WorldWideScience

Sample records for sustained long-term expression

  1. 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)

  2. Long term impacts of international outsourcing of manufacturing on sustainability

    DEFF Research Database (Denmark)

    Moosavirad, Seyed Hamed; Kara, Sami; Hauschild, Michael Zwicky

    2014-01-01

    International outsourcing seems to be a cost efficient way of production. However, there are serious concerns about its long term impacts on the environmental, social and economic sustainability. This paper aims to quantify these impacts by using input output analysis, linear programming and system......% international outsourcing scenario and the baseline scenario due to their differences in production technologies. © 2014 CIRP....... dynamics in a case study including European electrical industry (outsourcer), Chinese electrical industry (outsourcee) and their main suppliers. Results depict the differences related to the total CO2 emissions, the number of employees and the gross value added of these two regions between a 10...

  3. 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

  4. Long-term scenarios for sustainable energy use in Germany

    International Nuclear Information System (INIS)

    Fischedick, M.; Nitsch, J.; Lechtenboehmer, S.; Hanke, T.; Barthel, C.; Jungbluth, C.; Assmann, D.; Brueggen, T. vor der; Trieb, F.; Nast, M.; Langniss, O.; Brischke, L.A.

    2002-01-01

    The study was able to show, and explain vividly through scenarios describing change processes, that a sustainable use of energy (aimed, among other things, at reducing CO 2 emissions by 80% by 2050 compared with 1990 levels) is technically feasible, economically viable, compatible with farther-reaching objectives of energy policy (e.g. supply security), and does not, in spite of the substantial need for change, present the players involved with any insurmountable problems but, rather, constitutes both a challenge and an opportunity. Such a development is possible only if the efforts launched to give momentum to the increased use of renewable energy sources are continued consistently, the impending need for replacement and renewal within the generation system is consistently utilised for increasing efficiency and a reorientation mainly towards combined heat and power production, and energy saving is made a new focal point of energy policy. Furthermore, with regard to long-term infrastructure requirements (decentralisation, new fuels), the necessary decisions must be prepared at an early stage and sufficiently robust lines of development must be identified and followed. (orig.) [de

  5. Technologies for sustainable energy development in the long term. Proceedings

    DEFF Research Database (Denmark)

    Sønderberg Petersen, Leif; Larsen, Hans Hvidtfeldt

    2005-01-01

    The Risø International Energy Conference took place 23 - 25 May 2005 and the aim of the conference was to present and discuss new developments and trends in energy technologies which may make major contributions to sustainable energy developments in thecoming decades. The conference addressed R......&D related to the individual technologies as well as their integration into the local, regional and global energy systems. The proceedings are prepared from papers presented at the conference and received withcorrections, if any, until the final deadline on 15 June 2005....

  6. RED BULL: the Long term Business Sustainable Plan

    OpenAIRE

    Dhanasarnsombati, Tas

    2011-01-01

    According to number of studies shows that food and beverage market is one of the most sustainable markets of them all. As majority of super-power supermarkets continue to increase their profits, proven that despite either the up or down-turn of the economic situations, food and beverage always will be the basic need to everyone. However with the food and beverage products keep emerging though out rapidly into the market, leaving consumers with numbers of choices to choose to purchase. In the ...

  7. Sustainable Living in Long-Term Care: For People with Dementia/Alzheimer's

    Science.gov (United States)

    Simmons, Daniela

    2011-01-01

    Nonhome-based long-term care sustainable living arrangements for elderly people with Alzheimer's is presented. Characteristics contributing to sustainability are discussed. The ultimate goal in sustainable design for older adult communities is a people-centered model of care in environments that improve their quality of life. Without sustainable…

  8. Long-term sustainability of bio-components production

    Directory of Open Access Journals (Sweden)

    Souček Ivan

    2012-01-01

    Full Text Available Biofuels play an increasingly important role in motor fuel market. The list of biofuels (bio-components in accordance with EU legislations contains a number of substances not widely used in the market. Traditionally these include: fatty acid methyl esters (FAME, in the Czech Republic methyl ether of rape seed oil and bioethanol (also ethyl terc. buthyl ether ETBE, based on bioethanol. The availability and possible utilizations of bio-component fuels in Czech Republic and Serbia are discussed. Additional attention is paid on the identification of the possibilities to improve effectiveness of rape seeds cultivation and utilization of by-products from FAME production (utilization of sew, rape-meal and glycerol which will allow fulfilment of the sustainability criteria for the first generation biofuels. The new approaches on renewable co-processing are commented. The concept of 3E (emissions, energy demand, and economics is introduced specifying three main attributes for effective production of FAME production in accordance with legal compliances. Bio-components price change is analyzed in comparison to the price of motor fuels, identifying possible (speculative crude price break-even point at the level of 149-176 USD/bbl at which point bio-fuels would become economically cost effective for the use by refiners.

  9. 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

  10. Asset sustainability index : quick guide : proposed metrics for the long-term financial sustainability of highway networks.

    Science.gov (United States)

    2013-04-01

    "This report provides a Quick Guide to the concept of asset sustainability metrics. Such metrics address the long-term performance of highway assets based upon expected expenditure levels. : It examines how such metrics are used in Australia, Britain...

  11. Analysis on long-term perspectives of sustainable nuclear energy towards global warming protection

    International Nuclear Information System (INIS)

    Yamazawa, M.; Ichimura, E.; Shibata, Y.; Kobayashi, K.; Wajima, T.

    1998-01-01

    Study of long-term perspectives of the nuclear power generation was made from the point of views of both CO 2 emission constraints and sustainability of nuclear energy. To this end, STREAM (Semi-empirical TRiple E Analysis Model) program, as a social model, has been developed by Tokyo Electric Power Co. and Hitachi, Ltd. Using this program, long-term world demands of primary and nuclear energy were deduced, in view of the protection against the global warming due to the CO 2 gas accumulation. The inevitable conclusion has been drawn that nuclear energy plays an indispensable role in the reduction of green house effect. Evaluations were then made on conditions that the nuclear power system would be the long-term major sustainable energy source. (author)

  12. Nursing unit leaders' influence on the long-term sustainability of evidence-based practice improvements.

    Science.gov (United States)

    Fleiszer, Andrea R; Semenic, Sonia E; Ritchie, Judith A; Richer, Marie-Claire; Denis, Jean-Louis

    2016-04-01

    To describe how actions of nursing unit leaders influenced the long-term sustainability of a best practice guidelines (BPG) program on inpatient units. Several factors influence the initial implementation of evidence-based practice improvements in nursing, with leadership recognized as essential. However, there is limited knowledge about enduring change, including how frontline nursing leaders influence the sustainability of practice improvements over the long term. A qualitative descriptive case study included 39 in-depth interviews, observations, and document reviews. Four embedded nursing unit subcases had differing levels of program sustainability at 7 years (average) following implementation. Higher levels of BPG sustainability occurred on units where formal leadership teams used an integrated set of strategies and activities. Two key strategies were maintaining priorities and reinforcing expectations. The coordinated use of six activities (e.g., discussing, evaluating, integrating) promoted the continuation of BPG practices among staff. These leadership processes, fostering exchange and learning, contributed to sustainability-promoting environments characterized by teamwork and accountability. Unit leaders are required to strategically orchestrate several overlapping and synergistic efforts to achieve long-term sustainability of BPG-based practice improvements. As part of managing overall unit performance, unit leaders may influence practice improvement sustainability by aligning vision, strategies, and activities. © 2015 John Wiley & Sons Ltd.

  13. Long-term sustainability of the landscape in new climatic conditions

    Science.gov (United States)

    Kubeckova, D.; Krocova, S.

    2017-10-01

    The long-term sustainability of the landscape and its natural environment must be the decisive task of the public administration and, in the wider concept, of every citizen. In new climatic conditions, this need has intensified. The following article suggests in a basic scope whether the above-mentioned task can be accomplished, and what means of solution should be used.

  14. 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.

  15. Long-term storage of radioactive waste: IAEA perspectives on safety and sustainability

    International Nuclear Information System (INIS)

    Rowat, J.H.; Louvat, D.; Metcalf, P.E.

    2006-01-01

    As the amounts of radioactive waste in surface storage have increased, concern has grown over the safety and sustainability of storage in the long term. In response to increasing concerns, the International Atomic Energy Agency (IAEA) has included an action to address the safety implications of the long-term storage (LTS) of radioactive waste in its action plan for waste safety; the action plan was endorsed by the IAEA's Member States in 2001. In 2003, the IAEA published a position paper on the safety and sustainability of LTS as part fulfilment of the action in question. A key theme of the position paper is the contrast of safety and sustainability implications of LTS with those of disposal. The present paper provides a summary of the position paper, describes current IAEA activities that deal with the subject of LTS, and discusses findings from the 2004 Cordoba symposium on disposal of low activity radioactive waste that pertain to LTS. (author)

  16. Improving the long-term sustainability of health aid: are Global Health Partnerships leading the way?

    Science.gov (United States)

    Dodd, Rebecca; Lane, Christopher

    2010-09-01

    Over the last decade development assistance for health has more than doubled. This increase provides an unprecedented opportunity to scale up health services, and in doing so, achieve the health Millennium Development Goals. However, sustaining scaling up will in turn require sustainable donor support until domestic health financing can substitute for it. The provision of long-term predictable finance is of particular concern in health because the bulk of costs are recurrent and many interventions require sustained, multi-year support to be successful. This is also true for health systems strengthening efforts. As the bulk of new aid resources flow through Global Health Partnerships (GHPs), their ability to make long-term commitments is critical to health systems development. In order to better understand the constraints that prevent development partners from making long-term commitments of health aid, the World Health Organization reviewed the practices of seven major health partners in committing development assistance funds over the long term. The review found increasing evidence of long-term commitments of aid for health in each of the seven agencies. The GHPs and their funders have been at the forefront of this trend, pioneering many of the new approaches. The study concludes that all partners have scope to improve the duration of aid within existing rules and regulations, and that the main constraints to doing so are political. Predictability is even more of a concern in current global economic circumstances, as access to resources begins to be squeezed. In this context it is important that we learn from GHPs, which have successfully tested innovative approaches to both raising and disbursing health funds. The prospects for change associated with the new administration in the United States-the largest health donor and the most unpredictable, but also a major supporter of GHPs-make this task even more urgent.

  17. 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

  18. Analysis of the Italian generic medicines retail market: recommendations to enhance long-term sustainability.

    Science.gov (United States)

    Dylst, Pieter; Vulto, Arnold; Simoens, Steven

    2015-02-01

    Italy is among the European countries with the lowest uptake of generic medicines. This paper provides a perspective on the Italian generic medicines retail market. Fast market entrance of generic medicines in Italy is hindered by several factors: the existence of Complementary Protection Certificates in the past, the large market for copies and multiple cases of patent linkage. Prices of generic medicines in Italy are low compared to other European countries. To contain pharmaceutical expenditure, pharmaceutical companies are currently forced to pay back in case of overspending, which disproportionally penalizes small and fast growing companies, to which most generic companies belong to. Current demand-side policies do not successfully stimulate the use of generic medicines. The current market environment surrounding the Italian generic medicines retail market (i.e., low prices, low volumes) threatens its long-term sustainability. Recommendations to enhance the long-term sustainability of the Italian generic medicines retail market round off this perspective paper.

  19. Towards sustainable groundwater use: Setting long-term goals, backcasting, and managing adaptively

    Science.gov (United States)

    Gleeson, T.; Alley, W.M.; Allen, D.M.; Sophocleous, M.A.; Zhou, Y.; Taniguchi, M.; Vandersteen, J.

    2012-01-01

    The sustainability of crucial earth resources, such as groundwater, is a critical issue. We consider groundwater sustainability a value-driven process of intra- and intergenerational equity that balances the environment, society, and economy. Synthesizing hydrogeological science and current sustainability concepts, we emphasize three sustainability approaches: setting multigenerational sustainability goals, backcasting, and managing adaptively. As most aquifer problems are long-term problems, we propose that multigenerational goals (50 to 100 years) for water quantity and quality that acknowledge the connections between groundwater, surface water, and ecosystems be set for many aquifers. The goals should be set by a watershed- or aquifer-based community in an inclusive and participatory manner. Policies for shorter time horizons should be developed by backcasting, and measures implemented through adaptive management to achieve the long-term goals. Two case histories illustrate the importance and complexity of a multigenerational perspective and adaptive management. These approaches could transform aquifer depletion and contamination to more sustainable groundwater use, providing groundwater for current and future generations while protecting ecological integrity and resilience. ?? 2011, The Author(s). Ground Water ?? 2011, National Ground Water Association.

  20. Evaluating strategies for sustainable intensification of U.S. agriculture through the Long-Term Agroecosystem Research network

    Science.gov (United States)

    Sustainable intensification is an emerging model for agriculture designed to reconcile accelerating global demand for agricultural products with long-term environmental stewardship. Defined here as increasing agricultural production while maintaining or improving environmental quality, sustainable i...

  1. 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.

  2. 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.

  3. Ecological strategies for long-term sustainability of the Malaysian ricefield agroecosystem

    International Nuclear Information System (INIS)

    Mashhor Mansor

    2002-01-01

    Ecological concepts should be imposed in ricefield agroecosystem so that a long-term sustainability as well as a sound environmental condition could be achieved. Although several problems are envisaged, thus can be overcome by adopting various techniques which are based on ecological principles. Fundamental issues which involve biodiversity, environment and economic activities should be addressed. In the ricefield agroecosystem the water regime also plays a major role particularly in determining the temporal aspects of the ricefield niche. Different seasons in this case, the dry and wet can have different types of food webs. (Author)

  4. 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.

  5. 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.

