One hundred and forty three differential expression genes were identified according to the following criterion: the average changes were no less than 1.5 folds with q-value (similar to FDR) less than 0.05 or changes were no less than 1.5 folds in all three biological replications. Most of the differential expressed genes were mainly involved in metabolism, response to stimulus, biosynthesis, development and regulation. Particularly, we discussed the genes involved in protein metabolism, response to unfolded protein, carotenoid biosynthesis and photosynthesis that might be related to the fruit development and the accumulation of lycopene. What's more, we conducted QRT-PCR validation of five key genes (Fps, CrtL-b, CrtR-b, Zep and Nxs) in the lycopene biosynthesis pathway through time courses and that provided the direct molecular evidence for the hl phenotype. Our results demonstrate that long-term space flight, as a rarely used tool, can positively cause some beneficial mutations in the seeds and thus to help to generate a high quality variety, combined with ground selections.

  17. Guilt, shame and expressed emotion in carers of people with long-term mental health difficulties: A systematic review.

    Science.gov (United States)

    Cherry, Mary Gemma; Taylor, Peter James; Brown, Stephen Lloyd; Rigby, Jake Wilfred; Sellwood, William

    2017-03-01

    Expressed emotion (EE) is a global index of familial emotional climate, whose primary components are emotional over-involvement (EOI) and critical comments (CC)/hostility. There is a strong theoretical rationale for hypothesising that carers' guilt and shame may be differentially associated with their EOI and CC/hostility respectively. This systematic review investigates the magnitude of these theorised associations in carers of people with long-term mental health difficulties. Electronic searches (conducted in May 2016 across Medline, CINAHL, Embase, PsycINFO and ProQuest) were supplemented with iterative hand searches. Ten papers, reporting data from eight studies, were included. Risk of bias was assessed using a standardised checklist. Relevant data were extracted and synthesised narratively. EOI was positively associated with both guilt and shame, whereas CC/hostility was positively associated with shame. The strength of associations varied depending on whether or not guilt and shame were assessed within the context of the caring relationship. Based on these data, an argument can be made for the refinement, development and evaluation of systemic and individual interventions designed to target carers' guilt and shame. However, more research is needed to clarify the strength of these associations and their direction of effect before firm conclusions can be drawn. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Gene expression profile in long-term non progressor HIV infected patients: in search of potential resistance factors.

    Science.gov (United States)

    Luque, Maria Carolina; Santos, Camila C; Mairena, Eliane C; Wilkinson, Peter; Boucher, Genèvieve; Segurado, Aluisio C; Fonseca, Luiz A; Sabino, Ester; Kalil, Jorge E; Cunha-Neto, Edecio

    2014-11-01

    Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals. Genes that were up- or downregulated exclusively in LTNP, ST or in both groups in comparison to controls were identified and classified in functional categories using Ingenuity Pathway Analysis. ST and LTNP patient groups revealed distinct genetic profiles, regarding gene number in each category and up- or downregulation of specific genes, which could have a bearing on the outcome of each group. We selected some relevant genes to validate the differential expression using quantitative real-time qRT-PCR. Among others, we found several genes related to the canonical Wnt/beta-catenin signaling pathway. Our results identify new possible host genes and molecules that could be involved in the mechanisms leading to the slower progression to AIDS and sustained CD4+ T cell counts that is peculiar to LTNP patients. Copyright © 2014. Published by Elsevier Ltd.

  19. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    Directory of Open Access Journals (Sweden)

    Joke J. F. A. Van Vugt

    2015-09-01

    Full Text Available Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus in a classical conditioning paradigm, where plant odors become associated to the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM and one type of transcription-independent, anesthesia-resistant memory (ARM can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired-end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In

  20. Genome-Wide Expression Analysis of Reactive Oxygen Species Gene Network in Mizuna Plants Grown in Long-Term Spaceflight

    Science.gov (United States)

    Sugimoto, Manabu; Gusev, Oleg; Wheeler, Raymond; Levinskikh, Margarita; Sychev, Vladimir; Bingham, Gail; Hummerick, Mary; Oono, Youko; Matsumoto, Takashi; Yazawa, Takayuki

    We have developed a plant growth system, namely Lada, which was installed in ISS to study and grow plants, including vegetables in a spaceflight environment. We have succeeded in cultivating Mizuna, tomato, pea, radish, wheat, rice, and barley in long-term spaceflight. Transcription levels of superoxide dismutase, glutamyl transferase, catalase, and ascorbate peroxidase were increased in the barley germinated and grown for 26 days in Lada, though the whole-plant growth and development of the barley in spaceflight were the same as in the ground control barley. In this study, we investigated the response of the ROS gene network in Mizuna, Brassica rapa var. nipposinica, cultivated under spaceflight condition. Seeds of Mizuna were sown in the root module of LADA aboard the Zvezda module of ISS and the seedlings were grown under 24h lighting in the leaf chamber. After 27 days of cultivation, the plants were harvested and stored at -80(°) C in MELFI aboard the Destiny module, and were transported to the ground at < -20(°) C in GLACIER aboard Space Shuttle. Ground control cultivation was carried out under the same conditions in LADA. Total RNA isolated from leaves was subjected to mRNA-Seq using next generation sequencing (NGS) technology. A total of 20 in 32 ROS oxidative marker genes were up-regulated, including high expression of four hallmarks, and preferentially expressed genes associated with ROS-scavenging including thioredoxin, glutaredoxin, and alternative oxidase genes. In the transcription factors of the ROS gene network, MEKK1-MKK4-MPK3, OXI1-MKK4-MPK3, and OXI1-MPK3 of MAP cascades, induction of WRKY22 by MEKK1-MKK4-MPK3 cascade, induction of WRKY25 and repression of Zat7 by Zat12 were suggested. These results revealed that the spaceflight environment induced oxidative stress and the ROS gene network activation in the space-grown Mizuna.

  1. Evaluation of Gaussia luciferase and foot-and-mouth disease virus 2A translational interrupter chimeras as polycistronic reporters for transgene expression.

    Science.gov (United States)

    Puckette, Michael; Burrage, Thomas; Neilan, John G; Rasmussen, Max

    2017-06-12

    The Gaussia princeps luciferase is used as a stand-alone reporter of transgene expression for in vitro and in vivo expression systems due to the rapid and easy monitoring of luciferase activity. We sought to simultaneously quantitate production of other recombinant proteins by transcriptionally linking the Gaussia princeps luciferase gene to other genes of interest through the foot-and-mouth disease virus 2A translational interrupter sequence. We produced six plasmids, each encoding a single open reading frame, with the foot-and-mouth disease virus 2A sequence placed either N-terminal or C-terminal to the Gaussia princeps luciferase gene. Two plasmids included novel Gaussia princeps luciferase variants with the position 1 methionine deleted. Placing a foot-and-mouth disease virus 2A translational interrupter sequence on either the N- or C-terminus of the Gaussia princeps luciferase gene did not prevent the secretion or luminescence of resulting chimeric luciferase proteins. We also measured the ability of another polycistronic plasmid vector with a 2A-luciferase sequence placed downstream of the foot-and-mouth disease virus P1 and 3C protease genes to produce of foot-and-mouth disease virus-like particles and luciferase activity from transfected cells. Incorporation of the 2A-luciferase sequence into a transgene encoding foot-and-mouth disease virus structural proteins retained luciferase activity and the ability to form virus-like particles. We demonstrated a mechanism for the near real-time, sequential, non-destructive quantitative monitoring of transcriptionally-linked recombinant proteins and a valuable method for monitoring transgene expression in recombinant vaccine constructs.

  2. Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS.

    Science.gov (United States)

    Nichols, Nicole L; Satriotomo, Irawan; Harrigan, Daniel J; Mitchell, Gordon S

    2015-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600 μM; 12 μL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms

  3. Sex-Dependent and Independent Effects of Long-Term Voluntary Wheel Running on Bdnf mRNA and Protein Expression

    OpenAIRE

    Venezia, Andrew C.; Guth, Lisa M.; Sapp, Ryan M.; Spangenburg, Espen E.; Roth, Stephen M.

    2016-01-01

    The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited.

  4. High-level transfer and long-term expression of the human beta-globin gene in a mouse transplant model.

    Science.gov (United States)

    Raftopoulos, H; Ward, M; Bank, A

    1998-06-30

    Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.

  5. CREB expression in the brains of two closely related parasitic wasp species that differ in long-term memory formation

    NARCIS (Netherlands)

    Van den Berg, M.; Verbaarschot, P.; Hontelez, S.; Vet, L.E.M.; Dicke, M.; Smid, H.M.

    2010-01-01

    The cAMP/PKA signalling pathway and transcription factor cAMP response element-binding protein (CREB) play key roles in long-term memory (LTM) formation. We used two closely related parasitic wasp species, Cotesia glomerata and Cotesia rubecula, which were previously shown to be different in LTM

  6. Establishment of a luciferase assay-based screening system: Fumitremorgin C selectively inhibits cellular proliferation of immortalized astrocytes expressing an active form of AKT

    International Nuclear Information System (INIS)

    Wang Lei; Sasai, Ken; Akagi, Tsuyoshi; Tanaka, Shinya

    2008-01-01

    The AKT pathway is frequently activated in glioblastoma, and as such, inhibitors of this pathway could prove very useful as anti-glioblastoma therapies. Here we established immortalized astrocytes expressing Renilla luciferase as well as those expressing both an active form of AKT and firefly luciferase. Since both luciferase activities represent the numbers of corresponding cell lines, novel inhibitors of the AKT pathway can be identified by treating co-cultures containing the two types of luciferase-expressing cells with individual compounds. Indeed, such a screening system succeeded in identifying fumitremorgin C as an efficient inhibitor of the AKT pathway, which was further confirmed by the ability of fumitremorgin C to selectively inhibit the growth of immortalized astrocytes expressing an active form of AKT. The present study proposes a broadly applicable approach for identifying therapeutic agents that target the pathways and/or molecules responsible for cancer development

  7. R/L, a double reporter mouse line that expresses luciferase gene upon Cre-mediated excision, followed by inactivation of mRFP expression.

    Science.gov (United States)

    Jia, Junshuang; Lin, Xiaolin; Lin, Xia; Lin, Taoyan; Chen, Bangzhu; Hao, Weichao; Cheng, Yushuang; Liu, Yu; Dian, Meijuan; Yao, Kaitai; Xiao, Dong; Gu, Weiwang

    2016-10-01

    The Cre/loxP system has become an important tool for the conditional gene knockout and conditional gene expression in genetically engineered mice. The applications of this system depend on transgenic reporter mouse lines that provide Cre recombinase activity with a defined cell type-, tissue-, or developmental stage-specificity. To develop a sensitive assay for monitoring Cre-mediated DNA excisions in mice, we generated Cre-mediated excision reporter mice, designated R/L mice (R/L: mRFP(monomeric red fluorescent protein)/luciferase), express mRFP throughout embryonic development and adult stages, while Cre-mediated excision deletes a loxP-flanked mRFP reporter gene and STOP sequence, thereby activating the expression of the second reporter gene luciferase, as assayed by in vivo and ex vivo bioluminescence imaging. After germ line deletion of the floxed mRFP and STOP sequence in R/L mice by EIIa-Cre mice, the resulting luciferase transgenic mice in which the loxP-mRFP-STOP-loxP cassette is excised from all cells express luciferase in all tissues and organs examined. The expression of luciferase transgene was activated in liver of RL/Alb-Cre double transgenic mice and in brain of RL/Nestin-Cre double transgenic mice when R/L reporter mice were mated with Alb-Cre mice and Nestin-Cre mice, respectively. Our findings reveal that the double reporter R/L mouse line is able to indicate the occurrence of Cre-mediated excision from early embryonic to adult lineages. Taken together, these findings demonstrate that the R/L mice serve as a sensitive reporter for Cre-mediated DNA excision both in living animals and in organs, tissues, and cells following necropsy.

  8. Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

    Science.gov (United States)

    Rancillac, Armelle; Crépel, Francis

    2004-02-01

    Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy. In the present study, we show that long-term potentiation (LTP) and long-term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre- and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF-SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF-PC synapses for presynaptic LTP induced in the same conditions. Thus, long-term changes in synaptic efficacy can be accomplished by PF-SCs synapses as well as by PF-PC synapses, suggesting that both types of plasticity might co-operate during cerebellar motor learning.

  9. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-01-01

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca 2+ permeability, we investigated whether Ca 2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca 2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  10. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

    Science.gov (United States)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-10-15

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  11. Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

    Science.gov (United States)

    Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

    2015-12-01

    Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation

    OpenAIRE

    Dale, Erica A.; Fields, Daryl P.; Devinney, Michael J.; Mitchell, Gordon S.

    2016-01-01

    Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are n...

  13. Transplantation of mouse HSCs genetically modified to express a CD4-restricted TCR results in long-term immunity that destroys tumors and initiates spontaneous autoimmunity.

    Science.gov (United States)

    Ha, Sung P; Klemen, Nicholas D; Kinnebrew, Garrett H; Brandmaier, Andrew G; Marsh, Jon; Hangoc, Giao; Palmer, Douglas C; Restifo, Nicholas P; Cornetta, Kenneth; Broxmeyer, Hal E; Touloukian, Christopher E

    2010-12-01

    The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8+ T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4+ TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, high-efficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4+ T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.

  14. IFNy+ and IFNy- Treg subsets with stable and unstable Foxp3 expression in kidney transplant recipients with good long-term graft function.

    Science.gov (United States)

    Trojan, Karina; Unterrainer, Christian; Aly, Mostafa; Zhu, Li; Weimer, Rolf; Bulut, Nuray; Morath, Christian; Opelz, Gerhard; Daniel, Volker

    2016-10-29

    Treg are a heterogenous cell population. In the present study we attempted to identify Treg subsets that might contribute to stable and good long-term graft function. Lymphocyte and Treg subsets were studied in 136 kidney transplant recipients with good long-term graft function and in 52 healthy control individuals using eight-color-fluorescence flow cytometry. Foxp3 TSDR methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations using high resolution melt analysis. Compared with healthy controls, patients showed strong associations of IFNy secreting Helios+ and Helios- Treg with Treg that co-expressed perforin and/or CTLA4 (CD152; pterm graft function possess IFNy+ and IFNy- Treg with stable and unstable Foxp3 expression in the blood. They co-express CD28, HLADR, CTLA4, CXCR3, Lselectin, TGFβ, perforin and FasL and might contribute to the establishment and maintenance of good long-term graft function. Copyright © 2016. Published by Elsevier B.V.

  15. Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

    Science.gov (United States)

    Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A

    1993-03-01

    When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

  16. Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification.

    Science.gov (United States)

    Chan-On, Waraporn; Kuwahara, Kazuhiko; Kobayashi, Naoya; Ohta, Kazutaka; Shimasaki, Tatsuya; Sripa, Banchob; Leelayuwat, Chanvit; Sakaguchi, Nobuo

    2009-08-01

    Cholangiocarcinoma (CCA) represents a model of tumor development after long-term inflammation which causes DNA damage or impairs DNA repair mechanism. AID and GANP, both appearing in antigen-driven B cells, are involved in affinity maturation of the immunoglobulin V-region with increased somatic mutation. A normal cholangiocyte line showed the induction of AID transcripts after stimulation with TNF-alpha, whereas ganp transcripts appeared constitutively in this cell line. Next, we examined the expression of AID and GANP in clinical CCA specimens to obtain information whether their expression levels are associated with the malignant grade of CCA. AID expression was similarly detected in the clinical cases of both well-differentiated and poorly-differentiated CCAs. On the contrary, GANP expression was detected in CCA cells at a higher level in the nucleus of poorly-differentiated CCAs with shorter survivals than in that of well-differentiated CCAs. The high and low cases of nuclear GANP expression showed no change in the frequency of the TP53 mutations, however, further investigation by in vitro experiment demonstrated that the high GANP expression caused the increased number of gammaH2AX foci after DNA damage by ionizing-irradiation. These results suggest that GANP is involved in regulation of DNA repair mechanism and the abnormal over-expression of GANP together with AID might be associated with rigorous DNA damage, potentially causing the malignant development of CCAs during long-term inflammation.

  17. Heterogenic expression of stem cell markers in patient-derived glioblastoma spheroid cultures exposed to long-term hypoxia

    DEFF Research Database (Denmark)

    Rosenberg, Tine; Aaberg-Jessen, Charlotte; Petterson, Stine Asferg

    2018-01-01

    AIM: To investigate the time profile of hypoxia and stem cell markers in glioblastoma spheroids of known molecular subtype. MATERIALS & METHODS: Patient-derived glioblastoma spheroids were cultured up to 7 days in either 2% or 21% oxygen. Levels of proliferation (Ki-67), hypoxia (HIF-1α, CA9...... and VEGF) and stem cell markers (CD133, nestin and musashi-1) were investigated by immunohistochemistry. RESULTS: Hypoxia markers as well as CD133 and partially nestin increased in long-term hypoxia. The proliferation rate and spheroid size were highest in normoxia. CONCLUSION: We found differences...... in hypoxia and stem cell marker profiles between the patient-derived glioblastoma cultures. This heterogeneity should be taken into consideration in development of future therapeutic strategies....

  18. Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation.

    Science.gov (United States)

    Dale, Erica A; Fields, Daryl P; Devinney, Michael J; Mitchell, Gordon S

    2017-01-01

    Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are necessary for BDNF-dependent acute intermittent hypoxia-induced pLTF, demonstrating that phrenic motor neurons are a critical site of respiratory motor plasticity. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue.

    Science.gov (United States)

    Bozkaya, F; Atli, M O; Guzeloglu, A; Kayis, S A; Yildirim, M E; Kurar, E; Yilmaz, R; Aydilek, N

    2017-08-01

    The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22°C, while Groups III and IV were reared at 38°C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis. © 2016 Blackwell Verlag GmbH.

  20. Expression of Gast, Cckbr, Reg1α genes in rat duodenal epithelial cells upon long-term gastric hypoacidity and after a multiprobiotic administration

    Directory of Open Access Journals (Sweden)

    Dranitsina A. S.

    2014-11-01

    Full Text Available Aim. Determination of the Cckbr, Gast and Reg1α genes expression in rat duodenal epithelial cells upon long- term hypoacidity and with the administration of the multiprobiotic Symbiter. Methods. The experiments were carried out on white non-strain male rats. The hypoacidic state was induced through intraperitoneal injection of omeprazole for 28 days. The level of genes expression was determined by semi-quantitative analysis with RT-PCR Results. The elevation of mRNA levels of the Cckbr and Gast genes in rat duodenal villus and crypt epitheliocytes, the increased expression of the Reg1A gene in crypt epithelial cells were shown as well as the appearance of the Reg1a gene expression in villus epitheliocytes upon hypoacidic conditions were shown. The content of mRNAs of the above mentioned genes decreased or remained at the control level upon the treatment of hypoacidic rats with the multiprobiotic Symbiter. Conclusions. Long-term gastric hypoacidity is accompanied by the changes in expression of the Cckbr, Gast and Reg1a genes in rat duodenum, whereas upon administration of the multiprobiotic Symbiter the pattern of studied gene expression did not changed in the most cases.

  1. Human CRF2 α and β splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

    International Nuclear Information System (INIS)

    Ardati, A.; Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J.; Valdenaire, O.

    1999-01-01

    Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF 1 and CRF 2 ). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF 2 subtype receptors, CRF 2α and CRF 2β , have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF 2β receptor. We have used radioligand binding with [ 125 I]-tyr 0 -sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [ 125 I]-tyr 0 -sauvagine binding to the hCRF 2β receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF 2α receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF 2α receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [ 125 I]-tyr 0 -sauvagine to both hCRF 2 receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF 2 α-helical CRF (9-41) oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist α-helical CRF (9-41) exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF 2 receptor isoforms. Taken together, these results indicate that the pharmacological profiles of the CRF 2 splice variants are identical. This indicates that the region of the N-terminus that varies

  2. Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

    Science.gov (United States)

    Maggio, Nicola; Segal, Menahem

    2011-04-15

    The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.

    Science.gov (United States)

    Wang, Yiping; Wong, Matthew Man-Kin; Zhang, Xiaojian; Chiu, Sung-Kay

    2015-11-15

    When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

    Science.gov (United States)

    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  5. Antenatal maternal long-term hypoxia: acclimatization responses with altered gene expression in ovine fetal carotid arteries.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In humans and other species, long-term hypoxia (LTH during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF, and other problems. To identify the signal transduction pathways and critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified mRNA from 38 genes upregulated >2 fold (P2-fold (P<0.05. The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF binding protein 3, IGF type 2 receptor, transforming growth factor (TGF Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. Most genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3' un translated region (UTR. Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L. We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may play a role in the acclimatization response to high-altitude associated LTH.

  6. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  7. Reduced volume and increased training intensity elevate muscle Na+/K+ pump {alpha}2-subunit expression as well as short- and long-term work capacity in humans

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Gunnarsson, Thomas Petursson; Wendell, Jesper

    2009-01-01

    was unaltered, but the 3-K (3,000 m) time was reduced (Pexpression and performance remained unaltered in CON. The present data suggest that both short- and long-term......% reduction in the amount of training but including speed endurance training consisting of 6-12 30-s sprint runs 3-4 times a week (SET, n=12) or a control group (CON, n=5), which continued the endurance training (about 55 km(.)wk(-1)). For SET the expression of the muscle Na(+)/K(+) pump alpha2-subunit was 68...

  8. Emiliania huxleyi increases calcification but not expression of calcification-related genes in long-term exposure to elevated temperature and pCO2.

    Science.gov (United States)

    Benner, Ina; Diner, Rachel E; Lefebvre, Stephane C; Li, Dian; Komada, Tomoko; Carpenter, Edward J; Stillman, Jonathon H

    2013-01-01

    Increased atmospheric pCO2 is expected to render future oceans warmer and more acidic than they are at present. Calcifying organisms such as coccolithophores that fix and export carbon into the deep sea provide feedbacks to increasing atmospheric pCO2. Acclimation experiments suggest negative effects of warming and acidification on coccolithophore calcification, but the ability of these organisms to adapt to future environmental conditions is not well understood. Here, we tested the combined effect of pCO2 and temperature on the coccolithophore Emiliania huxleyi over more than 700 generations. Cells increased inorganic carbon content and calcification rate under warm and acidified conditions compared with ambient conditions, whereas organic carbon content and primary production did not show any change. In contrast to findings from short-term experiments, our results suggest that long-term acclimation or adaptation could change, or even reverse, negative calcification responses in E. huxleyi and its feedback to the global carbon cycle. Genome-wide profiles of gene expression using RNA-seq revealed that genes thought to be essential for calcification are not those that are most strongly differentially expressed under long-term exposure to future ocean conditions. Rather, differentially expressed genes observed here represent new targets to study responses to ocean acidification and warming.

  9. Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients.

    Science.gov (United States)

    Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K; Wijmenga, Cisca; Jassem, Ewa; Elberink, Joanne N G Oude

    2011-06-01

    Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of anaphylaxis, and monitoring and simplifying treatment of IVA. To find genes that are differentially expressed during the maintenance phase of VIT and after stopping, to get clues about the pathways involved in the long-term protective effect of immunotherapy. Whole genome gene expression analysis was performed on RNA samples from 50 patients treated with VIT and 43 healthy controls. Patients were divided into three groups: (1) before the start of VIT; (2) on maintenance phase of VIT for at least 3 years still receiving injections; and (3) after VIT. Of all 48,804 probes present in the array, 48,773 transcripts had sufficient data for further analysis. The list of genes that were differentially expressed (at least log2 FC > 2; P Immunology. Published by Elsevier Inc. All rights reserved.

  10. Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

    Directory of Open Access Journals (Sweden)

    Hui eHan

    2013-10-01

    Full Text Available Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD feeding resulted in higher levels of serum alanine aminotransferase (ALT, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months knockout females than in either middle-aged (6 months knockouts or older (aged 16 months wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2, Herpud1 (ubiquitin-like domain member, Wfs1 (wolfram syndrome gene, and Yod1 (deubiquinating enzyme 1 was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36, and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2 and STAT3 (the signal transducers and activators of transcription in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation.

  11. Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Takayoshi eMasuoka

    2016-03-01

    Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

  12. Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

    Directory of Open Access Journals (Sweden)

    Karina Trojan

    Full Text Available There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient.Helios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR served as indicators for stability of Foxp3 expression. Methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations originating from peripheral blood using high resolution melt analysis. A total of 136 transplant recipients and 52 healthy controls were studied.Proportions of IFNy+ Treg were similar in patients and healthy controls (0.05% and 0.04% of all CD4+ lymphocytes; p = n.s.. Patients also had similar absolute counts of IFNy producing Helios+ and Helios- Treg (p = n.s.. Most of the IFNy+ and IFNy- Treg in transplant recipients had a methylated Foxp3 TSDR, however, there was a sizeable proportion of IFNy+ and IFNy- Treg with demethylated Foxp3 TSDR. Male and female patients showed more frequently methylated IFNy+ and IFNy- Treg than male and female controls (all p<0.05.Kidney transplant recipients with good long-term stable graft function have similar levels of IFNy+ Treg as healthy controls. IFNy+ and IFNy- Treg subsets in patients consist of cells with stable and cells with transient Foxp3 expression; however, patients showed more frequently methylated IFNy+ and IFNy- Treg than controls. The data show increased levels of Treg subsets with stable as well as transient Foxp3 expression in patients with stable allograft acceptance compared to healthy controls.

  13. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

    KAUST Repository

    Tadi, Monika; Allaman, Igor; Lengacher, Sylvain; Grenningloh, Gabriele; Magistretti, Pierre J.

    2015-01-01

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  14. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

    Directory of Open Access Journals (Sweden)

    Monika Tadi

    Full Text Available We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4, alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  15. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

    KAUST Repository

    Tadi, Monika

    2015-10-29

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  16. Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

    Directory of Open Access Journals (Sweden)

    Guiqin He

    2017-11-01

    Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.

  17. Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.

    Science.gov (United States)

    Wang, Yiping; Cheng, Xiangdong; Samma, Muhammad Kaleem; Kung, Sam K P; Lee, Clement M; Chiu, Sung Kay

    2018-06-01

    c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses. Here, we generated a series of stable RPE cell clones expressing c-Myc at different levels, and found that consistent low level of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE cells, while the cells underwent cell death at high level of c-Myc. In addition, high level of c-Myc could override the effect of AP4 on cellular senescence. Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing low level of c-Myc, and accelerated cell death in cells with medium level of c-Myc, indicating that AP4 was required for cellular senescence induced by low level of c-Myc.

  18. Changes in mu-opioid receptor expression and function in the mesolimbic system after long-term access to a palatable diet.

    Science.gov (United States)

    Pitman, Kimberley A; Borgland, Stephanie L

    2015-10-01

    The incidence of obesity in both adults and children is rising. In order to develop effective treatments for obesity, it is important to understand how diet can induce changes in the brain that could promote excessive intake of high-calorie foods and alter the efficacy of therapeutic targets. The mu-opioid receptor is involved in regulating the motivation for and hedonic reaction to food. Here, we review the literature examining changes in the expression and function of mu-opioid receptors in the mesolimbic system of rodents after extended access to a high-fat diet. We also review how maternal diet can induce long-term changes in the expression or function of mu-opioid receptors in the mesolimbic system of offspring. Understanding the behavioural and therapeutic implications of these changes requires further study. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.

    Science.gov (United States)

    Fic, A; Mlakar, S Jurković; Juvan, P; Mlakar, V; Marc, J; Dolenc, M Sollner; Broberg, K; Mašič, L Peterlin

    2015-08-01

    The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10 nM BPA, BPAF, or BPS, for 8 h and 3 months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I and a more variable phase (stage-II. We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

  2. Digital gene expression analysis in the gills of Ruditapes philippinarum exposed to short- and long-term exposures of ammonia nitrogen.

    Science.gov (United States)

    Cong, Ming; Wu, Huifeng; Cao, Tengfei; Lv, Jiasen; Wang, Qing; Ji, Chenglong; Li, Chenghua; Zhao, Jianmin

    2018-01-01

    Previous study revealed severe toxic effects of ammonia nitrogen on Ruditapes philippinarum including lysosomal instability, disturbed metabolic profiles, gill tissues with damaged structure, and variation of neurotransmitter concentrations. However, the underlying molecular mechanism was not fully understood yet. In the present study, digital gene expression technology (DGE) was applied to globally screen the key genes and pathways involved in the responses to short- and long-term exposures of ammonia nitrogen. Results of DGE analysis indicated that short-term duration of ammonia exposure affected pathways in Dorso-ventral axis formation, Notch signaling, thyroid hormone signaling and protein processing in endoplasmic reticulum. The long-term exposure led to DEGs significantly enriched in gap junction, immunity, signal and hormone transduction, as well as key substance metabolism pathways. Functional research of significantly changed DEGs suggested that the immunity of R. philippinarum was weakened heavily by toxic effects of ammonia nitrogen, as well as neuro-transduction and metabolism of important substances. Taken together, the present study provides a molecular support for the previous results of the detrimental toxicity of ammonia exposure in R. philippinarum, further work will be performed to investigate the specific genes and their certain functions involved in ammonia toxicity to molluscs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  4. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

    Directory of Open Access Journals (Sweden)

    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  5. Acute suppression, but not chronic genetic deficiency, of c-fos gene expression impairs long-term memory in aversive taste learning.

    Science.gov (United States)

    Yasoshima, Yasunobu; Sako, Noritaka; Senba, Emiko; Yamamoto, Takashi

    2006-05-02

    Several lines of evidence have indicated that the establishment of long-term memory requires protein synthesis, including the synthesis of immediate-early gene products. Although the anatomical expression patterns of the c-fos gene, a transcription factor-encoding immediate-early gene, in conditioned taste aversion (CTA) are well documented, the functional roles of c-fos gene expression and Fos-mediated transcription remain to be clarified. Using the antisense oligodeoxynucleotide (AS-ODN) method in rats and gene-targeting knockout techniques in mice (c-fos(-/-) mice), we examined the roles of c-fos gene expression in the acquisition, retrieval, and retention of CTA. Preconditioning microinfusion of AS-ODN directed against c-fos mRNA (c-fos AS-ODN) into the parabrachial nucleus (PBN) impaired the acquisition, whereas infusion of control ODNs consisting of a randomized or inverted base order had no effect. Microinfusion of c-fos AS-ODN into either the amygdala or insular cortex did not impair the acquisition, whereas it attenuated the retention. Retrieval and subsequent retention of an acquired CTA were not disrupted by c-fos AS-ODN infusion into the PBN or amygdala. Microinfusion of another AS-ODN directed against zif268 (egr-1, krox-24, NGFI-A) mRNA into the PBN or amygdala did not affect the acquisition and retention. The genetic deficiency in c-fos(-/-) mice caused normal acquisition and retention. The present results suggest that the Fos-mediated gene transcription in the PBN, amygdala, or insular cortex plays critical roles in the acquisition and/or consolidation, but not the retrieval, of long-term taste memory; nevertheless, some other factors could compensate CTA mechanism when Fos-mediated transcription is not available.

  6. Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

    Science.gov (United States)

    Kuang, Qi; Zhang, Sheng; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2017-01-01

    Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

  7. Long-term recognition memory of individual conspecifics is associated with telencephalic expression of Egr-1 in the electric fish Apteronotus leptorhynchus.

    Science.gov (United States)

    Harvey-Girard, Erik; Tweedle, Jessica; Ironstone, Joel; Cuddy, Martin; Ellis, William; Maler, Leonard

    2010-07-15

    Primates and songbirds can learn to recognize individual conspecifics based on complex sensory cues; this requires a large, highly differentiated dorsal telencephalon. Here we show that the electric fish Apteronotus leptorhynchus can learn to recognize individual conspecifics based on a simple cue, the beat frequency of their summed sinusoidal electric organ discharges (EOD). Male fish produce transient communication signals (chirps) in response to mimic EODs. The chirp response habituates over repeated stimulus presentations within one experimental session, continues to habituate over successive daily sessions and is nearly extinguished after 5-7 days. Habituation of the chirp response was specific to the presented beat frequency. The conversion of short- to long-term habituation could be disrupted by cooling the head 30 minutes after the daily habituation trials. Consolidation of long-term memory in mammals is thought to involve induced expression of an immediate early gene, Egr-1. We cloned the Apteronotid homolog of the Egr-1 gene and found that chirp-evoking stimuli induced strong expression of its mRNA within the dorsal (Dd), central (DC), and lateral (DL) subdivisions of the dorsal telencephalon. Interestingly, the dorsolateral region is hypothesized to be homologous to the amniote hippocampal formation. We conclude that A. leptorhynchus can learn to identify individual conspecifics based on their EOD frequency and can remember these frequencies for several days. We hypothesize that this form of learning, as in primates and songbirds, requires a subset of dorsal telencephalic areas and involves a consolidation-like process that includes the expression of the transcription factor AptEgr-1.

  8. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    Directory of Open Access Journals (Sweden)

    Vladimir O. Pustylnyak

    2015-01-01

    Full Text Available Gene expression plays an important role in the mechanisms of long-term potentiation (LTP, which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity.

  9. Flt3 ligand-eGFP-reporter expression characterizes functionally distinct subpopulations of CD150+ long-term repopulating murine hematopoietic stem cells.

    Science.gov (United States)

    Tornack, Julia; Kawano, Yohei; Garbi, Natalio; Hämmerling, Günter J; Melchers, Fritz; Tsuneto, Motokazu

    2017-09-01

    The pool of hematopoietic stem cells (HSCs) in the bone marrow is a mixture of resting, proliferating, and differentiating cells. Long-term repopulating HSCs (LT-HSC) are routinely enriched as Lin - Sca1 + c-Kit + CD34 - Flt3 - CD150 + CD48 - cells. The Flt3 ligand (Flt3L) and its receptor Flt3 are important regulators of HSC maintenance, expansion and differentiation. Using Flt3L-eGFP reporter mice, we show that endogenous Flt3L-eGFP-reporter RNA expression correlates with eGFP-protein expression. This Flt3L-eGFP-reporter expression distinguishes two LT-HSC populations with differences in gene expressions and reconstituting potential. Thus, Flt3L-eGFP-reporter low cells are identified as predominantly resting HSCs with long-term repopulating capacities. In contrast, Flt3L-eGFP-reporter high cells are in majority proliferating HSCs with only short-term repopulating capacities. Flt3L-eGFP-reporter low cells express hypoxia, autophagy-inducing, and the LT-HSC-associated genes HoxB5 and Fgd5, while Flt3L-eGFP-reporter high HSCs upregulate genes involved in HSC differentiation. Flt3L-eGFP-reporter low cells develop to Flt3L-eGFP-reporter high cells in vitro, although Flt3L-eGFP-reporter high cells remain Flt3L-eGFP-reporter high . CD150 + Flt3L-eGFP-reporter low cells express either endothelial protein C receptor (EPCR) or CD41, while Flt3L-eGFP-reporter high cells do express EPCR but not CD41. Thus, FACS-enrichment of Flt3/ Flt3L-eGFP-reporter negative, Lin - CD150 + CD48 - EPCR + CD41 + HSCs allows a further 5-fold enrichment of functional LT-HSCs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure

    DEFF Research Database (Denmark)

    Olsen, A. K.; Salomonsson, M.; Sørensen, C. M.

    + channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone. Only scarce information is available on the role of K+ transporters in pathophysiological mechanisms induced by long-term feeding of laboratory rats with either high-fat, high-fructose or high-fat/high-fructose...... diet. HYPOTHESIS: A 28-week diet consisting of high-fat or high-fructose, or both, will lead to changes in K+ transporter expression and function, which will be linked with changes in blood pressure, arterial smooth muscle function, endothelial function and passive structural/mechanical properties....... METHODS: Male Sprague Dawley rats (4 weeks) were randomized into 4 diet groups receiving a diet with normal chow (CTR, N=19), high-fat chow (60% saturated fat, FAT, N=18), high-fructose (10% in drinking water; FRUC, N=15), or a combination of fat/fructose (FAT/FRUC, N=15) for 28 weeks. Systolic blood...

  11. Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice

    Science.gov (United States)

    Grundy, Trent; Toben, Catherine; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

    2014-01-01

    Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α. PMID:25484856

  12. Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels

    DEFF Research Database (Denmark)

    Gradel, Anna Katrina Jógvansdóttir; Salomonsson, Max; Sørensen, Charlotte Mehlin

    2018-01-01

    in long-term diet-induced hypertension in rats. Hypothesis: A 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Methods and Results: Male Sprague Dawley rats......RNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries. BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of SKCa, IKCa, and Kir2.1 K+ channels were reduced in the High Fat/Fruc group. Reduced EDH......-type relaxation to acetylcholine was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all experimental diet groups. Conclusions: Reduced expression and function of SKCa, IKCa and Kir2.1 channels is associated with elevated blood pressure in rats fed...

  13. Minimal doses of a sequence-optimized transgene mediate high-level and long-term EPO expression in vivo: challenging CpG-free gene design.

    Science.gov (United States)

    Kosovac, D; Wild, J; Ludwig, C; Meissner, S; Bauer, A P; Wagner, R

    2011-02-01

    Advanced gene delivery techniques can be combined with rational gene design to further improve the efficiency of plasmid DNA (pDNA)-mediated transgene expression in vivo. Herein, we analyzed the influence of intragenic sequence modifications on transgene expression in vitro and in vivo using murine erythropoietin (mEPO) as a transgene model. A single electro-gene transfer of an RNA- and codon-optimized mEPOopt gene into skeletal muscle resulted in a 3- to 4-fold increase of mEPO production sustained for >1 year and triggered a significant increase in hematocrit and hemoglobin without causing adverse effects. mEPO expression and hematologic levels were significantly lower when using comparable amounts of the wild type (mEPOwt) gene and only marginal effects were induced by mEPOΔCpG lacking intragenic CpG dinucleotides, even at high pDNA amounts. Corresponding with these observations, in vitro analysis of transfected cells revealed a 2- to 3-fold increased (mEPOopt) and 50% decreased (mEPOΔCpG) erythropoietin expression compared with mEPOwt, respectively. RNA analyses demonstrated that the specific design of the transgene sequence influenced expression levels by modulating transcriptional activity and nuclear plus cytoplasmic RNA amounts rather than translation. In sum, whereas CpG depletion negatively interferes with efficient expression in postmitotic tissues, mEPOopt doses <0.5 μg were sufficient to trigger optimal long-term hematologic effects encouraging the use of sequence-optimized transgenes to further reduce effective pDNA amounts.

  14. Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA rats.

    Directory of Open Access Journals (Sweden)

    Karen Schellong

    Full Text Available BACKGROUND: Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. METHODS AND FINDINGS: By rearing in normal (NL vs. small litters (SL, small-for-gestational-age (SGA rats were neonatally exposed to either normal (SGA-in-NL or over-feeding (SGA-in-SL, and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL. SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60, as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05, and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern 'westernized' lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05. Lasercapture microdissection (LMD-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc in SGA-in-SL rats (p<0.05. Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy, agouti-related-peptide (Agrp and galanin (Gal was not significantly altered. In essence, the 'orexigenic index', proposed here as a neuroendocrine 'net-indicator', was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01, correlated to food intake (p<0.05. CONCLUSION: Adult SGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding

  15. Tibetan Firefly Luciferase with Low Temperature Adaptation.

    Science.gov (United States)

    Mitani, Yasuo; Futahashi, Ryo; Liu, Zichao; Liang, Xingcai; Ohmiya, Yoshihiro

    2017-03-01

    Fireflies are widespread all over the world and a numerous numbers of luciferases have been isolated and characterized. In this study, we identified and characterized the luciferase and luciferase-like genes from a Tibetan firefly collected in Shangri-La, China. The altitude of this area is more than 3300 m. We saw this Tibetan firefly flying with strong luminescence after sunset at ~10°C. We analyzed the transcriptome of Tibetan firefly using head, thorax, abdomen (without light organ), and light organ tissue by RNA sequencing. We identified one luciferase gene, which was almost identical to luciferase from fireflies Pyrocoelia species, and expressed specifically in the light organ. Interestingly, the optimal temperature of the Tibetan firefly recombinant luciferase was 10°C. The K m for D-luciferin and ATP of the recombinant luciferase was 23 and 154 μm, respectively. The optimal pH was around 7.0-7.5. The emission peak was 556 nm at pH 8.0, while it shifted to 606 nm at pH 6.0. We also found a luciferase-like gene with 43% identical amino acids to the Tibetan firefly luciferase, which was scarcely expressed in any portion of the adult body. No luciferase activity was detected for this luciferase-like protein. © 2016 The American Society of Photobiology.

  16. Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication.

    Science.gov (United States)

    Arteche-López, A; Kreutzman, A; Alegre, A; Sanz Martín, P; Aguado, B; González-Pardo, M; Espiño, M; Villar, L M; García Belmonte, D; de la Cámara, R; Muñoz-Calleja, C

    2017-06-01

    The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4 + T-cells was lower in patients, whereas an increment in the percentage of CD4 + and CD8 + effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

  17. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  18. Long-Term Collection

    CERN Multimedia

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  19. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  20. Characterization of an acute molecular marker of nongenotoxic rodent hepatocarcinogenesis by gene expression profiling in a long term clofibric acid study.

    Science.gov (United States)

    Michel, Cécile; Roberts, Ruth A; Desdouets, Chantal; Isaacs, Kevin R; Boitier, Eric

    2005-04-01

    Evaluation of the nongenotoxic potential early during the development of a drug presents a major challenge. Recently, two genes were identified as potential molecular markers of rodent hepatic carcinogenesis: transforming growth factor-beta stimulated clone 22 (TSC-22) and NAD(P)H cytochrome P450 oxidoreductase (CYP-R) (1). They were identified after comparing the gene expression profiles obtained from the livers of Sprague-Dawley rats treated with different genotoxic and nongenotoxic compounds in a 5 day repeat dose in vivo study. To assess the potential of these two genes as acute markers of carcinogenesis, we investigated their modulation during a long-term nongenotoxic study in the rat using a classic initiation-promotion regime. Clofibric acid (CLO), which belongs to the broad class of chemicals known as peroxisome proliferators, was used as a nongenotoxic hepatocarcinogen. Male F344 rats were given a single nonnecrogenic injection of diethylnitrosamine (0 or 30 mg/kg) and fed a diet containing none or 5000 ppm CLO for up to 20 months. Necropsies of five rats per groups were performed at 18, 46, 102, 264, 377, 447 (control, DEN, and DEN + CLO rats), 524, and 608 days (for the CLO and control rats). Gross macroscopic and microscopic evaluation and gene expression profiling (on Affymetrix microarrays) were performed in peritumoral and tumoral liver tissues. Bioanalysis of the liver gene expression data revealed that TSC-22 was strongly down-regulated early in the study. Its underexpression was maintained throughout the study but disappeared upon CLO withdrawal. These modulations were confirmed by real-time polymerase chain reaction. However, CYP-R gene expression was not significantly altered in our study. Taken together, our results showed that TSC-22, but not CYP-R, has the potential to be an acute early molecular marker for nongenotoxic hepatocarcinogenesis in rodents.

  1. Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

    Science.gov (United States)

    Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

    2015-07-01

    Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

  2. Long term storage in liquid nitrogen leads to only minor phenotypic and gene expression changes in the mammary carcinoma model cell line BT474.

    Science.gov (United States)

    Fazekas, Judit; Grunt, Thomas W; Jensen-Jarolim, Erika; Singer, Josef

    2017-05-23

    Cancer cell lines are indispensible surrogate models in cancer research, as they can be used off-the-shelf, expanded to the desired extent, easily modified and exchanged between research groups for affirmation, reproduction or follow-up experiments.As malignant cells are prone to genomic instability, phenotypical changes may occur after certain passages in culture. Thus, cell lines have to be regularly authenticated to ensure data quality. In between experiments these cell lines are often stored in liquid nitrogen for extended time periods.Although freezing of cells is a necessary evil, little research is performed on how long-term storage affects cancer cell lines. Therefore, this study investigated the effects of a 28-year long liquid nitrogen storage period on BT474 cells with regard to phenotypical changes, differences in cell-surface receptor expression as well as cytokine and gene expressional variations. Two batches of BT474 cells, one frozen in 1986, the other directly purchased from ATCC were investigated by light microscopy, cell growth analysis, flow cytometry and cytokine as well as whole-transcriptome expression profiling. The cell lines were morphologically indifferent and showed similar growth rates and similar cell-surface receptor expression. Transcriptome analysis revealed significant differences in only 26 of 40,716 investigated RefSeq transcripts with 4 of them being up-regulated and 22 down-regulated. This study demonstrates that even after very long periods of storage in liquid nitrogen, cancer cell lines display only minimal changes in their gene expression profiles. However, also such minor changes should be carefully assessed before continuation of experiments, especially if phenotypic alterations can be additionally observed.

  3. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

    International Nuclear Information System (INIS)

    Kramer, M. Gabriela; Masner, Martín; Casales, Erkuden; Moreno, María; Smerdou, Cristian; Chabalgoity, José A.

    2015-01-01

    Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. 2×10 8 particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10 7 units of an aroC − Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90 % of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor

  4. A Luciferase-Expressing Leishmania braziliensis Line That Leads to Sustained Skin Lesions in BALB/c Mice and Allows Monitoring of Miltefosine Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Adriano C Coelho

    2016-05-01

    Full Text Available Leishmania braziliensis is the most prevalent species isolated from patients displaying cutaneous and muco-cutaneous leishmaniasis in South America. However, there are difficulties for studying L. braziliensis pathogenesis or response to chemotherapy in vivo due to the natural resistance of most mouse strains to infection with these parasites. The aim of this work was to develop an experimental set up that could be used to assess drug efficacy against L. braziliensis. The model was tested using miltefosine.A L. braziliensis line, originally isolated from a cutaneous leishmaniasis patient, was passaged repeatedly in laboratory rodents and further genetically manipulated to express luciferase. Once collected from a culture of parasites freshly transformed from amastigotes, 106 wild type or luciferase-expressing stationary phase promastigotes were inoculated subcutaneously in young BALB/c mice or golden hamsters. In both groups, sustained cutaneous lesions developed at the site of inoculation, no spontaneous self- healing being observed 4 months post-inoculation, if left untreated. Compared to the wild type line features, no difference was noted for the luciferase-transgenic line. Infected animals were treated with 5 or 15 mg/kg/day miltefosine orally for 15 days. At the end of treatment, lesions had regressed and parasites were not detected. However, relapses were observed in animals treated with both doses of miltefosine.Here we described experimental settings for a late-healing model of cutaneous leishmaniasis upon inoculation of a luciferase-expressing L. braziliensis line that can be applied to drug development projects. These settings allowed the monitoring of the transient efficacy of a short-term miltefosine administration.

  5. Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Scartabelli, Tania; Dolara, Piero; Casamenti, Fiorella; Pellegrini-Giampietro, Domenico E; Giovannelli, Lisa

    2016-01-01

    Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement.

    Science.gov (United States)

    Naugle, Michelle M; Gore, Andrea C

    2014-01-01

    Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responds to the primary regulatory sex steroid hormone, estradiol (E2), are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons and whether this changes with aging and/or E2 treatment. We used immunofluorescence double-labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2-year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double-labeled. Additionally, many GPER-labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust co-localization of GPER in GnRH in a clinically relevant model, and they support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates.

  7. Long-term effect of early nutrition on endocrine parameters and liver and endometrial gene expression of the members of the somatotrophic axis in Hereford heifers.

    Science.gov (United States)

    Guggeri, D; Meikle, A; Carriquiry, M; De Barbieri, I; Montossi, F; Viñoles, C

    2018-04-23

    This study compared the effect of different management systems on endocrine parameters, and gene expression of members of the somatotrophic axis in the liver and endometrium of beef heifers. Twenty-two 709-days-old heifers submitted to Early Weaning (EW, n = 8), Traditional Weaning (TW, n = 7) and TW plus creep feeding (TW+CF, n = 7) were used. Animals were synchronized with two prostaglandin (PG) injections at 11-day interval (Oestrus = Day 0). Blood samples were collected daily for progesterone (P4) determination, and endometrial and liver biopsies on Days 7 and 16 for transcript determination of members of the somatotrophic axis. Progesterone concentrations were greater on Days 15 and 16 (p < .02) of the cycle in TW+CF than TW and EW heifers. On Day 7, TW+CF heifers expressed greater liver total growth hormone receptor transcripts than TW heifers (p = .05) and greater insulin-like growth factor (IGF)-binding protein 3 mRNA than both EW and TW groups (p < .05). On Days 7 and 16, TW+CF expressed more endometrial IGF1 mRNA than the other groups (p < .01). We conclude that increasing the plane of nutrition of nursing calves may have a long-term effect on the functioning of the somatotrophic axis both in the liver and in the endometrium. © 2018 Blackwell Verlag GmbH.

  8. Expression of StAR and Key Genes Regulating Cortisol Biosynthesis in Near Term Ovine Fetal Adrenocortical Cells: Effects of Long-Term Hypoxia.

    Science.gov (United States)

    Vargas, Vladimir E; Myers, Dean A; Kaushal, Kanchan M; Ducsay, Charles A

    2018-02-01

    We previously demonstrated decreased expression of key genes regulating cortisol biosynthesis in long-term hypoxic (LTH) sheep fetal adrenals compared to controls. We also showed that inhibition of the extracellular signal-regulated kinases (ERKs) with the mitogen-activated protein kinase (MEK)/ERK inhibitor UO126 limited adrenocorticotropic (ACTH)-induced cortisol production in ovine fetal adrenocortical cells (FACs), suggesting a role for ERKs in cortisol synthesis. This study was designed to determine whether the previously observed decrease in LTH cytochrome P45011A1/cytochrome P450c17 (CYP11A1/CYP17) in adrenal glands was maintained in vitro, and whether ACTH alone with or without UO126 treatment had altered the expression of CYP11A1, CYP17, and steroidogenic acute regulatory protein (StAR) in control versus LTH FACs. Ewes were maintained at high altitude (3820 m) from ∼40 days of gestation (dG). At 138 to 141 dG, fetal adrenal glands were collected from LTH (n = 5) and age-matched normoxic controls (n = 6). Fetal adrenocortical cells were challenged with ACTH (10 -8 M) with or without UO126 (10 µM) for 18 hours. Media samples were collected for cortisol analysis and messenger RNA (mRNA) for CYP11A1, CYP17, and StAR was quantified by quantitative real-time polymerase chain reaction. Cortisol was higher in the LTH versus control ( P StAR mRNA was decreased in LTH versus control ( P StAR expression.

  9. NMDA and kainate receptor expression, long-term potentiation, and neurogenesis in the hippocampus of long-lived Ames dwarf mice.

    Science.gov (United States)

    Sharma, Sunita; Darland, Diane; Lei, Saobo; Rakoczy, Sharlene; Brown-Borg, Holly M

    2012-06-01

    In the current study, we investigated changes in N-methyl D-aspartate (NMDA) and kainate receptor expression, long-term potentiation (LTP), and neurogenesis in response to neurotoxic stress in long-living Ames dwarf mice. We hypothesized that Ames dwarf mice have enhanced neurogenesis that enables retention of spatial learning and memory with age and promotes neurogenesis in response to injury. Levels of the NMDA receptors (NR)1, NR2A, NR2B, and the kainate receptor (KAR)2 were increased in Ames dwarf mice, relative to wild-type littermates. Quantitative assessment of the excitatory postsynaptic potential in Schaffer collaterals in hippocampal slices from Ames dwarf mice showed an increased response in high-frequency induced LTP over time compared with wild type. Kainic acid (KA) injection was used to promote neurotoxic stress-induced neurogenesis. KA mildly increased the number of doublecortin-positive neurons in wild-type mice, but the response was significantly enhanced in the Ames dwarf mice. Collectively, these data support our hypothesis that the enhanced learning and memory associated with the Ames dwarf mouse may be due to elevated levels of NMDA and KA receptors in hippocampus and their ability to continue producing new neurons in response to neuronal damage.

  10. Intrathecal long-term gene expression by self-complementary adeno-associated virus type 1 suitable for chronic pain studies in rats

    Directory of Open Access Journals (Sweden)

    Janssen William GM

    2006-01-01

    Full Text Available Abstract Background Intrathecal (IT gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks impairing their utility in the chronic pain setting. The overall goal of this study was to develop IT gene transfer yielding true long-term transgene expression defined as ≥ 3 mo following a single vector administration. We defined "IT" administration as atraumatic injection into the lumbar cerebrospinal fluid (CSF modeling a lumbar puncture. Our studies focused on recombinant adeno-associated virus (rAAV, one of the most promising vector types for clinical use. Results Conventional single stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination with a modification of the inverted terminal repeat. The former alters vector tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV vectors. Combining both types of modification led to the identification of sc-rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 × 10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green fluorescent protein (EGFP for ≥ 3 mo detectable by Western blotting, quantitative PCR, and in a blinded study by confocal microscopy. Expression was strongest in the cauda equina and the lower sections of the spinal cord and only minimal in the forebrain. Microscopic examination of the SC fixed in situ with intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve roots. Conclusion sc-rAAVl mediates stable IT transgene expression for ≥ 3 mo. Our findings support the underlying hypothesis that IT target cells for gene transfer lack the machinery for efficient conversion of the single-stranded rAAV genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2

  11. Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

    Science.gov (United States)

    Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

    2017-01-06

    In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-01-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E 2 ). With these LTEE cells and with parallel control cells cultured without E 2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E 2 -dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E 2 .

  13. Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

    Science.gov (United States)

    Ling, Bey-Leei; Chiu, Chun-Tang; Lu, Hsiu-Chin; Lin, Jin-Jin; Kuo, Chiung-Yin; Chou, Fen-Pi

    2014-01-01

    To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR) ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α) and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC) analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, Pshort term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These metabolic changes could be the results of reduced circulating adiponectin that further influences the functions of insulin and hepatic HNF4α.

  14. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Beranger, G.

    2003-01-01

    Making a decision upon the right choice of a material appropriate to a given application should be based on taking into account several parameters as follows: cost, standards, regulations, safety, recycling, chemical properties, supplying, transformation, forming, assembly, mechanical and physical properties as well as the behaviour in practical conditions. Data taken from a private communication (J.H.Davidson) are reproduced presenting the life time range of materials from a couple of minutes to half a million hours corresponding to applications from missile technology up to high-temperature nuclear reactors or steam turbines. In the case of deep storage of nuclear waste the time required is completely different from these values since we have to ensure the integrity of the storage system for several thousand years. The vitrified nuclear wastes should be stored in metallic canisters made of iron and carbon steels, stainless steels, copper and copper alloys, nickel alloys or titanium alloys. Some of these materials are passivating metals, i.e. they develop a thin protective film, 2 or 3 nm thick - the so-called passive films. These films prevent general corrosion of the metal in a large range of chemical condition of the environment. In some specific condition, localized corrosion such as the phenomenon of pitting, occurs. Consequently, it is absolutely necessary to determine these chemical condition and their stability in time to understand the behavior of a given material. In other words the corrosion system is constituted by the complex material/surface/medium. For high level nuclear wastes the main features for resolving problem are concerned with: geological disposal; deep storage in clay; waste metallic canister; backfill mixture (clay-gypsum) or concrete; long term behavior; data needed for modelling and for predicting; choice of appropriate solution among several metallic candidates. The analysis of the complex material/surface/medium is of great importance

  15. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  16. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  17. Evaluating long term forecasts

    Energy Technology Data Exchange (ETDEWEB)

    Lady, George M. [Department of Economics, College of Liberal Arts, Temple University, Philadelphia, PA 19122 (United States)

    2010-03-15

    The U.S. Department of Energy's Energy Information Administration (EIA), and its predecessor organizations, has published projections of U.S. energy production, consumption, distribution and prices annually for over 30 years. A natural issue to raise in evaluating the projections is an assessment of their accuracy compared to eventual outcomes. A related issue is the determination of the sources of 'error' in the projections that are due to differences between the actual versus realized values of the associated assumptions. One way to do this would be to run the computer-based model from which the projections are derived at the time the projected values are realized, using actual rather than assumed values for model assumptions; and, compare these results to the original projections. For long term forecasts, this approach would require that the model's software and hardware configuration be archived and available for many years, possibly decades, into the future. Such archival creates many practical problems; and, in general, it is not being done. This paper reports on an alternative approach for evaluating the projections. In the alternative approach, the model is run many times for cases in which important assumptions are changed individually and in combinations. A database is assembled from the solutions and a regression analysis is conducted for each important projected variable with the associated assumptions chosen as exogenous variables. When actual data are eventually available, the regression results are then used to estimate the sources of the differences in the projections of the endogenous variables compared to their eventual outcomes. The results presented here are for residential and commercial sector natural gas and electricity consumption. (author)

  18. Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

    Directory of Open Access Journals (Sweden)

    Bey-Leei Ling

    Full Text Available OBJECTIVE: To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. METHODS: The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. RESULTS: No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, P<0.05 and negatively to glucose and insulin (r = -0.821 and -0.892 respectively, P<0.05. Eight weeks after the operation, the lipectomized animals revealed significant higher body and liver weights, weight gain, liver to body weight ratio, hepatic triacylglycerol and serum insulin level. CONCLUSIONS: In response to lipectomy a short term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These

  19. Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients

    NARCIS (Netherlands)

    Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K.; Wijmenga, Cisca; Jassem, Ewa; Oude Elberink, Joanne N. G.

    Background: Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of

  20. Long Term Financing of Infrastructure

    OpenAIRE

    Sinha, Sidharth

    2014-01-01

    Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

  1. Impact of protein supplementation and exercise in preventing changes in gene expression profiling in woman muscles after long-term bedrest as revealed by microarray analysis.

    Science.gov (United States)

    Chopard, Angele; Lecunff, Martine; Danger, Richard; Teusan, Raluca; Jasmin, Bernard J.; Marini, Jean-Francois; Leger, Jean

    Long duration space flights have a dramatic impact on human physiology and under such a condition, skeletal muscles are known to be one of the most affected systems. A thorough understanding of the basic mechanisms leading to muscle impairment under microgravity, which causes significant loss of muscle mass as well as structural disorders, is necessary for the development of efficient space flight countermeasures. This study was conducted under the aegis of the European Space Agency (ESA), the National Aeronautics and Space Administration of the USA (NASA), the Canadian Space Agency (CSA), and the French "Centre National d'Etudes Spatiales" (CNES). It gave us the opportunity to investigate for the first time the effects of prolonged disuse (long-term bedrest, LTBR) on the transcriptome of different muscle types in healthy women (control, n=8), as well as the potential beneficial impact of protein supplementation (nutrition, n=8) and a combined resistance and aerobic exercise training program (exercise, n=8). Pre- (LTBR -8) and post- (LTBR +59) biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles from each subject. Skeletal muscle gene expression profiles were obtained using a custom made microarray containing 6681 muscle-relevant genes. 555 differentiallyexpressed and statistically-significant genes were identified in control group following 60 days of LTBR, including 348 specific for SOL, 83 specific for VL, and 124 common for the two types of muscle (p<0.05). After LTBR, both muscle types exhibited a consistent decrease in pathways involved in fatty acid oxidation, ATP synthesis, and oxidative phosphorylation (p<0.05). However, the postural SOL muscle exhibited a higher level of changes with mRNA encoding proteins involved in protein synthesis and activation of protein degradation (mainly ubiquitinproteasome components) (p<0.05). Major changes in muscle function, such as those involved in calcium signaling and muscle structure including

  2. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  3. Human CRF{sub 2} {alpha} and {beta} splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

    Energy Technology Data Exchange (ETDEWEB)

    Ardati, A. [Rhone-Poulenc Rorer, Cardiovascular Biology, NW4, 500 Arcola Road, Collegeville, PA (United States); Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J. [Central Nervous System, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland); Valdenaire, O. [Cardiovascular Research, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland)

    1999-03-14

    Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF{sub 1} and CRF{sub 2}). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF{sub 2} subtype receptors, CRF{sub 2{alpha}} and CRF{sub 2{beta}}, have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF{sub 2{beta}} receptor. We have used radioligand binding with [{sup 125}I]-tyr{sup 0}-sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [{sup 125}I]-tyr{sup 0}-sauvagine binding to the hCRF{sub 2{beta}} receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF{sub 2{alpha}} receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF{sub 2{alpha}} receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [{sup 125}I]-tyr{sup 0}-sauvagine to both hCRF{sub 2} receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF{sub 2}{alpha}-helical CRF{sub (9-41)}oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist {alpha}-helical CRF{sub (9-41)} exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF{sub 2} receptor isoforms. Taken together, these results indicate that the

  4. Long term complications of diabetes

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  5. [Long-term psychiatric hospitalizations].

    Science.gov (United States)

    Plancke, L; Amariei, A

    2017-02-01

    Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

  6. Long-term changes in collagen formation expressed by serum carboxyterminal propeptide of type-I procollagen and relation to left ventricular function after acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Høst, N B; Egstrup, K

    2001-01-01

    and prognosis following acute myocardial infarction (AMI). Forty-eight consecutive patients with their first AMI and 15 control subjects were studied. Patients with AMI were stratified according to the changes in s-PICP levels between days 1 and 90 (DeltaPICP) and divided into group I with ...The purpose of this study was to investigate the long-term sequential changes in serum levels of the carboxyterminal propeptide of type-I procollagen (s-PICP), which is a marker of type-I collagen synthesis, and to assess its clinical value in relation to left ventricular (LV) function....../l or group II with >16.0 microg/l. Patients in group II were characterized by LV dilatation, no improvement in ejection fraction and development of impaired diastolic filling from day 1 to 360, findings which were in contrast to group I. Cox regression analysis identified changes in s-PICP of >16.0 microg...

  7. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

    Directory of Open Access Journals (Sweden)

    Alejandro Hernández

    2008-01-01

    Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  8. Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

    Science.gov (United States)

    Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

    2008-01-01

    Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  9. Gene silencing in primary and metastatic tumors by small interfering RNA delivery in mice: quantitative analysis using melanoma cells expressing firefly and sea pansy luciferases.

    Science.gov (United States)

    Takahashi, Yuki; Nishikawa, Makiya; Kobayashi, Naoki; Takakura, Yoshinobu

    2005-07-20

    Silencing of oncogenes or other genes contributing to tumor malignancy or progression by RNA interference (RNAi) offers a promising approach to treating tumor patients. To achieve RNAi-based tumor therapy, a small interfering RNA (siRNA) or siRNA-expressing vector needs to be delivered to tumor cells, but little information about its in vivo delivery has been reported. In this study, we examined whether the expression of the target gene in tumor cells can be suppressed by the delivery of RNAi effectors to primary and metastatic tumor cells. To quantitatively evaluate the RNAi effects in tumor cells, mouse melanoma B16-BL6 cells were stably transfected with both firefly (a model target gene) and sea pansy (an internal standard gene) luciferase genes to obtain B16-BL6/dual Luc cells. The target gene expression in subcutaneous primary tumors of B16-BL6/dual Luc cells was significantly suppressed by direct injection of the RNAi effectors followed by electroporation. The expression in metastatic hepatic tumors was also significantly reduced by an intravenous injection of either RNAi effector by the hydrodynamics-based procedure. These results indicate that the both RNAi effectors have a potential to silence target gene in tumor cells in vivo when successfully delivered to tumor cells.

  10. Flexible Measurement of Bioluminescent Reporters Using an Automated Longitudinal Luciferase Imaging Gas- and Temperature-optimized Recorder (ALLIGATOR).

    Science.gov (United States)

    Crosby, Priya; Hoyle, Nathaniel P; O'Neill, John S

    2017-12-13

    Luciferase-based reporters of cellular gene expression are in widespread use for both longitudinal and end-point assays of biological activity. In circadian rhythms research, for example, clock gene fusions with firefly luciferase give rise to robust rhythms in cellular bioluminescence that persist over many days. Technical limitations associated with photomultiplier tubes (PMT) or conventional microscopy-based methods for bioluminescence quantification have typically demanded that cells and tissues be maintained under quite non-physiological conditions during recording, with a trade-off between sensitivity and throughput. Here, we report a refinement of prior methods that allows long-term bioluminescence imaging with high sensitivity and throughput which supports a broad range of culture conditions, including variable gas and humidity control, and that accepts many different tissue culture plates and dishes. This automated longitudinal luciferase imaging gas- and temperature-optimized recorder (ALLIGATOR) also allows the observation of spatial variations in luciferase expression across a cell monolayer or tissue, which cannot readily be observed by traditional methods. We highlight how the ALLIGATOR provides vastly increased flexibility for the detection of luciferase activity when compared with existing methods.

  11. Effects of long-term environmental enrichment on anxiety, memory, hippocampal plasticity and overall brain gene expression in C57BL6 mice

    Directory of Open Access Journals (Sweden)

    Melanie Hüttenrauch

    2016-08-01

    Full Text Available There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging WT mice has not been studied in detail yet. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE paradigm for a duration of eleven months, leads to reduced anxiety and improved spatial reference memory in C57BL6 wildtype (WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH and EE mice, the number of dentate gyrus (DG neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders.

  12. Nuclear Energy, Long Term Requirements

    International Nuclear Information System (INIS)

    Knapp, V.

    2006-01-01

    There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

  13. Analysing long term discursive processes

    DEFF Research Database (Denmark)

    Horsbøl, Anders

    which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations......What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...

  14. Comparing long term energy scenarios

    International Nuclear Information System (INIS)

    Cumo, M.; Simbolotti, G.

    2001-01-01

    Major projection studies by international organizations and senior analysts have been compared with reference to individual key parameters (population, energy demand/supply, resources, technology, emissions and global warming) to understand trends and implications of the different scenarios. Then, looking at the long term (i.e., 2050 and beyond), parameters and trends have been compared together to understand and quantify whether and when possible crisis or market turbulence might occur due to shortage of resources or environmental problems [it

  15. Long term radioactive waste management

    International Nuclear Information System (INIS)

    Lavie, J.M.

    1984-01-01

    In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

  16. Long term expression of Drosophila melanogaster nucleoside kinase in thymidine kinase 2-deficient mice with no lethal effects caused by nucleotide pool imbalances.

    Science.gov (United States)

    Krishnan, Shuba; Paredes, João A; Zhou, Xiaoshan; Kuiper, Raoul V; Hultenby, Kjell; Curbo, Sophie; Karlsson, Anna

    2014-11-21

    Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2(-/-)) mice extended the life span of Tk2(-/-) mice from 3 weeks to at least 20 months. The Dm-dNK(+/-)Tk2(-/-) mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK(+/-)Tk2(-/-) mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK(+/-) mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Influence of bone morphogenetic protein-2 on the extracellular matrix, material properties, and gene expression of long-term articular chondrocyte cultures: loss of chondrocyte stability.