  6. Sustainability and Long Term-Tenure: Lion Trophy Hunting in Tanzania.

    Directory of Open Access Journals (Sweden)

    Henry Brink

    Full Text Available It is argued that trophy hunting of large, charismatic mammal species can have considerable conservation benefits but only if undertaken sustainably. Social-ecological theory suggests such sustainability only results from developing governance systems that balance financial and biological requirements. Here we use lion (Panthera leo trophy hunting data from Tanzania to investigate how resource ownership patterns influence hunting revenue and offtake levels. Tanzania contains up to half of the global population of free-ranging lions and is also the main location for lion trophy hunting in Africa. However, there are concerns that current hunting levels are unsustainable. The lion hunting industry in Tanzania is run by the private sector, although the government leases each hunting block to companies, enforces hunting regulation, and allocates them a species-specific annual quota per block. The length of these leases varies and theories surrounding property rights and tenure suggest hunting levels would be less sustainable in blocks experiencing a high turnover of short-term leases. We explored this issue using lion data collected from 1996 to 2008 in the Selous Game Reserve (SGR, the most important trophy hunting destination in Tanzania. We found that blocks in SGR with the highest lion hunting offtake were also those that experienced the steepest declines in trophy offtake. In addition, we found this high hunting offtake and the resultant offtake decline tended to be in blocks under short-term tenure. In contrast, lion hunting levels in blocks under long-term tenure matched more closely the recommended sustainable offtake of 0.92 lions per 1000 km2. However, annual financial returns were higher from blocks under short-term tenure, providing $133 per km2 of government revenue as compared to $62 per km2 from long-term tenure blocks. Our results provide evidence for the importance of property rights in conservation, and support calls for an overhaul

  7. Sustainability and Long Term-Tenure: Lion Trophy Hunting in Tanzania.

    Science.gov (United States)

    Brink, Henry; Smith, Robert J; Skinner, Kirsten; Leader-Williams, Nigel

    2016-01-01

    It is argued that trophy hunting of large, charismatic mammal species can have considerable conservation benefits but only if undertaken sustainably. Social-ecological theory suggests such sustainability only results from developing governance systems that balance financial and biological requirements. Here we use lion (Panthera leo) trophy hunting data from Tanzania to investigate how resource ownership patterns influence hunting revenue and offtake levels. Tanzania contains up to half of the global population of free-ranging lions and is also the main location for lion trophy hunting in Africa. However, there are concerns that current hunting levels are unsustainable. The lion hunting industry in Tanzania is run by the private sector, although the government leases each hunting block to companies, enforces hunting regulation, and allocates them a species-specific annual quota per block. The length of these leases varies and theories surrounding property rights and tenure suggest hunting levels would be less sustainable in blocks experiencing a high turnover of short-term leases. We explored this issue using lion data collected from 1996 to 2008 in the Selous Game Reserve (SGR), the most important trophy hunting destination in Tanzania. We found that blocks in SGR with the highest lion hunting offtake were also those that experienced the steepest declines in trophy offtake. In addition, we found this high hunting offtake and the resultant offtake decline tended to be in blocks under short-term tenure. In contrast, lion hunting levels in blocks under long-term tenure matched more closely the recommended sustainable offtake of 0.92 lions per 1000 km2. However, annual financial returns were higher from blocks under short-term tenure, providing $133 per km2 of government revenue as compared to $62 per km2 from long-term tenure blocks. Our results provide evidence for the importance of property rights in conservation, and support calls for an overhaul of the system in

  8. 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…

  9. 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.

  10. 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.

  11. Principles of the long-term sustainable development strategy of the SOCAR

    International Nuclear Information System (INIS)

    Akhundov, M.M.

    2002-01-01

    Full text: SOCAR intends to radically change its Health, Safety and Environmental Policy and to build it on the basis of Sustainable Development principles. Sustainable Development principles have been developed and accepted by the world community after the need of sensible prospects of its development has been recognized. The International Conference has initiated international discussions of the sustainable development issues for the Protection of Environment, which has hosted by UNESCO in Stockholm in 1968. Later, in 1972 the UN Environmental Conference was held in Stockholm, with the participation of 113 countries, which established a special structure- United Nations Environmental Programme (UNEP). Later, in 1993, at the UN World Conference for Human Rights, which was held in Vienna, following a discussions by the country leaders and representatives of civil society a provision was developed, which stated that no development could be long-term in the absence of full respect to human rights. SOCAR has just started to implement strategy and intends to continue its policy in this direction. In the future, SOCAR s business shall be carried out with account to the balance of economical, social and environmental components. SOCAR shall continue the development of required systems, instruments and indicators of management for achieving the goals of sustainable development

  12. Evaluating strategies for sustainable intensification of US agriculture through the Long-Term Agroecosystem Research network

    Science.gov (United States)

    Spiegal, S.; Bestelmeyer, B. T.; Archer, D. W.; Augustine, D. J.; Boughton, E. H.; Boughton, R. K.; Cavigelli, M. A.; Clark, P. E.; Derner, J. D.; Duncan, E. W.; Hapeman, C. J.; Harmel, R. D.; Heilman, P.; Holly, M. A.; Huggins, D. R.; King, K.; Kleinman, P. J. A.; Liebig, M. A.; Locke, M. A.; McCarty, G. W.; Millar, N.; Mirsky, S. B.; Moorman, T. B.; Pierson, F. B.; Rigby, J. R.; Robertson, G. P.; Steiner, J. L.; Strickland, T. C.; Swain, H. M.; Wienhold, B. J.; Wulfhorst, J. D.; Yost, M. A.; Walthall, C. L.

    2018-03-01

    Sustainable intensification is an emerging model for agriculture designed to reconcile accelerating global demand for agricultural products with long-term environmental stewardship. Defined here as increasing agricultural production while maintaining or improving environmental quality, sustainable intensification hinges upon decision-making by agricultural producers, consumers, and policy-makers. The Long-Term Agroecosystem Research (LTAR) network was established to inform these decisions. Here we introduce the LTAR Common Experiment, through which scientists and partnering producers in US croplands, rangelands, and pasturelands are conducting 21 independent but coordinated experiments. Each local effort compares the outcomes of a predominant, conventional production system in the region (‘business as usual’) with a system hypothesized to advance sustainable intensification (‘aspirational’). Following the logic of a conceptual model of interactions between agriculture, economics, society, and the environment, we identified commonalities among the 21 experiments in terms of (a) concerns about business-as-usual production, (b) ‘aspirational outcomes’ motivating research into alternatives, (c) strategies for achieving the outcomes, (d) practices that support the strategies, and (e) relationships between practice outreach and adoption. Network-wide, concerns about business as usual include the costs of inputs, opportunities lost to uniform management approaches, and vulnerability to accelerating environmental changes. Motivated by environmental, economic, and societal outcomes, scientists and partnering producers are investigating 15 practices in aspirational treatments to sustainably intensify agriculture, from crop diversification to ecological restoration. Collectively, the aspirational treatments reveal four general strategies for sustainable intensification: (1) reducing reliance on inputs through ecological intensification, (2) diversifying management

  13. Robotic Observatory System Design-Specification Considerations for Achieving Long-Term Sustainable Precision Performance

    Science.gov (United States)

    Wray, J. D.

    2003-05-01

    The robotic observatory telescope must point precisely on the target object, and then track autonomously to a fraction of the FWHM of the system PSF for durations of ten to twenty minutes or more. It must retain this precision while continuing to function at rates approaching thousands of observations per night for all its years of useful life. These stringent requirements raise new challenges unique to robotic telescope systems design. Critical design considerations are driven by the applicability of the above requirements to all systems of the robotic observatory, including telescope and instrument systems, telescope-dome enclosure systems, combined electrical and electronics systems, environmental (e.g. seeing) control systems and integrated computer control software systems. Traditional telescope design considerations include the effects of differential thermal strain, elastic flexure, plastic flexure and slack or backlash with respect to focal stability, optical alignment and angular pointing and tracking precision. Robotic observatory design must holistically encapsulate these traditional considerations within the overall objective of maximized long-term sustainable precision performance. This overall objective is accomplished through combining appropriate mechanical and dynamical system characteristics with a full-time real-time telescope mount model feedback computer control system. Important design considerations include: identifying and reducing quasi-zero-backlash; increasing size to increase precision; directly encoding axis shaft rotation; pointing and tracking operation via real-time feedback between precision mount model and axis mounted encoders; use of monolithic construction whenever appropriate for sustainable mechanical integrity; accelerating dome motion to eliminate repetitive shock; ducting internal telescope air to outside dome; and the principal design criteria: maximizing elastic repeatability while minimizing slack, plastic deformation

  14. Transitions to Sustainable Development. New Directions in the Study of Long Term Transformative Change

    International Nuclear Information System (INIS)

    Grin, J.; Rotmans, J.; Schot, J.; Geels, F.; Loorbach, D.

    2010-01-01

    Over the past few decades, there has been a growing concern about the social and environmental risks which have come along with the progress achieved through a variety of mutually intertwined modernization processes. In recent years these concerns are transformed into a widely-shared sense of urgency, partly due to events such as the various pandemics threatening livestock, and increasing awareness of the risks and realities of climate change, and the energy and food crises. This sense of urgency includes an awareness that our entire social system is in need of fundamental transformation. But like the earlier transition between the 1750s and 1890s from a pre-modern to a modern industrial society, this second transition is also a contested one. Sustainable development is only one of many options. This book addresses the issue on how to understand the dynamics and governance of the second transition dynamics in order to ensure sustainable development. It will be necessary reading for students and scholars with an interest in sustainable development and long-term transformative change.

  15. Transitions to Sustainable Development. New Directions in the Study of Long Term Transformative Change

    Energy Technology Data Exchange (ETDEWEB)

    Grin, J. [Department of Political Science, University of Amsterdam, Amsterdam (Netherlands); Rotmans, J. [Sustainability Transitions and Transition Management, Erasmus University Rotterdam, Rotterdam (Netherlands); Schot, J. [Eindhoven University of Technology, Eindhoven (Netherlands); Geels, F. [Science Policy Research Unit SPRU, University of Sussex, Brighton (United Kingdom); Loorbach, D. [Dutch Research Institute for Transitions Drift, Erasmus University Rotterdam, Rotterdam (Netherlands)

    2010-07-01

    Over the past few decades, there has been a growing concern about the social and environmental risks which have come along with the progress achieved through a variety of mutually intertwined modernization processes. In recent years these concerns are transformed into a widely-shared sense of urgency, partly due to events such as the various pandemics threatening livestock, and increasing awareness of the risks and realities of climate change, and the energy and food crises. This sense of urgency includes an awareness that our entire social system is in need of fundamental transformation. But like the earlier transition between the 1750s and 1890s from a pre-modern to a modern industrial society, this second transition is also a contested one. Sustainable development is only one of many options. This book addresses the issue on how to understand the dynamics and governance of the second transition dynamics in order to ensure sustainable development. It will be necessary reading for students and scholars with an interest in sustainable development and long-term transformative change.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Long-term Sustainability of Fracture Conductivity in Geothermal Systems using Proppants

    Energy Technology Data Exchange (ETDEWEB)

    Earl D Mattson; Ghanashyam Neupane; Mitchell Plummer; Clay Jones; Joe Moore

    2016-02-01

    Long-term sustainability of fracture conductivity is critical for commercial success of engineered geothermal system (EGS) and hydrogeothermal field sites. The injection of proppants has been suggested as a means to enhance the conductivity in these systems. Several studies have examined the chemical behavior of proppants that are not at chemical equilibrium with the reservoir rock and water. These studies have suggested that in geothermal systems, geochemical reactions can lead to enhance proppant dissolution and deposition alteration minerals. We hypothesize that proppant dissolution will decrease the strength of the proppant and can potentially reduce the conductivity of the fracture. To examine the geomechanical strength of proppants, we have performed modified crushing tests of proppants and reservoir rock material that was subjected to geothermal reservoir temperature conditions. The batch reactor experiments heated crushed quartz monzonite rock material, proppants (either quartz sand, sintered bauxite or kryptospheres) with Raft River geothermal water to 250 ºC for a period of 2 months. Solid and liquid samples were shipped to University of Utah for chemical characterization with ICP-OES, ICP-MS, and SEM. A separate portion of the rock/proppant material was subjected to a modified American Petroleum Institute ISO 13503-2 proppant crushing test. This test is typically used to determine the maximum stress level that can be applied to a proppant pack without the occurrence of unacceptable proppant crushing. We will use the test results to examine potential changes in proppant/reservoir rock geomechanical properties as compared to samples that have not been subjected to geothermal conditions. These preliminary results will be used to screen the proppants for long term use in EGS and hot hydrogeothermal systems.

  19. Integrated, long term, sustainable, cost effective biosolids management at a large Canadian wastewater treatment facility.

    Science.gov (United States)

    Leblanc, R J; Allain, C J; Laughton, P J; Henry, J G

    2004-01-01

    The Greater Moncton Sewerage Commission's 115,000 m3/d advanced, chemically assisted primary wastewater treatment facility located in New Brunswick, Canada, has developed an integrated, long term, sustainable, cost effective programme for the management and beneficial utilization of biosolids from lime stabilized raw sludge. The paper overviews biosolids production, lime stabilization, conveyance, and odour control followed by an indepth discussion of the wastewater sludge as a resource programme, namely: composting, mine site reclamation, landfill cover, land application for agricultural use, tree farming, sod farm base as a soil enrichment, topsoil manufacturing. The paper also addresses the issues of metals, pathogens, organic compounds, the quality control program along with the regulatory requirements. Biosolids capital and operating costs are presented. Research results on removal of metals from primary sludge using a unique biological process known as BIOSOL as developed by the University of Toronto, Canada to remove metals and destroy pathogens are presented. The paper also discusses an ongoing cooperative research project with the Université de Moncton where various mixtures of plant biosolids are composted with low quality soil. Integration, approach to sustainability and "cumulative effects" as part of the overall biosolids management strategy are also discussed.

  20. Integrated, long term, sustainable, cost effective biosolids management at a large Canadian wastewater treatment facility

    Energy Technology Data Exchange (ETDEWEB)

    LeBlance, R.J.; Allain, C.J.; Laughton, P.J.; Henry, J.G.