    Science.gov (United States)

    Krawczak, David A; Westendorf, Jennifer J; Carlson, Cathy S; Lewis, Jack L

    2009-06-01

    The aim of this study was to determine the effects of bone morphogenetic protein-2 (BMP-2) on articular chondrocyte tissues grown as monolayers in vitro for up to 8 weeks. Articular chondrocytes were isolated from New Zealand White rabbits and plated in monolayer cultures. The cultures were supplemented with 100 ng/mL of BMP-2 for up to 8 weeks and the extracellular matrix (ECM) composition, material properties, and messenger RNA (mRNA) expression were analyzed. mRNA expression of cartilage-specific genes, type II collagen, and aggrecan showed that BMP-2 enhanced chondrocyte stability for up to 3 weeks. After 3 weeks in culture, there was substantially more type I collagen expression and more osteopontin and runt-related transcription factor 2 expression in 5- and 8-week cultures treated with BMP-2 than in controls. Additionally, matrix metalloproteinase-13 and ADAMTS-5 (A disintegrin-like and metalloproteinase with thrombospondin 5) were upregulated in 5- and 8-week cultures treated with BMP-2, coinciding with a loss of ECM density, collagen, and proteoglycan. Eight-week tissue stimulated with BMP-2 was more fragile and tore more easily when removed from the culture dish as compared to controls, suggesting temporal limitations to the effectiveness of BMP-2 in monolayer systems and perhaps other models to enhance the generation of a cartilage-like tissue for tissue engineering purposes.

  18. Changes in Histopathology, Enzyme Activities, and the Expression of Relevant Genes in Zebrafish (Danio rerio) Following Long-Term Exposure to Environmental Levels of Thallium.

    Science.gov (United States)

    Hou, Li-Ping; Yang, Yang; Shu, Hu; Ying, Guang-Guo; Zhao, Jian-Liang; Chen, Yi-Bing; Chen, Yong-Heng; Fang, Gui-Zhen; Li, Xin; Liu, Ji-Sheng

    2017-11-01

    Thallium is a rare-earth element, but widely distributed in water environments, posing a potential risk to our health. This study was designed to investigate the chronic effects of thallium based on physiological responses, gene expression, and changes in the activity of relevant enzymes in adult zebra fish exposed to thallium at low doses. The endpoints assessed include mRNA expression of metallothionein (MT)2 and heat shock protein HSP70; enzymatic activities of superoxide dismutase (SOD) and Na + /K + -ATPase; and the histopathology of gill, gonad, and liver tissues. The results showed significant increases in HSP70 mRNA expression following exposure to 100 ng/L thallium and in MT2 expression following exposure to 500 ng/L thallium. Significantly higher activities were observed for SOD in liver and Na + /K + -ATPase activity in gill in zebra fish exposed to thallium (20 and 100 ng/L, respectively) in comparison to control fish. Gill, liver, and gonad tissues displayed different degrees of damage. The overall results imply that thallium may cause toxicity to zebra fish at environmentally relevant aqueous concentrations.

  19. Long-term intake of a high prebiotic fiber diet but not high protein reduces metabolic risk after a high fat challenge and uniquely alters gut microbiota and hepatic gene expression.

    Science.gov (United States)

    Saha, Dolan C; Reimer, Raylene A

    2014-09-01

    A mismatch between early developmental diet and adulthood may increase obesity risk. Our objective was to determine the effects of re-matching rats to their weaning diets high in protein or fiber after transient high-fat/high-sucrose challenge in adulthood. We hypothesize that a long-term high fiber diet will be associated with a gut microbiota and hepatic gene expression reflective of reduced adiposity. Wistar rat pups were fed a control (C), high prebiotic fiber (HF), or high protein (HP) diet from 3-15 weeks of age; a high-fat/high-sucrose diet from 15-21 weeks; their respective C, HF, or HP diets from 21-25 weeks. Gut microbiota of cecal contents and hepatic gene expression were measured when rats were terminated at 25 weeks of age. HF rats had higher total bacteria, bifidobacteria and Bacteroides/Prevotella spp than C and HP at 25 weeks (P diet attenuated the typical increase in Firmicutes:Bacteroidetes ratio associated with consumption of a high fat diet. Lower hepatic cholesterol with long-term HF diet intake may be related to alterations in gut microbiota and hepatic lipid metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Long Term Expression of Drosophila melanogaster Nucleoside Kinase in Thymidine Kinase 2-deficient Mice with No Lethal Effects Caused by Nucleotide Pool Imbalances*

    Science.gov (United States)

    Krishnan, Shuba; Paredes, João A.; Zhou, Xiaoshan; Kuiper, Raoul V.; Hultenby, Kjell; Curbo, Sophie; Karlsson, Anna

    2014-01-01

    Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2−/−) mice extended the life span of Tk2−/− mice from 3 weeks to at least 20 months. The Dm-dNK+/−Tk2−/− mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK+/−Tk2−/− mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK+/− mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues. PMID:25296759

  1. AHR over-expression in papillary thyroid carcinoma: clinical and molecular assessments in a series of Italian acromegalic patients with a long-term follow-up.

    Directory of Open Access Journals (Sweden)

    Caterina Mian

    Full Text Available Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3-7%. Germline mutations in the aryl-hydrocarbon receptor (AHR interacting protein (AIP have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer.Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied.12 DTCs (10 papillary and 2 follicular carcinomas were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status.The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma.

  2. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    International Nuclear Information System (INIS)

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-01-01

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life

  3. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  4. Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody.

    Science.gov (United States)

    Piperno, G M; López-Requena, A; Predonzani, A; Dorvignit, D; Labrada, M; Zentilin, L; Burrone, O R; Cesco-Gaspere, M

    2015-12-01

    The ganglioside GM3(Neu5Gc) has gained increasing attention as therapeutic target because of its selective expression in various human tumours, such as melanoma, breast and lung cancer. 14F7 is a mouse IgG1 with specific reactivity to GM3(Neu5Gc)-positive tumours. The therapeutic activity of 14F7 has also been demonstrated in vivo, through its repetitive passive administration in tumour-bearing animals. In this work we used an alternative strategy to deliver recombinant 14F7 in vivo and analysed the therapeutic efficacy of this approach. We engineered a recombinant adeno-associated vector to direct the expression of secretable recombinant 14F7 in BALB/c animals. A single administration of the rAAV induced efficient production and secretion of the antibody in the bloodstream, with an expression level reaching plateau at ∼3 weeks after injection and persisting for almost a year. Strikingly, upon challenge with GM3(Neu5Gc)-positive X63-AG8.653 myeloma cells, tumour development was significantly delayed in animals treated with rAAV-14F7 with respect to animals treated with a control rAAV codifying for an irrelevant antibody. Finally, no significant differences in survival proportion were detected in animals injected with rAAV-14F7 or treated by standard administration of repetitive doses of purified monoclonal antibody 14F7.

  5. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino.

    Science.gov (United States)

    Wu, Bo; Lu, Peijuan; Cloer, Caryn; Shaban, Mona; Grewal, Snimar; Milazi, Stephanie; Shah, Sapana N; Moulton, Hong M; Lu, Qi Long

    2012-08-01

    Exon skipping is capable of correcting frameshift and nonsense mutations in Duchenne muscular dystrophy. Phase 2 clinical trials in the United Kingdom and the Netherlands have reported induction of dystrophin expression in muscle of Duchenne muscular dystrophy patients by systemic administration of both phosphorodiamidate morpholino oligomers (PMO) and 2'-O-methyl phosphorothioate. Peptide-conjugated phosphorodiamidate morpholino offers significantly higher efficiency than phosphorodiamidate morpholino, with the ability to induce near-normal levels of dystrophin, and restores function in both skeletal and cardiac muscle. We examined 1-year systemic efficacy of peptide-conjugated phosphorodiamidate morpholino targeting exon 23 in dystrophic mdx mice. The LD(50) of peptide-conjugated phosphorodiamidate morpholino was determined to be approximately 85 mg/kg. The half-life of dystrophin expression was approximately 2 months in skeletal muscle, but shorter in cardiac muscle. Biweekly injection of 6 mg/kg peptide-conjugated phosphorodiamidate morpholino produced >20% dystrophin expression in all skeletal muscles and ≤5% in cardiac muscle, with improvement in muscle function and pathology and reduction in levels of serum creatine kinase. Monthly injections of 30 mg/kg peptide-conjugated phosphorodiamidate morpholino restored dystrophin to >50% normal levels in skeletal muscle, and 15% in cardiac muscle. This was associated with greatly reduced serum creatine kinase levels, near-normal histology, and functional improvement of skeletal muscle. Our results demonstrate for the first time that regular 1-year administration of peptide-conjugated phosphorodiamidate morpholino can be safely applied to achieve significant therapeutic effects in an animal model. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Modulation of innate immunity and gene expressions in white shrimp Litopenaeus vannamei following long-term starvation and re-feeding

    Science.gov (United States)

    Lin, Yong-Chin; Chen, Jiann-Chu; C. Man, Siti Nursafura; W. Morni, Wan Zabidii; N.A. Suhaili, Awangku Shahrir; Cheng, Sha-Yen; Hsu, Chih-Hung

    2012-01-01

    The survival rate, weight loss, immune parameters, resistance against Vibrio alginolyticus and white-spot syndrome virus (WSSV), and expressions of lipopolysaccharide- and ß-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase-activating enzyme (ppA), prophenoloxidase (proPO) I, proPO II, α2-macroglobulin (α2-M), integrin ß, heat shock protein 70 (HSP70), cytosolic manganese superoxide dismutase (cytMnSOD), mitochondrial manganese superoxide dismutase (mtMnSOD), and extracellular copper and zinc superoxide dismutase (ecCuZnSOD) were examined in the white shrimp Litopenaeus vannamei (8.18 ± 0.86 g body weight) which had been denied food (starved) for up to 14–28 days. Among shrimp which had been starved for 7, 14, 21, and 28 days, 100%, 90%, 71%, and 59% survived, and they lost 3.2%, 7.3%, 9.2%, and 10.4% of their body weight, respectively. Hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), and SOD activity significantly decreased in shrimp which had been starved for 1, 1, 1, 5, 14, and 3 days, respectively. The expression of integrin ß significantly decreased after 0.5–5 days of starvation, whereas the expressions of LGBP, PX, proPO I, proPO II, ppA, and α2-M increased after 0.5–1 days. Transcripts of all genes except ecCuZnSOD decreased to the lowest level after 5 days, and tended to background values after 7 and 14 days. Cumulative mortality rates of 7-day-starved shrimp challenged with V. alginolyticus and WSSV were significantly higher than those of challenged control-shrimp for 1–7 and 1–4 days, respectively. In another experiment, immune parameters of shrimp which had been starved for 7 and 14 days and then received normal feeding (at 5% of their body weight daily) were examined after 3, 6, and 12 h, and 1, 3, and 5 days. All immune parameters of 7-day-starved shrimp were able to return to their baseline values

  7. Murine model of long term obstructive jaundice

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A.; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-01-01

    Background With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of 3 murine models of obstructive jaundice. Methods C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Results 70% (7/10) of tCL mice died by Day 7, whereas majority 67% (10/15) of pCL mice survived with loss of jaundice. 19% (3/16) of LMHL mice died; however, jaundice continued beyond Day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 days after ligation but jaundice rapidly decreased by Day 7. The LHML group developed portal hypertension as well as severe fibrosis by Day 14 in addition to prolonged jaundice. Conclusion The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice but long term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. PMID:27916350

  8. Long-term biodosimetry Redux

    International Nuclear Information System (INIS)

    Simon, Steven L.; Bouville, Andre

    2016-01-01

    This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

  9. Effects of long-term theophylline exposure on recovery of respiratory function and expression of adenosine A1 mRNA in cervical spinal cord hemisected adult rats.

    Science.gov (United States)

    Nantwi, Kwaku D; Basura, Gregory J; Goshgarian, Harry G

    2003-07-01

    Our lab has previously shown that when administered acutely, the methylxanthine theophylline can activate a latent respiratory motor pathway to restore function to the hemidiaphragm paralyzed by an ipsilateral C2 spinal cord hemisection. The recovery is mediated by the antagonism of CNS adenosine A1 receptors. The objective of the present study was to assess quantitatively recovery after chronic theophylline administration, the effects of weaning from the drug, and the effects of the drug on adenosine A1 receptor mRNA expression in adult rats subjected to a C2 hemisection. Rats subjected to a left C2 hemisection received theophylline orally for 3, 7, 12, or 30 days and were classified as 3D, 7D, 12D, or 30D respectively. Separate groups of 3D animals were weaned from drug administration for 7, 12, and 30 days before assessment of respiratory recovery. Additional groups of 7D and 12D animals were also weaned from drug administration for 7 and 12 days prior to assessment. Sham-operated controls received theophylline vehicle for similar periods. Quantitative assessment of recovered respiratory activity was conducted under standardized electrophysiologic recording conditions approximately 18 h after each drug application period. Serum theophylline analysis was conducted at the end of electrophysiologic recordings. Adenosine A1 receptor mRNA expression in the phrenic nucleus was assessed with in situ hybridization and immunohistochemistry. Chronic theophylline induced a dose-dependent effect on respiratory recovery over a serum theophylline range of 1.2-1.9 microg/ml. Recovery was characterized as respiratory-related activity in the left phrenic nerve and expressed as a percentage of activity in the homolateral nerve in noninjured animals under similar recording conditions. Recovered activity was 34.13 +/- 2.07, 55.89 +/- 2.96, 74.78 +/- 1.93, and 79.12 +/- 1.75% respectively in the 3D, 7D, 12D, and 30D groups. Theophylline-induced recovered activity persisted for as

  10. Effects of Long-Term Exposure to 60 GHz Millimeter-Wavelength Radiation on the Genotoxicity and Heat Shock Protein (Hsp Expression of Cells Derived from Human Eye

    Directory of Open Access Journals (Sweden)

    Shin Koyama

    2016-08-01

    Full Text Available Human corneal epithelial (HCE-T and human lens epithelial (SRA01/04 cells derived from the human eye were exposed to 60 gigahertz (GHz millimeter-wavelength radiation for 24 h. There was no statistically significant increase in the micronucleus (MN frequency in cells exposed to 60 GHz millimeter-wavelength radiation at 1 mW/cm2 compared with sham-exposed controls and incubator controls. The MN frequency of cells treated with bleomycin for 1 h provided positive controls. The comet assay, used to detect DNA strand breaks, and heat shock protein (Hsp expression also showed no statistically significant effects of exposure. These results indicate that exposure to millimeter-wavelength radiation has no effect on genotoxicity in human eye cells.

  11. The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

    Science.gov (United States)

    Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  12. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  13. Expressed Emotions and Depressive Symptoms in Caregivers of Adolescents with First-Onset Anorexia Nervosa-A Long-Term Investigation over 2.5 Years.

    Science.gov (United States)

    Schwarte, Reinhild; Timmesfeld, Nina; Dempfle, Astrid; Krei, Melanie; Egberts, Karin; Jaite, Charlotte; Fleischhaker, Christian; Wewetzer, Christoph; Herpertz-Dahlmann, Beate; Seitz, Jochen; Bühren, Katharina

    2017-01-01

    High levels of expressed emotions (EE) and depressive symptoms (DS) are often found in caregivers of patients with anorexia nervosa (AN). Both parameters are considered to influence AN symptoms of the patient. One hundred seventy adolescent women with AN and their caregivers were assessed at admission, discharge, at 1-year and 2.5-year follow up to evaluate AN symptoms of the patient and EE and DS of caregivers. The EE and DS were elevated at admission and decreased during treatment, criticism (as part of EE) exhibited again at the 2.5-year follow up. Caregivers of more severely ill patients reported significantly greater levels of EE and DS. Mothers were more affected than fathers. EE and DS were interrelated. Caregivers of adolescent AN patients suffer from elevated levels of EE and DS. Further studies are needed to examine whether therapeutic interventions to reduce caregivers' EE and DS might have a positive influence on treatment outcome. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  14. Rare pneumoconiosis induced by long-term amorphous silica exposure: the histological characteristics and expression of cyclooxygenase-2 as an antifibrogenic mediator in macrophages.

    Science.gov (United States)

    Kumasaka, Toshio; Akaike, Yasushi; Nakamura, Osamu; Yamazaki, Kazuma; Moriyama, Hiroshi; Takemura, Tamiko

    2011-11-01

    Pneumoconiosis induced by non-crystalline silica is considered rare, although silicosis resulting from contact with crystalline silica is a well-known hazard associated with progressive pulmonary fibrosis. Here we describe a patient with pneumoconiosis induced by diatomaceous earth composed of amorphous silica detected by two-dimensional imaging of chemical elements. The histology revealed that the disease was characterized by a granulomatous reaction in the lung. A large number of macrophages laden with yellow and black pigments accumulated in alveolar spaces and were incorporated into the interstitial sites. Bronchiolar walls were destroyed by palisade macrophages, suggesting airflow obstruction. Packed macrophages adhering to and covering the denuded interstitium indicated that macrophages might be incorporated into pulmonary interstitium in this fashion. Immunohistochemistry showed that cyclooxygenase-2, an antifibrogenic mediator, was intensely expressed in the macrophages compared with macrophages in control lungs. No birefringent material was found in the tissues. When two-dimensional analysis of chemical elements was performed using an electron probe microanalyzer with a wavelength-dispersive spectrometer, the resultant fine mapping of silicon and oxygen on the tissue indicated that the pigments phagocytosed by macrophages corresponded to amorphous silica. In conclusion, two-dimensional analysis of elements is very useful for pathologists in correlating the presence of chemical elements with histological changes. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

  15. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.

    Science.gov (United States)

    Liu, E; Tong, Y; Dotti, G; Shaim, H; Savoldo, B; Mukherjee, M; Orange, J; Wan, X; Lu, X; Reynolds, A; Gagea, M; Banerjee, P; Cai, R; Bdaiwi, M H; Basar, R; Muftuoglu, M; Li, L; Marin, D; Wierda, W; Keating, M; Champlin, R; Shpall, E; Rezvani, K

    2018-02-01

    Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.

  16. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval.

    Science.gov (United States)

    Vanelzakker, Michael B; Zoladz, Phillip R; Thompson, Vanessa M; Park, Collin R; Halonen, Joshua D; Spencer, Robert L; Diamond, David M

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

  17. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala and Striatum Following Long-Term Spatial Memory Retrieval

    Directory of Open Access Journals (Sweden)

    Michael B VanElzakker

    2011-06-01

    Full Text Available We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 hr later. Rat brains were extracted 30 min after the 24 hr memory test trial for analysis of c-fos mRNA. Four groups were tested: 1 Rats given standard training (Standard; 2 Rats given cat exposure (Predator Stress 30 min prior to training (Pre-Training Stress; 3 Rats given water exposure only (Water Yoked; and 4 Rats given no water exposure (Home Cage. The Standard trained group exhibited excellent 24 hr memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA. The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

  18. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

    Science.gov (United States)

    VanElzakker, Michael B.; Zoladz, Phillip R.; Thompson, Vanessa M.; Park, Collin R.; Halonen, Joshua D.; Spencer, Robert L.; Diamond, David M.

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval. PMID:21738501

  19. Impact of AtNHX1, a vacuolar Na+/H+ antiporter, upon gene expression during short- and long-term salt stress in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Blumwald Eduardo

    2007-04-01

    Full Text Available Abstract Background AtNHX1, the most abundant vacuolar Na+/H+ antiporter in Arabidopsis thaliana, mediates the transport of Na+ and K+ into the vacuole, influencing plant development and contributing to salt tolerance. In this report, microarray expression profiles of wild type plants, a T-DNA insertion knockout mutant of AtNHX1 (nhx1, and a 'rescued' line (NHX1::nhx1 were exposed to both short (12 h and 48 h and long (one and two weeks durations of a non-lethal salt stress to identify key gene transcripts associated with the salt response that are influenced by AtNHX1. Results 147 transcripts showed both salt responsiveness and a significant influence of AtNHX1. Fifty-seven of these genes showed an influence of the antiporter across all salt treatments, while the remaining genes were influenced as a result of a particular duration of salt stress. Most (69% of the genes were up-regulated in the absence of AtNHX1, with the exception of transcripts encoding proteins involved with metabolic and energy processes that were mostly down-regulated. Conclusion While part of the AtNHX1-influenced transcripts were unclassified, other transcripts with known or putative roles showed the importance of AtNHX1 to key cellular processes that were not necessarily limited to the salt stress response; namely calcium signaling, sulfur metabolism, cell structure and cell growth, as well as vesicular trafficking and protein processing. Only a small number of other salt-responsive membrane transporter transcripts appeared significantly influenced by AtNHX1.

  20. Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain.

    Science.gov (United States)

    Mao, Qing-Qiu; Xian, Yan-Fang; Ip, Siu-Po; Tsai, Sam-Hip; Che, Chun-Tao

    2010-07-11

    The root part of Paeonia lactiflora Pall., commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have showed that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to investigate the mechanism(s) underlying the antidepressant-like action of TGP by measuring neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in non-stressed and chronic unpredictable mild stress (CUMS)-treated rats. TGP (80 or 160 mg/kg/day) was administered by oral gavage to the animals for 5 weeks. The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decreases in sucrose consumption and locomotor activity (assessed by open-field test). In addition, it was found that BDNF contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. CUMS treatment also significantly decreased the level of NGF in the frontal cortex of the animals. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the five weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. Treating non-stressed animals with TGP (160 mg/kg) for 5 weeks also significantly increased BDNF contents in the hippocampus and frontal cortex, and NGF contents in the frontal cortex. The results suggest that the antidepressant-like action of TGP is mediated, at least in part, by increasing the expression of BDNF and NGF in selective brain tissues. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Field performance of transgenic citrus trees: assessment of the long-term expression of uidA and nptII transgenes and its impact on relevant agronomic and phenotypic characteristics.

    Science.gov (United States)

    Pons, Elsa; Peris, Josep E; Peña, Leandro

    2012-07-15

    The future of genetic transformation as a tool for the improvement of fruit trees depends on the development of proper systems for the assessment of unintended effects in field-grown GM lines. In this study, we used eight transgenic lines of two different citrus types (sweet orange and citrange) transformed with the marker genes β-glucuronidase (uidA) and neomycin phosphotransferase II (nptII) as model systems to study for the first time in citrus the long-term stability of transgene expression and whether transgene-derived pleiotropic effects occur with regard to the morphology, development and fruit quality of orchard-grown GM citrus trees. The stability of the integration and expression of the transgenes was confirmed in 7-year-old, orchard-grown transgenic lines by Southern blot analysis and enzymatic assays (GUS and ELISA NPTII), respectively. Little seasonal variation was detected in the expression levels between plants of the same transgenic line in different organs and over the 3 years of analysis, confirming the absence of rearrangements and/or silencing of the transgenes after transferring the plants to field conditions. Comparisons between the GM citrus lines with their non-GM counterparts across the study years showed that the expression of these transgenes did not cause alterations of the main phenotypic and agronomic plant and fruit characteristics. However, when comparisons were performed between diploid and tetraploid transgenic citrange trees and/or between juvenile and mature transgenic sweet orange trees, significant and consistent differences were detected, indicating that factors other than their transgenic nature induced a much higher phenotypic variability. Our results indicate that transgene expression in GM citrus remains stable during long-term agricultural cultivation, without causing unexpected effects on crop characteristics. This study also shows that the transgenic citrus trees expressing the selectable marker genes that are most

  2. Navigating Long-Term Care

    Directory of Open Access Journals (Sweden)

    James D. Holt MD

    2017-03-01

    Full Text Available Americans over age 65 constitute a larger percentage of the population each year: from 14% in 2010 (40 million elderly to possibly 20% in 2030 (70 million elderly. In 2015, an estimated 66 million people provided care to the ill, disabled, and elderly in the United States. In 2000, according to the Centers for Disease Control and Prevention (CDC, 15 million Americans used some form of long-term care: adult day care, home health, nursing home, or hospice. In all, 13% of people over 85 years old, compared with 1% of those ages 65 to 74, live in nursing homes in the United States. Transitions of care, among these various levels of care, are common: Nursing home to hospital transfer, one of the best-studied transitions, occurs in more than 25% of nursing home residents per year. This article follows one patient through several levels of care.

  3. In vitro gene imaging by luciferase to detect the expression and effect of human tumor necrosis factor related apoptosis-inducing ligand in lung cancer A549 cells

    International Nuclear Information System (INIS)

    Zhao Na; Cui Jianling; Guo Zhiyuan; Guo Zhiping; Sun Yingcai; Liu Jicun

    2009-01-01

    Objective: To detect the expression and effect of human tumor necrosis factor related apoptosis-inducing ligand(hTRAIL) in vitro by using a novel double expressing adenoviral vector encoding hTRAIL and firefly luciferase (luc) gene (Ad-hTRAIL-luc), in which luc was used as reporter gene. Methods: A549 cells were transduced with the adenoviral vector encoding enhanced green fluorescent protein (EGFP) gene (Ad-EGFP) at variable multiplicity of infection (MOI). Adenoviral transduction efficiency was determined 48 h later. A549 cells were transduced with Ad-hTRAIL-luc at variable MOI, and the following tests were performed 48h later, respectively: the expressive ratio of hTRAIL and the apoptotic ratio of A549 cells were measured by flow cytometer; counts per minute (cpm) of luminescence were measured by scintillation counters. A549 cells were transduced with Ad-luc at variable MOI, and cpm of luminescence was measured by scintillation counters 48 h later. After A549 cells were transduced with Ad-hTRAIL-luc, the expressive ratio of hTRAIL, the apoptotic ratio of A549 cells and cpm of luminescence were analyzed by one-way ANOVA. The positive ratio of EGFP and cpm of luminescence (Ad-luc) were analyzed by nonparametric ANOVA. Results: After A549 cells were transfected with Ad-hTRAIL-luc, the expressive ratio of hTRAIL on the cell membrane of the groups were (2.37±0.04)%, (3.16±0.03)%, (3.64± 0.03)%, (3.96±0.02)%, (4.24±0.02)%, (4.34±0.02)% respectively, which showed significant difference between each other (P<0.01); and the apoptotic ratio of A549 cells were (1.52±0.04)%, (2.93±0.02)%, (3.39±0.02)%, (3.64±0.02)%, (3.86±0.02)%, (4.08±0.02)%, (4.20± 0.02)%, respectively, and it showed significant difference between each other (P<0.01); cpm of luminescence were 465 561 ± 26 801, 1 038 576 ± 29 417, 937 655 ± 23 197, 786 432 ± 20 028, 524 288 ± 16 338, 401 566 ± 15 961, respectively, and it also showed significant difference between each other (P<0

  4. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

    Directory of Open Access Journals (Sweden)

    Victor Manuel Blanco-Alvarez

    2015-01-01

    Full Text Available Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO. Male rats were grouped as follows: (1 Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days; (2 Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3 CCAO, rats with CCAO only; (4 Sham group, rats with mock CCAO; and (5 untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

  5. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

    Science.gov (United States)

    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  6. Long term study of mechanical

    Directory of Open Access Journals (Sweden)

    Ahmed M. Diab

    2016-06-01

    Full Text Available In this study, properties of limestone cement concrete containing different replacement levels of limestone powder were examined. It includes 0%, 5%, 10%, 15%, 20% and 25% of limestone powder as a partial replacement of cement. Silica fume was added incorporated with limestone powder in some mixes to enhance the concrete properties. Compressive strength, splitting tensile strength and modulus of elasticity were determined. Also, durability of limestone cement concrete with different C3A contents was examined. The weight loss, length change and cube compressive strength loss were measured for concrete attacked by 5% sodium sulfate using an accelerated test up to 525 days age. The corrosion resistance was measured through accelerated corrosion test using first crack time, cracking width and steel reinforcement weight loss. Consequently, for short and long term, the use of limestone up to 10% had not a significant reduction in concrete properties. It is not recommended to use blended limestone cement in case of sulfate attack. The use of limestone cement containing up to 25% limestone has insignificant effect on corrosion resistance before cracking.

  7. Long-term competence restoration.

    Science.gov (United States)

    Morris, Douglas R; DeYoung, Nathaniel J

    2014-01-01

    While the United States Supreme Court's Jackson v. Indiana decision and most state statutes mandate determinations of incompetent defendants' restoration probabilities, courts and forensic clinicians continue to lack empirical evidence to guide these determinations and do not yet have a consensus regarding whether and under what circumstances incompetent defendants are restorable. The evidence base concerning the restoration likelihood of those defendants who fail initial restoration efforts is even further diminished and has largely gone unstudied. In this study, we examined the disposition of a cohort of defendants who underwent long-term competence restoration efforts (greater than six months) and identified factors related to whether these defendants were able to attain restoration and adjudicative success. Approximately two-thirds (n = 52) of the 81 individuals undergoing extended restoration efforts were eventually deemed restored to competence. Lengths of hospitalization until successful restoration are presented with implications for the reasonable length of time that restoration efforts should persist. Older individuals were less likely to be restored and successfully adjudicated, and individuals with more severe charges and greater factual legal understanding were more likely to be restored and adjudicated. The significance of these findings for courts and forensic clinicians is discussed.

  8. Uranium ... long-term confidence

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    Half way through 1983 the outlook for the world's uranium producers was far from bright if one takes a short term view. The readily accessible facts present a gloomy picture. The spot prices of uranium over the past few years decreased from a high of $42-$43/lb to a low of $17 in 1982. It now hovers between $23 and $24. the contract prices negotiated between producers and consumers are not so accessible but they do not reflect the spot price. The reasons why contractual uranium prices do not follow the usual dictates of supply and demand are related to the position in which uranium and associated power industries find themselves. There is public reaction with strong emotional overtones as well as much reduced expectations about the electric power needs of the world. Furthermore the supply of uranium is not guaranteed despite present over production. However the people in the industry, taking the medium- and long-term view, are not despondent

  9. Long-term corrosion studies

    International Nuclear Information System (INIS)

    Gdowski, G.

    1998-01-01

    The scope of this activity is to assess the long-term corrosion properties of metallic materials under consideration for fabricating waste package containers. Three classes of metals are to be assessed: corrosion resistant, intermediate corrosion resistant, and corrosion allowance. Corrosion properties to be evaluated are general, pitting and crevice corrosion, stress-corrosion cracking, and galvanic corrosion. The performance of these materials will be investigated under conditions that are considered relevant to the potential emplacement site. Testing in four aqueous solutions, and vapor phases above them, and at two temperatures are planned for this activity. (The environmental conditions, test metals, and matrix are described in detail in Section 3.0.) The purpose and objective of this activity is to obtain the kinetic and mechanistic information on degradation of metallic alloys currently being considered for waste package containers. This information will be used to provide assistance to (1) waste package design (metal barrier selection) (E-20-90 to E-20-92), (2) waste package performance assessment activities (SIP-PA-2), (3) model development (E-20-75 to E-20-89). and (4) repository license application

  10. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression.

    Science.gov (United States)

    Ferris, Robert L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Docampo, Lara Carmen Iglesias; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Lynch, Mark; Jayaprakash, Vijayvel; Li, Li; Gillison, Maura L

    2018-06-01

    We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumor PD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). Patients with R/M SCCHN with tumor progression/recurrence within 6 months of platinum therapy were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017. With 24.2 months' minimum follow-up, nivolumab (n = 240) continued to improve OS vs IC (n = 121), hazard ratio (HR) = 0.68 (95% CI 0.54-0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumor PD-L1 expression ≥1% (HR [95% CI] = 0.55 [0.39-0.78]) and  < 1% (HR [95% CI] = 0.73 [0.49-1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30 months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3-4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively. Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636). Copyright © 2018. Published by Elsevier Ltd.

  11. Propensity score matched lesion-based comparison of long-term clinical and angiographic outcomes after placement of sirolimus (Cypher Bx Velocity) and paclitaxel (TAXUS Express)-eluting stents for de novo native coronary stenosis.

    Science.gov (United States)

    Nakano, Yosuke; Ishikawa, Tetsuya; Hino, Shoryoku; Mutoh, Makoto

    2014-04-01

    Long-term clinical and angiographic outcomes after sirolimus (SES: Cypher Bx Velocity) and paclitaxel (PES: TAXUS Express)-eluting stent implantation were firstly compared in Japan. During PES-available period from May 2007 to February 2009, 1068 nonrandomized consecutive de novo native coronary lesions treated either with a PES (682 lesions) or SES were enrolled in this study, and a retrospective examination was conducted in April 2013. During that interval, the use ratio of drug-eluting stent (i.e. SES plus PES) was 94.2 %. By adjusting the baselines with a propensity score matching analysis produced 383 lesions in each arm, the incidence of the clinical endpoint (1500-day cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis) after placement of SES (2.1 %; mean follow-up, 1400 ± 290 days) was not significantly different from that in the PES group (2.6 %; 1394 ± 325 days, p = 0.637). SES did not relate to the clinical endpoint (hazard ratio 1.04; 95 % CI 0.29-3.76; p = 0.949). In the baseline-adjusted angiographic followed up lesions (n = 234 in each arm), the incidence of binary restenosis (percent diameter stenosis [%DS] >50 %) in the SES group (12.0 %; mean follow-up, 477 ± 281 days) was not significantly different from that in the PES group (14.5 %; 497 ± 341 days, p = 0.431). SES did not relate to binary restenosis (Odds ratio 0.73; 95 % CI 0.40-1.32; p = 0.295). In conclusion, the present propensity score matched lesion-based analysis firstly showed the statistical equivalent long-term clinical and angiographic outcomes after either SES or PES placement for de novo native coronary lesion in Japanese patients in a daily practice environment.

  12. Detection and Quantization of the Expression of Two mu-Opioid Receptor Splice Variants mRNA (hMOR-1A and hMOR-1O in Peripheral Blood Lymphocytes of Long-Term Abstinent Former Opioid Addicts

    Directory of Open Access Journals (Sweden)

    N Vousooghi, Pharm

    2012-05-01

    Full Text Available

    Background and Objectives

    The mu-Opioid receptor (MOR exerts a critical role on effects of opiodis. The objective of this study is to find a peripheral bio-marker in addiction studies through quantization of the expression of two MOR splice variants mRNA (hMOR-1A and hMOR-1O in peripheral blood lymphocytes (PBLs of long-term abstinent former opioids addicts.

    Methods

    In this case-control study, case and control people were male and divided in two groups: people who gave up addiction to opioids (case and healthy individuals without history of addiction (control. The mRNA expression in PBLs of participants was detected and measured by real-time Polymerase Chain Reaction (PCR using SYBR Green Dye.

    Results

    The hMOR-1A mRNA expression in PBLs of abstinent group was significantly reduced and reached to 0.33 of the control group (p<0.001. Similar results were obtained for the other splice variant with the mRNA expression of hMOR-1O in PBLs of abstinent group reaching to 0.38 of that of the control group (p < 0.001.

    Conclusion

    mRNA expression deficiency of two mu-opioid receptor splice variants, hMOR-1A and nMOR-1O, seams to be a risk factor making individuals vulnerable to drug addiction. Based on this analysis measuring the amount of mRNA expression of these two splice variants in PBLs can serve as a peripheral bio-marker for detecting people at risk.

  13. The expression of β-galactosidase during long-term cultured goat skin fibroblasts and the effect of donor cell passage on in vitro development of nuclear transfer embryos.

    Science.gov (United States)

    Liu, Haijun; Peng, Hui; Liu, Fang; Ma, Qun; Zhang, Wenchang

    2016-05-01

    The present study aimed to detect the expression of β-galactosidase during long-term cultured goat skin fibroblasts and investigate the effects of donor goat age, sex, and cell passage on senescence and the effects of donor cell passage on in vitro development of nuclear transfer embryos. The results showed that, in the same cell passage, more β-galactosidase-positive cells were detected in cells from older donors than younger donors. Irrespective of the donor age, the number of positive cells was higher in later passages from passages 20 to 50. In the same passage from 20 to 50, the β-galactosidase-positive rate was higher in cells from 5-yr female goat than 5-yr male goat. Using fibroblasts from male goats at various passages as donor cells, reconstructed embryos had similar fusion and cleavage rates, but the blastocyst rate was higher for cells at passages 10 and 20 than passage 30. In conclusion, donor goat age and cell passage had significant effects on the β-galactosidase-positive rate; also, cells from 5-yr female goat had a higher β-galactosidase-positive rate than those from 5-yr male goat, and the donor cell passage affected the developmental potential of nuclear transfer embryos.

  14. Adverse event reporting in Czech long-term care facilities.

    Science.gov (United States)

    Hěib, Zdenřk; Vychytil, Pavel; Marx, David

    2013-04-01

    To describe adverse event reporting processes in long-term care facilities in the Czech Republic. Prospective cohort study involving a written questionnaire followed by in-person structured interviews with selected respondents. Long-term care facilities located in the Czech Republic. Staff of 111 long-term care facilities (87% of long-term care facilities in the Czech Republic). None. Sixty-three percent of long-term health-care facilities in the Czech Republic have adverse event-reporting processes already established, but these were frequently very immature programs sometimes consisting only of paper recording of incidents. Compared to questionnaire responses, in-person interview responses only partially tended to confirm the results of the written survey. Twenty-one facilities (33%) had at most 1 unconfirmed response, 31 facilities (49%) had 2 or 3 unconfirmed responses and the remaining 11 facilities (17%) had 4 or more unconfirmed responses. In-person interviews suggest that use of a written questionnaire to assess the adverse event-reporting process may have limited validity. Staff of the facilities we studied expressed an understanding of the importance of adverse event reporting and prevention, but interviews also suggested a lack of knowledge necessary for establishing a good institutional reporting system in long-term care.

  15. Financing long term liabilities (Germany)

    International Nuclear Information System (INIS)

    2003-01-01

    charges and fees levied from the waste producers. Altogether, financial resources for decommissioning are needed for the following steps: the post-operational phase in which the facility is prepared for dismantling after its final shut-down, dismantling of the radioactive part of the facility, management, storage and disposal of the radioactive waste, restoration of the site, licensing and regulatory supervision of all these steps. Additional means are necessary for the management, storage and disposal of the spent fuel. The way in which the availability of financial resources is secured differs between public owned installations and installations of the private power utilities. In Germany, past practices has resulted in singular contaminated sites of limited extent, mainly during the first half of the 20. century. Those contaminated sites have been or are being cleaned up and redeveloped. In large areas of Saxony and Thuringia, the geological formations permitted the surface and underground mining of Uranium ore. Facilities of the former Soviet-German WISMUT Ltd. where ore was mined and processed from 1946 until the early 1990's can be found at numerous sites. In the course of the re-unification of Germany, the soviet shares of the WISMUT were taken over by the Federal Republic of Germany and the closure of the WISMUT facilities was initiated. In that phase the extent of the damages to the environment and of the necessary remediation work became clear. All mining and milling sites are now closed and are under decommissioning. A comprehensive remediation concept covers all WISMUT sites. Heaps and mill-tailing ponds are transferred into a long-term stable condition. The area of the facilities to be remediated amounts to more than 30 km 2 . Heaps cover a total area of ca. 15,5 km 2 , tailing ponds in which the tailings resulting from the Uranium production are stored as sludges cover 6,3 km 2 ). In total, the remediation issues are very complex and without precedent. The

  16. A Long-term Plan for Kalk

    DEFF Research Database (Denmark)

    2017-01-01

    In this case, the author demonstrates together with the owner-manager of KALK A/S, Mr Rasmus Jorgensen, how to use the Family Business Map to frame a constructive discussion about long-term planning. The Family Business Map is a tool for long-term planning in family firms developed by Professor...

  17. Virtual Models of Long-Term Care

    Science.gov (United States)

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  18. Long-term In Vitro Treatment of Human Glioblastoma Cells with Temozolomide Increases Resistance In Vivo through Up-regulation of GLUT Transporter and Aldo-Keto Reductase Enzyme AKR1C Expression

    Directory of Open Access Journals (Sweden)

    Benjamin Le Calvé

    2010-09-01

    Full Text Available Glioblastoma (GBM is the most frequent malignant glioma. Treatment of GBM patients is multimodal with maximum surgical resection, followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide (TMZ. The present study aims to identify genes implicated in the acquired resistance of two human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ was induced by culturing these cells in vitro for months with incremental TMZ concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and T98G xenografts. Our data show that long-term treatment of human astroglioma cells with TMZ induces increased expression of facilitative glucose transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing enzymes involved in the maintenance of steroid homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3 has been previously suggested to exert roles in GBM neovascularization processes, and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1 was previously shown to be associated with oncogenic potential, with proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance. Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of jasmonates, for example could thus delay the acquisition of resistance to TMZ of astroglioma cells in the context of prolonged treatment with this drug.

  19. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    Science.gov (United States)

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  20. Inhibition of metastatic tumor growth in mouse lung by repeated administration of polyethylene glycol-conjugated catalase: quantitative analysis with firefly luciferase-expressing melanoma cells.

    Science.gov (United States)

    Hyoudou, Kenji; Nishikawa, Makiya; Umeyama, Yukari; Kobayashi, Yuki; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2004-11-15

    To develop a novel and effective approach to inhibit tumor metastasis based on controlled delivery of catalase, we first evaluated the characteristics of the disposition and proliferation of tumor cells. Then, we examined the effects of polyethylene glycol-conjugated catalase (PEG-catalase) on tumor metastasis. On the basis of the results obtained, PEG-catalase was repetitively administered to completely suppress the growth of tumor cells. Murine melanoma B16-BL6 cells were stably transfected with firefly luciferase gene to obtain B16-BL6/Luc cells. These cells were injected intravenously into syngeneic C57BL/6 mice. PEG-catalase was injected intravenously, and the effect was evaluated by measuring the luciferase activity as the indicator of the number of tumor cells. At 1 hour after injection of B16-BL6/Luc cells, 60 to 90% of the injected cells were recovered in the lung. The numbers decreased to 2 to 4% at 24 hours, then increased. An injection of PEG-catalase just before inoculation significantly reduced the number of tumor cells at 24 hours. Injection of PEG-catalase at 1 or 3 days after inoculation was also effective in reducing the cell numbers. Daily dosing of PEG-catalase greatly inhibited the proliferation and the number assayed at 14 days after inoculation was not significantly different from the minimal number observed at 1 day, suggesting that the growth had been markedly suppressed by the treatment. These findings indicate that sustained catalase activity in the blood circulation can prevent the multiple processes of tumor metastasis in the lung, which could lead to a state of tumor dormancy.

  1. Sexuality and physical intimacy in long-term care.

    Science.gov (United States)

    Lichtenberg, Peter A

    2014-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long-term care settings. Because older adults in medical rehabilitation and long-term care beds present with significant frailties, and often significant neurocognitive disorders, it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long-term care, and presents two case examples. A semistructured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing the needs for protection with the needs for autonomy.

  2. Development and application of hepatitis C reporter viruses with genotype 1 to 7 core-nonstructural protein 2 (NS2) expressing fluorescent proteins or luciferase in modified JFH1 NS5A

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Jensen, Tanja B; Mathiesen, Christian K

    2011-01-01

    to 2a(J6) tagged with EGFP, DsRed-Express2, mCherry, or Renilla luciferase (RLuc), yielding peak supernatant infectivity titers of 4 to 5 log(10) focus-forming units (FFU)/ml. 2a(J6) with ¿40 or ¿25 was fully viable in Huh7.5 cells. In human liver chimeric mice, 2a(J6)-EGFP¿40 acquired various...... deletions in EGFP, while 2a(J6)¿40 did not show an impaired viability. We further developed panels of JFH1-based genotype 1 to 7 core-NS2 recombinants expressing EGFP- or RLuc-NS5A¿40 fusion proteins. In cell culture, the different EGFP recombinants showed growth characteristics comparable to those...

  3. The long-term lasting effectiveness on self-efficacy, attribution style, expression of emotions and quality of life of a body awareness program for chronic a-specific psychosomatic symptoms

    NARCIS (Netherlands)

    Landsman-Dijkstra, Jeanet J. A.; van Wijck, R; Groothoff, JW

    Objective: A 3-day residential body awareness program (BAP) was developed to teach people with chronic a-specific psychosomatic symptoms (CAPS) to react adequately to disturbances of the balance between a daily workload and the capacity to deal with it. The long-term effects of the program on body

  4. Long term wet spent nuclear fuel storage

    International Nuclear Information System (INIS)

    1987-04-01

    The meeting showed that there is continuing confidence in the use of wet storage for spent nuclear fuel and that long-term wet storage of fuel clad in zirconium alloys can be readily achieved. The importance of maintaining good water chemistry has been identified. The long-term wet storage behaviour of sensitized stainless steel clad fuel involves, as yet, some uncertainties. However, great reliance will be placed on long-term wet storage of spent fuel into the future. The following topics were treated to some extent: Oxidation of the external surface of fuel clad, rod consolidation, radiation protection, optimum methods of treating spent fuel storage water, physical radiation effects, and the behaviour of spent fuel assemblies of long-term wet storage conditions. A number of papers on national experience are included

  5. Industrial Foundations as Long-Term Owners

    DEFF Research Database (Denmark)

    Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

    Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... frequently. They have conservative capital structures with low financial leverage. They score higher on an index of long-termism in finance, investment, and employment. They survive longer. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures...

  6. Coping with PH over the Long Term

    Science.gov (United States)

    ... a job, a volunteer commitment, or even a hobby can take a toll on long-term survivors ... people find solace in meditation, faith, humor, writing, hobbies and more. Find an outlet that you enjoy ...

  7. Long term effects of radiation in man

    International Nuclear Information System (INIS)

    Tso Chih Ping; Idris Besar

    1984-01-01

    An overview of the long term effects of radiation in man is presented, categorizing into somatic effects, genetic effects and teratogenic effects, and including an indication of the problems that arise in their determination. (author)

  8. Long term liquidity analysis of the firm

    Directory of Open Access Journals (Sweden)

    Jaroslav Gonos

    2009-09-01

    Full Text Available Liquidity control is a very difficult and important function. If the business is not liquid in the long term, it is under threatof bankruptcy, and on the other hand surplus of the cash in hand threaten its future efficiency, because the cash in hand is a sourceof only limited profitability. Long term liquidity is related to the ability of the short term and long term liabilities payment. Articleis trying to point out to the monitoring and analyzing of the long term liquidity in the concrete business, in this case the printing industrycompany. Hereby at the end of the article mentioned monitored and analyzed liquidity is evaluated in the five years time period.

  9. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  10. Sleep facilitates long-term face adaptation

    OpenAIRE

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted imag...

  11. Very long-term sequelae of craniopharyngioma.

    Science.gov (United States)

    Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

    2017-06-01

    Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

  12. Long-term prisoner in prison isolation

    Directory of Open Access Journals (Sweden)

    Karolina Grudzińska

    2013-06-01

    Full Text Available Long-term prisoner belongs to a particular category of people who are imprisoned in prisons. On the one hand in this group are often heavily demoralized people who committed the most serious crimes, on the other hand it is a group of prisoners, who should be well thought out and programmed the impact of rehabilitation. The situation of man trapped for years poses in a complicated situation not only the prisoners, but also the entire prison staff. They have to take care of the fact that the prison isolation did not cause the state in which convicts form itself in learned helplessness and lack of skills for self-planning and decision-making. In addition, planning the rehabilitation impact of long-term prisoners should not be forgotten that these prisoners in the short or the long term will return to the libertarian environment therefore, should prevent any negative effects of long-term imprisonment. This article presents the main issues related to the execution of imprisonment against long-term prisoners. It is an attempt to systematize the knowledge of this category of people living in prison isolation.

  13. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  14. Long-Term Prognosis of Plantar Fasciitis

    DEFF Research Database (Denmark)

    Hansen, Liselotte; Krogh, Thøger Persson; Ellingsen, Torkell

    2018-01-01

    , exercise-induced symptoms, bilateral heel pain, fascia thickness, and presence of a heel spur) could predict long-term outcomes, (3) to assess the long-term ultrasound (US) development in the fascia, and (4) to assess whether US-guided corticosteroid injections induce atrophy of the heel fat pad. Study....... The risk was significantly greater for women (P heel...... regardless of symptoms and had no impact on prognosis, and neither did the presence of a heel spur. Only 24% of asymptomatic patients had a normal fascia on US at long-term follow-up. A US-guided corticosteroid injection did not cause atrophy of the heel fat pad. Our observational study did not allow us...

  15. Long-term dependence in exchange rates

    Directory of Open Access Journals (Sweden)

    A. Karytinos

    2000-01-01

    Full Text Available The extent to which exchange rates of four major currencies against the Greek Drachma exhibit long-term dependence is investigated using a R/S analysis testing framework. We show that both classic R/S analysis and the modified R/S statistic if enhanced by bootstrapping techniques can be proven very reliable tools to this end. Our findings support persistence and long-term dependence with non-periodic cycles for the Deutsche Mark and the French Franc series. In addition a noisy chaos explanation is favored over fractional Brownian motion. On the contrary, the US Dollar and British Pound were found to exhibit a much more random behavior and lack of any long-term structure.

  16. In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters.

    OpenAIRE

    Buckley, SM; Delhove, JM; Perocheau, DP; Karda, R; Rahim, AA; Howe, SJ; Ward, NJ; Birrell, MA; Belvisi, MG; Arbuthnot, P; Johnson, MR; Waddington, SN; McKay, TR

    2015-01-01

    The application of transcription factor activated luciferase reporter cassettes in vitro is widespread but potential for in vivo application has not yet been realized. Bioluminescence imaging enables non-invasive tracking of gene expression in transfected tissues of living rodents. However the mature immune response limits luciferase expression when delivered in adulthood. We present a novel approach of tissue-targeted delivery of transcription factor activated luciferase reporter lentiviruse...

  17. Long term planning for wind energy development

    International Nuclear Information System (INIS)

    Trinick, M.

    1995-01-01

    In a planning system intended to be governed primarily by policies in statutory plans a reasonable horizon for long term planning is 10 years or longer. Because of statutory requirements, developers have no option but to pay due regard to, and take a full part in, long term planning. The paper examines the type of policies which have emerged in the last few years to cater for wind energy development. It canvasses the merits of different types of policies. Finally, it discusses the policy framework which may emerge to cater for development outside NFFO. (Author)

  18. Long-term characteristics of nuclear emulsion

    International Nuclear Information System (INIS)

    Naganawa, N; Kuwabara, K

    2010-01-01

    Long-term characteristics of the nuclear emulsion so called 'OPERA film' used in the neutrino oscillation experiment, OPERA, has been studied for 8 years since its production or refreshing after it. In the results, it turned out to be excellent in sensitivity, amount of random noise, and refreshing characteristics. The retention capacity of latent image of tracks was also studied. The result will open the way to the recycling of 7,000,000 emulsion films which will remain not developed after 5 years of OPERA's run, and other long-term experiments with emulsion.

  19. Long-term characteristics of nuclear emulsion

    Science.gov (United States)

    Naganawa, N.; Kuwabara, K.

    2010-02-01

    Long-term characteristics of the nuclear emulsion so called ``OPERA film'' used in the neutrino oscillation experiment, OPERA, has been studied for 8 years since its production or refreshing after it. In the results, it turned out to be excellent in sensitivity, amount of random noise, and refreshing characteristics. The retention capacity of latent image of tracks was also studied. The result will open the way to the recycling of 7,000,000 emulsion films which will remain not developed after 5 years of OPERA's run, and other long-term experiments with emulsion.

  20. Long-term home care scheduling

    DEFF Research Database (Denmark)

    Gamst, Mette; Jensen, Thomas Sejr

    In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

  1. Long term storage techniques for 85Kr

    International Nuclear Information System (INIS)

    Foster, B.A.; Pence, D.T.; Staples, B.A.

    1975-01-01

    As new nuclear fuel reprocessing plants go on stream, the collection of fission product 85 Kr will be required to avoid potential local release problems and long-term atmospheric buildup. Storage of the collected 85 Kr for a period of at least 100 years will be necessary to allow approximately 99.9 percent decay before it is released. A program designed to develop and evaluate proposed methods for long-term storage of 85 Kr is discussed, and the results of a preliminary evaluation of three methods, high pressure steel cylinders, zeolite encapsulation, and clathrate inclusion are presented. (U.S.)

  2. The developmental environment, epigenetic biomarkers and long-term health.

    Science.gov (United States)

    Godfrey, K M; Costello, P M; Lillycrop, K A

    2015-10-01

    Evidence from both human and animal studies has shown that the prenatal and early postnatal environments influence susceptibility to chronic disease in later life and suggests that epigenetic processes are an important mechanism by which the environment alters long-term disease risk. Epigenetic processes, including DNA methylation, histone modification and non-coding RNAs, play a central role in regulating gene expression. The epigenome is highly sensitive to environmental factors in early life, such as nutrition, stress, endocrine disruption and pollution, and changes in the epigenome can induce long-term changes in gene expression and phenotype. In this review we focus on how the early life nutritional environment can alter the epigenome leading to an altered susceptibility to disease in later life.

  3. DNA Nanoparticles: Detection of Long-Term Transgene Activity in Brain using Bioluminescence Imaging

    Directory of Open Access Journals (Sweden)

    David M. Yurek

    2011-09-01

    Full Text Available In this study, we used bioluminescence imaging (BLI to track long-term transgene activity following the transfection of brain cells using a nonviral gene therapy technique. Formulations of deoxyribonucleic acid (DNA combined with 30-mer lysine polymers (substituted with 10 kDa polyethylene glycol form nanoparticles that transfect brain cells in vivo and produce transgene activity. Here we show that a single intracerebral injection of these DNA nanoparticles (DNPs into the rat cortex, striatum, or substantia nigra results in long-term and persistent luciferase transgene activity over an 8- to 11-week period as evaluated by in vivo BLI analysis, and single injections of DNPs into the mouse striatum showed stable luciferase transgene activity for 1 year. Compacted DNPs produced in vivo signals 7- to 34-fold higher than DNA alone. In contrast, ex vivo BLI analysis, which is subject to less signal quenching from surrounding tissues, demonstrated a DNP to DNA alone ratio of 76- to 280-fold. Moreover, the ex vivo BLI analysis confirmed that signals originated from the targeted brain structures. In summary, BLI permits serial analysis of luciferase transgene activity at multiple brain locations following gene transfer with DNPs. Ex vivo analysis may permit more accurate determination of relative activities of gene transfer vectors.

  4. Experiences of long-term tranquillizer use

    DEFF Research Database (Denmark)

    Skinhoj, K T; Larsson, S; Helweg-Joergensen, S

    2001-01-01

    , the psychodynamic perspective is integrated within a multi-dimensional model that considers biological, cognitive, identity, gender and social learning factors. The analysis reveals the possibility of achieving a detailed understanding of the dynamic processes involved in the development of long-term tranquillizer...

  5. Long-Term Orientation in Trade

    NARCIS (Netherlands)

    Hofstede, G.J.; Jonker, C.M.; Verwaart, D.

    2008-01-01

    Trust does not work in the same way across cultures. This paper presents an agent model of behavior in trade across Hofstedes cultural dimension of long-term vs. short-term orientation. The situation is based on a gaming simulation, the Trust and Tracing game. The paper investigates the

  6. Safety of long-term PPI therapy

    DEFF Research Database (Denmark)

    Reimer, Christina

    2013-01-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

  7. Long term consequences of early childhood malnutrition

    NARCIS (Netherlands)

    Kinsey, B.H.; Hoddinott, J; Alderman, H.

    2006-01-01

    This paper examines the impact of pre-school malnutrition on subsequent human capital formation in rural Zimbabwe using a maternal fixed effects - instrumental variables (MFE-IV) estimator with a long term panel data set. Representations of civil war and drought shocks are used to identify

  8. Financial Incentives in Long-Term Care

    NARCIS (Netherlands)

    P.L.H. Bakx (Pieter)

    2015-01-01

    markdownabstract__Abstract__ Long-term care (ltc) aims to help individuals to cope with their impairments. In my thesis, I describe ltc financing alternatives and their consequences for the allocation of ltc. This thesis consists of two parts. In the first part, I investigate how alternative ways

  9. Long-term outcomes of patellofemoral arthroplasty.

    NARCIS (Netherlands)

    Jonbergen, J.P.W. van; Werkman, D.M.; Barnaart, L.F.; Kampen, A. van

    2010-01-01

    The purpose of this study was to correlate the long-term survival of patellofemoral arthroplasty with primary diagnosis, age, sex, and body mass index. One hundred eighty-five consecutive Richards type II patellofemoral arthroplasties were performed in 161 patients with isolated patellofemoral

  10. Long-Term Memory and Learning

    Science.gov (United States)

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  11. The 2013 Long-Term Budget Outlook

    Science.gov (United States)

    2013-09-01

    number of years, leading to substantial additional federal spending. For example, the nation could experience a massive earthquake, a nuclear meltdown...budget surpluses remaining after paying down publicly held debt available for redemption . a. For comparison with the current long-term projections, CBO

  12. Long-term effects of ionizing radiation

    International Nuclear Information System (INIS)

    Kaul, Alexander; Burkart, Werner; Grosche, Bernd; Jung, Thomas; Martignoni, Klaus; Stephan, Guenther

    1997-01-01

    This paper approaches the long-term effects of ionizing radiation considering the common thought that killing of cells is the basis for deterministic effects and that the subtle changes in genetic information are important in the development of radiation-induced cancer, or genetic effects if these changes are induced in germ cells

  13. Pituitary diseases : long-term psychological consequences

    NARCIS (Netherlands)

    Tiemensma, Jitske

    2012-01-01

    Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing’s disease, Cushing’s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the

  14. The long term stability of lidar calibrations

    DEFF Research Database (Denmark)

    Courtney, Michael; Gayle Nygaard, Nicolai

    Wind lidars are now used extensively for wind resource measurements. One of the requirements for the data to be accepted in support of project financing (so-called ‘banka-bility’) is to demonstrate the long-term stability of lidar cali-brations. Calibration results for six Leosphere WindCube li...

  15. Rebalancing for Long-Term Investors

    NARCIS (Netherlands)

    Driessen, Joost; Kuiper, Ivo

    2017-01-01

    In this study we show that the rebalance frequency of a multi-asset portfolio has only limited impact on the utility of a long-term passive investor. Although continuous rebalancing is optimal, the loss of a suboptimal strategy corresponds to up to only 30 basis points of the initial wealth of the

  16. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    Energy Technology Data Exchange (ETDEWEB)

    Calin-Jageman, Robert J

    2009-09-12

    Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by

  17. Archiving Primary Data: Solutions for Long-Term Studies.

    Science.gov (United States)

    Mills, James A; Teplitsky, Céline; Arroyo, Beatriz; Charmantier, Anne; Becker, Peter H; Birkhead, Tim R; Bize, Pierre; Blumstein, Daniel T; Bonenfant, Christophe; Boutin, Stan; Bushuev, Andrey; Cam, Emmanuelle; Cockburn, Andrew; Côté, Steeve D; Coulson, John C; Daunt, Francis; Dingemanse, Niels J; Doligez, Blandine; Drummond, Hugh; Espie, Richard H M; Festa-Bianchet, Marco; Frentiu, Francesca; Fitzpatrick, John W; Furness, Robert W; Garant, Dany; Gauthier, Gilles; Grant, Peter R; Griesser, Michael; Gustafsson, Lars; Hansson, Bengt; Harris, Michael P; Jiguet, Frédéric; Kjellander, Petter; Korpimäki, Erkki; Krebs, Charles J; Lens, Luc; Linnell, John D C; Low, Matthew; McAdam, Andrew; Margalida, Antoni; Merilä, Juha; Møller, Anders P; Nakagawa, Shinichi; Nilsson, Jan-Åke; Nisbet, Ian C T; van Noordwijk, Arie J; Oro, Daniel; Pärt, Tomas; Pelletier, Fanie; Potti, Jaime; Pujol, Benoit; Réale, Denis; Rockwell, Robert F; Ropert-Coudert, Yan; Roulin, Alexandre; Sedinger, James S; Swenson, Jon E; Thébaud, Christophe; Visser, Marcel E; Wanless, Sarah; Westneat, David F; Wilson, Alastair J; Zedrosser, Andreas

    2015-10-01

    The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Long-term selenium status in humans

    International Nuclear Information System (INIS)

    Baskett, C.K.; Spate, V.L.; Mason, M.M.; Nichols, T.A.; Williams, A.; Dubman, I.M.; Gudino, A.; Denison, J.; Morris, J.S.

    2001-01-01

    The association of sub-optimal selenium status with increased risk factors for some cancers has been reported in two recent epidemiological studies. In both studies the same threshold in selenium status was observed, below which, cancer incidence increased. To assess the use of nails as a biologic monitor to measure the long-term selenium status, an eight-year longitudinal study was undertaken with a group of 11 adult subjects, 5 women and 6 men. Selenium has been measured by instrumental neutron activation analysis. Differences between fingernails and toenails with be discussed. In addition, the results will be discussed in the context of the long-term stability of the nail monitor to measure selenium status during those periods when selenium determinants are static; and the changes that occur as a result of selenium supplementation. (author)

  19. Influenza in long-term care facilities.

    Science.gov (United States)

    Lansbury, Louise E; Brown, Caroline S; Nguyen-Van-Tam, Jonathan S

    2017-09-01

    Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  20. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas

    2016-01-01

    in Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long......-term in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper supports...... the hypothesis that time horizons are influenced by ownership structures and particularly that industrial foundations promote longtermism. Policymakers which are interested in promoting longtermism should allow and perhaps even encourage the creation of industrial foundations. More generally they should consider...

  1. Analysis of long-term energy scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Lemming, J.; Morthorst, P.E.

    1998-09-01

    When addressing the role of fusion energy in the 21. century, the evaluation of possible future structures in the electricity market and the energy sector as a whole, can be a useful tool. Because fusion energy still needs demonstration, commercialized fusion energy is not likely to be a reality within the next few decades. Therefore long-term scenarios are needed describing the energy markets, which fusion energy eventually will be part of. This report performs an analysis of two of the most detailed existing long-term scenarios describing possible futures of the energy system. The aim is to clarify the frames in which the future development of the global energy demand, as well as the structure of the energy system can be expected to develop towards the year 2100. (au) 19 refs.

  2. Long-term effects of radiation

    International Nuclear Information System (INIS)

    Smith, J.; Smith, T.

    1981-01-01

    It is pointed out that sources of long-term damage from radiation are two-fold. People who have been exposed to doses of radiation from initial early fallout but have recovered from the acute effects may still suffer long-term damage from their exposure. Those who have not been exposed to early fallout may be exposed to delayed fallout, the hazards from which are almost exclusively from ingesting strontium, caesium and carbon isotopes present in food; the damage caused is relatively unimportant compared with that caused by the brief doses from initial radiation and early fallout. A brief discussion is presented of the distribution of delayed long-lived isotope fallout, and an outline is sketched of late biological effects, such as malignant disease, cataracts, retarded development, infertility and genetic effects. (U.K.)

  3. Long term economic relationships from cointegration maps

    Science.gov (United States)

    Vicente, Renato; Pereira, Carlos de B.; Leite, Vitor B. P.; Caticha, Nestor

    2007-07-01

    We employ the Bayesian framework to define a cointegration measure aimed to represent long term relationships between time series. For visualization of these relationships we introduce a dissimilarity matrix and a map based on the sorting points into neighborhoods (SPIN) technique, which has been previously used to analyze large data sets from DNA arrays. We exemplify the technique in three data sets: US interest rates (USIR), monthly inflation rates and gross domestic product (GDP) growth rates.

  4. Long-term course of opioid addiction.

    Science.gov (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  5. Long-term economic outlook. Annual review

    Energy Technology Data Exchange (ETDEWEB)

    1988-01-01

    This review provides economic growth forecast tables for Ontario, Canada, the US, Western Europe, and Japan. Economic growth, government policy, the long-term prospects for inflation, interest rates and foreign exchange rates, trends in the Canadian dollar, and energy markets and prices are also reviewed. Data generally cover 1965-2025. Appendices give a summary of historical and forecast data. 18 figs., 16 tabs.

  6. Long-term data storage in diamond

    OpenAIRE

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV?) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV? optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multic...

  7. French Approach for Long Term Storage Safety

    International Nuclear Information System (INIS)

    Marciano, Jacob; Carreton, Jean-Pierre; Lizot, Marie Therese; Lhomme, Veronique

    2014-01-01

    IRSN presents its statement regarding long-term storage facilities; in France, the regulatory documents do not define the long term duration. The storage facility lifetime can only be appreciated according to the needs and materials stored therein. However, the magnitude of the long-term can be estimated at a few hundred years compared to a few decades for current storage. Usually, in France, construction of storage facilities is driven from the necessity various necessities, linked to the management of radioactive material (eg spent fuel) and to the management of radioactive waste. Because of the variety of 'stored materials and objects' (fission product solutions, plutonium oxide powders, activated solids, drums containing technological waste, spent fuel...), a great number of storage facility design solutions have been developed (surface, subsurface areas, dry or wet conditions...) in the World. After describing the main functions of a storage facility, IRSN displays the safety principles and the associated design principles. The specific design principles applied to particular storage (dry or wet spent fuel storage, depleted uranium or reprocessed uranium storage, plutonium storage, waste containing tritium storage, HLW and ILLW storage...) are also presented. Finally, the concerns due to the long-term duration storage and related safety assessment are developed. After discussing these issues, IRSN displays its statement. The authorization procedures governing the facility lifetime are similar to those of any basic nuclear installation, the continuation of the facility operation remaining subject to periodic safety reviews (in France, every 10 years). The applicant safety cases have to show, that the safety requirements are always met; this requires, at minimum, to take into account at the design stage, comfortable design margins. (author)

  8. Accounting of Long-Term Biological Assets

    OpenAIRE

    Valeriy Mossakovskyy; Vasyl Korytnyy

    2015-01-01

    The article is devoted to generalization of experience in valuation of long-term biological assets of plant-growing and animal-breeding, and preparation of suggestions concerning improvement of accounting in this field. Recommendations concerning accounting of such assets are given based on the study of accounting practice at specific agricultural company during long period of time. Authors believe that fair value is applicable only if price level for agricultural products is fixed by the gov...

  9. Optimal long-term contracting with learning

    OpenAIRE

    He, Zhiguo; Wei, Bin; Yu, Jianfeng; Gao, Feng

    2016-01-01

    We introduce uncertainty into Holmstrom and Milgrom (1987) to study optimal long-term contracting with learning. In a dynamic relationship, the agent's shirking not only reduces current performance but also increases the agent's information rent due to the persistent belief manipulation effect. We characterize the optimal contract using the dynamic programming technique in which information rent is the unique state variable. In the optimal contract, the optimal effort is front-loaded and decr...

  10. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...... integral nail-plates and nailed steel and plywood gussets. The report is intended for designers and researchers in timber engineering....

  11. Inflation Hedging for Long-Term Investors

    OpenAIRE

    Shaun K. Roache; Alexander P. Attie

    2009-01-01

    Long-term investors face a common problem-how to maintain the purchasing power of their assets over time and achieve a level of real returns consistent with their investment objectives. While inflation-linked bonds and derivatives have been developed to hedge the effects of inflation, their limited supply and liquidity lead many investors to continue to rely on the indirect hedging properties of traditional asset classes. In this paper, we assess these properties over different time horizons,...

  12. Long term evolution 4G and beyond

    CERN Document Server

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania

    2016-01-01

    This book focus on Long Term Evolution (LTE) and beyond. The chapters describe different aspects of research and development in LTE, LTE-Advanced (4G systems) and LTE-450 MHz such as telecommunications regulatory framework, voice over LTE, link adaptation, power control, interference mitigation mechanisms, performance evaluation for different types of antennas, cognitive mesh network, integration of LTE network and satellite, test environment, power amplifiers and so on. It is useful for researchers in the field of mobile communications.

  13. Long-Term Care Services for Veterans

    Science.gov (United States)

    2017-02-14

    includes but is not limited to home physical , occupational, or speech therapy ; wound care; and intravenous (IV) care. A VA physician determines that a...restoring/rehabilitating the veteran’s health, such as skilled nursing care, physical therapy , occupational therapy , and IV therapy Same as HBPC... geriatric evaluation,  palliative care,  adult day health care,  homemaker/home health aide care,  respite care, Long-Term Care Services for

  14. Long term adequacy of uranium resources

    International Nuclear Information System (INIS)

    Steyn, J.