    2003-07-01

    The Greater Moncton Sewerage Commission's 115 000 m{sup 3}/d advanced, chemically assisted primary wastewater treatment facility located in New Brunswick, Canada, has developed an integrated, long term, sustainable, cost effective programme for the management and beneficial utilization of biosolids from lime stabilized raw sludge. The paper overviews biosolids production, lime stabilization, conveyance, and odour control followed by an indepth discussion of the wastewater sludge as a resource programme, namely: composting, mine site reclamation, landfill cover, land application for agricultural use, tree farming, sod farm base as a soil enrichment, topsoil manufacturing. The paper also addresses the issues of metals, pathogens, organic compounds, the quality control program along with the regulatory requirements. Biosolids capital and operating costs are presented. Research results on removal of metals from primary sludge using a unique biological process known as BIOSOL as developed by the University of Toronto, Canada to remove metals and destroy pathogens are presented. The paper also discusses an ongoing cooperative research project with the Universite de Moncton where various mixtures of plant biosolids are composted with low quality soil. Integration, approach to sustainability and ''cumulative effects'' as part of the overall biosolids management strategy is also discussed. (author)

  1. Long-term sustainability of microbial-induced CaCO3 precipitation in aqueous media.

    Science.gov (United States)

    Gat, Daniella; Ronen, Zeev; Tsesarsky, Michael

    2017-10-01

    Microbially induced CaCO 3 precipitation (MICP) via urea hydrolysis is an emerging technique for soil amelioration, building materials rehabilitation and pollutants sequestration amongst other various environmental applications. The successful application of MICP requires the sustainability of the precipitated CaCO 3 ; to which the fate of ammonia, the main by-product of ureolysis, is potentially significante. Ammonia volatilization and biological ammonia oxidation both induce a pH decrease, which, in turn, might cause CaCO 3 dissolution. To examine the potential effect of accumulated ammonia on precipitated CaCO 3 , we conducted a long-term MICP batch experiment, using environmental enrichment cultures of ureolytic bacteria. Here we show that CaCO 3 precipitation was completed within 15-27 days, along with a rise in ammonium concentration. Following completion of ureolysis and precipitation, ammonium concentrations decreased, leading to a pH decrease. About 30 days after precipitation was completed, as much as 30% CaCO 3 dissolution, was observed. A two-step model, describing urea hydrolysis followed by the removal of ammonia from the precipitation solution, predicted CaCO 3 dissolution due to ammonia volatilization. We suggest that ureolytic MICP might result in ammonia volatilization, leading to significant CaCO 3 dissolution. These results provide basic insights into the sustainability of ureolytic MICP and should further encourage removal of the accumulated ammonia from the treated site. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Long-Term Protection of Genetically Ablated Rabbit Retinal Degeneration by Sustained Transscleral Unoprostone Delivery.

    Science.gov (United States)

    Nagai, Nobuhiro; Koyanagi, Eri; Izumida, Yasuko; Liu, Junjun; Katsuyama, Aya; Kaji, Hirokazu; Nishizawa, Matsuhiko; Osumi, Noriko; Kondo, Mineo; Terasaki, Hiroko; Mashima, Yukihiko; Nakazawa, Toru; Abe, Toshiaki

    2016-12-01

    To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry. In situ hybridization and immunohistochemistry evaluated the retinal distribution of big potassium (BK) channels, and RT-PCR evaluated the expressions of BK channels and m-opsin at 1 week after URD treatment. The URD released UNO at a rate of 10.2 ±1.0 μg/d, and the release rate and amount of UNO decreased during 32 weeks. Higher ERG amplitudes were observed in the URD-treated Tg rabbits compared with the placebo-URD, or nontreated controls. At 24 weeks after implantation into the URD-treated Tg rabbits, OCT images showed preservation of retinal thickness, and histologic examinations (44 weeks) showed greater thickness of outer nuclear layers. Unoprostone was detected in the retina, choroid, and plasma of Wt rabbits. Retina/plasma ratio of UNO levels were 38.0 vs. 0.68 ng UNO*hour/mL in the URD-treated group versus control (topical UNO), respectively. Big potassium channels were observed in cone, cone ON-bipolar, and rod bipolar cells. Reverse-transcriptase PCR demonstrated BK channels and m-opsins increased in URD-treated eyes. In Tg rabbits, URD use slowed the decline of retinal function for more than 32 weeks, and therefore provides a promising tool for long-term treatment of RP.

  3. Sustaining complex interventions in long-term care: a qualitative study of direct care staff and managers

    OpenAIRE

    Col?n-Emeric, Cathleen; Toles, Mark; Cary, Michael P.; Batchelor-Murphy, Melissa; Yap, Tracey; Song, Yuting; Hall, Rasheeda; Anderson, Amber; Burd, Andrew; Anderson, Ruth A.

    2016-01-01

    Background Little is known about the sustainability of behavioral change interventions in long-term care (LTC). Following a cluster randomized trial of an intervention to improve staff communication (CONNECT), we conducted focus groups of direct care staff and managers to elicit their perceptions of factors that enhance or reduce sustainability in the LTC setting. The overall aim was to generate hypotheses about how to sustain complex interventions in LTC. Methods In eight facilities, we cond...

  4. An ethical dimension to sustainable restoration and long-term management of contaminated areas

    International Nuclear Information System (INIS)

    Oughton, Deborah; Forsberg, Ellen-Marie; Bay, Ingrid; Kaiser, Matthias; Howard, Brenda

    2004-01-01

    Experience after the Chernobyl accident has shown that restoration strategies need to consider a wide range of different issues to ensure the long-term sustainability of large and varied contaminated areas. Thus, the criteria by which we evaluate countermeasures need to be extended from simple cost-benefit effectiveness and radiological protection standards to a more integrated, holistic approach, including social and ethical aspects. Within the STRATEGY project, the applicability of many countermeasures is being critically assessed using a wide range of criteria. Attention is being given to issues such as practicability, feasibility, capacity and environmental side-effects, as well as social factors such as public perceptions of risk, communication of information and the need for dialogue and consultation with affected communities, and ethical aspects such as informed consent and the fair distribution of costs and doses. Although such socio-ethical factors are now the subject of a substantial field of research, there has been little attempt to integrate them in a practical context for decision makers. Within this paper, we specifically consider the ethical aspects of restoration strategies and suggest practical means by which these can be taken into account in the decision making process, introducing a value matrix. The paper covers two critical areas: evaluation of individual countermeasures, and use of the matrix to ensure transparent and systematic consideration of values in selection of a restoration strategy

  5. Evaluation of nuclear power development scenarios in romania envisaging the long-term national energy sustainability

    International Nuclear Information System (INIS)

    Margeanu, C.; Apostol, M.; Visan, I.; Prodea, I.

    2015-01-01

    The paper summarizes the results of RATEN ICN Pitesti experts' activities in the IAEA's Collaborative Project INPRO-SYNERGIES. Romanian study proposes to evaluate and analyze development of the nuclear capacity and increasing of its share in national energy sector, envisaging the long term national and regional energy sustainability by keeping options open for the future while bringing solutions to short/medium-term challenges. The study focused on the modelling of national NES (Nuclear Energy System) development on short and medium-term (time horizon 2050), considering the existing NFC (Nuclear Fuel Cycle) infrastructure and legislation, provisions of strategic documents in force and including also the possibility of regional collaboration regarding U/fresh fuel supply and SF (Spent Fuel) storage, as services provided at international market prices. The energy system modelling was realized by using the IAEA's MESSAGE program. The study results offer a clear image and also the possible answer to several key questions regarding: potential of nuclear energy to participate with an important share in national energy mix, in conditions of cost competitiveness, safety and security of supply; impact on national energy mix portfolio of capacities and electricity production; impact on Uranium domestic resources; economic projection/investments needed for new nuclear capacities addition; fresh fuel requirements for nuclear capacities; SF annually discharged and transferred to interim wet storage for cooling; SF volume in interim dry storage, etc. (authors)

  6. 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

    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

  7. 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

  8. Australia's TERN: Building, Sustaining and Advancing Collaborative Long Term Ecosystem Research Networks

    Science.gov (United States)

    HEld, A. A.; Phinn, S. R.

    2012-12-01

    TERN is Australia's Terrestrial Ecosystem Research Network (www.tern.org.au) is one of several environmental data collection, storage and sharing projects developed through the government's research infrastructure programs 2008-2014. This includes terrestrial and coastal ecosystem data collection infrastructure across multiple disciplines, hardware, software and processes used to store, analyse and integrate data sets. TERN's overall objective is to build the collaborations, infrastructure and programs to meet the needs of ecosystem science communities in Australia in the long term, through institutional frameworks necessary to establish a national terrestrial ecosystem site and observational network, coordinated networks enabling cooperation and operational experience; public access to quality assured and appropriately licensed data; and allowing the terrestrial ecosystem research community to define and sustain the terrestrial observing paradigm into the longer term. This paper explains how TERN was originally established, and now operates, along with plans to sustain itself in the future. TERN is implemented through discipline/technical groups referred to as "TERN Facilities". Combined, the facilities provide observations of surface mass and energy fluxes over key ecosystems, biophysical remote sensing data, ecological survey plots, soils information, and coastal ecosystems and associated water quality variables across Australia. Additional integrative facilities cover elements of ecoinformatics, data-scaling and modelling, and linking science to management. A central coordination and portal facility provides meta-data storage, data identification, legal and licensing support. Data access, uploading, meta-data generation, DOI attachment and licensing is completed at each facility's own portal level. TERN also acts as the open-data repository of choice for Australian scientists required to publish their data. Several key lessons we have learnt, will be presented

  9. Sustainability of Long-term Care: Puzzling Tasks Ahead for Policy-Makers.

    Science.gov (United States)

    Mosca, Ilaria; van der Wees, Philip J; Mot, Esther S; Wammes, Joost J G; Jeurissen, Patrick P T

    2016-08-17

    The sustainability of long-term care (LTC) is a prominent policy priority in many Western countries. LTC is one of the most pressing fiscal issues for the growing population of elderly people in the European Union (EU) Member States. Country recommendations regarding LTC are prominent under the EU's European Semester. This paper examines challenges related to the financial- and organizational sustainability of LTC systems in the EU. We combined a targeted literature review and a descriptive selected country analysis of: (1) public- and private funding; (2) informal care and externalities; and (3) the possible role of technology in increasing productivity. Countries were selected via purposive sampling to establish a cohort of country cases covering the spectrum of differences in LTC systems: public spending, private funding, informal care use, informal care support, and cash benefits. The aging of the population, the increasing gap between availability of informal care and demand for LTC, substantial market failures of private funding for LTC, and fiscal imbalances in some countries, have led to structural reforms and enduring pressures for LTC policy-makers across the EU. Our exploration of national policies illustrates different solutions that attempt to promote fairness while stimulating efficient delivery of services. Important steps must be taken to address the sustainability of LTC. First, countries should look deeper into the possibilities of complementing public- and private funding, as well as at addressing market failures of private funding. Second, informal care externalities with spill-over into neighboring policy areas, the labor force, and formal LTC workers, should be properly addressed. Thirdly, innovations in LTC services should be stimulated to increase productivity through technology and process innovations, and to reduce costs. The analysis shows why it is difficult for EU Member State governments to meet all their goals for sustainable LTC

  10. Sustainability of Long-term Care: Puzzling Tasks Ahead for Policy-Makers

    Directory of Open Access Journals (Sweden)

    Ilaria Mosca

    2017-04-01

    Full Text Available Background The sustainability of long-term care (LTC is a prominent policy priority in many Western countries. LTC is one of the most pressing fiscal issues for the growing population of elderly people in the European Union (EU Member States. Country recommendations regarding LTC are prominent under the EU’s European Semester. Methods This paper examines challenges related to the financial- and organizational sustainability of LTC systems in the EU. We combined a targeted literature review and a descriptive selected country analysis of: (1 public- and private funding; (2 informal care and externalities; and (3 the possible role of technology in increasing productivity. Countries were selected via purposive sampling to establish a cohort of country cases covering the spectrum of differences in LTC systems: public spending, private funding, informal care use, informal care support, and cash benefits. Results The aging of the population, the increasing gap between availability of informal care and demand for LTC, substantial market failures of private funding for LTC, and fiscal imbalances in some countries, have led to structural reforms and enduring pressures for LTC policy-makers across the EU. Our exploration of national policies illustrates different solutions that attempt to promote fairness while stimulating efficient delivery of services. Important steps must be taken to address the sustainability of LTC. First, countries should look deeper into the possibilities of complementing public- and private funding, as well as at addressing market failures of private funding. Second, informal care externalities with spill-over into neighboring policy areas, the labor force, and formal LTC workers, should be properly addressed. Thirdly, innovations in LTC services should be stimulated to increase productivity through technology and process innovations, and to reduce costs. Conclusion The analysis shows why it is difficult for EU Member State

  11. 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.

  12. Sustained favorable long-term outcome in the treatment of schizophrenia: a 3-year prospective observational study

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum Haya

    2011-08-01

    Full Text Available Abstract Background This study of chronically ill patients with schizophrenia aimed to identify patients who achieve sustained favorable long-term outcome - when the outcome incorporates severity of symptoms, level of functioning, and use of acute care services - and to identify the best baseline predictors of achieving this sustained favorable long-term outcome. Methods Using data from the United States Schizophrenia Care and Assessment Program (US-SCAP (N = 2327, a large 3-year prospective, multisite, observational study of individuals treated for schizophrenia in the US, a hierarchical cluster analysis was performed to group patients based upon baseline symptom severity. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS scores, level of functioning, and use of acute care services. Level of functioning reflected patient-reported productivity and clinician-rated occupational role functioning. Use of acute care services reflected self-reported psychiatric hospitalization and emergency service use. Change of health state was determined over the 3-year period. A patient was classified as having a sustained favorable long-term outcome if their health state values had the closest distance to the defined "best baseline cluster" at each point over the length of the study. Stepwise logistic regression was used to determine baseline predictors of sustained favorable long-term outcome. Results At baseline, 5 distinct health state clusters were identified, ranging from "best" to "worst." Of 1635 patients with sufficient data, only 157 (10% experienced sustained favorable long-term outcome during the 2-years postbaseline. The baseline predictors associated with sustained favorable long-term outcome included better quality of life, more daily activities, patient-reported clearer thinking from medication, better global functioning, being employed, not being a victim of a crime, not having received individual therapy, and not

  13. Arctic plants are capable of sustained responses to long-term warming

    Directory of Open Access Journals (Sweden)

    Robert T. Barrett

    2016-05-01

    Full Text Available Previous studies have shown that Arctic plants typically respond to warming with increased growth and reproductive effort and accelerated phenology, and that the magnitude of these responses is likely to change over time. We investigated the effects of long-term experimental warming on plant growth (leaf length and reproduction (inflorescence height, reproductive phenology and reproductive effort using 17–19 years of measurements collected as part of the International Tundra Experiment (ITEX at sites near Barrow and Atqasuk, Alaska. During the study period, linear regressions indicated non-significant tendencies towards warming air temperatures at our study sites. Results of our meta-analyses on the effect size of experimental warming (calculated as Hedges’ d indicated species generally responded to warming by increasing inflorescence height, increasing leaf length and flowering earlier, while reproductive effort did not respond consistently. Using weighted least-squares regressions on effect sizes, we found a significant trend towards dampened response to experimental warming over time for reproductive phenology. This tendency was consistent, though non-significant, across all traits. A separate analysis revealed significant trends towards reduced responses to experimental warming during warmer summers for all traits. We therefore propose that tendencies towards dampened plant responses to experimental warming over time are the result of regional warming. These results show that Arctic plants are capable of sustained responses to warming over long periods of time but also suggest that, as the region continues to warm, factors such as nutrient availability, competition and herbivory will become more limiting to plant growth and reproduction than temperature.