    1990-01-01

    This paper examines the adequacy of world economic uranium resources to meet requirements in the very long term, that is until at least 2025 and beyond. It does so by analysing current requirements forecasts, existing and potential production centre supply capability schedules and national resource estimates. It takes into account lead times from resource discovery to production and production rate limitations. The institutional and political issues surrounding the question of adequacy are reviewed. (author)

  15. Development and characterization of enhanced green fluorescent protein and luciferase expressing cell line for non-destructive evaluation of tissue engineering constructs.

    NARCIS (Netherlands)

    Blum, J.S.; Temenoff, J.S.; Park, H.; Jansen, J.A.; Mikos, A.G.; Barry, M.A.

    2004-01-01

    This study investigates the utility of genetically modified cells developed for the qualitative and quantitative non-destructive evaluation of cells on biomaterials. The Fisher rat fibroblastic cell line has been genetically modified to stably express the reporter genes enhanced green fluorescence

  16. 长时程增强与长时程抑制的研究%Advances in long - term potentiation and long - term depression

    Institute of Scientific and Technical Information of China (English)

    张敬军; 夏作理

    2000-01-01

    The impairment of learning and memory function in the central nervous system(CNS)is one of the main features of aging and Alzheimer' s disease (AD). Many experimental results have showed that long- term memory(LTM) is related to long- term potentiation(LTP) and long- term depression (LTD). They intluenee each other. The relationship between LTP and LTD is complex. Therefore, it is important to study the learning and memory mechanism from LTP、LTD and gene expression in the CNS.

  17. Sexuality and Physical Intimacy in Long Term Care: Sexuality, long term care, capacity assessment

    OpenAIRE

    Lichtenberg, Peter A.

    2014-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literatur...

  18. On the very long term delayed behavior of concrete

    International Nuclear Information System (INIS)

    Torrenti, J.M.; Benboudjema, F.; Barre, F.; Gallitre, E.

    2015-01-01

    The prediction of very long-term deformation of prestressed concrete structures is a major challenge considering the service life of these structures. It is therefore necessary to correctly model the delayed behavior of these structures. Using a review of laboratory tests and observations of the delayed behavior of structures (bridges and nuclear power plants), the main conclusions of this work are the following ones. First, very long term creep in laboratory or of real structures seems to be non asymptotic. In the actual Eurocode-2, creep is calculated by means of an asymptotic hyperbolic function while in the recent Model Code 2010 creep is expressed as a combination of an asymptotic and a logarithmic functions. In the latter case the logarithmic function corresponds to basic creep while drying creep is asymptotic. Secondly, using a long test (3 years) in a laboratory is not enough to assess the long term behaviour of a massive structure. We need physical relations for creep in codes in order to predict the delayed behavior of massive structures. Thirdly, the biaxial creep of nuclear power plant could be modelled but using data of the structure itself. This would allow to predict the delayed behavior of these structures. Further work is needed to improve the prediction in the design phase

  19. Murine model of long-term obstructive jaundice.

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-11-01

    With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of three murine models of obstructive jaundice. C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Overall, 70% (7 of 10) of tCL mice died by day 7, whereas majority 67% (10 of 15) of pCL mice survived with loss of jaundice. A total of 19% (3 of 16) of LMHL mice died; however, jaundice continued beyond day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 d after ligation but jaundice rapidly decreased by day 7. The LHML group developed portal hypertension and severe fibrosis by day 14 in addition to prolonged jaundice. The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice, but long-term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA.

    Science.gov (United States)

    Schumer, Maya C; Panza, Kaitlyn E; Mulqueen, Jilian M; Jakubovski, Ewgeni; Bloch, Michael H

    2015-10-01

    To examine long-term outcome in children with trichotillomania. We conducted follow-up clinical assessments an average of 2.8 ± 0.8 years after baseline evaluation in 30 of 39 children who previously participated in a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) for pediatric trichotillomania. Our primary outcome was change in hairpulling severity on the Massachusetts General Hospital Hairpulling Hospital Hairpulling Scale (MGH-HPS) between the end of the acute phase and follow-up evaluation. We also obtained secondary measures examining styles of hairpulling, comorbid anxiety and depressive symptoms, as well as continued treatment utilization. We examined both correlates and predictors of outcome (change in MGH-HPS score) using linear regression. None of the participants continued to take NAC at the time of follow-up assessment. No significant changes in hairpulling severity were reported over the follow-up period. Subjects reported significantly increased anxiety and depressive symptoms but improvement in automatic pulling symptoms. Increased hairpulling symptoms during the follow-up period were associated with increased depression and anxiety symptoms and increased focused pulling. Older age and greater focused pulling at baseline assessment were associated with poor long-term prognosis. Our findings suggest that few children with trichotillomania experience a significant improvement in trichotillomania symptoms if behavioral treatments are inaccessible or have failed to produce adequate symptom relief. Our findings also confirm results of previous cross-sectional studies that suggest an increased risk of depression and anxiety symptoms with age in pediatric trichotillomania. Increased focused pulling and older age among children with trichotillomania symptoms may be associated with poorer long-term prognosis. © 2015 Wiley Periodicals, Inc.

  1. Long-term EEG in children.

    Science.gov (United States)

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development. Copyright © 2015. Published by Elsevier SAS.

  2. Long-term governance for sustainability

    International Nuclear Information System (INIS)

    Martell, M.

    2007-01-01

    Meritxell Martell spoke of the long-term aspects of radioactive waste management. She pointed out that decision-making processes need to be framed within the context of sustainability, which means that a balance should be sought between scientific considerations, economic aspects and structural conditions. Focusing on structural aspects, Working Group 3 of COWAM-Spain came to the conclusion that the activity of the regulator is a key factor of long-term management. Another finding is that from a sustainability perspective multi-level governance is more effective for coping with the challenges of radioactive waste management than one tier of government-making decisions. The working group also felt that the current Local Information Committees need to evolve towards more institutionalized and legitimized mechanisms for long-term involvement. Ms. Martell introduced a study comparing the efficiency of economic instruments to advance sustainable development in nuclear communities vs. municipalities in mining areas. The study found that funds transferred to nuclear zones had become a means to facilitate local acceptance of nuclear facilities rather than a means to promote socio-economic development. Another finding is that economic instruments are not sufficient guarantees of sustainable development by themselves; additional preconditions include leadership, vision and entrepreneur-ship on the part of community leaders, private or public investments, among others. Finally, Ms. Martell summarised the challenges faced by the Spanish radioactive waste management programme, which include the need for strategic thinking, designing the future in a participatory fashion, and working with local and regional governments and citizens to devise mechanisms for social learning, economic development and environmental protection. (author)

  3. Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

    Directory of Open Access Journals (Sweden)

    Juan Ruiz-Bañobre

    2016-11-01

    Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

  4. Long term aspects of uranium tailings management

    International Nuclear Information System (INIS)

    Bragg, K.

    1980-05-01

    This paper sets out the background issues which lead to the development of interim close-out criteria for uranium mill tailings. It places the current state-of-the-art for tailings management into both a national and international perspective and shows why such interim criteria are needed now. There are seven specific criteria proposed dealing with the need to have: passive barriers, limits on surface water recharge, durable systems, long term performance guarantees, limits to access, controls on water and airborne releases and finally to have a knowledge of exposure pathways. This paper is intended to serve as a focus for subsequent discussions with all concerned parties. (auth)

  5. Human Behaviour in Long-Term Missions

    Science.gov (United States)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  6. Optimal Long-Term Financial Contracting

    OpenAIRE

    Peter M. DeMarzo; Michael J. Fishman

    2007-01-01

    We develop an agency model of financial contracting. We derive long-term debt, a line of credit, and equity as optimal securities, capturing the debt coupon and maturity; the interest rate and limits on the credit line; inside versus outside equity; dividend policy; and capital structure dynamics. The optimal debt-equity ratio is history dependent, but debt and credit line terms are independent of the amount financed and, in some cases, the severity of the agency problem. In our model, the ag...

  7. Determination of relative assay response factors for toxic chlorinated and brominated dioxins/furans using an enzyme immunoassay (EIA) and a chemically-activated luciferase gene expression cell bioassay (CALUX).

    Science.gov (United States)

    Samara, Fatin; Gullett, Brian K; Harrison, Robert O; Chu, Andrew; Clark, George C

    2009-04-01

    Determination of toxic activity requires knowledge of both the concentration and toxicity to evaluate the risk for adverse human health and environmental effects. A chemically-activated luciferase gene expression cell bioassay system (CALUX) and an antibody-based method enzyme immunoassay (EIA) were used to detect the dioxin-like response of several polybrominated, polychlorinated, and polybrominated/chlorinated dibenzo-p-dioxins/furans (PBDDs/Fs, PCDDs/Fs, and PBCDDs/Fs, respectively). It has been suggested that the biological activity of the brominated and mixed bromo/chloro compounds is similar to their chlorinated analogues (measured by binding to the Ah receptor). PBDD/F, PCDD/F, and PBCDD/F laboratory standards exhibited biological activity ranging over three orders of magnitude. The highest relative potency (REP) values from CALUX analysis, when compared to 2,3,7,8-TCDD, were 2,3,7,8-TBDD at 0.99 (+/-0.07), 1,2,3,7,8-PeCDD at 0.69, and 2-Br-3,7,8-TriCDD at 0.72 (+/-0.02). Cross-reactivities were calculated using EIA for several PBDDs/Fs and PBCDDs. The highest percent cross-reactivity was found for 2,3,7,8-TBDD at 138 (+/-34%), and 2,3,7-TriBDD at 84 (+/-36%).

  8. Long-Term Implications of the Fiscal Year 2009 Future Years Defense Program

    National Research Council Canada - National Science Library

    Talaber, Adam; Arthur, David; Bass, Elizabeth; Bennett, Michael; Eveker, Kevin; Frisk, Daniel; Labs, Eric J; Lussier, Frances; Percy, Allison; Hall, Raymond; Newman, David; Regan, Dawn S; Schmit, Matthew; Wheelock, Jason; Kelley, Kate

    2009-01-01

    ...) has published a series of reports about its projections of the resources that might be needed over the long term to carry out the Bush Administration's plans as expressed in the Future Years Defense Program (FYDP...

  9. Long-term environmental behaviour of radionuclides

    International Nuclear Information System (INIS)

    Brechignac, F.; Moberg, L.; Suomela, M.

    2000-04-01

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: i) redistribution in the soil-plant system, ii) modelling, iii) countermeasures, iv) runoff v) spatial variations, and vi) dose assessment. The long term behaviour of the radionuclides 137 Cs, 90 Sr and 239-240 Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  10. Craniopharyngioma in Children: Long-term Outcomes

    Science.gov (United States)

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  11. Institutionalization and Organizational Long-term Success

    Directory of Open Access Journals (Sweden)

    Denise L. Fleck

    2007-05-01

    Full Text Available Institutionalization processes have an ambivalent effect on organizational long-term success. Even though they foster organizational stability and permanence, they also bring about rigidity and resistance to change. As a result, successful organizations are likely to lose their competitive advantage over time. The paper addresses this issue through the investigation of the institutionalization processes of two long-lived companies: General Electric, a firm that has been a long-term success and its rival, Westinghouse, which was broken up after eleven decades of existence. The longitudinal, multilevel analysis of firms and industry has identified two different modes of organizational institutionalization. The reactive mode gives rise to rigidity and change resistance, much like institutional theory predicts; the proactive mode, on the other hand, neutralizes those negative effects of institutionalization processes. In the reactive mode, structure predominates. In the proactive mode, agency plays a major role in organizational institutionalization, and in managing the organization’s relations with the environment, clearly contributing to environmental institutionalization.

  12. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

    Huslage, J; Brack, H P; Geiger, F; Buechi, F N; Tsukada, A; Scherer, G G [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  13. Neo bladder long term follow-up

    International Nuclear Information System (INIS)

    Fakhr, I.; Mohamed, A. M.; Moustafa, A.; Al-Sherbiny, M.; Salama, M.

    2013-01-01

    One of the commonest forms of orthotopic bladder substitution for bladder cancer surivors, used in our institute, is the use of ileocecal segment. Sometimes, the need for Indiana pouch heterotropic continent diversion arises. Aim: To compare the long-term effect of orthotopic ileocecal bladder and heterotropic Indiana pouch following radical cystectomy in bladder cancer patients. Patients and methods: Between January 2008 and December 2011, 91 patients underwent radical cystectomy/anterior pelvic exentration and ortho topic ileocecal bladder reconstruction (61 patients) and Indiana pouch (30 patients), when orthotopic diversion could not be technically or oncologically feasible. Results: Convalescence was uneventful in most patients. All minor and major urinary leakage cases, in both diversions groups, where successfully conservatively treated. Only one patient in the ileocecal group with major urinary leak required re-exploration with successful revision of uretro-colonic anastomosis. Only one patient in the Indiana pouch group had accidentally discovered sub-centimetric stone, which was simply expelled. The overall survival proportion of ileocecal group was 100% compared to 80% in the Indiana pouch group (p < 0.001). The disease free survival proportion of ileocecal group was 90.8% compared to 80% in the Indiana pouch group (p = 0.076). Effective comparative daytime and nighttime urinary continence as well as renal function deterioration were not statistically significant between both reconstruction types. Conclusion: Both ileocecal bladder and Indiana pouch are safe procedures in regard to long-term effects over kidney function following radical cystectomy

  14. Toward a comprehensive long term nicotine policy.

    Science.gov (United States)

    Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

    2005-06-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

  15. Long term ground movement of TRISTAN synchrotron

    International Nuclear Information System (INIS)

    Endo, K.; Ohsawa, Y.; Miyahara, M.

    1989-01-01

    The long term ground movement is estimated through the geological survey before a big accelerator is planned. For the case of TRISTAN-MR (main ring), its site was surveyed to reflect the underground information to the building prior to the construction. The movement of the synchrotron magnet mainly results from the structure of the tunnel. If an individual movement of the magnet exceeds a certain threshold limit, it gives a significant effect on the particle behavior in a synchrotron. Height of the quadrupole magnets were observed periodically during past two years at the TRISTAN-MR and their height differences along the 3 km circumference of the accelerator ring were decomposed into the Fourier components depicting the causes of the movements. Results shows the movement of the tunnel foundation which was also observed by the simultaneous measurement of both magnets and fiducial marks on the tunnel wall. The long term movement of the magnets is summarized with the geological survey prior to construction. 1 ref., 6 figs., 1 tab

  16. Long-term environmental behaviour of radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Brechignac, F.; Moberg, L.; Suomela, M

    2000-04-01

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: (i) redistribution in the soil-plant system, (ii) modelling, (iii) countermeasures, (iv) runoff (v) spatial variations, and (vi) dose assessment. The long term behaviour of the radionuclides {sup 137}Cs, {sup 90}Sr and {sup 239-240}Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  17. Long-term preservation of anammox bacteria.

    Science.gov (United States)

    Rothrock, Michael J; Vanotti, Matias B; Szögi, Ariel A; Gonzalez, Maria Cruz Garcia; Fujii, Takao

    2011-10-01

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass was frozen or lyophilized at two different freezing temperatures (-60°C and in liquid nitrogen (-200°C)) in skim milk media (with and without glycerol), and the reactivation of anammox activity was monitored after a 4-month storage period. Of the different preservation treatments tested, only anammox biomass preserved via freezing in liquid nitrogen followed by lyophilization in skim milk media without glycerol achieved stoichiometric ratios for the anammox reaction similar to the biomass in both the parent bioreactor and in the freshly harvested control treatment. A freezing temperature of -60°C alone, or in conjunction with lyophilization, resulted in the partial recovery of the anammox bacteria, with an equal mixture of anammox and nitrifying bacteria in the reactivated biomass. To our knowledge, this is the first report of the successful reactivation of anammox biomass preserved via sub-zero freezing and/or lyophilization. The simple preservation protocol developed from this study could be beneficial to accelerate the integration of anammox-based processes into current treatment systems through a highly efficient starting anammox biomass.

  18. Andra long term memory project - 59277

    International Nuclear Information System (INIS)

    Charton, Patrick; Boissier, Fabrice; Martin, Guillaume

    2012-01-01

    Document available in abstract form only. Full text of publication follows: Long term memory of repositories is required by safety, reversibility and social expectations. Thus Andra has implemented since 2010 a long-term memory project to reinforce and diversify its current arrangements in this field, as well as to explore opportunities to extend memory keeping over thousands years. The project includes opportunity studies of dedicated facilities. The 'Ecotheque' and 'Geotheque' projects contribute to memory respectively through environmental and geological samples preservation. The options of creating (i) an archive centre for Andra's interim and permanent archives, (ii) an artist center to study the contribution of arts to memory preservation, (iii) a museum of radioactive waste disposal history and technology (radium industry..., sea disposal, current solutions...) are considered. Other studies provided by the project examine our heritage. This includes the continuity of languages and symbolic systems, the continuity of writing and engraving methods, the archaeology of landscapes (memory of the earths evolution, multi-century memory of industrial and agricultural landscapes), the archaeology practices (how might a future archaeologist be interested in our current activity?), the preservation of historical sites and industrial memory, the continuity of institutional organizations, the memory and history of science evolution as well as broad history

  19. Long term creep behavior of concrete

    International Nuclear Information System (INIS)

    Kennedy, T.W.

    1975-01-01

    This report presents the findings of an experimental investigation to evaluate the long term creep behavior of concrete subjected to sustained uniaxial loads for an extended period of time at 75 0 F. The factors investigated were (1) curing time (90, 183, and 365 days); (2) curing history (as-cast and air-dried); and (3) uniaxial stress (600 and 2400 psi). The experimental investigation applied uniaxial compressive loads to cylindrical concrete specimens and measured strains with vibrating wire strain gages that were cast in the concrete specimen along the axial and radial axes. Specimens cured for 90 days prior to loading were subjected to a sustained load for a period of one year, at which time the loads were removed; the specimens which were cured for 183 or 365 days, however, were not unloaded and have been under load for 5 and 4.5 years, respectively. The effect of each of the above factors on the instantaneous and creep behavior is discussed and the long term creep behavior of the specimens cured for 183 or 365 days is evaluated. The findings of these evaluations are summarized. (17 figures, 10 tables) (U.S.)

  20. Sleep facilitates long-term face adaptation.

    Science.gov (United States)

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  1. Luciferase assay to study the activity of a cloned promoter DNA fragment.

    Science.gov (United States)

    Solberg, Nina; Krauss, Stefan

    2013-01-01

    Luciferase based assays have become an invaluable tool for the analysis of cloned promoter DNA fragments, both for verifying the ability of a potential promoter fragment to drive the expression of a luciferase reporter gene in various cellular contexts, and for dissecting binding elements in the promoter. Here, we describe the use of the Dual-Luciferase(®) Reporter Assay System created by Promega (Promega Corporation, Wisconsin, USA) to study the cloned 6.7 kilobases (kb) mouse (m) Tcf3 promoter DNA fragment in mouse embryonic derived neural stem cells (NSC). In this system, the expression of the firefly luciferase driven by the cloned mTcf3 promoter DNA fragment (including transcription initiation sites) is correlated with a co-transfected control reporter expressing Renilla luciferase from the herpes simplex virus (HSV) thymidine kinase promoter. Using an internal control reporter allows to normalize the activity of the experimental reporter to the internal control, which minimizes experimental variability.

  2. Wnt Signaling Is Required for Long-Term Memory Formation

    Directory of Open Access Journals (Sweden)

    Ying Tan

    2013-09-01

    Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

  3. Long-term stability of salivary cortisol

    DEFF Research Database (Denmark)

    Garde, A H; Hansen, Åse Marie

    2005-01-01

    either stored in small vials or spiked to polyester Salivette tampons before analysis for cortisol using Spectria RIA kits. The effects of storage were evaluated by a linear regression model (mixed procedure) on a logarithmic scale. No effects on cortisol concentrations were found after storage of saliva......The measurement of salivary cortisol provides a simple, non-invasive, and stress-free measure frequently used in studies of the hypothalamic-pituitary-adrenal axis activity. In research projects, samples are often required to be stored for longer periods of time either because of the protocol...... of the project or because of lack of funding for analysis. The aim of the present study was to explore the effects of long-term storage of samples on the amounts of measurable cortisol. Ten pools of saliva were collected on polyester Salivette tampons from five subjects. After centrifugation the samples were...

  4. Long-term cryogenic space storage system

    Science.gov (United States)

    Hopkins, R. A.; Chronic, W. L.

    1973-01-01

    Discussion of the design, fabrication and testing of a 225-cu ft spherical cryogenic storage system for long-term subcritical applications under zero-g conditions in storing subcritical cryogens for space vehicle propulsion systems. The insulation system design, the analytical methods used, and the correlation between the performance test results and analytical predictions are described. The best available multilayer insulation materials and state-of-the-art thermal protection concepts were applied in the design, providing a boiloff rate of 0.152 lb/hr, or 0.032% per day, and an overall heat flux of 0.066 Btu/sq ft hr based on a 200 sq ft surface area. A six to eighteen month cryogenic storage is provided by this system for space applications.

  5. Long-term control of root growth

    Science.gov (United States)

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  6. Long term performance of radon mitigation systems

    International Nuclear Information System (INIS)

    Prill, R.; Fisk, W.J.

    2002-01-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes

  7. Rising Long-term Interest Rates

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    Rather than chronicle recent developments in European long-term interest rates as such, this paper assesses the impact of increases in those interest rates on economic performance and inflation. That puts us in a position to evaluate the economic pressures for further rises in those rates......, the first question posed in this assignment, and the scope for overshooting (the second question), and then make some illustrative predictions of future interest rates in the euro area. We find a wide range of effects from rising interest rates, mostly small and mostly negative, focused on investment...... till the emerging European recovery is on a firmer basis and capable of overcoming increases in the cost of borrowing and shrinking fiscal space. There is also an implication that worries about rising/overshooting interest rates often reflect the fact that inflation risks are unequally distributed...

  8. Prediction of long-term creep curves

    International Nuclear Information System (INIS)

    Oikawa, Hiroshi; Maruyama, Kouichi

    1992-01-01

    This paper aims at discussing how to predict long-term irradiation enhanced creep properties from short-term tests. The predictive method based on the θ concept was examined by using creep data of ferritic steels. The method was successful in predicting creep curves including the tertiary creep stage as well as rupture lifetimes. Some material constants involved in the method are insensitive to the irradiation environment, and their values obtained in thermal creep are applicable to irradiation enhanced creep. The creep mechanisms of most engineering materials definitely change at the athermal yield stress in the non-creep regime. One should be aware that short-term tests must be carried out at stresses lower than the athermal yield stress in order to predict the creep behavior of structural components correctly. (orig.)

  9. Hanford grout: predicting long-term performance

    International Nuclear Information System (INIS)

    Sewart, G.H.; Mitchell, D.H.; Treat, R.L.; McMakin, A.H.

    1987-01-01

    Grouted disposal is being planned for the low-level portion of liquid radioactive wastes at the Hanford site in Washington state. The performance of the disposal system must be such that it will protect people and the environment for thousands of years after disposal. To predict whether a specific grout disposal system will comply with existing and foreseen regulations, a performance assessment (PA) is performed. Long-term PAs are conducted for a range of performance conditions. Performance assessment is an inexact science. Quantifying projected impacts is especially difficult when only scant data exist on the behavior of certain components of the disposal system over thousands of years. To develop defensible results, we are honing the models and obtaining experimental data. The combination of engineered features and PA refinements is being used to ensure that Hanford grout will meet its principal goal: to protect people and the environment in the future

  10. The discovery of long-term potentiation.

    Science.gov (United States)

    Lømo, Terje

    2003-04-29

    This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.

  11. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P

    2017-01-01

    significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

  12. Long Term Planning at IQ Metal

    DEFF Research Database (Denmark)

    2017-01-01

    This is a Danish version. This case about long term planning at the owner-managed manufacturing firm IQ Metal shows how the future management and ownership may be organized to utilize owner assets and minimize roadblocks. Initially, the owner-manager Bo Fischer Larsen explains how he acquired...... a stake in 2007 in the company which at that time was named Braendstrup Maskinfabrik. He furthermore expalins how he has developed the company based on a strategic plan focusing on professionalization and outsourcing. Next, the video shows how to type Bo Fischer Larsen's replies to the questions...... in The Owner Strategy Map into the questionnaire available on www.ejerstrategi-kortet.dk. Lastly, the Owner Strategy Map's recommendation of how to organize the future management and ownership of IQ Metal is explained....

  13. Long-term Consequences of Early Parenthood

    DEFF Research Database (Denmark)

    Johansen, Eva Rye; Nielsen, Helena Skyt; Verner, Mette

    (and to lesser extent employment), as fathers appear to support the family, especially when early parenthood is combined with cohabitation with the mother and the child. Heterogeneous effects reveal that individuals with a more favorable socioeconomic background are affected more severely than......Having children at an early age is known to be associated with unfavorable economic outcomes, such as lower education, employment and earnings. In this paper, we study the long-term consequences of early parenthood for mothers and fathers. Our study is based on rich register-based data that......, importantly, merges all childbirths to the children’s mothers and fathers, allowing us to study the consequences of early parenthood for both parents. We perform a sibling fixed effects analysis in order to account for unobserved family attributes that are possibly correlated with early parenthood...

  14. Long term radiological impact of thorium extraction

    International Nuclear Information System (INIS)

    Menard, S.; Schapira, J.P.

    1995-01-01

    Thorium extraction produces a certain amount of radioactive wastes. Potential long term radiological impact of these residues has been calculated using the recent ICRP-68 ingestion dose factors in connection with the computing code DECAY, developed at Orsay and described in this work. This code solves the well known Bateman's equations which govern the time dependence of a set of coupled radioactive nuclei. Monazites will be very likely the minerals to be exploited first, in case of an extensive use of thorium as nuclear fuel. Because monazites contain uranium as well, mining residues will contain not only the descendants of 232 Th and a certain proportion of non-extracted thorium (taken here to be 5%), but also this uranium, if left in the wastes for economical reasons. If no uranium would be present at all in the mineral, the potential radiotoxicity would strongly decrease in approximately 60 years, at the pace of the 5.8 years period of 228 Ra, which becomes the longest-lived radionuclide of the 4n radioactive family in the residues. Moreover, there is no risk due to radon exhalation, because of the very short period of 220 Rn. These significant differences between uranium and thorium mining have to be considered in view of some estimated long term real radiological impacts due to uranium residues, which could reach a value of the order of 1 mSv/year, the dose limit recommended for the public by the recent ICRP-60. (authors). 15 refs., 4 figs., 3 tabs., 43 appendices

  15. Managing Records for the Long Term - 12363

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, John V. [U.S. Department of Energy, Office of Legacy Management, Morgantown, West Virginia (United States); Gueretta, Jeanie [U.S. Department of Energy, Office of Legacy Management, Grand Junction, Colorado (United States)

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the

  16. Pension system in Romania. Long term imbalances and inconsistent policies

    Directory of Open Access Journals (Sweden)

    Ph. D. Associate Professor Razvan Papuc

    2012-05-01

    Full Text Available Public policies on retirement, both in Romania and in other EU countries, have been and still are conditioned by numerous short-term budgetary constaints and by long term major sustainability problems. Alongside objective, demographic developments known in all European countries , support systems for the elderly are facing numerous constraints, both due to government policies marked by fiscal indiscipline and lack of consistency of decisions and, hence, credibility phenomena caused by the phenomenon "the captive politician of a redistributive policy model". Modeling support institutions for pensioners by political actors was most of the times the expression of elections marked by Weberian instrumental rationality and not by wertrationalitat, using the axiom- guide for the behaviour of decision markers to "meet social interests in order to come to power" and not by the concern for a more long term efficient trans-redistributive approach. This paper aims to pursue the most important imbalances that chartacterize the public pension system in Romania, expression of decisions determined by aggregating in group individual preferences and noy by both rational and ethical analysis without redistribution centres.

  17. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  18. Robotics for Long-Term Monitoring

    International Nuclear Information System (INIS)

    Shahin, Sarkis; Duran, Celso

    2002-01-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  19. Long-Term Clock Behavior of GPS IIR Satellites

    National Research Council Canada - National Science Library

    Epstein, Marvin; Dass, Todd; Rajan, John; Gilmour, Paul

    2007-01-01

    .... Rubidium clocks, as opposed to cesium clocks, have significant long-term drift. The current literature describes an initial model of drift aging for rubidium atomic clocks followed by a long-term characteristic...

  20. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  1. Long term results of mandibular distraction

    Directory of Open Access Journals (Sweden)

    Batra Puneet

    2006-03-01

    Full Text Available Mandibular distraction osteogenesis has become a popular surgical modality due to its many advantages over conventional orthognathic surgical procedures. However, in spite of the technique having been used for over 15 years, no concrete long term results are available regarding the stability of results. We discuss the various studies which have reported either in favour or against the stablility of results after distraction. We report a series of 6 cases (3 unilateral and 3 bilateral distraction where distraction was carried out before puberty and followed them up to seven years after removal of distractors. This case series shows that results achieved by distraction osteogenesis are unstable or best unpredictable with respect to producing a permanent size increase in the mandible. The role of the distraction osteogenesis in overcoming the pterygomassetric sling is questionable. We suggest a multicenter study with adequate patient numbers treated with a similar protocol and documented after growth cessation to have meaningful conclusions on the debate of distraction osteogenesis versus orthognathic surgery.

  2. [Perioperative management of long-term medication].

    Science.gov (United States)

    Vogel Kahmann, I; Ruppen, W; Lurati Buse, G; Tsakiris, D A; Bruggisser, M

    2011-01-01

    Anesthesiologists and surgeons are increasingly faced with patients who are under long-term medication. Some of these drugs can interact with anaesthetics or anaesthesia and/or surgical interventions. As a result, patients may experience complications such as bleeding, ischemia, infection or severe circulatory reactions. On the other hand, perioperative discontinuation of medication is often more dangerous. The proportion of outpatient operations has increased dramatically in recent years and will probably continue to increase. Since the implementation of DRGs (pending in Switzerland, introduced in Germany for some time), the patient enters the hospital the day before operation. This means that the referring physician as well as anesthesiologists and surgeons at an early stage must deal with issues of perioperative pharmacotherapy. This review article is about the management of the major drug classes during the perioperative period. In addition to cardiac and centrally acting drugs and drugs that act on hemostasis and the endocrine system, special cases such as immunosuppressants and herbal remedies are mentioned.

  3. Long term agreements energy efficiency. Progress 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-11-01

    Long Term Agreements (LTAs) on energy efficiency have been contracted with various business sectors since 1992, as part of energy conservation policy: industrial sectors, commercial services, agrarian sectors and non-profit services. LTAs are voluntary agreements between a specific sector and the Minister of Economic Affairs. In some cases, the Minister of Agriculture, Nature Management and Fisheries is also involved. The sector commits to an effort to improve energy efficiency by a particular percentage within an agreed period. As at 31 December 1999, a total of 29 LTAs had been contracted with industrial sectors and 14 with non-industrial ones. This report describes the progress of the LTAs in 1999. It reviews the energy efficiency improvements realised through the LTAs, both overall and in each individual sector. The aim is to make the efforts and results in the various sectors accessible to the general public. Appendix 1 describes the positioning of the LTA instrument. This Appendix provides and insight into the position of the LTAs within the overall set of policy instruments. It also covers the subsidy schemes and fiscal instruments that support the LTAs, the relationships between LTAs and environmental policy and new developments relating to the LTAs in the years ahead. Appendices 2 to 6 contain the reports on the LTAs and a list of abbreviations (Appendix 7)

  4. Long-term outcome of neuroparacoccidioidomycosis treatment

    Directory of Open Access Journals (Sweden)

    Fabio Francesconi

    2011-02-01

    Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

  5. Long term prospects for world gas trade

    International Nuclear Information System (INIS)

    Linder, P.T.

    1991-01-01

    Results are presented from a world gas trade model used to forecast long term gas markets. Assumptions that went into the model are described, including the extent of current proven gas reserves, production ratios, total energy and gas demand, gas supply cost curves for each producing country, available gas liquefaction and transportation facilities, and liquefied natural gas (LNG) shipping costs. The results indicate that even with generally very low supply costs for most gas producing basins, gas trade will continue to be restricted by the relatively high cost of transportation, whether by pipeline or tanker. As a consequence, future gas trade will tend to be regionally oriented. United States gas imports will come mostly from Canada, Venezuela, and Mexico; Western Europe will largely be supplied by the Soviet Union and Africa, and Japan's requirements will generally be met by Pacific Rim producers. Although the Middle East has vast quantities of gas reserves, its export growth will continue to be hampered by its remote location from major markets. 16 figs

  6. Long term results of childhood dysphonia treatment.

    Science.gov (United States)

    Mackiewicz-Nartowicz, Hanna; Sinkiewicz, Anna; Bielecka, Arleta; Owczarzak, Hanna; Mackiewicz-Milewska, Magdalena; Winiarski, Piotr

    2014-05-01

    The aim of this study was to assess the long term results of treatment and rehabilitation of childhood dysphonia. This study included a group of adolescents (n=29) aged from 15 to 20 who were treated due to pediatric hyperfunctional dysphonia and soft vocal fold nodules during their pre-mutational period (i.e. between 5 and 12 years of age). The pre-mutational therapy was comprised of proper breathing pattern training, voice exercises and psychological counseling. Laryngostroboscopic examination and perceptual analysis of voice were performed in each patient before treatment and one to four years after mutation was complete. The laryngostroboscopic findings, i.e. symmetry, amplitude, mucosal wave and vocal fold closure, were graded with NAPZ scale, and the GRBAS scale was used for the perceptual voice analysis. Complete regression of the childhood dysphonia was observed in all male patients (n=14). Voice disorders regressed completely also in 8 out of 15 girls, but symptoms of dysphonia documented on perceptual scale persisted in the remaining seven patients. Complex voice therapy implemented in adolescence should be considered as either the treatment or preventive measure of persistent voice strain, especially in girls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Long-term data storage in diamond

    Science.gov (United States)

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies. PMID:27819045

  8. Long-term data storage in diamond.

    Science.gov (United States)

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A

    2016-10-01

    The negatively charged nitrogen vacancy (NV - ) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV - optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV - ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center's charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV - ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.

  9. Long-term predictions using natural analogues

    International Nuclear Information System (INIS)

    Ewing, R.C.

    1995-01-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10 3 -10 5 years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., open-quotes natural analoguesclose quotes) provide perhaps the only means of partial open-quotes validation,close quotes as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10 3 -10 8 years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the open-quotes validationclose quotes of performance assessments

  10. Long-term effects of islet transplantation.

    Science.gov (United States)

    Holmes-Walker, D Jane; Kay, Thomas W H

    2016-10-01

    Islet transplantation has made great progress in recent years. This is a remarkable technical feat but raises the question of what the long-term benefits and risks are for type I diabetes recipients. Graft survival continues to improve, and recent multicenter studies show that islet transplantation is particularly effective to prevent hypoglycemic events even in those who do not become insulin-independent and to achieve excellent glycemic control. Concerns include histocompatability leucocyte antigen (HLA) sensitization and other risks including from immunosuppression that islet transplantation shares with other forms of allotransplantation. Reversal of hypoglycemia unawareness and protection from severe hypoglycemia events are two of the main benefits of islet transplantation and they persist for the duration of graft function. Islet transplantation compares favorably with other therapies for those with hypoglycemia unawareness, although new technologies have not been tested head-to-head with transplantation. HLA sensitization increases with time after transplantation especially if immunosuppression is ceased and is a risk for those who may require future transplantation as well as being associated with loss of graft function.

  11. CERN Services for Long Term Data Preservation

    CERN Document Server

    Shiers, Jamie; Blomer, Jakob; Ganis, Gerardo; Dallmeier-Tiessen, Sunje; Simko, Tibor; Cancio Melia, German; CERN. Geneva. IT Department

    2016-01-01

    In this paper we describe the services that are offered by CERN for Long Term preservation of High Energy Physics (HEP) data, with the Large Hadron Collider (LHC) as a key use case. Data preservation is a strategic goal for European High Energy Physics (HEP), as well as for the HEP community worldwide and we position our work in this global content. Specifically, we target the preservation of the scientific data, together with the software, documentation and computing environment needed to process, (re-)analyse or otherwise (re-)use the data. The target data volumes range from hundreds of petabytes (PB – 10^15 bytes) to hundreds of exabytes (EB – 10^18 bytes) for a target duration of several decades. The Use Cases driving data preservation are presented together with metrics that allow us to measure how close we are to meeting our goals, including the possibility for formal certification for at least part of this work. Almost all of the services that we describe are fully generic – the exception being A...

  12. Containment long-term operational integrity

    International Nuclear Information System (INIS)

    Sammataro, R.F.

    1990-01-01

    Periodic integrated leak rate tests are required to assure that containments continue to meet allowable leakage limits. Although overall performance has been quite good to date, several major containment aging and degradation mechanisms have been identified. Two pilot plant life extension (PLEX) studies serve as models for extending the operational integrity of present containments for light-water cooled nuclear power plants in the United States. One study is for a Boiling-Water Reactor (BWR) and the second is for a Pressurized-Water Reactor (PWR). Research and testing programs for determining the ultimate pressure capacity and failure mechanisms for containments under severe loading conditions and studies for extending the life of current plants beyond the present 40-year licensed lifetime are under way. This paper presents an overview of containment designs in the United States. Also presented are a discussion of the American Society of Mechanical Engineers Boiler and Pressure Vessel Code (ASME Code) and regulatory authority requirements for the design, construction, inservice inspection, leakage testing and repair of steel and concrete containments. Findings for containments from the pilot PLEX studies and continuing containment integrity research and testing programs are discussed. The ASME Code and regulatory requirements together with recommendations from the PLEX studies and containment integrity research and testing provide a basis for continued containment long-term operational integrity. (orig./GL)

  13. Long term results of compression sclerotherapy.

    Science.gov (United States)

    Labas, P; Ohradka, B; Cambal, M; Reis, R; Fillo, J

    2003-01-01

    To compare the short and long term results of different techniques of compression sclerotherapy. In the past 10 years the authors treated 1622 pts due to chronic venous insufficiency. There were 3 groups of patients: 1) Pts treated by Sigg's technique using Aethoxysclerol, 2) Pts treated by Fegan's technique with Fibrovein, and 3) Pts treated by Fegan's procedure, but using a combination of both sclerosants. In all cases, the techniques of empty vein, bubble air, uninterrupted 6-week compression and forced mobilisation were used. In the group of pats. treated by Sigg's procedure, the average cure rate was 67.47% after 6 months, 60.3% after 5 years of follow-up. In Fegan's group this rate was 83.6% after 6 months and 78.54% after 5 year assessment. Statistically, significant differences were found only by the disappearance of varices and reduction of pain in favour of Fegan's technique. In the group of pts treated by Fegan's (Aethoxysclerol + Fibrovein) this rate after 5 years was 86%. The only statistically significant difference was found by the disappearance of varices in favour of Fegan's technique using a combination of 2 detergent sclerosants. Sclerotherapy is effective when properly executed in any length of vein no matter how dilated it has become. The recurrences are attributed more to inadequate technique than to the shortcoming of the procedure. Sclerotherapy is miniinvasive, with few complications, and can be repeated on out-patient basis. (Tab. 1, Ref. 22.).

  14. Transuranic waste: long-term planning

    International Nuclear Information System (INIS)

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig

  15. Long-term plutonium storage: Design concepts

    International Nuclear Information System (INIS)

    Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

    1994-01-01

    An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs

  16. Cloning and expression analysis of myostatin, fibroblast growth factor 6, insulin-like growth factor I and II in liver and muscle of sea bass (Dicentrarchus labrax, L. during long-term fasting and refeeding

    Directory of Open Access Journals (Sweden)

    M. Saroglia

    2010-04-01

    Full Text Available The exceptionally fast growth that fish experience after periods of fasting has been called “compensatory growth”. This phenomenon has been studied in intensive aquaculture as a means of enhancing growth rates, but the mechanisms by which food intake activates an increase in somatic growth, and especially in muscle growth, are complex and not yet fully understood. In the present paper, we describe the molecular cloning and sequencing of sea bass (Dicentrarchus labrax myostatin (MSTN and fibroblast growth factor 6 (FGF6, which have been shown to be major genetic determinants of skeletal muscle growth, together with insulin-like growth factor I (IGFI and IGF-II, which are potent mitogens known to play important roles in growth and development. We then report the pattern of expression of the four aforementioned genes, in liver and myotomal muscle in response to prolonged fasting and refeeding. Nutritional status significantly influenced the expression of IGF-I, IGF-II and MSTN, whereas the muscular FGF6 expression levels were not affected by the feeding status of the animals. Taken together these data indicate that IGF-I, IGF-II and MSTN are involved in the sea bass muscle compensatory growth induced by refeeding, whereas FGF6 probably has not a role in this phenomenon.

  17. Essays on long-term mortality and interest rate risk

    NARCIS (Netherlands)

    de Kort, J.P.

    2017-01-01

    This dissertation comprises a study of long-term risks which play a major role in actuarial science. In Part I we analyse long-term mortality risk and its impact on consumption and investment decisions of economic agents, while Part II focuses on the mathematical modelling of long-term interest

  18. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  19. Acute and long-term nutrient-led modifications of gene expression: potential role of SIRT1 as a central co-ordinator of short and longer-term programming of tissue function.

    Science.gov (United States)

    Holness, Mark J; Caton, Paul W; Sugden, Mary C

    2010-05-01

    Environmental factors can influence the acute and longer-term risks of developing diseases, including type 2 diabetes mellitus and cardiovascular disease; however, the underlying mechanism remains elusive. Increasing evidence suggests that these effects can be achieved by modification of metabolic gene expression. These include acute changes in histone methylation, acetylation, phosphorylation, and ubiquitination and longer-term DNA silencing elicited by DNA methylation. Thus, an increased risk of disease may reflect acute or chronic stable modification of genes that regulate nutrient handling, leading to altered nutrient utilization (increased lipid oxidation at the expense of glucose utilization) and/or changes in the balance between nutrient storage and energy production, thereby favoring the development of obesity. The review addresses the hypothesis that early-life epigenetic programming of gene expression could be mirrored by changes in acute function of nuclear receptors, in particular the peroxisome proliferator-activated receptors, achieved by enzymes that are more conventionally involved in regulating DNA methylation and post-transcriptional modification of histones. Emphasis is placed on the potential importance of the protein deacetylase sirtuin-1 as a central co-ordinator. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Energy in 2010 - 2020. Long term challenges; Energie 2010-2020. Les defis du long terme

    Energy Technology Data Exchange (ETDEWEB)

    Dessus, Benjamin [ed.] [Centre National de la Recherche Scientifique (CNRS), 75 - Paris (France)

    2000-02-02

    This report presents the results of a workshop intending to anticipate the long term challenges, to guide better the short term power options, to understand the available political, economical and technical assumptions for the prospective world situation, to give some strategic hints on the necessary transition. Indeed, the difficult issue which the workshop tried to tackle was how should we prepare to reveal the energetic challenge of the development of the eight to ten billion inhabitants of our Planet in the next century without jeopardizing its existence. The energetic problems, a hardcore of the international preoccupation of both growth and environment, as it was recently evidenced by the climatic conference in Kyoto, have ever been the object of a particular attention on the part of General Commissariat of Plan. Thus, the commission 'Energy in 2010 - 2020' has been instituted in April 1996 in order to update the works done in 1990 - 1991 by the commission 'Energy 2010'. Soon it occurred to this new commission the task of illuminating its works by a long term (2050 - 2100) world prospective analysis of the challenges and problems linked to energy, growth and environment. In conclusion, this document tried to find answers to questions like: - which are the risks the energy consumption augmentation entail? - can we control them by appropriate urbanism and transport policies or technological innovation?. Four options for immediate action are suggested: - the energy efficiency should become a priority objective of policies; -coping with the long term challenges requires acting at present; - building the transition between governmental leadership and market; - taking profit of all the possible synergies between short and long term planning.

  1. Monitoring long-term oral corticosteroids.

    Science.gov (United States)

    Mundell, Lewis; Lindemann, Roberta; Douglas, James

    2017-01-01

    Corticosteroids are synthetic analogues of human hormones normally produced by the adrenal cortex. They have both glucocorticoid and mineralocorticoid properties. The glucocortoid components are anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictive. They influence the metabolism of carbohydrate and protein, in addition to playing a key role in the body's stress response. Mineralocorticoid's main significance is in the balance of salt and water concentrations. Due to the combination of these effects, corticosteroids can cause many adverse effects. Oral corticosteroids are absorbed systemically and are therefore more likely to cause adverse effects than topical or inhaled corticosteroids. Furthermore, it is assumed that greater duration of treatment will lead to a greater number of adverse effects, and therefore the most at risk group are those taking high dose, long-term oral corticosteroids (LTOC). High dose is defined as a prescription of >5 mg oral prednisolone and long term as duration of treatment >1 month (based on National Institute for Health and Care Excellence guidance for patient's 'at risk' of systemic side effects). Parameters to be monitored in primary care include weight, blood pressure, triglycerides, glucose and urea and electrolytes. From clinical experience within the general practice setting, the authors propose that these patients do not receive adequate baseline monitoring before starting corticosteroids nor are these markers monitored consistently thereafter. This project intended to evidence this claim, evaluate the adverse effect profile and improve monitoring in this patient group. The initial audit of 22 patients, within a single general practice, detected at least one documented adverse effect in 64% of patients, while 41% reported more than one adverse effect. 45% had recorded weight gain, 18% had recorded osteoporosis, 18% had at least one recorded cataract, 14% had recorded Hypertension, 14% had recorded

  2. A security/safety survey of long term care facilities.

    Science.gov (United States)

    Acorn, Jonathan R

    2010-01-01

    What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

  3. HLW Long-term Management Technology Development

    International Nuclear Information System (INIS)

    Choi, Jong Won; Kang, C. H.; Ko, Y. K.

    2010-02-01

    Permanent disposal of spent nuclear fuels from the power generation is considered to be the unique method for the conservation of human being and nature in the present and future. In spite of spent nuclear fuels produced from power generation, based on the recent trends on the gap between supply and demand of energy, the advance on energy price and reduction of carbon dioxide, nuclear energy is expected to play a role continuously in Korea. It means that a new concept of nuclear fuel cycle is needed to solve problems on spent nuclear fuels. The concept of the advanced nuclear fuel cycle including PYRO processing and SFR was presented at the 255th meeting of the Atomic Energy Commission. According to the concept of the advanced nuclear fuel cycle, actinides and long-term fissile nuclides may go out of existence in SFR. And then it is possible to dispose of short term decay wastes without a great risk bearing. Many efforts had been made to develop the KRS for the direct disposal of spent nuclear fuels in the representative geology of Korea. But in the case of the adoption of Advanced nuclear fuel cycle, the disposal of PYRO wastes should be considered. For this, we carried out the Safety Analysis on HLW Disposal Project with 5 sub-projects such as Development of HLW Disposal System, Radwaste Disposal Safety Analysis, Feasibility study on the deep repository condition, A study on the Nuclide Migration and Retardation Using Natural Barrier, and In-situ Study on the Performance of Engineered Barriers

  4. The long-term nuclear explosives predicament

    International Nuclear Information System (INIS)

    Swahn, J.

    1992-01-01

    A scenario is described, where the production of new military fissile materials is halted and where civil nuclear power is phased out in a 'no-new orders' case. It is found that approximately 1100 tonnes of weapons-grade uranium, 233 tonnes of weapons-grade plutonium and 3795 tonnes of reactor-grade plutonium have to be finally disposed of as nuclear waste. This material could be used for the construction of over 1 million nuclear explosives. Reactor-grade plutonium is found to be easier to extract from spent nuclear fuel with time and some physical characteristics important for the construction of nuclear explosives are improved. Alternative methods for disposal of the fissile material that will avoid the long-term nuclear explosives predicament are examined. Among these methods are dilution, denaturing or transmutation of the fissile material and options for practicably irrecoverable disposal in deep boreholes, on the sea-bed, and in space. It is found that the deep boreholes method for disposal should be the primary alternative to be examined further. This method can be combined with an effort to 'forget' where the material was put. Included in the thesis is also an evaluation of the possibilities of controlling the limited civil nuclear activities in a post-nuclear world. Some surveillance technologies for a post-nuclear world are described, including satellite surveillance. In a review part of the thesis, methods for the production of fissile material for nuclear explosives are described, the technological basis for the construction of nuclear weapons is examined, including use of reactor-grade plutonium for such purposes; also plans for the disposal of spent fuel from civil nuclear power reactors and for the handling of the fissile material from dismantled warheads is described. The Swedish plan for the handling and disposal of spent nuclear fuel is described in detail. (490 refs., 66 figs., 27 tabs.)

  5. Long term results of pyeloplasty in adults

    International Nuclear Information System (INIS)

    Tayib, Abdul Malik

    2004-01-01

    To determine the presenting systems, complications, stone coincidence in adult patients with primary ureteropelvic junction (UPJ) obstruction seen at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. We are also reporting the success rate and long term results of adult pyeloplasty. We reviewed the records of 34 patients who underwent 37 pyeloplasty operations during the period January 1992 through to June 2002. The preoperative radiological diagnosis made by intravenous urogram or renal isotopes scan. We excluded from our study patients with previous history of passage of stones, renal or ureteral surgeries, large renal pelvis stone that may cause UPJ obstruction or abnormalities that may lead to secondry UPJ obstruction such as vesicoureteral reflux. There were 28 male patients and 8 females, their age varied between 16 and 51-years, the mean age was 36.1 years, and 18 (52.9%) patients had concomitant renal stones. Ispsilateral split renal function improved by 3-7% post pyeloplasty in 23 patients, while in one patient the function stayed the same, and in another patient the split function reduced by 4%. T1/2 renal isotopes washout time became less than 15 minutes in 19 patients and less than 20 minutes in 6 patients. Intravenous urogram revealed disappearence of the obstruction at UPJ in 7 patients while in 2 patients it became poorly functioning. Anderson Hynes pyeloplasty is an excellent procedure for treating UPJ obstruction in adults. Our success rate is comparable to the international repoted rates, while our study revealed a higher incidence of concomitant renal stones than the international studies. (author)

  6. Nutritional deficit and Long Term Potentiation alterations

    Directory of Open Access Journals (Sweden)

    M. Petrosino

    2009-01-01

    Full Text Available In the present work we examined the ability of prenatally malnourished offspring to produce and maintain long-term potentiation (LTP of the perforant path/dentate granule cell synapse in freely moving rats at 15,30, and 90 days of age. Population spike amplitude (PSA was calculated from dentate field potential recordings prior to and at 15, 30, 60 min. and 3, 5, 18 and 24 h following tetanization of the perforant pathway. All animals of both malnourished and well-nourished diet groups at 15 days of age showed potentiation of PSA measures but the measures obtained from 15-day-old prenatally malnourished animals were significantly less than that of age-matched, well-nourished controls. At 30 days of age, remarkable effect of tetanization was likely observed from PSA measures for this age group followed much the same pattern. At 90 days of age, PSA measures obtained from malnourished animals decreased from pretetanization levels immediately following tetanization. At this age, however, at three hours time recordings, this measure growing up to a level which did not differ significantly from that of the control group. These results indicate that the width of tetanization induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals is signifacantly affected fromgestational protein malnutrition and this trend is kept in animals tested at 30 and 90 days of age. The fact, however, that considerable limitation in LTP generation was gained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation starting at birth is an intervention strategy not capable to imbrove the effects of the gestational stress.

  7. Perinatal respiratory infections and long term consequences

    Directory of Open Access Journals (Sweden)

    Luciana Indinnimeo

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the

  8. Short- and long-term reproducibility of radioisotopic examination of gastric emptying

    Energy Technology Data Exchange (ETDEWEB)

    Jonderko, K. (Silesian School of Medicine, Katowice (Poland). Dept. of Gastroenterology)

    1990-01-01

    Reproducibility of gastric emptying (GE) of a radiolabelled solid meal was assessed. The short-term reproducibility was evaluated on the basis of 12 paired GE examinations performed 1-3 days apart. Twelve paired GE examinations taken 3-8 months apart enabled long-term reproducibility assessment. Reproducibility of GE parameters was expressed in terms of the coefficient of variation, CV. No significant between-day variation of solid GE was found either regarding the short-term or the long-term reproducibility. Although slightly higher CV values characterized the long-term reproducibility of the GE parameters considered, the variations of the differences between repeated GE examinations did not differ significantly between short- and long-term GE reproducibility. The results obtained justify the use of radioisotopic GE measurement for the assessment of early and late results of pharmacologic or surgical management. (author).

  9. Long term results of trabeculectomy surgery

    Directory of Open Access Journals (Sweden)

    Ferhat Evliyaoğlu

    2015-09-01

    Full Text Available Objective: Evaluation of long-term results of primary trabeculectomy operation Methods: The cases that are followed up with diagnosis of glaucoma in Okmeydanı Training and Research Hospital Eye Clinic between January 2000 and December 2001 were evaluated retrospectively. All of the cases, despite maximum therapy, have high intraocular pressure (IOP, undergone primary trabeculectomy operation, are followed at least 6 months and regularly followed through 10 years were included in this study. IOP with or without medical treatment 18mmg or less than 18 mmHg accepted as successful. IOL pressure measured with applanation tonometry. Results: 89 eyes of 70 cases were included in this study. The cases included in the study, 42 male (60%, and 28 (40% were female. The mean age was 63.65±12.18 years. Preoperative intraocular pressure determined as 30.36 ± 3.2 mmHg. In the follow up examination mean intra ocular pressure was 15.31 ± 1.2 mmHg at 1st month, 15.47± 1.1mmHg at 3rd month, 15.02±1.8 mmHg at 6th month, 15.34± 2.1 mmHg at 1st year, 15.82 ± 2.1mmHg at 2nd year, 17.06 ± 2.3mmHg at 5th year and 18.02 ± 2.2 mmHg at 10th year. Statistical analysis of these data showed significant decreased of intra ocular pressure in the post operative period in compare to the preoperative period, 1st month, 3rd month, 6th month, 1st year, 2nd year, 5th year an 10th year (p < 0.01. The follow-up period in the study was 91.10 ± 40.15 months (6-120 months. Conclusion: Primary trabeculectomy can be considered as an alternative treatment procedure especially in patients who does not use drugs regularly and unable to attend regular medical examination. J Clin Exp Invest 2015; 6 (3: 263-268

  10. Northern European long term climate archives

    Energy Technology Data Exchange (ETDEWEB)

    Hohl, Veronica [Stockholm Univ. (Sweden)

    2005-01-01

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the

  11. Northern European long term climate archives

    International Nuclear Information System (INIS)

    Hohl, Veronica

    2005-01-01

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the varying

  12. Hot functional test chemistry - long term experience

    International Nuclear Information System (INIS)

    Vonkova, K.; Kysela, J.; Marcinsky, M.; Martykan, M.

    2010-01-01

    Primary circuit materials undergo general corrosion in high temperature, deoxygenated, neutral or mildly alkaline solutions to form thin oxide films. These oxide layers (films) serve as protective film and mitigate the further corrosion of primary materials. Inner chromium-rich oxide layer has low cation diffusion coefficients and thus control iron and nickel transport from the metal surface to the outer layer and their dissolution into the coolant. Much less corrosion products are generated by the compact, integral and stable oxide (passivation) layer. For the latest Czech and Slovak stations commissioned (Temelin and Mochovce) a modified Hot Functional Test (HFT) chemistry was developed in the NRI Rez. Chromium rich surface layer formatted due to modified HTF chemistry ensures lower corrosion rates and radiation field formation and thus also mitigates crud formation during operation. This procedure was also designed to prepare the commissioned unit for the further proper water chemistry practise. Mochovce 1 (SK) was the first station commissioned using these recommendations in 1998. Mochovce 2 (1999) and Temelin 1 and 2 (CZ - 2000 and 2002) were subsequently commissioned using these guidelines too. The main principles of the controlled primary water chemistry applied during the hot functional tests are reviewed and importance of the water chemistry, technological and other relevant parameters is stressed regarding to the quality of the passive layer formed on the primary system surfaces. Samples from Mochovce indicated that duplex oxide layers up to 20 μm thick were produced, which were mainly magnetite substituted with nickel and chromium (e.g. 60-65% Fe, 18-28% Cr, 9-12% Ni, <1% Mn and 1-2% Si on a stainless steel primary circuit sample). Long term operation experience from both nuclear power plants are discussed in this paper. Radiation field, occupational radiation exposure and corrosion layers evolution during the first c. ten years of operation are

  13. Long-term dietary replacement of fishmeal and fish oil in diets for rainbow trout (Oncorhynchus mykiss): Effects on growth, whole body fatty acids and intestinal and hepatic gene expression.

    Science.gov (United States)

    Lazzarotto, Viviana; Médale, Françoise; Larroquet, Laurence; Corraze, Geneviève

    2018-01-01

    The effects of replacing fishmeal and fish oil with a plant-based diet were studied in juvenile (10g) and ongrowing (250-350g) rainbow trout from first-feeding. Feed-related differences in the intestinal and hepatic transcriptome were examined in juveniles after 7 months of feeding at 7°C. Based on microarray results obtained for juveniles, the expression of selected genes related to lipid, cholesterol and energy metabolisms, was assessed by RT-qPCR in ongrowing trout after 6 additional months of feeding at 17°C. Plasma glucose and cholesterol, lipid content and fatty acid profile of whole body were analyzed at both stages. After 7 months at 7°C, all juveniles reached the same body weight (10g), while at 13 months ongrowing fish fed the totally plant-based diet exhibited lower body weight (234 vs 330-337g). Body lipid content was higher in juveniles fed the totally plant-based diet (13.2 vs 9.4-9.9%), and plasma cholesterol was about 2-times lower in trout fed the plant-based diets at both stages. Fatty acid profile mirrored that of the respective diet, with low proportions of long-chain n-3 polyunsaturated fatty acids in fish fed plant-based diets. Genes involved in protein catabolism, carbohydrate metabolism and trafficking were down-regulated in the intestines of juveniles fed the plant-based diets. This was not true for ongrowing fish. Genes involved in lipid and cholesterol metabolisms were up-regulated in the livers of fish fed plant-based diets for both stages. In this study, feeding trout a totally plant-based diet from first-feeding affect a relatively low proportion of metabolism-related genes. In the longer term, when fish were reared at a higher temperature, only some of these changes were maintained (i.e. up-regulation of lipid/cholesterol metabolism). Although the plant-based diets tested in this study had no major deficiencies, small adjustments in the feed-formula are needed to further optimize growth performance while sparing marine resources.

  14. Long-Term Visual Functioning After Eclampsia

    NARCIS (Netherlands)

    Wiegman, Marjon J.; de Groot, Jan C.; Jansonius, Nomdo M.; Aarnoudse, Jan G.; Groen, Henk; Faas, Marijke M.; Zeeman, Gerda G.

    OBJECTIVE: Complete neurocognitive recovery after eclampsia has been questioned with the expression of neurocognitive deficits by affected women and demonstration of cerebral white matter lesions on magnetic resonance imaging years after eclampsia. We hypothesized that formerly eclamptic women may

  15. Fe65 does not stabilize AICD during activation of transcription in a luciferase assay

    International Nuclear Information System (INIS)

    Huysseune, Sandra; Kienlen-Campard, Pascal; Octave, Jean-Noel

    2007-01-01

    The APP intracellular domain (AICD) could be involved in signaling via interaction with the adaptor protein Fe65, and with the histone acetyl transferase Tip60. However, the real function of AICD and Fe65 in regulation of transcription remains controversial. In this study, the human APPGal4 fusion protein was expressed in CHO cells and the transcriptional activity of AICDGal4 was measured in a luciferase-based reporter assay. AICDGal4 was stabilized by expression of Fe65 and levels of AICDGal4 controlled luciferase activity. On the contrary, when human APP was expressed in CHO cells, coexpression of Fe65 increased luciferase activity without affecting the amount of AICD fragment. AICD produced from APP was protected from degradation by orthophenanthroline, but not by lactacystine, indicating that AICD is not a substrate of the chymotryptic activity of the proteasome. It is concluded that Fe65 can control luciferase activity without stabilizing the labile AICD fragment

  16. Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice.

    Science.gov (United States)

    Chartoumpekis, Dionysios V; Ziros, Panos G; Psyrogiannis, Agathoklis I; Papavassiliou, Athanasios G; Kyriazopoulou, Venetsana E; Sykiotis, Gerasimos P; Habeos, Ioannis G

    2011-10-01

    Obesity is characterized by chronic oxidative stress. Fibroblast growth factor 21 (FGF21) has recently been identified as a novel hormone that regulates metabolism. NFE2-related factor 2 (Nrf2) is a transcription factor that orchestrates the expression of a battery of antioxidant and detoxification genes under both basal and stress conditions. The current study investigated the role of Nrf2 in a mouse model of long-term high-fat diet (HFD)-induced obesity and characterized its crosstalk to FGF21 in this process. Wild-type (WT) and Nrf2 knockout (Nrf2-KO) mice were fed an HFD for 180 days. During this period, food consumption and body weights were measured. Glucose metabolism was assessed by an intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Total RNA was prepared from liver and adipose tissue and was used for quantitative real-time RT-PCR. Fasting plasma was collected and analyzed for blood chemistries. The ST-2 cell line was used for transfection studies. Nrf2-KO mice were partially protected from HFD-induced obesity and developed a less insulin-resistant phenotype. Importantly, Nrf2-KO mice had higher plasma FGF21 levels and higher FGF21 mRNA levels in liver and white adipose tissue than WT mice. Thus, the altered metabolic phenotype of Nrf2-KO mice under HFD was associated with higher expression and abundance of FGF21. Consistently, the overexpression of Nrf2 in ST-2 cells resulted in decreased FGF21 mRNA levels as well as in suppressed activity of a FGF21 promoter luciferase reporter. The identification of Nrf2 as a novel regulator of FGF21 expands our understanding of the crosstalk between metabolism and stress defense.

  17. Unified pre- and postsynaptic long-term plasticity enables reliable and flexible learning.

    Science.gov (United States)

    Costa, Rui Ponte; Froemke, Robert C; Sjöström, P Jesper; van Rossum, Mark Cw

    2015-08-26

    Although it is well known that long-term synaptic plasticity can be expressed both pre- and postsynaptically, the functional consequences of this arrangement have remained elusive. We show that spike-timing-dependent plasticity with both pre- and postsynaptic expression develops receptive fields with reduced variability and improved discriminability compared to postsynaptic plasticity alone. These long-term modifications in receptive field statistics match recent sensory perception experiments. Moreover, learning with this form of plasticity leaves a hidden postsynaptic memory trace that enables fast relearning of previously stored information, providing a cellular substrate for memory savings. Our results reveal essential roles for presynaptic plasticity that are missed when only postsynaptic expression of long-term plasticity is considered, and suggest an experience-dependent distribution of pre- and postsynaptic strength changes.

  18. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    International Nuclear Information System (INIS)

    Zeng, Jing; See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob; Durham, Nicholas; Meyer, Christian; Harris, Timothy J.; Albesiano, Emilia; Pradilla, Gustavo; Ford, Eric; Wong, John; Hammers, Hans-Joerg; Mathios, Dimitris; Tyler, Betty; Brem, Henry; Tran, Phuoc T.; Pardoll, Drew; Drake, Charles G.

    2013-01-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  19. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Durham, Nicholas [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Meyer, Christian [Department of Oncology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Harris, Timothy J. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Albesiano, Emilia; Pradilla, Gustavo [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Ford, Eric; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Hammers, Hans-Joerg [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Mathios, Dimitris; Tyler, Betty; Brem, Henry [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Pardoll, Drew; Drake, Charles G. [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); and others

    2013-06-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  20. Long-Term Patency of Lymphovenous Anastomoses: A Systematic Review.

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2016-08-01

    With advancements in technology and microsurgical techniques, lymphovenous anastomosis has become a popular reconstructive procedure in the treatment of chronic lymphedema. However, the long-term patency of these anastomoses is not clear in the literature. A systematic review of the MEDLINE and EMBASE databases was performed to assess the reported long-term patency of lymphovenous anastomoses. A total of eight studies satisfied the inclusion criteria. Pooled data from four similar experiments in normal dogs showed an average long-term (≥5 months) patency of 52 percent. The only experiment in dogs with chronic lymphedema failed to show any long-term patency. The creation of peripheral lymphovenous anastomoses with a moderate long-term patency rate has become technically possible. However, the long-term results in chronic lymphedema are limited.

  1. Reforming Long-Term Care Funding in Alberta.

    Science.gov (United States)

    Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

    2015-01-01

    Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

  2. A cost of long-term memory in Drosophila

    OpenAIRE

    Mery, Frederic; Kawecki, Tadeusz J.

    2005-01-01

    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  3. Private long-term care insurance and state tax incentives.

    Science.gov (United States)

    Stevenson, David G; Frank, Richard G; Tau, Jocelyn

    2009-01-01

    To increase the role of private insurance in financing long-term care, tax incentives for long-term care insurance have been implemented at both the federal and state levels. To date, there has been surprisingly little study of these initiatives. Using a panel of national data, we find that market take-up for long-term care insurance increased over the last decade, but state tax incentives were responsible for only a small portion of this growth. Ultimately, the modest ability of state tax incentives to lower premiums implies that they should be viewed as a small piece of the long-term care financing puzzle.

  4. The molecular and metabolic influence of long term agmatine consumption.

    Science.gov (United States)

    Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne L; Nissim, Ilana; Yudkoff, Marc

    2014-04-04

    Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used (13)C or (15)N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.

  5. The Molecular and Metabolic Influence of Long Term Agmatine Consumption*

    Science.gov (United States)

    Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne L.; Nissim, Ilana; Yudkoff, Marc

    2014-01-01

    Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used 13C or 15N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming. PMID:24523404

  6. Luciferase genes cloned from the unculturable luminous bacteroid symbiont of the Caribbean flashlight fish, Kryptophanaron alfredi.

    Science.gov (United States)

    Haygood, M G; Cohn, D H

    1986-01-01

    Light organs of anomalopid (flashlight) fish contain luminous bacteroids that have never been cultured and, consequently, have been difficult to study. We have characterized the luciferase (lux) region of DNA extracted from light organs of the Caribbean flashlight fish Kryptophanaron alfredi by hybridization of cloned Vibrio harveyi lux genes to restriction-endonuclease-digested, light organ DNA. Comparison of the hybridization pattern of light organ DNA with that of DNA of a putative symbiotic isolate provides a method for identifying the authentic luminous symbiont regardless of its luminescence, and was used to reject one such isolate. Light organ DNA was further used to construct a cosmid clone bank and the luciferase genes were isolated. Unlike other bacterial luciferase genes, the genes were not expressed in Escherichia coli. When placed under the control of the E. coli trp promoter, the genes were transcribed but no luciferase was detected, suggesting a posttranscriptional block to expression.

  7. A new image for long-term care.

    Science.gov (United States)

    Wager, Richard; Creelman, William

    2004-04-01

    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  8. Setting the stage for long-term reproductive health.