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

    Science.gov (United States)

    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.

  15. Riding The Waves Of Quality Improvement : Sustainability and spread in a Dutch quality improvement program for long-term care

    NARCIS (Netherlands)

    S.S. Slaghuis (Sarah)

    2016-01-01

    markdownabstractIncreasingly, sustainability and spread have become part and parcel of organizational strategy in health care. This applies in particular to organizations in the long-term care sector, which faces an increasing care demand, ageing population and labor shortage. Unfortunately,

  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. Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study.

    Science.gov (United States)

    Stumbo, Scott P; Ford, James H; Green, Carla A

    2017-11-01

    A greater understanding of the factors that influence long-term sustainment of quality improvement (QI) initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007-2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1) finding alignment between business- and client-centered practices; (2) staff engagement early in QI process added legitimacy which facilitated sustainment; (3) commitment to integrating data into monitoring practices and the identification of a data champion; and (4) adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1) lack of evidence of impact on business practices led to discontinuation; (2) disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3) no data integration into overall business practices and no identified data champion; and (4) high staff turnover. In addition, we found that many agencies' current use of NIATx methods and tools suggested a legacy effect that might improve quality elsewhere, even absent overall sustainment of

  19. Modeling and analysis of long-term energy scenarios for sustainable strategies of Ethiopia

    Energy Technology Data Exchange (ETDEWEB)

    Senshaw, Dereje Azemraw

    2014-04-15

    Despite robust economic growth, Ethiopia is one of the countries with poor energy accesses. Contributing factors are poor availability of energy, unreliable and insufficient quality of energy, and insufficient policy. Recognizing that energy access and security are indispensable to economic transformation, Ethiopia needs to cope with key challenges related to energy security, climate change mitigation and also diversification of energy supply. In order to achieve these targets and strive towards sustainable energy for all, Ethiopia's energy system requires a major transformation. The main achievement of this research has been the development of alternative energy options under different conditions for Ethiopia up to 2050. To identify an energy pathway that would meet Ethiopia's energy needs in a sustainable manner, three scenarios are considered: the business-as usual (BAU), moderate shift (Scenario1) and the advanced shift scenario (Scenario 2). The scenarios were developed, quantified and analyzed using a bottom-up model for Long Term Alternative Energy Planning (LEAP). These scenarios represent a range of energy policy measures that Ethiopia could adopt to achieve its sustainable development goals. The BAU scenario reflects a continuation of the current policy trend and considers on economic growth rate of 7%, while Scenario 1 and Scenario 2 represent moderate and advanced levels of commitment in economic growth, energy diversity and reduction of energy import dependency and CO{sub 2} emissions limits, respectively. The scenario analysis shows that the primary energy requirements for Ethiopia's socio-economic development will increase sharply over the period (2010-2050) in all three scenarios. BAU, Scenario 1 and Scenario 2 show an expected to growth at annual rates of 4.1, 4.9 and 5.7% respectively. If the current policy trends (as represented by BAU) continue, the total energy demand in Ethiopia is expected to reach 6,553 Petajoule (PJ) by 2050

  20. Modeling and analysis of long-term energy scenarios for sustainable strategies of Ethiopia

    International Nuclear Information System (INIS)

    Senshaw, Dereje Azemraw

    2014-04-01

    Despite robust economic growth, Ethiopia is one of the countries with poor energy accesses. Contributing factors are poor availability of energy, unreliable and insufficient quality of energy, and insufficient policy. Recognizing that energy access and security are indispensable to economic transformation, Ethiopia needs to cope with key challenges related to energy security, climate change mitigation and also diversification of energy supply. In order to achieve these targets and strive towards sustainable energy for all, Ethiopia's energy system requires a major transformation. The main achievement of this research has been the development of alternative energy options under different conditions for Ethiopia up to 2050. To identify an energy pathway that would meet Ethiopia's energy needs in a sustainable manner, three scenarios are considered: the business-as usual (BAU), moderate shift (Scenario1) and the advanced shift scenario (Scenario 2). The scenarios were developed, quantified and analyzed using a bottom-up model for Long Term Alternative Energy Planning (LEAP). These scenarios represent a range of energy policy measures that Ethiopia could adopt to achieve its sustainable development goals. The BAU scenario reflects a continuation of the current policy trend and considers on economic growth rate of 7%, while Scenario 1 and Scenario 2 represent moderate and advanced levels of commitment in economic growth, energy diversity and reduction of energy import dependency and CO 2 emissions limits, respectively. The scenario analysis shows that the primary energy requirements for Ethiopia's socio-economic development will increase sharply over the period (2010-2050) in all three scenarios. BAU, Scenario 1 and Scenario 2 show an expected to growth at annual rates of 4.1, 4.9 and 5.7% respectively. If the current policy trends (as represented by BAU) continue, the total energy demand in Ethiopia is expected to reach 6,553 Petajoule (PJ) by 2050 from

  1. Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study

    Directory of Open Access Journals (Sweden)

    Scott P. Stumbo

    2017-11-01

    Full Text Available Abstract Background A greater understanding of the factors that influence long-term sustainment of quality improvement (QI initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. Methods We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007–2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. Results We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1 finding alignment between business- and client-centered practices; (2 staff engagement early in QI process added legitimacy which facilitated sustainment; (3 commitment to integrating data into monitoring practices and the identification of a data champion; and (4 adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1 lack of evidence of impact on business practices led to discontinuation; (2 disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3 no data integration into overall business practices and no identified data champion; and (4 high staff turnover. In addition, we found that many agencies’ current use of NIATx methods and tools suggested a legacy effect that might improve

  2. Long-term risks of inadequate management practices on the sustainability of agricultural soils

    NARCIS (Netherlands)

    Vries, de W.; Groenenberg, J.E.; Murányi, A.; Curlík, J.; Sefcík, P.; Römkens, P.F.A.M.; Reinds, G.J.; Bril, J.; Modin, A.K.; Sverdrup, H.U.; Alloway, B.J.

    2003-01-01

    This report describes the major result of a research project funded by the INCO-Copernicus programma of European Commission under Contract number ERB-IC15-CT98-0133. The study focused on the long-term environmental risk of soil acidification on: (i) mobilisation and leaching and (ii) plant uptake of

  3. 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

  4. 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.

  5. Assessment of a novel alder biorefinery concept to meet demands of economic feasibility, energy production and long term environmental sustainability

    DEFF Research Database (Denmark)

    Thomsen, Tobias; Ahrenfeldt, Jesper; Thomsen, Sune Tjalfe

    2013-01-01

    A biorefinery concept based on alder tree plantations on degenerated soil is developed to comply with indicators of economic feasibility, fossil fuel depletion concerns, and long term sustainability issues. The potential performance of feedstock and biorefinery has been assessed through a literat......A biorefinery concept based on alder tree plantations on degenerated soil is developed to comply with indicators of economic feasibility, fossil fuel depletion concerns, and long term sustainability issues. The potential performance of feedstock and biorefinery has been assessed through...... degenerated soils. Integrating a biomass handling system, an LTCFB gasifier, a diarylheptanoids production chain, an anaerobic digestion facility, a slow pyrolysis unit, gas upgrading and various system integration units, the biorefinery could obtain the following production characteristics accounted...

  6. Long-term outlook for Alberta's primary petrochemical industry : panel discussion : sustainability, feedstocks, infrastructure, transportation

    International Nuclear Information System (INIS)

    Lauzon, D.

    1997-01-01

    The long-term outlook for Dow Chemical's involvement in Alberta's petrochemical industry was discussed. Dow Chemical Canada is a company with annual sales of more than $20 billion that manufactures and supplies chemicals, plastics, energy, agricultural products, consumer goods and environmental services in 157 countries in the world. Alberta is the centre of growth and development for the Canadian petrochemical industry because of the proximity to feedstocks. Alberta is seen as a good, long-term source of ethane. Dow Chemical intends to continue being a major player in the further development of the industry in Alberta. As proof of that confidence, there are 11 capital projects in progress at Dow's Western Canada Operation, totaling $600 million. An important ingredient of the continuing success of the petrochemical industry in Alberta will be the willingness and ability of the federal and provincial governments to work in partnership with industry to develop support infrastructure and policies

  7. Compromise between Short- and Long-Term Financial Sustainability: A Hybrid Model for Supporting R&D Decisions

    Directory of Open Access Journals (Sweden)

    Kao-Yi Shen

    2017-03-01

    Full Text Available The debate of “short-termism” has gained increasing interests from various fields, ranging from management to economics; it mainly concerns the decisions or actions taken by businesses that might yield short-term returns at the cost of long-term value or sustainability. Previous studies have highlighted this dilemma faced by managers, mainly from the pressure of capital markets or short-sighted shareholders who crave for immediate financial outcomes; intelligent decision aids that can compromise between the short- and long-term financial sustainability, based on a company’s policy, are highly needed. Therefore, the aim of this study is to develop a multiple-rule-based hybrid decision model to support management teams on prioritizing new R&D projects, considering the financial prospects in dual timeframes (i.e., short- and long-term for sustainability. Furthermore, in the presence of business uncertainty and the limited knowledge of managers on new projects, the intuitionistic fuzzy technique is incorporated. A case of selecting new R&D projects for an IC design company is illustrated using the proposed approach, and the financial data from a group of public-listed IC stocks from Taiwan are inducted to form the decision model. The findings not only support the IC design company to select new projects but also provide business insights to facilitate the understandings of this controversial issue in managerial practice.

  8. Sustained transfer of knowledge to practice in long-term care: facilitators and barriers of a mental health learning initiative.

    Science.gov (United States)

    Stolee, Paul; McAiney, Carrie A; Hillier, Loretta M; Harris, Diane; Hamilton, Pam; Kessler, Linda; Madsen, Victoria; Le Clair, J Kenneth

    2009-01-01

    This article explores facilitators and barriers to the impact and sustainability of a learning initiative to increase capacity of long-term care (LTC) homes to manage the mental health needs of older persons, through development of in-house Psychogeriatric Resource Persons (PRPs). Twenty interviews were conducted with LTC staff. Management support, particularly designation of time for PRP activities, development of PRP teams, and supportive learning strategies were significant factors affecting sustained knowledge transfer. Continuing education that is provided and evaluated on an ongoing basis, secures management commitment, is integrated within a broader system strategy, and provides on-the-job support has the greatest potential to affect care.

  9. 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

  10. EDF - Activity and sustainable development 2011 - electricity, choices on the long term

    International Nuclear Information System (INIS)

    2012-05-01

    This publication notably contains a set of articles about choices on the long term related to electricity production and distribution. Different aspects are addressed: arbitration (the diversity of the French energy mix), grids (investments and evolution towards smart grids), electricity cost (for households and for industry), nuclear energy (actions and results regarding safety and availability, the EPR project), renewable energies, the design and construction of a dam (Nam Theun 2) in Thailand with an important human development dimension in the project, thermal energy (the future of flame-based power stations using gas or biomass for example), and EDF's commercial policy

  11. 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.

  12. The STRATEGY project: decision tools to aid sustainable restoration and long-term management of contaminated agricultural ecosystems.

    Science.gov (United States)

    Howard, B J; Beresford, N A; Nisbet, A; Cox, G; Oughton, D H; Hunt, J; Alvarez, B; Andersson, K G; Liland, A; Voigt, G

    2005-01-01

    The STRATEGY project (Sustainable Restoration and Long-Term Management of Contaminated Rural, Urban and Industrial Ecosystems) aimed to provide a holistic decision framework for the selection of optimal restoration strategies for the long-term sustainable management of contaminated areas in Western Europe. A critical evaluation was carried out of countermeasures and waste disposal options, from which compendia of state-of-the-art restoration methods were compiled. A decision support system capable of optimising spatially varying restoration strategies, that considered the level of averted dose, costs (including those of waste disposal) and environmental side effects was developed. Appropriate methods of estimating indirect costs associated with side effects and of communicating with stakeholders were identified. The importance of stakeholder consultation at a local level and of ensuring that any response is site and scenario specific were emphasised. A value matrix approach was suggested as a method of addressing social and ethical issues within the decision-making process, and was designed to be compatible with both the countermeasure compendia and the decision support system. The applicability and usefulness of STRATEGY outputs for food production systems in the medium to long term is assessed.

  13. The STRATEGY project: decision tools to aid sustainable restoration and long-term management of contaminated agricultural ecosystems

    International Nuclear Information System (INIS)

    Howard, B.J.; Beresford, N.A.; Nisbet, A.; Cox, G.; Oughton, D.H.; Hunt, J.; Alvarez, B.; Andersson, K.G.; Liland, A.; Voigt, G.

    2005-01-01

    The STRATEGY project (Sustainable Restoration and Long-Term Management of Contaminated Rural, Urban and Industrial Ecosystems) aimed to provide a holistic decision framework for the selection of optimal restoration strategies for the long-term sustainable management of contaminated areas in Western Europe. A critical evaluation was carried out of countermeasures and waste disposal options, from which compendia of state-of-the-art restoration methods were compiled. A decision support system capable of optimising spatially varying restoration strategies, that considered the level of averted dose, costs (including those of waste disposal) and environmental side effects was developed. Appropriate methods of estimating indirect costs associated with side effects and of communicating with stakeholders were identified. The importance of stakeholder consultation at a local level and of ensuring that any response is site and scenario specific were emphasised. A value matrix approach was suggested as a method of addressing social and ethical issues within the decision-making process, and was designed to be compatible with both the countermeasure compendia and the decision support system. The applicability and usefulness of STRATEGY outputs for food production systems in the medium to long term is assessed

  14. Long-term climatic change and sustainable ground water resources management

    International Nuclear Information System (INIS)

    Loaiciga, Hugo A

    2009-01-01

    Atmospheric concentrations of greenhouse gases (GHGs), prominently carbon dioxide (CO 2 ), methane (CH 4 ), nitrous oxide (N 2 O), and halocarbons, have risen from fossil-fuel combustion, deforestation, agriculture, and industry. There is currently heated national and international debate about the consequences of such increasing concentrations of GHGs on the Earth's climate, and, ultimately, on life and society in the world as we know it. This paper reviews (i) long-term patterns of climate change, secular climatic variability, and predicted population growth and their relation to water resources management, and, specifically, to ground water resources management, (ii) means available for mitigating and adapting to trends of climatic change and climatic variability and their impacts on ground water resources. Long-term (that is, over hundreds of millions of years), global-scale, climatic fluctuations are compared with more recent (in the Holocene) patterns of the global and regional climates to shed light on the meaning of rising mean surface temperature over the last century or so, especially in regions whose historical hydroclimatic records exhibit large inter-annual variability. One example of regional ground water resources response to global warming and population growth is presented.

  15. Long-Term Sustainable Development of Tourism in South Tyrol: An Analysis of Tourists’ Perception

    Directory of Open Access Journals (Sweden)

    Katia Laura Sidali

    2017-10-01

    Full Text Available Although sustainable tourism concepts are gaining in importance everywhere, related research is quite fragmented with many studies concentrating on environmental sustainability. Seeking to contribute to the general discussion, we first examine the perceptions of sustainability among tourists using a best–worst scaling method applied to important aspects of sustainable tourism. Our results show that experiencing nature in an intense and profound way is considered the most important aspect of sustainable tourism whereas grappling with the culture of the host region is perceived as the least important aspect of sustainable tourism in our sample. Second, we analyze if socio-demographic and/or other factors have significant implications for the propensity to increase expenditures for sustainable holiday offers. Applying a simple regression model, we can show that age has a significant and positive impact on the propensity to spend more on a sustainable holiday offer such as overnight stays in an accommodation that is carbon-neutral. Other socio-demographic variables such as gender, education, and income are not significant. Moreover, hotel stars and average expenditures per person per night are significant and have a positive effect on the propensity to spend more on carbon-neutral housing. Two simple policy implications can be drawn: (1 sustainable tourism experiences should prioritize landscape and natural beauty; and (2 sustainable tourism offers are best suited for higher-priced and/or higher starred hotels.

  16. Geochemical constraints on sustainable development: Can an advanced global economy achieve long-term stability?

    Science.gov (United States)

    Pickard, William F.

    2008-04-01

    The eighty-one stable chemical elements are examined individually with respect to (i) recent annual demand and (ii) worst case long-term availability in a distant future in which they must be extracted from the background sources of air, seawater, and ordinary rock. It is shown that, if a conventional use scenario is envisioned, the supplies of ruthenium, rhodium, palladium, tellurium, rhenium, osmium, iridium, platinum, gold, and especially phosphorus will be questionable while the supplies of copper, zinc, molybdenum, silver, cadmium, tin, antimony, tungsten, mercury, lead, and bismuth will be inadequate. It is therefore concluded that, in the long run, only the promotion of massive recycling and substitution technologies will suffice to maintain the global industrial society now developing.

  17. Long-term sustainability in the management of acid mine drainage ...

    African Journals Online (AJOL)

    2013-08-14

    Aug 14, 2013 ... It was shown, in what became known as the Rhodes BioSURE Process, that with ...... and social sustainability audit criteria has been summarised by .... HARTNADY CJH (2009) South Africa's gold production and reserves.

  18. Characterization of unsaturated fatty acid sustained-release microspheres for long-term algal inhibition.

    Science.gov (United States)

    Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Hu, Shuzhen; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-02-01

    The unsaturated fatty acid (linoleic acid) sustained-release microspheres were prepared with linoleic acid (LA) using alginate-chitosan microcapsule technology. These LA sustained-release microspheres had a high encapsulation efficiency (up to 62%) tested by high performance liquid chromatography with a photo diode array. The dry microspheres were characterized by a scanning electron microscope, X-ray diffraction measurement, dynamic thermogravimetric analysis and Fourier transform infrared spectral analysis. The results of characterization showed that the microspheres had good thermal stability (decomposition temperature of 236°C), stable and temperature independent release properties (release time of more than 40 d). Compared to direct dosing of LA, LA sustained-released microspheres could inhibit Microcystis aeruginosa growth to the non-growth state. The results of this study suggested that the LA sustained-release microspheres may be a potential candidate for algal inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Compromising Long-Term Sustainability for Short-Term Profit Maximization: Unethical Business Practice

    Directory of Open Access Journals (Sweden)

    Doorasamy Mishelle

    2016-01-01

    Full Text Available The current environmental challenges caused by the dependence on nonrenewable energy, increased waste disposal, the toxic emissions created by operational activities, and also the scarce supply of water are so complex and important that it requires immediate attention. Strict environmental legislation, market pressures, and urgent need for sustainability have given businesses no option but to ensure that they do all that is possible to ensure that their business operations are sustainable. This paper addresses the underlying factors that determine the extent to which organizations adopt sustainable business practices and cleaner production techniques and technologies. It had been concluded that ethics is linked to sustainable business practices, because the objectives of both these concepts are to think about doing what’s right for others and the world, including the environment. According to the organizational corporate compliance regulations, a company’s commitment to ethical business and sustainable business practices should be detailed in their policy handbook and communicated to all employees within the company (Sustainability Report 2013/2014.

  20. Long Term Fuel Sustainable Fission Energy Perspective Relevant for Combating Climate Change

    International Nuclear Information System (INIS)

    Knapp, V.; Matijevic, M.; Pevec, D.; Crnobrnja, B.; Lale, D.

    2016-01-01

    In recent research we outlined climate relevant and immediately available proven light water nuclear strategy with a potential to contribute essentially and timely to reduction of carbon dioxide emission to the year 2065. We consider in this paper what is the perspective of fission energy after that year should its contribution be needed. Singling out two technologies with long term perspective which need no or small amounts of uranium, fast breeders and molten salt thorium reactors, we consider their main technical and safety characteristics. In both of these technologies it is essential to have starter nuclides as neither U238 nor Th232 are fissile. We investigated whether plutonium from spent fuel of light water reactors generated to the year 2065 would be present in quantities sufficient to continue operation on the same or similar level in both technologies. However in operational safety, proliferation risks, waste production, in our judgement we must give preference to thorium technology, if it would be ready in second half of the century.(author).

  1. Sustained long-term benefit of patent foramen ovale closure on migraine.

    Science.gov (United States)

    Trabattoni, Daniela; Fabbiocchi, Franco; Montorsi, Piero; Galli, Stefano; Teruzzi, Giovanni; Grancini, Luca; Gatto, Pamela; Bartorelli, Antonio L

    2011-03-01

    This single-center, observational, prospective study evaluated the impact of patent foramen ovale (PFO) closure on migraine attacks over time. PFO closure may reduce the frequency and severity of migraine headaches in patients with significant right-to-left shunts. Between May 2000 and September 2009, 305 consecutive patients (mean age, 43 ± 12 years; 54.5% women) with a prior embolic cerebrovascular event underwent PFO closure with the Amplatzer PFO occluder for recurrence prevention. All patients had right-to-left shunts; the shunts were associated with migraine symptoms in 77 (25%), either alone (n = 64, 83%) or with aura (n = 13, 17%). Septal aneurysm was present in 15 (19.5%) migraine patients, and 43 (56%) had a previous transient brain ischemic attack. All migraine patients had a computed tomography scan or magnetic resonance imaging, indicating a previous brain ischemic lesion. All 305 patients underwent transthoracic echocardiography with clinical follow-up at 24 hr, at 3, 6, and 12 months, and then yearly. An acute migraine attack occurred 24-48 hr after PFO closure in 28 (36.4%) of 77 patients. There was a significant reduction (>50%) in the number and intensity of attacks in 46 (60.5%) of 77 patients at the 3-month follow-up. At the 12-month follow-up, migraine had ceased in 23 (46%) patients, and 20 (40%) had a reduction in the migraine recurrence rate and disabling symptoms. These results were maintained at follow-up (mean, 28 ± 27 months). There was overall improvement in migraine in 89% of the treated patients. Percutaneous PFO closure in migraineurs may provide beneficial mid-term and long-term results, with significant reduction in the intensity and frequency of headache symptoms. Copyright © 2010 Wiley-Liss, Inc.

  2. A framework and a measurement instrument for sustainability of work practices in long-term care

    NARCIS (Netherlands)

    S.S. Slaghuis (Sarah); M.M.H. Strating (Mathilde); R.A. Bal (Roland); A.P. Nieboer (Anna)

    2011-01-01

    textabstractBackground: In health care, many organizations are working on quality improvement and/or innovation of their care practices. Although the effectiveness of improvement processes has been studied extensively, little attention has been given to sustainability of the changed work practices

  3. A framework and a measurement instrument for sustainability of work practices in long-term care

    Directory of Open Access Journals (Sweden)

    Slaghuis Sarah S

    2011-11-01

    Full Text Available Abstract Background In health care, many organizations are working on quality improvement and/or innovation of their care practices. Although the effectiveness of improvement processes has been studied extensively, little attention has been given to sustainability of the changed work practices after implementation. The objective of this study is to develop a theoretical framework and measurement instrument for sustainability. To this end sustainability is conceptualized with two dimensions: routinization and institutionalization. Methods The exploratory methodological design consisted of three phases: a framework development; b instrument development; and c field testing in former improvement teams in a quality improvement program for health care (N teams = 63, N individual = 112. Data were collected not until at least one year had passed after implementation. Underlying constructs and their interrelations were explored using Structural Equation Modeling and Principal Component Analyses. Internal consistency was computed with Cronbach's alpha coefficient. A long and a short version of the instrument are proposed. Results The χ2- difference test of the -2 Log Likelihood estimates demonstrated that the hierarchical two factor model with routinization and institutionalization as separate constructs showed a better fit than the one factor model (p Conclusions The theoretical framework offers a valuable starting point for the analysis of sustainability on the level of actual changed work practices. Even though the two dimensions routinization and institutionalization are related, they are clearly distinguishable and each has distinct value in the discussion of sustainability. Finally, the subscales conformed to psychometric properties defined in literature. The instrument can be used in the evaluation of improvement projects.

  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. Sustaining complex interventions in long-term care: a qualitative study of direct care staff and managers.

    Science.gov (United States)

    Colón-Emeric, Cathleen; Toles, Mark; Cary, Michael P; Batchelor-Murphy, Melissa; Yap, Tracey; Song, Yuting; Hall, Rasheeda; Anderson, Amber; Burd, Andrew; Anderson, Ruth A

    2016-07-16

    Little is known about the sustainability of behavioral change interventions in long-term care (LTC). Following a cluster randomized trial of an intervention to improve staff communication (CONNECT), we conducted focus groups of direct care staff and managers to elicit their perceptions of factors that enhance or reduce sustainability in the LTC setting. The overall aim was to generate hypotheses about how to sustain complex interventions in LTC. In eight facilities, we conducted 15 focus groups with 83 staff who had participated in at least one intervention session. Where possible, separate groups were conducted with direct care staff and managers. An interview guide probed for staff perceptions of intervention salience and sustainability. Framework analysis of coded transcripts was used to distill insights about sustainability related to intervention features, organizational context, and external supports. Staff described important factors for intervention sustainability that are particularly challenging in LTC. Because of the tremendous diversity in staff roles and education level, interventions should balance complexity and simplicity, use a variety of delivery methods and venues (e.g., group and individual sessions, role-play/storytelling), and be inclusive of many work positions. Intervention customizability and flexibility was particularly prized in this unpredictable and resource-strapped environment. Contextual features noted to be important include addressing the frequent lack of trust between direct care staff and managers and ensuring that direct care staff directly observe manager participation and support for the program. External supports suggested to be useful for sustainability include formalization of changes into facility routines, using "train the trainer" approaches and refresher sessions. High staff turnover is common in LTC, and providing materials for new staff orientation was reported to be important for sustainability. When designing or

  6. 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...

  7. Long-term sustainability of a worksite canteen intervention of serving more fruit and vegetables

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke; Lassen, Anne Dahl; Tetens, Inge

    2010-01-01

    Objective: To analyse the 5-year sustainability of a worksite canteen intervention of serving more fruit and vegetables (F&V). Design: Average F&V consumption per customer per meal per day was assessed in five worksite canteens by weighing F&V served and subtracting waste. Data were collected by ...... where the participatory and empowering approach, self-monitoring, environmental change, dialogue with suppliers and networking among worksite canteens are applied....