    Science.gov (United States)

    Payne, Craig A; Vander Ley, Brian; Poock, Scott E

    2013-11-01

    This article discusses some of the aspects of heifer development that contribute to long-term health and productivity, such as disease prevention and control. Nutrition is also an important component of long-term health, and body condition score is discussed as a way to determine whether the nutrient demands of heifers are being met. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Long-term effects of a preoperative smoking cessation programme

    DEFF Research Database (Denmark)

    Villebro, Nete Munk; Pedersen, Tom; Møller, Ann M

    2008-01-01

    Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation.......Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation....

  10. Pediatric polytrauma : Short-term and long-term outcomes

    NARCIS (Netherlands)

    vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

    Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

  11. Inflammatory markers in relation to long-term air pollution

    NARCIS (Netherlands)

    Mostafavi Montazeri, Nahid|info:eu-repo/dai/nl/375290575; Vlaanderen, Jelle|info:eu-repo/dai/nl/31403160X; Chadeau-Hyam, Marc; Beelen, Rob|info:eu-repo/dai/nl/30483100X; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard|info:eu-repo/dai/nl/069553475; Kyrtopoulos, Soterios Α; Vermeulen, Roel|info:eu-repo/dai/nl/216532620

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term

  12. Factors associated with long-term mortality in acute pancreatitis

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Matzen, Peter; Bendtsen, Flemming

    2011-01-01

    Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes...

  13. Sacrococcygeal teratoma: Clinical characteristics and long-term ...

    African Journals Online (AJOL)

    Background/Purpose : The excision of sacrococcygeal teratoma (SCT) may be associated with significant long-term morbidity for the child. We reviewed our experience with SCT in a tertiary health care facility in a developing country with particular interest on the long-term sequelae. Methods : Between January 1990 and ...

  14. Albumin: Creatinine Ratio during long term Diabetes Mellitus in the ...

    African Journals Online (AJOL)

    Albumin: Creatinine Ratio during long term Diabetes Mellitus in the Assessment of early Nephropathy in Sudanese Population. ... Further studies with 24 hour urine sample are recommended for assessment of Microalbuminuria in long term Diabetic patients, provided that the patients are on a normal diet with regular ...

  15. Developmental Dyslexia and Explicit Long-Term Memory

    Science.gov (United States)

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  16. Long term physical and chemical stability of polyelectrolyte multilayer membranes

    NARCIS (Netherlands)

    de Grooth, Joris; Haakmeester, Brian; Wever, Carlos; Potreck, Jens; de Vos, Wiebe Matthijs; Nijmeijer, Dorothea C.

    2015-01-01

    This work presents a detailed investigation into the long term stability of polyelectrolyte multilayer (PEM) modified membranes, a key factor for the application of these membranes in water purification processes. Although PEM modified membranes have been frequently investigated, their long term

  17. Long-term hearing preservation in vestibular schwannoma

    DEFF Research Database (Denmark)

    Stangerup, Sven-Eric; Thomsen, Jens; Tos, Mirko

    2010-01-01

    The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas.......The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas....

  18. Quantification of long term emission potential from landfills

    NARCIS (Netherlands)

    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate

  19. Long-term effects of childbirth in MS

    NARCIS (Netherlands)

    D'hooghe, M.B.; Nagels, G.; Uitdehaag, B.M.J.

    2010-01-01

    Background: The uncertainty about long-term effects of childbirth presents MS patients with dilemmas. Methods: Based on clinical data of 330 female MS patients, the long-term effects of childbirth were analysed, using a cross-sectional study design. Four groups of patients were distinguished: (1)

  20. Long-Term Orientation and Educational Performance. Working Paper 174

    Science.gov (United States)

    Figlio, David; Giuliano, Paola; Özek, Umut; Sapienza, Paola

    2017-01-01

    We use remarkable population-level administrative education and birth records from Florida to study the role of Long-Term Orientation on the educational attainment of immigrant students living in the US. Controlling for the quality of schools and individual characteristics, students from countries with long-term oriented attitudes perform better…

  1. Transcriptional regulation of long-term memory in the marine snail Aplysia

    Directory of Open Access Journals (Sweden)

    Lee Yong-Seok

    2008-06-01

    Full Text Available Abstract Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF. The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT, a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT induce a transcription- and translation-dependent long-term facilitation (LTF lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced

  2. Transcriptional regulation of long-term memory in the marine snail Aplysia.

    Science.gov (United States)

    Lee, Yong-Seok; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

    2008-06-17

    Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF). The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB) acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription- and translation-dependent long-term facilitation (LTF) lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced by different

  3. Long-Term Dynamics of Autonomous Fractional Differential Equations

    Science.gov (United States)

    Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

    This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

  4. Experimental Researches on Long-Term Strength of Granite Gneiss

    Directory of Open Access Journals (Sweden)

    Lin Liu

    2015-01-01

    Full Text Available It is important to confirm the long-term strength of rock materials for the purpose of evaluating the long-term stability of rock engineering. In this study, a series of triaxial creep tests were conducted on granite gneiss under different pore pressures. Based on the test data, we proposed two new quantitative methods, tangent method and intersection method, to confirm the long-term strength of rock. Meanwhile, the isochronous stress-strain curve method was adopted to make sure of the accuracy and operability of the two new methods. It is concluded that the new methods are suitable for the study of the long-term strength of rock. The effect of pore pressure on the long-term strength of rock in triaxial creep tests is also discussed.

  5. Long-Term Memory Performance in Adult ADHD.

    Science.gov (United States)

    Skodzik, Timo; Holling, Heinz; Pedersen, Anya

    2017-02-01

    Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

  6. The Genomic, Epigenomic, and Psychosocial Characteristics of Long-Term Survivors of Ovarian Cancer

    Science.gov (United States)

    2016-12-01

    enjoy life…………................................. 0 1 2 3 4 4. I have accepted my illness…………......................... 0 1 2 3 4 5. I am sleeping well...cancer. We have thus generated gene expression heat maps for 26 long-term survivors and 26 short-term survivors indicating a differential trend...between the 2 survival groups in: mRNA expression, miRNA expression, and DNA methylation. Each analysis was performed at the dedicated scientific

  7. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    Science.gov (United States)

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  8. Speaking up and Speaking Out? Long-Term Impact of Critical Multicultural Pedagogy

    Science.gov (United States)

    Flynn, Jill Ewing

    2017-01-01

    This study explores the long-term effects of critical multicultural pedagogy on seven adolescents. Four years later, participants continued to demonstrate awareness of privilege and racism, yet few were actively engaged in antiracist work. Participants also expressed disillusionment and lamented the lack of productive discussions of critical…

  9. Puzzling stakeholder views for long-term planning in the bio-economy

    NARCIS (Netherlands)

    Sisto, Roberta; Vliet, van Mathijs; Prosperi, Maurizio

    2016-01-01

    Planning long-term actions in the South of Italy is often characterised by a 'vicious circle of non-participation'. Stakeholders are increasingly not aware of the relevant role they have in supporting policy-making processes, even if they are usually keen to express their opinions. The aim of the

  10. Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

    Science.gov (United States)

    White, André O; Wood, Marcelo A

    2014-07-01

    It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Long-term decline of a winter-resident bird community in Puerto Rico

    Science.gov (United States)

    J. Faaborg; W. J. Arendt; J. D. Toms; K. M. Dugger; W. A. Cox; M. Canals Mora

    2013-01-01

    Despite concern expressed two decades ago, there has been little recent discussion about continuing declines of migrant bird populations. Monitoring efforts have been focused almost exclusively on the breeding grounds. We describe the long-term decline of a winter-resident bird population in Guanica Commonwealth Forest, Puerto Rico, one of the last remaining tracts of...

  12. Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

    Science.gov (United States)

    White, André O.; Wood, Marcelo A.

    2013-01-01

    It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. PMID:24149059

  13. Audit of long-term and short-term liabilities

    Directory of Open Access Journals (Sweden)

    Korinko M.D.

    2017-03-01

    Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

  14. Modeling long-term dynamics of electricity markets

    International Nuclear Information System (INIS)

    Olsina, Fernando; Garces, Francisco; Haubrich, H.-J.

    2006-01-01

    In the last decade, many countries have restructured their electricity industries by introducing competition in their power generation sectors. Although some restructuring has been regarded as successful, the short experience accumulated with liberalized power markets does not allow making any founded assertion about their long-term behavior. Long-term prices and long-term supply reliability are now center of interest. This concerns firms considering investments in generation capacity and regulatory authorities interested in assuring the long-term supply adequacy and the stability of power markets. In order to gain significant insight into the long-term behavior of liberalized power markets, in this paper, a simulation model based on system dynamics is proposed and the underlying mathematical formulations extensively discussed. Unlike classical market models based on the assumption that market outcomes replicate the results of a centrally made optimization, the approach presented here focuses on replicating the system structure of power markets and the logic of relationships among system components in order to derive its dynamical response. The simulations suggest that there might be serious problems to adjust early enough the generation capacity necessary to maintain stable reserve margins, and consequently, stable long-term price levels. Because of feedback loops embedded in the structure of power markets and the existence of some time lags, the long-term market development might exhibit a quite volatile behavior. By varying some exogenous inputs, a sensitivity analysis is carried out to assess the influence of these factors on the long-run market dynamics

  15. Long-Term Resource Adequacy, Long-Term Flexibility Requirements, and Revenue Sufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Milligan, Michael [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bloom, Aaron P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Townsend, Aaron [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ela, Erik [Electric Power Research Institute; Botterud, Audun [Argonne National Laboratory; Levin, Todd [Argonne National Laboratory

    2018-02-15

    Variable generation (VG) can reduce market prices over time and also the energy that other suppliers can sell in the market. The suppliers that are needed to provide capacity and flexibility to meet the long-term reliability requirements may, therefore, earn less revenue. This chapter discusses the topics of resource adequacy and revenue sufficiency - that is, determining and acquiring the quantity of capacity that will be needed at some future date and ensuring that those suppliers that offer the capacity receive sufficient revenue to recover their costs. The focus is on the investment time horizon and the installation of sufficient generation capability. First, the chapter discusses resource adequacy, including newer methods of determining adequacy metrics. The chapter then focuses on revenue sufficiency and how suppliers have sufficient opportunity to recover their total costs. The chapter closes with a description of the mechanisms traditionally adopted by electricity markets to mitigate the issues of resource adequacy and revenue sufficiency and discusses the most recent market design changes to address these issues.

  16. Long-Term Stewardship Baseline Report and Transition Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  17. The long-term power purchase: Recovery of capacity costs

    International Nuclear Information System (INIS)

    Cross, P.S.

    1990-01-01

    As electric utilities increase their reliance on the long-term power purchase as an alternative to utility-owned generation, the appropriate rate treatment of the costs established in the purchase agreement assumes growing importance. In the November 9, 1989, issue, the authors examined the recent trend among state regulators to treat the long-term purchase in a manner similar to the addition by a utility of a new plant, including a full-scale prudence review. This installment will review recent rulings on the related issue of rate recovery of long-term capacity costs through the fuel cost adjustment clause

  18. Space ventures and society long-term perspectives

    Science.gov (United States)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  19. Long-term care financing through Federal tax incentives.

    Science.gov (United States)

    Moran, D W; Weingart, J M

    1988-12-01

    Congress and the Administration are currently exploring various methods of promoting access to long-term care. In this article, an inventory of recent legislative proposals for using the Federal tax code to expand access to long-term care services is provided. Proposals are arrayed along a functional typology that includes tax mechanisms to encourage accumulation of funds, promote purchase of long-term care insurance, or induce the diversion of funds accumulated for another purpose (such as individual retirement accounts). The proposals are evaluated against the public policy objective of encouraging risk pooling to minimize social cost.

  20. Evaluation of long term leaching of borosilicate glasses

    International Nuclear Information System (INIS)

    Lanza, F.; Parnisari, E.

    1978-01-01

    For the evaluation of long term hazard of glass, data on long term glass leaching are needed. Moreover for long term leaching a model of homogeneous dissolution seems reasonable and ask for confirmation. Tests were performed at 30 0 , 80 0 , 100 0 , using an apparatus of the Soxhlet type, to 3.600 hours. Results were obtained as a weight loss and analysed following a relation with time composed by a parabolic and a linear part. Analysis of the surface layer using energy dispersion X ray spectrometry were performed. A critical analysis of the results and of the apparatus is presented

  1. The design of long term care insurance contracts.

    Science.gov (United States)

    Cremer, Helmuth; Lozachmeur, Jean-Marie; Pestieau, Pierre

    2016-12-01

    This paper studies the design of long term care (LTC) insurance contracts in the presence of ex post moral hazard. While this problem bears some similarity with the study of health insurance (Blomqvist, 1997) the significance of informal LTC affects the problem in several crucial ways. It introduces the potential crowding out of informal care by market care financed through insurance coverage. Furthermore, the information structure becomes more intricate. Informal care is not publicly observable and, unlike the insurer, caregivers know the true needs of their relatives. We determine the optimal second-best contract and show that the optimal reimbursement rate can be written as an A-B-C expression à la Diamond (1998). These terms respectively reflect the efficiency loss as measured by the inverse of the demand elasticity, the distribution of needs and the preferences for risk sharing. Interestingly, informal care directly affects only the first term. More precisely the first term decreases with the presence and significance of informal care. Roughly speaking this means that an efficient LTC insurance contract should offer lower (marginal) reimbursement rates than its counterpart in a health insurance context. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Communication on energy: who pays for the long-term costs of nuclear power

    International Nuclear Information System (INIS)

    Jeffery, J.W.

    1987-01-01

    The question in the title arises in making a fair comparison between a coal-fired station, which has no long-term costs, and a nuclear station, whose large long-term costs are discounted into insignificance by the present method of calculation. This problem was raised by the present author in his evidence to the Sizewell Inquiry, and has recently been discussed by the House of Commons Select Committee on Energy, who expressed grave disquiet that 'the costs of decommissioning become almost irrelevant to the current economics of nuclear power'. The present article analyses the bizarre effects of long-term discounting, and suggests a method of making a fair and symmetrical comparison between coal-fired and nuclear stations. (author)

  3. HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

    Science.gov (United States)

    McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

    2011-01-01

    Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

  4. Managerial Long-Term Responsibility in Family-Controlled Firms

    Directory of Open Access Journals (Sweden)

    Dietmar Sternad

    2013-01-01

    Full Text Available Evidence suggests that long-term orientation (LTO as a dominantstrategic logic contributes to the sustainable performance offamily-controlled firms (FCFS. Combining a review of the literatureon lto with stewardship theory and upper echelons theoryreasoning, this article presents a typology of managerial responsibilityand introduces the concept of long-term responsibility as amanagerial characteristic constituting a major driving force behindcreating lto. The antecedents of long-term responsibilityunder family firm-specific conditions (stemming from the familysystem, the governance system, and family-firm managers’ personalcharacteristics are also identified and presented in an integratedmodel. The paper contributes to a more comprehensiveunderstanding of intertemporal choice in fcfs and explains whythey tend to be more long-term oriented than other types of firms.

  5. Long-term bridge performance high priority bridge performance issues.

    Science.gov (United States)

    2014-10-01

    Bridge performance is a multifaceted issue involving performance of materials and protective systems, : performance of individual components of the bridge, and performance of the structural system as a whole. The : Long-Term Bridge Performance (LTBP)...

  6. Long-Term Visual Prognosis of Peripheral Multifocal Chorioretinitis

    NARCIS (Netherlands)

    Ossewaarde-van Norel, J; ten Dam-van Loon, NH; de Boer, JH; Rothova, A.

    2015-01-01

    Purpose To report on the clinical manifestations, complications, and long-term visual prognosis of patients with peripheral multifocal chorioretinitis and to search for predictors for a lower visual outcome. Design Retrospective consecutive observational case series. Methods setting: Institutional.

  7. In search of the elusive long-term price

    International Nuclear Information System (INIS)

    Connor, M.J.; Combs, J.

    1989-01-01

    The Uranium Institute, WNFM, and past USCEA sessions described and compared existing price reporting systems. The McGraw-Hill conference led to a rather heated discussion as to the propriety of spot prices having the influence they do on amounts paid in long-term contracts. The Ux representative proposed a future's market as a way that producers could hedge against some of the uncertainty of volatile spot market. In discussing the search for the elusive long-term price, there are two interrelated issues. The first is obvious-the search for a starting or initializing price that is representative of recently-signed or pending long-term contracts. The second is less obvious, but perhaps more important-the search for a successful mechanism for determining later delivery values in long-term contracts. This paper addresses the question of pricing mechanisms first

  8. Long-Term Stewardship Science and Technology Requirements

    International Nuclear Information System (INIS)

    McDonald, J.K.; Nickelson, R.A.

    2002-01-01

    To ensure technology developed for long-term stewardship will meet existing requirements, a review of requirements was performed. In addition to identifying existing science and technology related requirements, gaps and conflicts of requirements were identified

  9. Advancing an ethical framework for long-term care.

    Science.gov (United States)

    Carter, Mary Whelan

    2002-02-01

    This article represents an effort to formulate an ethical framework for long-term care with the explicit purpose of providing a catalyst to promote further discourse and expand consideration of what an ethic of long-term care might entail. Grounding the discussion, an introduction to traditional ethical philosophy is presented, focusing mainly on the fundamentals of deontological and teleological ethical theories. Attention then shifts to a review of the more frequently cited principles found in the long-term care ethics literature, followed by a critique of the current reliance upon principlism to resolve ethical dilemmas in long-term care. In response to this criticism, an agent-driven ethical framework stressing dignity and respect for personhood, drawn from the philosophy of Immanuel Kant, is advanced.

  10. Vulnerable long-term psychiatric in- patients need screening for ...

    African Journals Online (AJOL)

    as prominent medical issues in long-term care and provide guidelines for their ..... described in the literature.7,28 These patients might benefit from a renewed emphasis on ..... costs associated with marijuana comorbidity. Drug & Alcohol.

  11. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad; Shahzad, Muhammad Wakil; Ng, Kim Choon

    2017-01-01

    estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available

  12. Strategies to meet the need for long-term data.

    Science.gov (United States)

    Chalmers, John; Woodward, Mark; Borghi, Claudio; Manolis, Athanasios; Mancia, Giuseppe

    2016-08-01

    Chronic diseases afflict patients for many years, often to the end of life, and there is increasing need for estimating lifelong risk and for evaluating the effects of treatment in the long term. Yet recommendations for lifelong treatment are most frequently based on findings from randomized clinical trials lasting only a few years. There is therefore a clear need for much longer term data, and here we present the advantages and disadvantages of many strategies, including the use of long-term posttrial follow-up, of long-term prospective cohort studies, registry databases, and of administrative databases. We also emphasize the need for long-term cost-effectiveness studies. One of the most promising strategies comes from linkage of data gathered through the ever-expanding pool of administrative databases worldwide with data from other sources, including randomized trials and the many forms of observational study.

  13. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    International Nuclear Information System (INIS)

    T. Haney R. VanHorn

    2007-01-01

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used to determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality

  14. Long-term memory, sleep, and the spacing effect.

    Science.gov (United States)

    Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

    2014-01-01

    Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

  15. The Long-Term Retention of Knowledge and Skills

    National Research Council Canada - National Science Library

    Healy, Alice

    1998-01-01

    .... The second class of guidelines concerned ways to optimize the strategies used. We found that in tasks that require deliberate retrieval from memory, training that promotes efficient encoding strategies maximizes long-term retention...

  16. Radiation effects after low dose chronic long-term exposure

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Friesecke, I.

    1997-01-01

    This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

  17. Statistical analysis of long term spatial and temporal trends of ...

    Indian Academy of Sciences (India)

    Statistical analysis of long term spatial and temporal trends of temperature ... CGCM3; HadCM3; modified Mann–Kendall test; statistical analysis; Sutlej basin. ... Water Resources Systems Division, National Institute of Hydrology, Roorkee 247 ...

  18. Modelled long term trends of surface ozone over South Africa

    CSIR Research Space (South Africa)

    Naidoo, M

    2011-10-01

    Full Text Available timescale seeks to provide a spatially comprehensive view of trends while also creating a baseline for comparisons with future projections of air quality through the forcing of air quality models with modelled predicted long term meteorology. Previous...

  19. Long-term risks of kidney living donation

    DEFF Research Database (Denmark)

    Maggiore, Umberto; Budde, Klemens; Heemann, Uwe

    2017-01-01

    Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science...... and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information...... to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors...

  20. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    Energy Technology Data Exchange (ETDEWEB)

    T. Haney

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  1. Long-term Consequences of Childhood ADHD on Criminal Activities*

    OpenAIRE

    Fletcher, Jason; Wolfe, Barbara

    2009-01-01

    The question of whether childhood mental illness has long term consequences in terms of criminal behavior has been little studied, yet it could have major consequences for both the individual and society more generally. In this paper, we focus on Attention-Deficit/Hyperactivity Disorder (ADHD), one of the most prevalent mental conditions in school-age children, to examine the long-term effects of childhood mental illness on criminal activities, controlling for a rich set of individual, family...

  2. Long-term patient survival in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten

    2011-01-01

    Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain.......Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain....

  3. Aspects of long-term variability in sun and stars

    International Nuclear Information System (INIS)

    Skumanich, A.; Eddy, J.A.

    1981-01-01

    Evidence of long-term solar variability is reviewed, including historical data and the tree-ring record of radiocarbon. Epochs of suppressed activity like the Maunder Minimum are shown to be frequent occurences of the last several thousand years, but without no obvious period of recurrence. Weak evidence exists for the 11-year cycle as early as Medieval times, although with insufficient accuracy to establish long-term phase stability. (orig.)

  4. Rapid internationalization and long-term performance: The knowledge link

    OpenAIRE

    García-García, Raquel; García-Canal, Esteban; Guillén, Mauro F.

    2017-01-01

    Drawing on the knowledge-based view and organizational learning theory, we develop and test a set of hypotheses to provide a first attempt at analyzing the effect of speed of internationalization on long-term performance. Using a panel-data sample of Spanish listed firms (1986-2010), we find that there is an inverted U-shaped relationship between speed of internationalization and long-term performance. We also find that whereas technological knowledge steepens this relationship, the diversity...

  5. Preclinical rodent toxicity studies for long term use of ceftriaxone

    Directory of Open Access Journals (Sweden)

    Elena Ratti

    2015-01-01

    Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 h. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 h after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials.

  6. Long-term outcome of craniopharyngioma in children. A review

    International Nuclear Information System (INIS)

    Tamiya, Takashi; Okada, Masaki; Miyake, Keisuke; Kawai, Nobuyuki

    2011-01-01

    The treatment for pediatric craniopharyngioma remains challenging and controversial. Although this tumor is histologically benign, the treatments include radical surgery, conservative surgery, radiotherapy, intracystic chemotherapy and multimodality approaches. In addition, the long-term functional outcomes including visual function, endocrine function, cognitive function, hypothalamic function, and quality of life are complex and major problems among survivors. In this paper, we reviewed the recent treatments for pediatric craniopharyngioma and the long-term outcomes after treatment in literatures. (author)

  7. Long-term care: a substantive factor in financial planning.

    Science.gov (United States)

    Willis, D A

    2000-01-01

    More than 50 percent of women will enter a nursing home at some point in their lives. About one-third of men living to age 65 will also need nursing home care. Planning for long-term care is even more important since Medicare covers very little of the cost of such care. The Indiana Partnership Plan is one program designed to help fund the long-term care costs while allowing individuals protect other financial assets.

  8. The Myth That Insulating Boards Serves Long-Term Value

    OpenAIRE

    Bebchuk, Lucian Arye

    2013-01-01

    According to an influential view in corporate law writings and debates, pressure from shareholders leads companies to take myopic actions that are costly in the long term, and insulating boards from such pressure serves the long-term interests of companies as well as their shareholders. This board insulation claim has been regularly invoked in a wide range of contexts to support existing or tighter limits on shareholder rights and involvement. This paper subjects this view to a comprehensive ...

  9. Long-Term Prognosis of Ischemic Stroke in Young Adults

    OpenAIRE

    Varona, Jose F.

    2010-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

  10. Long-term stability of sodium caseinate-stabilized nanoemulsions.

    Science.gov (United States)

    Yerramilli, Manispuritha; Ghosh, Supratim

    2017-01-01

    Oil-in-water (5 wt%) nanoemulsions were prepared with different concentration (2.5-10 wt%) of sodium caseinate as a sole emulsifier and their long-term storage stability was investigated for 6 months. Previous studies associated with sodium caseinate looked only into nanoemulsion formation; hence the challenges with long-term stability were not addressed. All nanoemulsions displayed an average droplet size sodium caseinate-stabilized nanoemulsions.

  11. Introduction of long term cycle of reactor operation

    International Nuclear Information System (INIS)

    Aoyati, M.; Tanaka, T.

    2004-01-01

    Introduction of long term cycle of LWR reactor operation at NPP in Japan is considered, and problems of technical, legislative and economical character, increase of power coefficient are discussed. More long term operation period provides decreasing frequency of periodic inspections and reduction of personnel radiation doses. Reliability of fuel, energetic equipment, mechanisms and devices must be taken into account for the decision of technical problems. Consumptions for electric power generation are studied [ru

  12. Long term acroecosystem research in the Southern Plains

    Science.gov (United States)

    Jean L. Steiner; Patrick J. Starks; Jurgen Garbrecht; Daniel Moriasi; Paul Bartholomew; Jim Neel; Kenneth E. Turner; Brian Northup

    2016-01-01

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at the USDA-ARS Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita River Experimental Watershed (LWREW) in 1961 and in the Fort Cobb...

  13. Utilización de la toxina botulínica para mejorar la funcionalidad y la expresión del labio en parálisis facial de larga evolución Use of botulinum toxin to improve the functionality and expression of the lip in long-term facial palsy

    Directory of Open Access Journals (Sweden)

    C. Gómez Martín

    2010-06-01

    Full Text Available La parálisis de la rama marginal del nervio facial en el contexto de una parálisis facial de larga evolución, produce una deformidad estética y funcional que puede ser mejorada con la inyección de toxina botulínica. Utilizamos esta técnica en 2 pacientes consiguiendo unos resultados casi inmediatos en lo que se refiere a la apertura bucal, a la expresión y a la continencia oral. Indicamos esta técnica en pacientes de edad avanzada, con múltiples operaciones previas y que aceptan este procedimiento no invasivo para mejorar su autoestima y su calidad de vida.Paralysis of the marginal branch of the facial nerve in the context of a long-term facial paralysis, produces an aesthetic and functional deformity that can be improved with botulinum toxin injection. We use this technique in 2 patients who achieved almost immediate results in terms of oral opening, oral expression and continence. Botulinum toxin injection can be used in elderly patients with multiple previous operations who accept this non-invasive procedure, improving their selfesteem and their quality of life.

  14. Changing incentives for long-term gas contracts

    International Nuclear Information System (INIS)

    Bohi, D.R.

    1992-01-01

    There is much concern about the absence of long-term gas contracts with fixed price and quantity conditions, which until recent years was the standard way of doing business in the gas industry. These types of contracts performed a valuable service in the development of the gas industry, and there comparative absence today is sometimes thought to be one reason for the current malaise in the industry. One hears the argument that there must be some kind of 'market failure' that prevents buyers and sellers from entering into these long term arrangements, and recent changes in state and federal regulations are often cited as the cause of the problem. The purpose of the author's remarks is to argue that what is taken as a breakdown in the market may be simply a reaction to a decline in economic incentives to enter into long-term contracts with rigid price and quantity terms. This is, in other words, simply one more aspect of change in the gas business that Frank Heintz referred to in his opening remarks this morning. The author starts by giving a brief description of the motives for engaging in long-term contracts, and then describes how incentives to use long-term contracts have declined for both gas buyers and gas sellers. He concludes that the decline in the use of long-term contracts is not cause for regulatory concern, but a result of the continuing transformation of the gas business to one that more closely resembles other commodity markets

  15. Characterization of CG6178 gene product with high sequence similarity to firefly luciferase in Drosophila melanogaster.

    Science.gov (United States)

    Oba, Yuichi; Ojika, Makoto; Inouye, Satoshi

    2004-03-31

    This is the first identification of a long-chain fatty acyl-CoA synthetase in Drosophila by enzymatic characterization. The gene product of CG6178 (CG6178) in Drosophila melanogaster genome, which has a high sequence similarity to firefly luciferase, has been expressed and characterized. CG6178 showed long-chain fatty acyl-CoA synthetic activity in the presence of ATP, CoA and Mg(2+), suggesting a fatty acyl adenylate is an intermediate. Recently, it was revealed that firefly luciferase has two catalytic functions, monooxygenase (luciferase) and AMP-mediated CoA ligase (fatty acyl-CoA synthetase). However, unlike firefly luciferase, CG6178 did not show luminescence activity in the presence of firefly luciferin, ATP, CoA and Mg(2+). The enzymatic properties of CG6178 including substrate specificity, pH dependency and optimal temperature were close to those of firefly luciferase and rat fatty acyl-CoA synthetase. Further, phylogenic analyses strongly suggest that the firefly luciferase gene may have evolved from a fatty acyl-CoA synthetase gene as a common ancestral gene.

  16. The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila.

    Science.gov (United States)

    Freymuth, Patrick S; Fitzsimons, Helen L

    2017-08-29

    Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton. Rearrangement of the actin cytoskeleton drives both neuronal morphogenesis and the structural changes in neurons that are required for long-term memory formation. Moesin has been identified as a candidate memory gene in Drosophila, however, whether it is required for memory formation has not been evaluated. Here, we investigate the role of Moesin in neuronal morphogenesis and in short- and long-term memory formation in the courtship suppression assay, a model of associative memory. We found that both knockdown and overexpression of Moesin led to defects in axon growth and guidance as well as dendritic arborization. Moreover, reduction of Moesin expression or expression of a constitutively active phosphomimetic in the adult Drosophila brain had no effect on short term memory, but prevented long-term memory formation, an effect that was independent of its role in development. These results indicate a critical role for Moesin in both neuronal morphogenesis and long-term memory formation.

  17. Characterization of the rapid transcriptional response to long-term sensitization training in Aplysia californica.

    Science.gov (United States)

    Herdegen, Samantha; Holmes, Geraldine; Cyriac, Ashly; Calin-Jageman, Irina E; Calin-Jageman, Robert J

    2014-12-01

    We used a custom-designed microarray and quantitative PCR to characterize the rapid transcriptional response to long-term sensitization training in the marine mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to one side of the body, a procedure known to induce a long-lasting, transcription-dependent increase in reflex responsiveness that is restricted to the side of training. One hour after training, pleural ganglia from the trained and untrained sides of the body were harvested; these ganglia contain the sensory nociceptors which help mediate the expression of long-term sensitization memory. Microarray analysis from 8 biological replicates suggests that long-term sensitization training rapidly regulates at least 81 transcripts. We used qPCR to test a subset of these transcripts and found that 83% were confirmed in the same samples, and 86% of these were again confirmed in an independent sample. Thus, our new microarray design shows strong convergent and predictive validity for analyzing the transcriptional correlates of memory in Aplysia. Fully validated transcripts include some previously identified as regulated in this paradigm (ApC/EBP and ApEgr) but also include novel findings. Specifically, we show that long-term sensitization training rapidly up-regulates the expression of transcripts which may encode Aplysia homologs of a C/EBPγ transcription factor, a glycine transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36). Copyright © 2014 Elsevier Inc. All rights reserved.

  18. BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort

    Directory of Open Access Journals (Sweden)

    Nesli Avgan

    2017-03-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265 and long-term visual memory (p-value = 0.003 in a small cohort (n = 181 comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale—Fourth Edition subtests Visual Reproduction I and II (VR I and II. VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism (p-value = 0.006 that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF, and its anti-sense transcript BDNF-AS, in long-term visual memory performance.

  19. BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort.

    Science.gov (United States)

    Avgan, Nesli; Sutherland, Heidi G; Spriggens, Lauren K; Yu, Chieh; Ibrahim, Omar; Bellis, Claire; Haupt, Larisa M; Shum, David H K; Griffiths, Lyn R

    2017-03-17

    Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory ( p -value = 0.003) in a small cohort ( n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale-Fourth Edition subtests Visual Reproduction I and II (VR I and II). VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism ( p -value = 0.006)) that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus) that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF , and its anti-sense transcript BDNF-AS , in long-term visual memory performance.

  20. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.; Button, Tom; Tuohy, Orla C.; Jones, Joanne L.; May, Karen; Somerfield, Jennifer; Green, Alison J E; Giovannoni, Gavin; Compston, Alastair D.; Fahey, Michael T.; Coles, Alasdair J.

    2011-01-01

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  1. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  2. Transcriptional diversity of long-term glioblastoma survivors.

    Science.gov (United States)

    Gerber, Naamit K; Goenka, Anuj; Turcan, Sevin; Reyngold, Marsha; Makarov, Vladimir; Kannan, Kasthuri; Beal, Kathryn; Omuro, Antonio; Yamada, Yoshiya; Gutin, Phillip; Brennan, Cameron W; Huse, Jason T; Chan, Timothy A

    2014-09-01

    Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Risk assessment for long-term post-accident sequences

    International Nuclear Information System (INIS)

    Ellia-Hervy, A.; Ducamp, F.