  8. The future of Alberta's oil and gas: Long-term strategies necessary to sustain markets

    International Nuclear Information System (INIS)

    Anon

    2002-01-01

    The Canadian Association of Petroleum Producers predicts that based on current combustion and depending on world oil prices, Canadian oil sands can supply North American demand for 40 years and Canadian natural gas can meet North American requirements for 20 years. Natural gas production in the U.S. is greater in total energy output than oil production of the world's largest oil producer, Saudi Arabia. At the same time the U.S. gas industry is confronting a unique and profound combination of events, namely it is facing the first true shortage of deliverable reserves in its history. This may be harsh news for the consumer, however, for Alberta's oil and gas industry, the new world energy order has the potential to be a huge blessing. With relatively large, unexploited oil and gas reserves and a next door neighbour with the world's most voracious appetite for fossil fuels, it is inevitable that much of this shortage is going to be satisfied by oil and gas from Canadian sources. Nevertheless, there are some barriers to be overcome. The greatest barriers to an assured U. S. market for Canadian oil and gas is competition from Venezuelan heavy crude and synthetic crude and light sour crude from the Gulf of Mexico. To assure a ready market for Canadian heavy crude in the U. S. Midwest, Canadian producers need to be pro-active in working with U. S. refiners to develop new conversion capacity, or develop upgrading in Canada. Mexico and Venezuela have been successfully participating in major U. S. expansions in coker projects to allow projects to run heavy crude. This will eventually result in an additional 600,000 barrels per day of heavy crude available on the U. S. market, putting further pressure on Canadian markets. The challenge is for Albertan producers to undertake similar strategies with U. S. Midwest refiners for heavy and synthetic crude. Long-term supply arrangements appear to be the only way to induce American Midwest refiners to make more investment to process

  9. Modeling sustainable long-term electricity supply-demand in Africa

    International Nuclear Information System (INIS)

    Ouedraogo, Nadia S.

    2017-01-01

    Highlights: • This study is one of the first detailed and complete representation of the African power system. • It models, within LEAP, possible future paths for the regional power systems. • All the end-users and supply side activities and actors are considered. • Three scenarios are examined: the baseline, the renewable energy, and the energy efficiency. • The energy efficiency scenario has allowed to draw a sustainable pathway for electrification. - Abstract: This paper develops a scenario-based model to identify and provide an array of electricity demand in Africa, and to derive them from the African power system of development. A system-based approach is performed by applying the scenario methodology developed by Schwartz in the context of the energy-economic modeling platform ‘Long-range Energy Alternative Planning’. Four scenarios are investigated. The Business as Usual scenario (BAU) replicates the regional and national Master Plans. The renewable-promotion scenario increases the share of renewable energy in the electricity mix. The demand and supply side efficiency scenarios investigate the impact of energy efficiency measures on the power system. The results show an increase in electricity demand by 4% by 2040, supply shortages and high emissions of Greenhouse Gases. Contrary to expectations, the renewable energy scenario did not emerge as the best solution to a sustainable electrification of the region. The energy efficiency scenarios have allowed us to draw a sustainable pathway for electrification.

  10. 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

  11. 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.

  12. Design and assessment of long-term sustainable transport system scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Nijkamp, P.; Rienstra, S.A.; Vleugel, J.M. [Systems and Control Group, Faculty of Mechanical and Marine Engineering, Delft University of Technology, Delft (Netherlands)

    1995-03-01

    Current trends in transport indicate that the system is moving away from a sustainable development because of a sky-rocketing mobility growth and a modal shift towards the most polluting modes. These trends are reinforced by several underlying factors, which may be found in the spatial, institutional, economic and social/psychological fields. It may be concluded that major changes in technology, public policy as well as in the behaviour of individuals are necessary to make the transport system more compatible with environmental sustainability. This provokes the need for assessing a set of future images for transport in relation to the environment. In this paper expert scenarios are constructed on the basis of the recently developed `spider model`. Based on a set of distinct characteristics of a transport system, represented by eight axes in the above mentioned fields, an evaluation framework is constructed, which visualizes the main discussed driving forces. Scenarios can be constructed by connecting points on the successive axes, which may lead to entirely different transport systems. An expected and desired scenario are constructed next, by means of opinions of Dutch transport experts, which have been investigated by means of a nation-wide survey. The expected scenario indicates that many current trends will continue, while the transport system is largely the same as the current one. The desired scenario on the other hand, gives a more collective system, in which also many new modes are operating. The conclusion is that expected trends may not lead to a sustainable transport system, but that the desired road will be very hard to follow. 5 figs., 2 tabs., 27 refs.

  13. 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.

  14. 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.

  15. Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation.

    Science.gov (United States)

    Chen, Weiyu; Zuo, Huali; Li, Bei; Duan, Chengcheng; Rolfe, Barbara; Zhang, Bing; Mahony, Timothy J; Xu, Zhi Ping

    2018-05-01

    Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC-antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50-60% antigen released after 35 d. In contrast, Alum-antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T-cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Optimizing long-term investments for a sustainable development of the ASEAN power system

    International Nuclear Information System (INIS)

    Huber, Matthias; Roger, Albert; Hamacher, Thomas

    2015-01-01

    The electricity consumption in the ASEAN (Association of East Asian Nations) region is one of the fastest growing in the world and will lead to a dramatic increase in greenhouse gas emissions in the next decades. A decarbonization of the region's electricity supply is thus a very important measure when taking action on global climate change. This paper defines cost-optimal pathways towards a sustainable power system in the region by employing linear optimization. The proposed model simultaneously optimizes the required capacities and the hourly operation of generation, transmission, and storage. The obtained results show that all different kinds of renewable sources will have to be utilized, while none of them should have a share of more than one third. The findings give reason for setting up an ASEAN power grid, as it enables the transportation of electricity from the best sites to load centers and leads to a balancing of the fluctuations from wind and solar generation. We suggest fostering a diversified extension of renewables and to elaborate on political and technical solutions that enable the build up an transnational supergrid. - Highlights: • Article presents an optimization model of the ASEAN power system with high temporal and spatial resolution. • Cost-optimal investment options for achieving a sustainable electricity system are explored. • All types of renewable energies have to be employed while none of them should provide more than one third of overall supply. • Large transcontinental transmission grids will be crucial for a cost-minimal decarbonization of the ASEAN electricity sector

  17. Long-Term Educational Sustainability: Educational Innovation in Social Vulnerability Contexts

    Directory of Open Access Journals (Sweden)

    Ana Tur-Porcar

    2017-09-01

    Full Text Available This paper investigates the behavior of children from low socioeconomic status families and examines the effects of a socioemotional education program on aggression in children. The results of the program are compared according to the children’s gender and age, the family structure, the parents’ educational attainment, and social status. The results show that applying socioemotional education programs reduces children’s aggression and encourages positive development during adolescence. This positive development fosters open, expressive behavior.

  18. 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...

  19. 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...

  20. 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

  1. 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.

  2. Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency.

    Science.gov (United States)

    Barat, Corinne; Proust, Alizé; Deshiere, Alexandre; Leboeuf, Mathieu; Drouin, Jean; Tremblay, Michel J

    2018-02-21

    The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4 + T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy. © 2018 Wiley Periodicals, Inc.

  3. SCOPEOUT: sustainability and spread of quality improvement activities in long-term care- a mixed methods approach.

    Science.gov (United States)

    Cranley, Lisa A; Hoben, Matthias; Yeung, Jasper; Estabrooks, Carole A; Norton, Peter G; Wagg, Adrian

    2018-03-12

    Interventions to improve quality of care for residents of long-term care facilities, and to examine the sustainability and spread of such initiatives, remain a top research priority. The purpose of this exploratory study was to assess the extent to which activities initiated in a quality improvement (QI) collaborative study using care aide led teams were sustained or spread following cessation of the initial project and to identify factors that led to its success. This study used an exploratory mixed methods study design and was conducted in seven residential long-term care facilities in two Canadian provinces. Sustainability and spread of QI activities were assessed by a questionnaire over five time points for 18 months following the collaborative study with staff from both intervention with non-intervention units. Semi-structured interviews were conducted with care managers at six and 12 months. QI team success in applying the QI model was ranked as high, medium, or low using criteria developed by the research team. Descriptive statistics, bivariate analyses, and General Estimating Equations were used to analyze the data. Interview data were analyzed using thematic analysis. In total, 683 surveys were received over the five time periods from 476 unique individuals on a facility unit. Seven managers were interviewed. A total of 533 surveys were analyzed. While both intervention and non-intervention units experienced a decline over time in all outcome measures, this decline was significantly less pronounced on intervention units. Facilities with medium and high success ranking had significantly higher scores in all four outcomes than facilities with a low success ranking. Care aides reported significantly less involvement of others in QI activities, less empowerment and less satisfaction with the quality of their work life than regulated care providers. Manager interviews provided evidence of sustainability of QI activities on the intervention units in four of

  4. 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...

  5. Long-term nutrient fertilization and the carbon balance of permanent grassland: any evidence for sustainable intensification?

    Science.gov (United States)

    Fornara, Dario A.; Wasson, Elizabeth-Anne; Christie, Peter; Watson, Catherine J.

    2016-09-01

    Sustainable grassland intensification aims to increase plant yields while maintaining the ability of soil to act as a sink rather than sources of atmospheric CO2. High biomass yields from managed grasslands, however, can be only maintained through long-term nutrient fertilization, which can significantly affect soil carbon (C) storage and cycling. Key questions remain about (1) how long-term inorganic vs. organic fertilization influences soil C stocks, and (2) how soil C gains (or losses) contribute to the long-term C balance of managed grasslands. Using 43 years of data from a permanent grassland experiment, we show that soils not only act as significant C sinks but have not yet reached C saturation. Even unfertilized control soils showed C sequestration rates of 0.35 Mg C ha-1 yr-1 (i.e. 35 g C m-2 yr-1; 0-15 cm depth) between 1970 and 2013. High application rates of liquid manure (i.e. cattle slurry) further increased soil C sequestration to 0.86 Mg C ha-1 yr-1 (i.e. 86 g C m-2 yr-1) and a key cause of this C accrual was greater C inputs from cattle slurry. However, average coefficients of slurry-C retention in soils suggest that 85 % of C added yearly through liquid manure is lost possibly via CO2 fluxes and organic C leaching. Inorganically fertilized soils (i.e. NPK) had the lowest C-gain efficiency (i.e. unit of C gained per unit of N added) and lowest C sequestration (similar to control soils). Soils receiving cattle slurry showed higher C-gain and N-retention efficiencies compared to soils receiving NPK or pig slurry. We estimate that net rates of CO2-sequestration in the top 15 cm of the soil can offset 9-25 % of GHG (greenhouse gas) emissions from intensive management. However, because of multiple GHG sources associated with livestock farming, the net C balance of these grasslands remains positive (9-12 Mg CO2-equivalent ha-1 yr-1), thus contributing to climate change. Further C-gain efficiencies (e.g. reduced enteric fermentation and use of feed

  6. 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.

  7. 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.

  8. [Effect of long-term application of NPK fertilizer on maize yield and yellow soil nutrients sustainability in Guizhou, China].

    Science.gov (United States)

    Liu, Yan Ling; Li, Yu; Zhang, Ya Rong; Huang, Xing Cheng; Zhang, Wen An; Jiang, Tai Ming

    2017-11-01

    A long-term fertilization field experiment was conducted to investigate the effect of nitrogen (N), phosphorus (P), and potassium (K) fertilizer on maize relative yield, yield-increasing effect and the changes of nutrients in yellow soil in Guizhou Province. Five fertilizer combinations were evaluated, including balanced fertilization (NPK) and nutrient deficiency treatments (N, NK, NP, and PK). The maize relative yield, contribution efficiency of N, P, K fertilizer application, sustainability index of soil N, P, K nutrients, and other indicators were measured. The results revealed that the balanced fertilization (NPK) significantly increased maize yield, and the average yield under each treatment ranked as: NPK>NP>NK>PK>CK. The contribution efficiency and agronomic efficiency of N, P, K fertilizer application was N>P>K. The fertilization dependence was ranked as: combined application of N, P and K>N>P>K. But in the lack of P treatment (NK), the maize relative yield significantly decreased at a speed of 1.4% per year, with the contribution efficiency and fertilization dependence of applied P significantly increasing at a speed of 2.3% per year and 1.4% per year, respectively. Over time, the effect of P fertilizer on maize yield gradually became equal to that of N fertilizer. The pH and soil organic matter content were the lowest in the P-lack treatment (NK), while they were higher in the N-lack treatment (PK). The application of chemical P significantly improved the sustainability index of soil P, but the application of chemical N and K did not significantly change the sustainability index of soil N and K nutrients compared to the N- and K-lack treatments, respectively. In summary, the use of balanced fertilizer application is critical for achieving high maize yield in typical yellow soil regions in Guizhou Province. P and N fertilizers are equally important for improving maize yield, and long-term application of unbalanced chemical fertilizer, especially the lack

  9. 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.

  10. Sustainability strategies for real-estates. Thinking long-term and shoulder entrepreneurial responsibility; Nachhaltigkeitsstrategien fuer Immobilien. Langfristig denken und unternehmerische Verantwortung wahrnehmen

    Energy Technology Data Exchange (ETDEWEB)

    Kaeding, Uta; Sigg, Rene [Intep - Integrale Planung GmbH, Hamburg (Germany); Intep - Integrale Planung GmbH, Muenchen (Germany)

    2011-07-01

    On the basis of their corporate strategy and sustainability strategy responsible companies set suitable objectives for their real-estate portfolio. The companies recognized that sustainable real-estates offer long-term economic advantages and reduced risks. For the development and conversion of a sustainability strategy for real-estates innovative tools and aids are available today which make the life cycle costs or the surplus value of sustainable real-estates transparent.

  11. A two-dimensional three-level sustainability framework for achieving short- and long-term gains: empirical evidence from the Chinese automotive sector

    OpenAIRE

    Wu, Lin

    2016-01-01

    A topic of academic research and business practice which has grown in importance recently is sustainability. Its main objective is to ensure the development of the current generation and protect the right of future generations to prosper. In the business context, sustainability should be reflected in firms’ efforts to simultaneously ensure short- and long-term gains. A time dimension is thus an important feature in the concept of sustainability. In the past two decades, sustainability res...

  12. Straw-to-soil or straw-to-energy? An optimal trade off in a long term sustainability perspective

    International Nuclear Information System (INIS)

    Monteleone, Massimo; Cammerino, Anna Rita Bernadette; Garofalo, Pasquale; Delivand, Mitra Kami

    2015-01-01

    Highlights: • Energy balance and GHG savings of a straw-to-electricity value chain were determined. • An “expanded” LCA was performed, from farm field to electricity delivery. • Both direct and indirect factors of land use change have been considered in the analysis. • No-tillage and crop rotation significantly improved the system performance. • A win–win, sustainable solution for the energy use of straw has been identified. - Abstract: This study examined some management strategies of wheat cultivation system and its sustainability in using straw as an energy feedstock. According to the EU regulatory framework on biofuels, no GHG emissions should be assigned to straws when they are used for energy. Given this relevance in the current energy policy, it is advisable to include all possible marginal effects related to land use, resource utilization and management changes in the comparison of different biomass options. Coherently, an expanded life cycle assessment (LCA) was applied to include the upstream cultivation phase and to make a comparison between “straw to soil” and “straw to energy”. Different crop management conditions in Southern Italy were simulated, by using the CropSyst model, to estimate the long-term soil organic carbon and annual N 2 O soil emissions. Three wheat cropping systems were considered: the conventional single wheat system without straw removal (W0) and with partial straw removal (W1), together with a no-tillage “wheat-wheat-herbage” rotation system with partial straw removal (W2). The results of the simulations were integrated in the LCA to compare fossil energy consumption and greenhouse gas (GHG) emissions of straw-to-electricity with respect to the fossil-based electricity system. The “improved” rotational wheat cropping system (W2) gave the best performance in terms both of GHG savings and fossil displacement, thus stressing that straw use for energy generation in parallel with the optimization of the

  13. Boundary Organizations: Creating a Unique Model for Sustained Dialog Among Scientists and Decison Makers About Long-term Change

    Science.gov (United States)

    Duncan, B.; Carter, H.; Knight, E.; Meyer, R.

    2015-12-01

    California Ocean Science Trust is a boundary organization formed by the state of California. We work across traditional boundaries between government, science, and communities to build trust and understanding in ocean and coastal science. We work closely with decision makers to understand their priority needs and identify opportunities for science to have a meaningful impact, and we engage scientists and other experts to compile and translate information into innovative products that help to meet those needs. This often sparks new collaborations that live well beyond the products themselves. Through this unique model, we are deepening relationships and facilitating an ongoing dialogue between scientists, decision-makers, and communities. The West Coast of the United States is already experiencing climate-driven changes in marine conditions at both large and small spatial scales. Decision makers are increasingly concerned with the potential threats that these changes pose to coastal communities, industries, ecosystems, and species. Detecting and understanding these multi-stressor changes requires consideration across scientific disciplines and management jurisdictions. Research and monitoring programs must reflect this new reality: they should be designed to connect with the decision makers who may use their results. In this presentation, I will share how we are drawing from the West Coast Ocean Acidification and Hypoxia Science Panel - an interdisciplinary team of scientists convened by Ocean Science Trust from California, Oregon, Washington, and British Columbia - to develop actionable guidance for long-term monitoring for long-term change. Building on our experiences working with the Panel, I will discuss the unique model that boundary organizations provide for sustained dialog across traditionally siloed disciplines and management regimes, and share best practices and lessons learned in working across those boundaries.

  14. Increasing the Frequency and Timeliness of Pain Assessment and Management in Long-Term Care: Knowledge Transfer and Sustained Implementation

    Directory of Open Access Journals (Sweden)

    Thomas Hadjistavropoulos

    2016-01-01

    Full Text Available Background. Although feasible protocols for pain assessment and management in long-term care (LTC have been developed, these have not been implemented on a large-scale basis. Objective. To implement a program of regular pain assessment in two LTC facilities, using implementation science principles, and to evaluate the process and success of doing so. Methods. The implementation protocol included a pain assessment workshop and the establishment of a nurse Pain Champion. Quality indicators were tracked before and after implementation. Focus groups and interviews with staff were also conducted. Results. The implementation effort was successful in increasing and regularizing pain assessments. This was sustained during the follow-up period. Staff members reported enthusiasm about the protocol at baseline and positive results following its implementation. Despite the success in increasing assessments, we did not identify changes in the percentages of patients reported as having moderate-to-severe pain. Discussion. It is our hope that our feasibility demonstration will encourage more facilities to improve their pain assessment/management practices. Conclusions. It is feasible to implement regular and systematic pain assessment in LTC. Future research should focus on ensuring effective clinical practices in response to assessment results, and determination of longer-term sustainability.

  15. Holistic countermeasures evaluation and the sustainable restoration and long-term management of contaminated rural, urban and industrial ecosystems

    International Nuclear Information System (INIS)

    Beresford, N.A.; Wright, S.M.; Barnett, C.L.; Howard, B.J.; Cox, G.; Crout, N.M.J.

    2002-01-01

    Emergency planning as conducted by most national authorities is often focussed upon short-term response (few days - weeks) and addresses issues such as the need for evacuation, problems associated with 1 31I and immediate requirements for restrictions on food and water. There is limited systematic consideration of the long-term management of contaminated areas to ensure their sustainability. Experience following the Chernobyl accident, most especially within the countries of the former Soviet Union (fSU) but also in Scandinavia and the United Kingdom, have demonstrated that countermeasures may have to be employed for a number of decades. The evaluation criteria for the many countermeasures which have been developed needs to be extended from simply effectiveness and radiological protection criteria to a more integrated, holistic approach. Specifically, there needs to be an assessment as to whether countermeasures: can be practically applied; incur considerable direct or side-effect costs; have significant environmental side-effects; and are acceptable to society. In addition, suitable approaches for successfully communicating with a wide range of stake holders must be explored. This is an essential step in developing a decision framework and avoiding problems previously experienced in emergency management. This paper presents results from an ongoing project (see www.strategy-ec.org.uk) to develop a framework for the identification of strategies for the sustainable management of contaminated urban, rural and industrial areas

  16. Improvement of Renal Function by Long-Term Sustained Eculizumab Treatment in a Patient with Paroxysmal Nocturnal Hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Haruhiko Ninomiya

    2015-01-01

    Full Text Available Chronic kidney disease (CKD is one of the major manifestations of paroxysmal nocturnal hemoglobinuria (PNH. CKD in PNH is induced mainly by intravascular hemolysis of PNH-affected red blood cells (RBC missing the glycosylphosphatidylinositol-anchored proteins with complement-regulatory activities, CD55 and CD59. CKD develops by heme absorption in the proximal tubules resulting in the interstitial deposition of iron in the kidneys. We administered eculizumab to a patient with PNH, who was one of 29 patients enrolled in the AEGIS clinical trial, an open-label study of eculizumab in Japan. The patient was complicated by stage 3 CKD with impaired estimated glomerular filtration rate (eGFR, at grade G3b, and had obvious proteinuria (2-3+, 1-2 g/day. In a two-year extension to the 12-week AEGIS study, eGFR improved significantly, and the eGFR has since been maintained at grade G2 without proteinuria by sustained eculizumab treatment (>6 years. Renal function improved and maintained by long-term sustained eculizumab treatment, presumably by clearance of iron from the kidney as well as inhibition of the production of anaphylatoxin C5a, even in advanced stages of CKD, is one of the benefits of eculizumab treatment in PNH.

  17. 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

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. Quality of life long-term after body contouring surgery following bariatric surgery: sustained improvement after 7 years.

    Science.gov (United States)

    van der Beek, Eva S J; Geenen, Rinie; de Heer, Francine A G; van der Molen, Aebele B Mink; van Ramshorst, Bert

    2012-11-01

    Bariatric surgery for morbid obesity results in massive weight loss and improvement of health and quality of life. A downside of the major weight loss is the excess of overstretched skin, which may influence the patient's quality of life by causing functional and aesthetic problems. The purpose of the current study was to evaluate the patient's quality of life long-term after body contouring following bariatric surgery. Quality of life was measured with the Obesity Psychosocial State Questionnaire in 33 post-bariatric surgery patients 7.2 years (range, 3.2 to 13.3 years) after body contouring surgery. Data were compared with previous assessments 4.1 years (range, 0.7 to 9.2 years) after body contouring surgery of the quality of life at that time and before body contouring surgery. Compared with appraisals of quality of life before body contouring surgery, a significant, mostly moderate to large, sustained improvement of quality of life was observed in post-bariatric surgery patients 7.2 years after body contouring surgery in six of the seven psychosocial domains. A small deterioration occurred between 4.1- and 7.2-year follow-up on two of the seven domains except for the domain efficacy toward eating, which showed a significant improvement. At 7-year follow-up, 18 patients (55 percent) were satisfied with the result of body contouring surgery. This study indicates a sustained quality-of-life improvement in post-bariatric surgery patients after body contouring surgery. This suggests the importance of including reconstructive surgery as a component in the multidisciplinary approach in the surgical treatment of morbid obesity. Therapeutic, IV.

  5. 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.

  6. Energy Efficiency in Building as a Basic Prerequisite for a Long Term Energy Strategies Realization, Environmental Protection and Sustainability

    International Nuclear Information System (INIS)

    Miscevic, Lj.

    2006-01-01

    Energy efficiency in buildings at the low-energy and 'passive house' standard levels is presently the basic prerequisite for considering and formulating long term strategies, which with the task of meeting energy needs and system maintenance respond to requests of environmental protection and improvements in the context of sustainable development. Orientation to sustainable development is integrated in the development strategies of Croatia. The application of renewable energy sources, in particular solar energy in passive and active systems in the architecture is permanently confirmed by conducting energy monitoring and growing number of domestic studies, projects and realizations. The long-time research project of the European Union Cost Efficient Passive Houses as European Standards (CEPHEUS) with scientific monitoring corroborated energy and economic efficiency of such architectural designs in Germany, France, Austria, and Switzerland. Thus, the 'passive house' is proposed as a standard of residential architecture, but also of the construction of other functional types of architecture in general. The accomplished energy efficiency and verified favorable profitability of investment developed new forms of incentives to low-energy and passive architecture and relevant changes in concepts of long term energy strategies in the European Union member states. In Austria the 1000th passive house was built, and the city of Frankfurt/M brought decision regarding financing building construction through the city budget at the 'passive house' level. The new Technical Regulation on energy savings and thermal protection in Croatia, which is effectively in force as of 1 July, is a long-awaited step towards energy efficiency. Although, according to this Regulation the tolerance in energy use for space heating goes, in worst case calculation, up to 89 kWh/m2 a year, any other more favorable calculation with obligation to calculate the share of solar radiation for buildings, opens

  7. 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.

  8. 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.

  9. 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

  10. Assessment of nuclear energy cost competitiveness against alternative energy sources in Romania envisaging the long-term national energy sustainability

    International Nuclear Information System (INIS)

    Margeanu, C. A.

    2016-01-01

    The paper includes some of the results obtained by RATEN ICN Pitesti experts in the IAEA.s Collaborative Project INPRO-SYNERGIES. The case study proposed to evaluate and analyze the nuclear capacity development and increasing of its share in the national energy sector, envisaging the long term national and regional energy sustainability by keeping collaboration options open for the future while bringing solutions to short/medium-term challenges. The following technologies, considered as future competing technologies for electric energy generation in Romania, were selected: nuclear technology (represented by PHWR CANDU Units 3 and 4 - CANDU new, advanced HWR - Adv. HWR, and advanced PWR - Adv. PWR) and, as alternative energy sources, classical technology (represented by Coal-fired power plant using lignite fossil fuel, with carbon capture - Coal_new, and Gas-fired power plant operating on combined cycle, with carbon capture - Gas_new). The study included assessment of specific economic indicators, sensitivity analyses being performed on Levelised Unit Energy Cost (LUEC) variation due to different perturbations (e.g. discount rate, overnight costs, etc). Robustness indices (RI) of LUEC were also calculated by considering simultaneous variation of input parameters for the considered power plants. The economic analyses have been performed by using the IAEA.s NEST program. The study results confirmed that in Romania, under the national specific conditions defined, electricity produced by nuclear power plants is cost competitive against coal and gas fired power plants electricity. The highest impact of considered perturbations on LUEC has been observed for capital intensive technologies (nuclear technologies) comparatively with the classic power plants, especially for discount rate changes. (authors)

  11. DOE-NE Light Water Reactor Sustainability Program and EPRI Long-Term Operations Program. Joint Research and Development Plan

    International Nuclear Information System (INIS)

    Williams, Don

    2014-01-01

    Nuclear power has contributed almost 20% of the total amount of electricity generated in the United States over the past two decades. High capacity factors and low operating costs make nuclear power plants (NPPs) some of the most economical power generators available. Further, nuclear power remains the single largest contributor (nearly 70%) of non-greenhouse gas-emitting electric power generation in the United States. Even when major refurbishments are performed to extend operating life, these plants continue to represent cost-effective, low-carbon assets to the nation's electrical generation capability. By the end of 2014, about one-third of the existing domestic fleet will have passed their 40th anniversary of power operations, and about one-half of the fleet will reach the same 40-year mark within this decade. Recognizing the challenges associated with pursuing extended service life of commercial nuclear power plants, the U.S. Department of Energy's (DOE) Office of Nuclear Energy [NE] and the Electric Power Research Institute (EPRI) have established separate but complementary research and development programs (DOE-NE's Light Water Reactor Sustainability [LWRS] Program and EPRI's Long-Term Operations [LTO] Program) to address these challenges. To ensure that a proper linkage is maintained between the programs, DOE-NE and EPRI executed a memorandum of understanding in late 2010 to @@@establish guiding principles under which research activities (between LWRS and LTO) could be coordinated to the benefit of both parties.@@@ This document represents the third annual revision to the initial version (March 2011) of the plan as called for in the memorandum of understanding.

  12. DOE-NE Light Water Reactor Sustainability Program and EPRI Long-Term Operations Program. Joint Research and Development Plan

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Don

    2014-04-01

    Nuclear power has contributed almost 20% of the total amount of electricity generated in the United States over the past two decades. High capacity factors and low operating costs make nuclear power plants (NPPs) some of the most economical power generators available. Further, nuclear power remains the single largest contributor (nearly 70%) of non-greenhouse gas-emitting electric power generation in the United States. Even when major refurbishments are performed to extend operating life, these plants continue to represent cost-effective, low-carbon assets to the nation’s electrical generation capability. By the end of 2014, about one-third of the existing domestic fleet will have passed their 40th anniversary of power operations, and about one-half of the fleet will reach the same 40-year mark within this decade. Recognizing the challenges associated with pursuing extended service life of commercial nuclear power plants, the U.S. Department of Energy’s (DOE) Office of Nuclear Energy (NE) and the Electric Power Research Institute (EPRI) have established separate but complementary research and development programs (DOE-NE’s Light Water Reactor Sustainability [LWRS] Program and EPRI’s Long-Term Operations [LTO] Program) to address these challenges. To ensure that a proper linkage is maintained between the programs, DOE-NE and EPRI executed a memorandum of understanding in late 2010 to “establish guiding principles under which research activities (between LWRS and LTO) could be coordinated to the benefit of both parties.” This document represents the third annual revision to the initial version (March 2011) of the plan as called for in the memorandum of understanding.