    1987-11-01

    Probabilistic risk analysis, currently conducted by the CEA (French Atomic Energy Commission) for the French replicate series of 900 MWe power plants, has identified accident sequences requiring long-term operation of some systems after the initiating event. They have been named long-term sequences. Quantification of probabilities of such sequences cannot rely exclusively on equipment failure-on-demand data: it must also take into account operating failures, the probability of which increase with time. Specific studies have therefore been conducted for a number of plant systems actuated during these long-term sequences. This has required: - Definition of the most realistic equipment utilization strategies based on existing emergency procedures for 900 MWe French plants. - Evaluation of the potential to repair failed equipment, given accessibility, repair time, and specific radiation conditions for the given sequence. - Definition of the event bringing the long-term sequence to an end. - Establishment of an appropriate quantification method, capable of taking into account the evolution of assumptions concerning equipment utilization strategies or repair conditions over time. The accident sequence quantification method based on realistic scenarios has been used in the risk assessment of the initiating event loss of reactor coolant accident occurring at power and at shutdown. Compared with the results obtained from conventional methods, this method redistributes the relative weight of accident sequences and also demonstrates that the long term can be a significant contribution to the probability of core melt

  4. Long-term psychosocial consequences of surgical congenital malformations.

    Science.gov (United States)

    Diseth, Trond H; Emblem, Ragnhild

    2017-10-01

    Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

  5. ERDA's long-term waste management goals and programs

    International Nuclear Information System (INIS)

    Perge, A.F.; Trice, V.G. Jr.; Walton, R.D. Jr.

    1976-01-01

    This paper presents an overview of the ERDA's major program for the long-term waste management of radioactive waste and provides a perspective for symposium participants with regard to the interrelationship of specific components of the program that are discussed in detail in other ERDA-sponsored papers. Needs, goals, and plans are reviewed for ERDA's management of the commercially generated wastes which are expected to be delivered to ERDA in accordance with Federal regulations. At present, ERDA responsibilities include long-term management of commercial-level wastes. Possible future regulations may give ERDA responsibility for the long-term management of commercial low-level solid wastes contaminated with transuranic nuclides. Primary planning goals and programs for the development of terminal storage facilities and waste processing technology to produce acceptable waste forms for long-term management are reviewed for each of the waste types identified above. The status of development programs for the long-term management of airborne radionuclides, which may be required at some time in the future, is also reviewed. (author)

  6. Child maltreatment: pathway to chronic and long-term conditions?

    Science.gov (United States)

    Taylor, Julie; Bradbury-Jones, Caroline; Lazenbatt, Anne; Soliman, Francesca

    2016-09-01

    The manifesto Start Well, Live Better by the UK Faculty of Public Health (Start Well, Live Better-A Manifesto for the Public's Health. London: UK Faculty of Public Health, 2014) sets out 12 compelling priorities for the protection of people's health. The focus of this document is preventative, calling for a comprehensive strategy to target a wide-ranging set of challenges to public health; however, it fails to mention child maltreatment and its negative impact on long-term health outcomes. In this article, we explore the long-term negative consequences of child maltreatment and how these can be conceptually aligned with four different characteristics of long-term health conditions. We suggest that situating child maltreatment within a long-term conditions framework could have significant advantages and implications for practice, policy and research, by strengthening a commitment across disciplines to apply evidence-based principles linked with policy and evaluation and recognizing the chronic effects of maltreatment to concentrate public, professional and government awareness of the extent and impact of the issue. We argue that a public health approach is the most effective way of focusing preventative efforts on the long-term sequelae of child maltreatment and to foster cooperation in promoting children's rights to grow and develop in a safe and caring environment free from violence and abuse. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Long-Term Retardation of Uranium in the KURT Environment

    International Nuclear Information System (INIS)

    Baik, Min Hoon; Shin, Joo Do; Park, Tae Jin

    2016-01-01

    One of possibilities resolving this issue is to study the migration and retardation processes of radionuclides in the subsurface environments by using naturally occurring radionuclides as analogues of radioactive waste. To date, however, the long-term behavior of radionuclides in a granitic groundwater system is not yet fully understood. The ubiquitous presence of uranium (U) in rocks makes it an ideal natural analogue for studying the behaviors of radionuclides in a deep geological repository for the final disposal of HLW. In this study, long-term retardation behavior of natural uranium was investigated using granite rock samples taken from the KURT (KAERI Underground Research Tunnel), located in Daejeon city. The distribution of uranium and its binding mechanism in granite samples were investigated using the sequential chemical extraction (SCE) technique combined with X-ray diffraction (XRD) and ICP-MS methods. In this study, the long-term retardation of uranium in the KURT environment was investigated using SCE and EPMA techniques combined with ICP-MS and XRD. Results showed that long-term interaction of rock with groundwater can change U species and mineralize dissolved U, which can consequently contribute to the retardation of U in the fractured granitic rock environment. This study will help us to understand the long-term behavior of radionuclides migrating through the fractured granite rock and then enhance the reliability of the safety assessment for a HLW repository

  8. Long-Term Stewardship Program Science and Technology Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Joan McDonald

    2002-09-01

    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

  9. Firefly luciferase gene contains a cryptic promoter

    Czech Academy of Sciences Publication Activity Database

    Vopálenský, V.; Mašek, T.; Horváth, Ondřej; Vicenová, B.; Mokrejš, M.; Pospíšek, M.

    2008-01-01

    Roč. 14, č. 9 (2008), s. 1720-1729 ISSN 1355-8382 Grant - others:GAČR(CZ) GA204/03/1487; GAČR(CZ) GA301/07/0607; Mšk(CZ) LC06066 Program:LC Institutional research plan: CEZ:AV0Z50520514 Keywords : luciferase * cryptic promoter * hepatitis C virus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.018, year: 2008

  10. The long-term benefits of director stock ownership

    Directory of Open Access Journals (Sweden)

    Brian Bolton

    2009-11-01

    Full Text Available In October 2009, the United States Treasury Department and Congress considered new regulations requiring executives and directors to receive much of their compensation in the form of long-term stock. One concern with this is that it may have negative consequences by entrenching managers and directors over the long term. This study compares the potential benefits of long-term director ownership with the potential costs of entrenchment. Using the dollar amount of stock owned by independent directors, the results suggest that the incentive effect dominates any costs related to entrenchment: firms with greater stock ownership outperform other firms, regardless of the degree of managerial entrenchment that may be present. The implication for policy-makers is that providing directors with incentives through stock ownership can be a very effective corporate governance mechanism.

  11. Long-term visual associations affect attentional guidance.

    Science.gov (United States)

    Olivers, Christian N L

    2011-06-01

    When observers perform a visual search task, they are assumed to adopt an attentional set for what they are looking for. The present experiment investigates the influence of long-term visual memory associations on this attentional set. On each trial, observers were asked to search a display for a grayscale version of a known traffic sign. On each trial, a distractor sign was drawn in full color. This color could either be related or unrelated to the target sign. Distractors interfered more with search when their color was related (e.g. red when the target was a stop sign), implying that long-term color associations resulted in inadvertent attentional guidance, even though color was irrelevant to the task. The results add to the growing body of evidence that long-term memory representations automatically affect attentional orienting. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Winning market positioning strategies for long term care facilities.

    Science.gov (United States)

    Higgins, L F; Weinstein, K; Arndt, K

    1997-01-01

    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application.

  13. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for the long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are related to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product

  14. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are ralated to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product. (author)

  15. On the relationship between short- and long-term memory

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik

    James (1890) divided memory into separate stores; primary and secondary – or short-term and long-term memory. The interaction between the two stores often assumes that information initially is represented in volatile short-term store before entering and consolidating in the more durable long-term......, accepted). Counter to popular beliefs this suggest that long-term memory precedes short-term memory and not vice versa....... memory system (e.g. Atkinson & Shiffrin, 1968). Short-term memory seems to provide a surprising processing bottleneck where only a very limited amount of information can be represented at any given moment (Miller, 1956; Cowan, 2001). A number of studies have investigated the nature of this processing...

  16. Ethics and Intimate Sexual Activity in Long-Term Care.

    Science.gov (United States)

    Metzger, Eran

    2017-07-01

    A case is presented in which the staff of a long-term care facility discovers that the husband of a resident with dementia is engaged in sexual activity with her. The case illustrates a dilemma for long-term care facilities that create a home-like environment with a goal of maximizing residents' autonomy while ensuring their safety. An approach to assessing capacity to consent to intimate sexual activity is described, followed by guidelines that nursing homes can implement to support residents who wish to engage in sexual activity. Recommendations are also offered for supporting long-term care staff and family members of residents who are interested in intimate sexual activity. © 2017 American Medical Association. All Rights Reserved.

  17. Marijuana effects on long-term memory assessment and retrieval.

    Science.gov (United States)

    Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

    1977-05-09

    The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

  18. Long-term impact of sales promotion on brand image

    Directory of Open Access Journals (Sweden)

    Danijela Mandić

    2009-12-01

    Full Text Available Sales promotion (SP is an inevitable tool in the marketing communications mix, especially in the FMCG markets, due to pressures such as retailers’ growing demands and increasing competition. This has proven to be an issue for many companies, especially those with a premium brand positioning and those concerned about the impact that SP might have on the long-term image of the company. Despite the fact that literature is replete with research on SP, it seems to be vastly generalized and mostly focused on price reductions. Thus, this paper aims to analyze and discuss the issue of the long-term impact that SP has on companies, especially on premium brands in the FMCG markets. It concludes that, when used properly and strategically, SP may have a positive long-term impact on brands.

  19. Long-term multipactor discharge in multicarrier systems

    International Nuclear Information System (INIS)

    Anza, S.; Vicente, C.; Gimeno, B.; Boria, V. E.; Armendariz, J.

    2007-01-01

    A new mechanism of long-term multipactor in multicarrier systems is studied employing both analytical and numerical methods. In particular, the investigation is focused on the impact that a realistic secondary emission yield at low energies produces on the development of long term multipactor. A novel analytical model for this interperiod charge accumulation is presented using the traditional multipactor theory for parallel plates, and approximating the multicarrier signal as a single-carrier signal modulated by a pulsed signal envelope. The analytical predictions are verified by numerical simulations for a typical rectangular waveguide. The analytical and numerical results demonstrate that the susceptibility of the system to develop a long-term multipactor discharge increases with higher values of low-energy secondary emission yield

  20. Long-term Internship through Cooperative Education with Regional Industries

    Science.gov (United States)

    Takahashi, Kenzo; Hase, Hiroyuki

    The long term internship is one of special educational programs for graduate students of Graduate School of Engineering in University of Fukui. This is a collaborative program between university and industries where selected post-graduate students are dispatched to companies for a long term and educated in real business environments. It is the final goal of the program to develop sophisticated specialists who would be able to catch the business strategy in industries and solve any problems by themselves. The program is managed in a semester (6 months) and contains 1.5 month prior education of preliminary special knowledge, ethics and secrecy, about 3 month dispatch with long-term internship, and 1.5 month post-education for complementary education and presentation. This paper presents the effect of this program which has been evolving since 2005.

  1. HIV-1 Gag-specific exosome-targeted T cell-based vaccine stimulates effector CTL responses leading to therapeutic and long-term immunity against Gag/HLA-A2-expressing B16 melanoma in transgenic HLA-A2 mice

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2014-01-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1-specific dendritic cell (DC vaccines have been applied to clinical trials that show only induction of some degree of immune responses, warranting the search of other more efficient vaccine strategies. Since HIV-1-specific CD8+ cytotoxic T lymphocytes (CTLs have been found to recognize some HIV-1 structural protein Gag conserved and cross-strain epitopes, Gag has become one of the most attractive target candidates for HIV-1 vaccine development. In this study, we generated HIV-1 Gag-specific Gag-Texo vaccine by using ConA-stimulated polyclonal CD8+ T-cells with uptake of Gag-expressing adenoviral vector AdVGag-transfected DC (DCGag-released exosomes (EXOs, and assessed its stimulation of Gag-specific CD8+ CTL responses and antitumor immunity. We demonstrate that Gag-Texo and DCGag vaccines comparably stimulate Gag-specific effector CD8+ CTL responses. Gag-Texo-stimulated CTL responses result in protective immunity against Gag-expressing BL6-10Gag melanoma in 8/8 wild-type C57BL/6 mice. In addition, we show that Gag-Texo vaccine also induces CTL responses leading to protective and long-term immunity against Gag/HLA-A2-expressing BL6-10Gag/A2 melanoma in 8/8 and 2/8 transgenic HLA-A2 mice, respectively. The average number of lung tumor colonies in mice with 30-days post-immunization is only 23, which is significantly less than that (>300 in control ConA-T-immunized HLA-A2 mice. Furthermore, Gag-Texo vaccine also induces some degree of therapeutic immunity. The average number (50 and size (0.23 mm in diameter of lung tumor colonies in Gag-Texo-immunized HLA-A2 mice bearing 6-day-established lung BL6-10Gag/A2 melanoma metastasis are significantly less than the average number (>300 and size (1.02 mm in diameter in control ConA-T-immunized HLA-A2 mice. Taken together, HIV-1 Gag-Texo vaccine capable of stimulating Gag-specific CTL responses and therapeutic immunity may be useful as a new immunotherapeutic

  2. A basic strategy for financing long term care.

    Science.gov (United States)

    Greenberg, J A; Leutz, W N

    1984-02-01

    As pressure mounts to contain Medicaid long term care spending, short-range "quick fixes" must be avoided. Three such false solutions in particular have shortcomings that may actually exacerbate long term care's financial dilemma because they are based on inadequate definitions of the problem. Two of these proposals--legislation to broaden family responsibility toward institutionalized elders on Medicaid and expanded state power to put liens on such elders' real property--err by trying to mandate "caring" and are predicated on a misunderstanding of the "spend-down" problem. The other proposal--to provide tax incentives to family members who care for elders--requires a large administrative apparatus, assumes an elasticity of supply that may not exist, and could disrupt the "gift relationship" on which family exchanges are often based. What is needed is a strategy with short term, intermediate, and long term objectives that move toward an insurance approach. The short term plan should lay the groundwork for intermediate strategy and control costs by changing rate-setting methods and putting limits on facility construction. The intermediate plan should change the problem's definition from one of merely controlling Medicaid long term care expenditures to one of efficiently managing state resources for the elderly through the development of state financing and local delivery systems that target older persons in greatest need. An effective means of doing this is through the creation of social/HMOs, which have five key features: integration of service responsibility and authority; flexibility in organizational design; balanced clientele; pooled prepaid funding; and financial risk for the provider organization. Finally, the long term strategy should transfer much of the long term care financial burden from individuals and state Medicaid agencies to insurance mechanisms. Many individuals would thus avoid impoverishment caused by health care spending and Medicaid would

  3. Assessing the market for long-term care services.

    Science.gov (United States)

    Rice, J A; Taylor, S

    1984-02-01

    Traditionally, long-term care services have been used by a diverse marketplace. The chronically ill, developmentally disabled, mentally ill and aging population has looked to long-term care support services as a means of physical and emotional support. Much of the time these services were housed together for the sake of efficiency. The enormous burden these services are creating on the economy, and the growing aging population, have forced the recognition that long-term care service delivery systems must change. Alternate programming for long-term care services that reach out into the community and into individual homes is becoming an attractive approach to meeting the growing demands of the marketplace. Home health, specialized housing and creative funding mechanisms such as HMOs, are examples of initiatives undertaken by healthcare organizations that view diversification as a vehicle for survival. Market research techniques that have been used in other industries are being adapted to the healthcare industry to ensure the proper mix of services that are demanded by older, more knowledgeable consumers. The programs of the future will be market driven, with the ability of the individual to pay for such services playing a significant role. The healthcare provider of today is in a position to serve the community in new ways. By becoming an integral link in the long-term care system and by developing new programs, the organization can serve as a catalyst for change. It is up to the governing bodies and managers of these facilities to become visionaries and to accept responsibility for assessing the market for long-term care services and to guide their organization into the future.

  4. Long-Term Effects of School Size on Students' Outcomes

    DEFF Research Database (Denmark)

    Humlum, Maria Knoth; Smith, Nina

    We estimate the effect of school size on students' long-term outcomes such as high school completion, being out of the labor market, and earnings at the age of 30. We use rich register data on the entire population of Danish children attending grade 9 in the period 1986-2004. This allows us...... school size and alternative measures of long-term success in the educational system and the labor market. The positive impact of school size seems mainly to be driven by boys, students from families with a low educational level and students attending schools in urban areas....

  5. Mapping long-term wetland response to climate

    Science.gov (United States)

    Zhou, Q.; Gallant, A.; Rover, J.

    2016-12-01

    Wetlands provide unique feeding and breeding habitat for numerous waterfowl species. The distribution of wetlands has been considerably changed due to agricultural land conversion and hydrologic modification. Climate change may further impact wetlands through altered moisture regimes. This study characterized long-term variation in wetland conditions by using dense time series from all available Landsat data from 1985 to 2014. We extracted harmonic frequencies from 30 years to two years to delineate the long-term variation in all seven Landsat bands. A cluster analysis and unsupervised classification then enabled us to map different classes of wetland response. We demonstrated the method in the Prairie Pothole Region in North Dakota.

  6. Long-term recurrence and death rates after acute pancreatitis

    DEFF Research Database (Denmark)

    Lund, Helle; Tønnesen, Hanne; Tønnesen, Maja Hanne

    2006-01-01

    The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death.......The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death....

  7. Long-term creep test with finite elements

    International Nuclear Information System (INIS)

    Argyris, J.H.; Szimmat, J.; Willam, K.J.

    1975-01-01

    Following a presentation of concrete creep, a brief summary of the direct and incremental calculation methods for long-term creep behaviour is given. In addition, a survey on the methods of the inner state variables is given which, on the one hand, gives a uniform framework for the various formulations of concrete creep, and on the other hand leads to a computable calculation method. Two examples on long-term creep behaviour illustrate the application field of the calculation method. (orig./LH) [de

  8. On the long-term analysis with finite elements

    International Nuclear Information System (INIS)

    Argyris, J.H.; Szimmat, J.; Willam, K.J.

    1975-01-01

    Following a presentation of concrete creep, a brief summary of the direct and incremental calculation methods on long-term behaviour is given. This is followed by a survey of the method of the inner state variables, which on the one hand gives a uniform framework for the various formulations of concrete creep, and on the other hand leads to a computer-ready calculation process. Two examples on long-term behaviour illustrate the regions of application of the computer methods. (orig./LH) [de

  9. Long-term duration of function of ovarian tissue transplants

    DEFF Research Database (Denmark)

    Andersen, Claus; Silber, Sherman J; Berghold, Stinne Holm

    2012-01-01

    These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian...... or to alleviate its symptoms. These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had...

  10. Long-term stability scintillation tiles for LHCb detector

    International Nuclear Information System (INIS)

    Grinyov, B.V.; Khlapova, N.P.; Senchyshyn, V.G.; Lebedev, V.N.; Adadurov, A.F.; Melnychuk, S.V.

    2004-01-01

    Accelerated thermal aging tests of materials - UPS-923A, UPS-96G, UPS-96GM and their analogues, SCSN-81 (Kuraray) and BC-408 (Bicron) - were made. A forecast of tile lifetime was made for normal conditions of usage (20% reduction of light output and 50% reduction of the bulk attenuation length (BAL) and technical attenuation length (TAL). Scintillator UPS-96GM has the most long-term stability of parameters--more than 11 yr. BC-408 samples have the minimum lifetime ∼7 yr. The long-term stability, calculated by light yield reduction, of UPS-96G, UPS-923A and SCSN-81 is 10, 9 and 8 yr, respectively

  11. Long-term stability scintillation tiles for LHCb detector

    CERN Document Server

    Grinyov, B V; Khlapova, N P; Lebedev, V N; Melnychuk, S V; Senchyshyn, V G

    2004-01-01

    Accelerated thermal aging tests of materials-UPS-923A, UPS-96G, UPS-96GM and their analogues, SCSN-81 (Kuraray) and BC-408 (Bicron)- were made. A forecast of tile lifetime was made for normal conditions of usage (20% reduction of light output and 50% reduction of the bulk attenuation length (BAL) and technical attenuation length (TAL). Scintillator UPS-96GM has the most long-term stability of parameters- more than 11 yr. BC-408 samples have the minimum lifetime ~7 yr. The long-term stability, calculated by light yield reduction, of UPS-96G, UPS-923A and SCSN-81 is 10, 9 and 8 yr, respectively.

  12. Long Term Incentives for Residential Customers Using Dynamic Tariff

    DEFF Research Database (Denmark)

    Huang, Shaojun; Wu, Qiuwei; Nielsen, Arne Hejde

    2015-01-01

    This paper reviews several grid tariff schemes, including flat tariff, time-of-use, time-varying tariff, demand charge and dynamic tariff (DT), from the perspective of the long term incentives. The long term incentives can motivate the owners of flexible demands to change their energy consumption...... behavior in such a way that the power system operation issues, such as system balance and congestion, can be alleviated. From the comparison study, including analysis and case study, the DT scheme outperforms the other tariff schemes in terms of cost saving and network operation condition improving....

  13. The long-term outlook for nuclear capacity in Ontario

    International Nuclear Information System (INIS)

    Archinoff, G.H.

    1979-04-01

    This report derives three estimates of long-term nuclear growth in Ontario for use in strategy studies of alternate nuclear fuel cycles. The low and high estimates encompass the full range of possible long-term nuclear growth rates. The middle, or base growth, estimate represents the nuclear growth pattern which seems at the present time most likely to occur. For the base growth estimate, nuclear capacity in Ontario reaches 31 GWe in 2000, grows to 175 GWe by 2060, and then remains constant. For the high growth estimate, the capacity in 2000 is 33 GWe, and climbs continuously to 833 GWe by the year 2100. (auth)

  14. Long-term skeletal findings in Menkes disease

    International Nuclear Information System (INIS)

    Amador, Eva; Domene, Ruth; Fuentes, Cristian; Carreno, Juan-Carlos; Enriquez, Goya

    2010-01-01

    Skeletal findings in infants with Menkes disease, the most characteristic of which are metaphyseal spurs, long-bone fractures and wormian bones, have been widely reported. However, the changes in skeletal features over time are not well known. The long-term findings differ completely from those initially observed and consist of undertubulation and metaphyseal flaring, similar to the findings seen in some types of bone dysplasia. The initial and long-term radiological features in an 8-year-old boy with Menkes disease are illustrated. (orig.)

  15. Nurse as a support of long - term hospitalized senior

    OpenAIRE

    TUŠLOVÁ, Michaela

    2017-01-01

    This thesis "Nurse as a support of long-term hospitalized senior" is divided into a theoretical and an empirical part. It deals with the issue of long-term hospitalization of seniors at the aftercare department, especially with the nurses' support to seniors and their interrelationships. Three main goals were appointed. It was examined how the seniors perceive nurses who takes care of them. Then in which areas nurses are supportive and which techniques they try to use to be a support for seni...

  16. Long-term Morbidity of Testicular Cancer Treatment.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

    2015-08-01

    Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Regional cerebral blood flow in Alzheimer's disease. Comparison between short and long-term donepezil therapy

    International Nuclear Information System (INIS)

    Ushijima, Yo; Okuyama, Chio; Kubota, Takao; Nakai, Takako; Nishimura, Tsunehiko; Mori, Satoru

    2006-01-01

    Treatment with donepezil improves cognitive function of patients with Alzheimer's disease (AD) when compared to a placebo-controlled group. The purpose of this study was to investigate changes in regional cerebral blood flow (rCBF) of AD patients in short-term and long-term treatment with donepezil. rCBF was measured by N-isopropyl-p- 123 I-iodoamphetamine (IMP) autoradiography method. CBF measurements were performed in 17 AD patients before treatment and after 3 months (short-term therapy) and 1 year (long-term therapy). Regions of interest were set at cerebral cortex and cerebellar hemisphere. We used absolute CBF and relative CBF expressed as ratio to cerebellar CBF. Significant increases in relative rCBF were noted in the frontal, parietal and temporal lobes at the end of short-term therapy. rCBF was decreased after the long-term therapy, whereas rCBF was still increased to a slight extent, as compared with the pre-treatment levels. Absolute rCBF showed minimal change and a tendency to decline. Relative rCBF significantly increased in the short-term donepezil therapy, while following the long-term therapy, rCBF decreased to the pre-treatment level. (author)

  18. Short-term memory and long-term memory are still different.

    Science.gov (United States)

    Norris, Dennis

    2017-09-01

    A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. The Interval Slope Method for Long-Term Forecasting of Stock Price Trends

    Directory of Open Access Journals (Sweden)

    Chun-xue Nie

    2016-01-01

    Full Text Available A stock price is a typical but complex type of time series data. We used the effective prediction of long-term time series data to schedule an investment strategy and obtain higher profit. Due to economic, environmental, and other factors, it is very difficult to obtain a precise long-term stock price prediction. The exponentially segmented pattern (ESP is introduced here and used to predict the fluctuation of different stock data over five future prediction intervals. The new feature of stock pricing during the subinterval, named the interval slope, can characterize fluctuations in stock price over specific periods. The cumulative distribution function (CDF of MSE was compared to those of MMSE-BC and SVR. We concluded that the interval slope developed here can capture more complex dynamics of stock price trends. The mean stock price can then be predicted over specific time intervals relatively accurately, in which multiple mean values over time intervals are used to express the time series in the long term. In this way, the prediction of long-term stock price can be more precise and prevent the development of cumulative errors.

  20. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    Science.gov (United States)

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

    Science.gov (United States)

    Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

    2016-12-02

    Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. A long-term risk management tool for electricity markets using swarm intelligence

    International Nuclear Information System (INIS)

    Azevedo, F.; Vale, Z.A.; Khodr, H.M.; Oliveira, P.B. Moura

    2010-01-01

    This paper addresses the optimal involvement in derivatives electricity markets of a power producer to hedge against the pool price volatility. To achieve this aim, a swarm intelligence meta-heuristic optimization technique for long-term risk management tool is proposed. This tool investigates the long-term opportunities for risk hedging available for electric power producers through the use of contracts with physical (spot and forward contracts) and financial (options contracts) settlement. The producer risk preference is formulated as a utility function (U) expressing the trade-off between the expectation and the variance of the return. Variance of return and the expectation are based on a forecasted scenario interval determined by a long-term price range forecasting model. This model also makes use of particle swarm optimization (PSO) to find the best parameters allow to achieve better forecasting results. On the other hand, the price estimation depends on load forecasting. This work also presents a regressive long-term load forecast model that make use of PSO to find the best parameters as well as in price estimation. The PSO technique performance has been evaluated by comparison with a Genetic Algorithm (GA) based approach. A case study is presented and the results are discussed taking into account the real price and load historical data from mainland Spanish electricity market demonstrating the effectiveness of the methodology handling this type of problems. Finally, conclusions are dully drawn. (author)

  3. Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Kim D Allen

    Full Text Available Long-term memory (LTM formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose polymerase-1 (PARP-1, are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosylation (PAR dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP ribose molecules (pADPr after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA and extracellular signal-regulated kinase (ERK--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I, responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.

  4. Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

    OpenAIRE

    Guilherme T Silva; Guilherme T Silva; Jean-Vincent Le Bé; Imad Riachi; Tania Rinaldi; Kamila Markram; Henry Markram

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm). In the present study, we explored whether Long Term Microcircuit ...

  5. Functional Connectivity of the Precuneus in Female University Students with Long-Term Musical Training

    OpenAIRE

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    Conceiving concrete mental imagery is critical for skillful musical expression and performance. The precuneus, a core component of the default mode network (DMN), is a hub of mental image processing that participates in functions such as episodic memory retrieval and imagining future events. The precuneus connects with many brain regions in the frontal, parietal, temporal, and occipital cortices. The aim of this study was to examine the effects of long-term musical training on the resting-sta...

  6. Long-Term Outcomes of Early Reading Intervention

    Science.gov (United States)

    Hurry, Jane; Sylva, Kathy

    2007-01-01

    This study explores the long-term effectiveness of two differing models of early intervention for children with reading difficulties: Reading Recovery and a specific phonological training. Approximately 400 children were pre-tested, 95 were assigned to Reading Recovery, 97 to Phonological Training and the remainder acted as controls. In the short…

  7. Long-term trajectories of posttraumatic stress disorder in veterans

    DEFF Research Database (Denmark)

    Karstoft, Karen-Inge; Armour, Cherie; Elklit, Ask

    2013-01-01

    OBJECTIVE: To (1) identify long-term trajectories of combat-induced posttraumatic stress disorder (PTSD) symptoms over a 20-year period from 1983 to 2002 in veterans with and without combat stress reaction (CSR) and (2) identify social predictors of these trajectories. METHOD: A latent growth...

  8. The long-term concerns post cochlear implantation as experienced ...

    African Journals Online (AJOL)

    Background. Cochlear implantation aims to provide an effective means of spoken communication for prelingually deaf children. However, studies in this field are mostly clinically orientated, with little focus on the experiences and long-term concerns of families post cochlear implantation (CI). Objective. To describe the ...

  9. Subintimal angioplasty: predictors of long-term success.

    LENUS (Irish Health Repository)

    Keeling, Aoife N

    2009-08-01

    To determine the clinical outcomes and success rates after percutaneous subintimal angioplasty (SIA) in patients with lower-limb occlusive lesions causing intermittent claudication (IC) or critical limb ischemia (CLI) at midterm to long-term follow-up. The secondary aim was to elicit factors predictive of a successful outcome.

  10. Nurses struggle to help pupils with long-term conditions.

    Science.gov (United States)

    Longhurst, Chris

    2016-10-07

    Most school nurses are not confident they can give essential support to pupils with long-term health conditions. Research by the National Children's Bureau found that, due to heavy workloads and the need to work across several schools, nine out of ten school nurses were less confident they can help children with conditions such as diabetes and asthma.

  11. Gap filling strategies for long term energy flux data sets

    NARCIS (Netherlands)

    Falge, E.; Baldocchi, D.; Olson, R.; Anthoni, P.; Aubinet, M.; Bernhofer, C.; Burba, G.; Ceulemans, R.; Clement, R.; Dolman, H.; Granier, A.; Gross, P.; Grünwald, T.; Hollinger, D.; Jensen, N.O.; Katul, G.; Keronen, P.; Kowalski, A.; Lai, C.T.; Law, B.E.; Meyers, T.; Moncrieff, J.; Moors, E.J.; Munger, J.W.; Pilegaard, K.; Rebmann, C.; Suyker, A.; Tenhunen, J.; Tu, K.

    2001-01-01

    At present a network of over 100 field sites are measuring carbon dioxide, water vapor and sensible heat fluxes between the biosphere and atmosphere, on a nearly continuous basis. Gaps in the long term measurements of evaporation and sensible heat flux must be filled before these data can be used

  12. Are long-term bisphosphonate users a reality?

    DEFF Research Database (Denmark)

    Abrahamsen, B

    2012-01-01

    The prevalence of long-term bisphosphonate use may be low due to low refill compliance and gaps in treatment. An analysis of the prescription history of 58,674 bisphosphonate users in Denmark found that only 2.8 % had received ten dose years of treatment or above. INTRODUCTION: This study aims...... to describe the demographics of present bisphosphonate (BP) users, to determine the prevalence of long-term BP use, and to establish if long-term use (a 10-year history of osteoporosis treatment) translated to ten dose years of bisphosphonate prescriptions filled, given the propensity for treatment gaps...... more than ten dose years of a BP. For any osteoporosis drug, 3.0 % had received ten dose years or more, while 23.2 % had received between 5 and 10 years of treatment. CONCLUSION: Long-term users with ten dose years or more of a BP are rare due to periods of low compliance and gaps, with a discrepancy...

  13. Long-term outcome of Tunisian children with primary ciliary ...

    African Journals Online (AJOL)

    Background: Primary ciliary dyskinesia (PCD) is rare. Its diagnosis requires experienced specialists and expensive infrastructure. Its prognosis is variable. Objective: To study the long-term outcome of PCD in Tunisian children with ciliary ultra-structure defects detected by electron microscope. Methods: Covering a period of ...

  14. Modelling the Long-term Periglacial Imprint on Mountain Landscapes

    DEFF Research Database (Denmark)

    Andersen, Jane Lund; Egholm, David Lundbek; Knudsen, Mads Faurschou

    Studies of periglacial processes usually focus on small-scale, isolated phenomena, leaving less explored questions of how such processes shape vast areas of Earth’s surface. Here we use numerical surface process modelling to better understand how periglacial processes drive large-scale, long-term...

  15. Long-term results of peripheral arterial disease rehabilitation

    NARCIS (Netherlands)

    Menard, J.R.; Smith, H.E.; Riebe, D.; Braun, C.M.; Blissmer, B.; Patterson, R.B.

    2004-01-01

    Purpose Although the Peripheral Arterial Disease Rehabilitation Program (PADRx) improves walking ability and quality of life over brief periods of follow-up, the long-term durability of results has not been established. This study examined functional status, walking ability, and quality of life in

  16. A cross cultural comparison of long-term supply relationships

    NARCIS (Netherlands)

    Jong, Gjalt de; Nooteboom, Bart

    2003-01-01

    This paper challenges the received view that long-term supply relationships are a typically Japanese feature, embedded and developed in a typically Japanese society characterized by high levels of trust and cooperation, and for that reason cannot be established in the typically a-cooperative,

  17. Methodology of long term behaviour study of containment materials

    International Nuclear Information System (INIS)

    Vernaz, E.; Godon, N.

    1994-01-01

    Here is the presentation of the papers shown in the colloquium on environment and ceramics; the Atomic Energy Commissariat (Cea) have been working for fifteen years on the long term behaviour of fission products glasses on very long periods, about several millions years. The method of studies is detailed. 2 refs

  18. Consolidation of long-term memory: Evidence and alternatives.

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how

  19. Sexuality and Aging: Implications for Long Term Care.

    Science.gov (United States)

    Hinkley, Nancy E.

    With increasing emphasis on treating the whole person, on the maintenance of an individual's former life style, and on patients' rights, long-term care personnel need to become aware that many nursing home residents experience needs related to their sexuality. A model two-day workshop is presented wlth a focus on the following topics: (1) a broad…

  20. Long-term survival and causes of death after stroke

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Davidsen, M; Thorvaldsen, P

    2001-01-01

    As part of the Danish contribution to the World Health Organization (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Project, a register of patients with stroke was established in 1982. The purpose of the present study was to analyze long-term survival and causes of death...