  13. 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.

  14. 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...

  15. Field-scale monitoring of the long-term impact and sustainability of drainage water reuse on the west side of California’s San Joaquin Valley

    Science.gov (United States)

    Diminishing freshwater resources have brought attention to the reuse of degraded water as a potential water resource rather than as a disposal problem. Drainage water from tile-drained, irrigated agricultural land is degraded water that is often in large supply, but the long-term impact and sustain...

  16. Field-scale monitoring of the long-term impact and sustainability of drainage water reuse using ECa-directed soil sampling

    Science.gov (United States)

    Diminishing freshwater resources have brought attention to the reuse of degraded water as a water resource rather than a disposal problem. Drainage water from tile-drained, irrigated agricultural land is degraded water that is often in large supply, but the long-term impact and sustainability of it...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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....

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  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

    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

  11. Developing a long-term global tourism transport model using a behavioural approach: implications for sustainable tourism policy making.

    NARCIS (Netherlands)

    Peeters, P.M.

    2013-01-01

    This paper explores the creation and use of a long-term global tourism transport model for private and public sector tourism policy makers. Given that technology is unlikely to reduce tourism transport's impact on climate change sufficiently to avoid serious dangers, behavioural change is necessary.

  12. Sustainability and Substitution of Exhaustible Natural Resources : How Resource Prices Affect Long-Term R&D Investments

    NARCIS (Netherlands)

    Bretschger, L.; Smulders, J.A.

    2003-01-01

    Traditional resource economics has been criticised for assuming too high elasticities of substitution, not observing material balance principles and relying too much on planner solutions to obtain long-term growth.By analysing a multi-sector R&D based endogenous growth model with exhaustible natural

  13. 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.

  14. 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.

  15. A unit-level perspective on the long-term sustainability of a nursing best practice guidelines program: An embedded multiple case study.

    Science.gov (United States)

    Fleiszer, Andrea R; Semenic, Sonia E; Ritchie, Judith A; Richer, Marie-Claire; Denis, Jean-Louis

    2016-01-01

    Best practice guidelines are a tool for narrowing research-to-practice gaps and improving care outcomes. There is some empirical understanding of guideline implementation in nursing settings, yet there has been almost no consideration of the longer-term sustainability of guideline-based practice improvements. Many healthcare innovations are not sustained, underscoring the need for knowledge about how to promote their survival. To understand how a nursing best practice guidelines program was sustained on acute healthcare center nursing units. We undertook a qualitative descriptive case study of an organization-wide nursing best practice guidelines program with four embedded nursing unit subcases. The setting was a large, tertiary/quaternary urban health center in Canada. The nursing department initiated a program to enhance patient safety through the implementation of three guidelines: falls prevention, pressure ulcer prevention, and pain management. We selected four inpatient unit subcases that had differing levels of program sustainability at an average of almost seven years post initial program implementation. Data sources included 39 key informant interviews with nursing leaders/administrators and frontline nurses; site visits; and program-related documents. Data collection and content analysis were guided by a framework for the sustainability of healthcare innovations. Program sustainability was characterized by three elements: benefits, routinization, and development. Seven key factors most accounted for the differences in the level of program sustainability between subcases. These factors were: perceptions of advantages, collaboration, accountability, staffing, linked levels of leadership, attributes of formal unit leadership, and leaders' use of sustainability activities. Some prominent relationships between characteristics and factors explained long-term program sustainability. Of primary importance was the extent to which unit leaders used sustainability

  16. Sustainable Change Sequence: a framework for developing behavior change interventions for patients with long-term conditions

    OpenAIRE

    Elwyn, Glyn; Marrin, Katy; Frosch, Dominick; White, James

    2014-01-01

    Objective\\ud \\ud Interactive interventions are increasingly advocated to support behavior change for patients who have long-term conditions. Such interventions are most likely to achieve behavior change when they are based on appropriate theoretical frameworks. Developers of interventions are faced with a diverse set of behavioral theories that do not specifically address intervention development. The aim of our work was to develop a framework to guide the developers of interactive healthcare...

  17. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    International Nuclear Information System (INIS)

    Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-01-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Observational evidence of a long-term increase in precipitation due to urbanization effects and its implications for sustainable urban living.

    Science.gov (United States)

    Wai, K M; Wang, X M; Lin, T H; Wong, M S; Zeng, S K; He, N; Ng, E; Lau, K; Wang, D H

    2017-12-01

    Although projected precipitation increases in East Asia due to future climate change have aroused concern, less attention has been paid by the scientific community and public to the potential long-term increase in precipitation due to rapid urbanization. A ten-year precipitation dataset was analysed for both a rapidly urbanized megacity and nearby suburban/rural stations in southern China. Rapid urbanization in the megacity was evident from satellite observations. A statistically significant, long-term, increasing trend of precipitation existed only at the megacity station (45.6mm per decade) and not at the other stations. The increase was attributed to thermal and dynamical modifications of the tropospheric boundary layer related to urbanization, which was confirmed by the results of our WRF-SLUCM simulations. The results also suggested that a long-term regional increase in precipitation, caused by greenhouse gas-induced climate change, for instance, was not evident within the study period. The urbanization-induced increase was found to be higher than the precipitation increase (18.3mm per decade) expected from future climate change. The direct climate impacts due to rapid urbanization is highlighted with strong implications for urban sustainable development and the planning of effective adaptation strategies for issues such as coastal defenses, mosquito-borne disease spread and heat stress mortality. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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

  7. A Biobank for Long-term and Sustainable Research in the Field of Congenital Heart Disease in Germany

    Directory of Open Access Journals (Sweden)

    Thomas Pickardt

    2016-08-01

    Full Text Available Congenital heart disease (CHD is the most frequent birth defect (0.8%–1% of all live births. Due to the advance in prenatal and postnatal early diagnosis and treatment, more than 90% of these patients survive into adulthood today. However, several mid- and long-term morbidities are dominating the follow-up of these patients. Due to the rarity and heterogeneity of the phenotypes of CHD, multicenter registry-based studies are required. The CHD-Biobank was established in 2009 with the aim to collect DNA from patients and their parents (trios or from affected families, as well as cardiovascular tissues from patients undergoing corrective heart surgery for cardiovascular malformations. Clinical/phenotype data are matched to the International Paediatric and Congenital Cardiac Code (IPCCC and the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10. The DNA collection currently comprises samples from approximately 4200 participants with a wide range of CHD phenotypes. The collection covers about 430 trios and 120 families with more than one affected member. The cardiac tissue collection comprises 1143 tissue samples from 556 patients after open heart surgery. The CHD-Biobank provides a comprehensive basis for research in the field of CHD with high standards of data privacy, IT management, and sample logistics.

  8. Comparative assessment of different energy sources and their potential role in long-term sustainable energy mix

    International Nuclear Information System (INIS)

    Kagramanian, V.S.

    2001-01-01

    In the debate on sustainable energy future, the role of nuclear power is a contentious issue. Many, who are outside of the nuclear community, do not even consider nuclear, because of public concerns on nuclear safety, radioactive waste and non-proliferation issues. For example, the United Nations Development Program, in its document Energy After Rio does not suggest a specific role for nuclear power except in the most doubtful of terms. On the contrary, most nuclear organisations and related industries see nuclear power as the only mature carbon-free electricity generating option that can be deployed even on a much larger scale than today. This paper analyses the potential role of nuclear power in the context of the global sustainable energy future. The fundamental features of sustainable energy development are examined in terms of the following compatibility constraints: Demand driven compatibility; Natural resource compatibility; Environmental compatibility; Geopolitical compatibility; and Economic compatibility

  9. 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.

  10. 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.

  11. 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

  12. Firewood harvest from forests of the Murray-Darling Basin, Australia. Part 1: Long-term, sustainable supply available from native forests

    International Nuclear Information System (INIS)

    West, P.W.; Cawsey, E.M.; Stol, J.; Freudenberger, D.

    2008-01-01

    The Murray-Darling Basin is a 1 million km 2 agricultural region of south-eastern Australia, although 29% of it retains native forests. Some are mallee eucalypt types, whilst the 'principal' types are dominated mainly by other eucalypt species. One-third of the 6-7 million oven-dry tonne of firewood burnt annually in Australia is obtained from these forests, principally through collection of coarse woody debris. There are fears that removal of this debris may prejudice the floral and faunal biodiversity of the Basin. The present work considers what silvicultural management practices will allow the long-term maintenance of the native forests of the Basin and their continued contribution to its biodiversity. It then estimates that the maximum, long-term, annual, sustainable yield of firewood which could be harvested, by collection of coarse woody debris, from principal forest types of the Basin would be 10 million oven-dry tonne yr -1 . An alternative, harvest of firewood from live trees by thinning the principal forests and clear-felling mallee forests, would be able to supply 2.3 million tonne yr -1 sustainably. Whilst coarse woody debris harvests could supply far more than the present demand for firewood from the Basin, they would lead to substantial reductions of the debris remaining in the forests; this may be detrimental to biodiversity maintenance. Live tree harvest does not lead to this problem, but would barely be able to supply existing firewood demand

  13. Influence of Silica Fume Addition in the Long-Term Performance of Sustainable Cement Grouts for Micropiles Exposed to a Sulphate Aggressive Medium

    Directory of Open Access Journals (Sweden)

    José Marcos Ortega

    2017-08-01

    Full Text Available At present, sustainability is of major importance in the cement industry, and the use of additions such as silica fume as clinker replacement contributes towards that goal. Special foundations, and particularly micropiles, are one of the most suitable areas for the use of sustainable cements. The aim of this research is to analyse the effects in the very long-term (for 600 days produced by sulphate attack in the microstructure of grouts for micropiles in which OPC (ordinary Portland cement has been replaced by 5% and 10% silica fume. This line of study is building on a previous work, where these effects were studied in slag and fly ash grouts. Grouts made using a commercial sulphate-resisting Portland cement were also studied. The non-destructive impedance spectroscopy technique, mercury intrusion porosimetry, and Wenner resistivity testing were used. Mass variation and the compressive strength have also been analysed. Apparently, impedance spectroscopy is the most suitable technique for studying sulphate attack development. According to the results obtained, grouts for micropiles with a content of silica fume up to 10% and exposed to an aggressive sulphate medium, have a similar or even better behaviour in the very long-term, compared to grouts prepared using sulphate-resisting Portland cement.

  14. Sustained long-term improvement with clozapine in schizophrenia Clozapina na esquizofrenia grave: melhora duradoura e sustentada

    Directory of Open Access Journals (Sweden)

    RICARDO DE OLIVEIRA-SOUZA

    1999-03-01

    Full Text Available The present paper reports the long-term use of clozapine in a prospective sample of 46 chronic schizophrenics. In six months, 21 subjects had been excluded for a number of reasons. In four of them the reasons for exclusion were related to lack of response or adverse effects. The median daily clozapine dose was 400 mg in the remaining 25 patients. As a whole, there were remarkable improvements in core dimensions of psychopathology, global cognitive status, and level of functioning. We confirmed that clozapine is effective in a subgroup of schizophrenics with the severest forms of the disease. If tolerated after the first few months it leads to progressive gains in several domains of behavior. Clozapine should be tried in every patient with schizophrenia in whom positive symptoms, disorganization, or bizarre behavior are a matter of incapacitation despite efforts to keep them under control with other drugs.O presente estudo, prospectivo, relata o uso de longo-prazo da clozapina em 46 esquizofrênicos graves, com mais de cinco anos de doença. Com seis meses de uso da droga, 21 indivíduos haviam sido excluídos por diversas razões. Em quatro, a exclusão se deveu a efeitos adversos ou ausência de resposta. A dose mediana de clozapina foi de 400 mg nos demais 25 pacientes. No todo, observamos melhora em dimensões de psicopatologia, estado cognitivo global, e nível funcional. Concluímos que a clozapina é eficaz em um subgrupo de esquizofrênicos com formas graves da doença. Se tolerada depois dos primeiros meses, produz benefícios progressivos em diversos domínios do comportamento. Clozapina deve ser tentada em todo paciente com esquizofrenia incapacitado por sintomas positivos, desorganização, e/ou comportamentos bizarros, que persistem a despeito de esforços para mantê-los sob controle com outras drogas.

  15. Repetitive transcranial magnetic stimulation once a week induces sustainable long-term relief of central poststroke pain.

    Science.gov (United States)

    Kobayashi, Masahito; Fujimaki, Takamitsu; Mihara, Ban; Ohira, Takayuki

    2015-06-01

    Central poststroke pain is a serious problem for some patients after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been reported to relieve poststroke pain but its efficacy is still controversial. We tested the possibility that rTMS, when applied once a week, would induce sustainable relief of poststroke pain. Eighteen patients with central poststroke pain were included in this study. rTMS (10 trains of 10-sec 5 Hz-rTMS) was delivered over the primary motor cortex on the affected side. The rTMS session was repeated once a week for 12 weeks, and for six patients the intervention was continued for one year. The degree of the pain was assessed before each weekly rTMS session to evaluate sustainable effects. The effects of the rTMS reached a plateau at the eighth week. At the 12th week, the rTMS was effective in 61.1% of the patients; 5 of the 18 patients showed more than 70% reduction based on a visual analog scale, 6 patients showed 40-69% reduction, and 7 remained at a pain reduction level of less than 40%. When patients were divided into two groups with or without severe dysesthesia, it was found that eight patients with severe dysesthesia showed less pain relief than those without. In the six patients who continued rTMS for one year, the pain relief effects also were sustained. Although this was an open-label study without a control group, our findings suggest that rTMS of the primary motor cortex, when maintained once a week, could help to relieve poststroke pain. © 2015 International Neuromodulation Society.

  16. 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.

  17. Modeling Costs and Impacts of Introducing Early Infant Male Circumcision for Long-Term Sustainability of the Voluntary Medical Male Circumcision Program.

    Directory of Open Access Journals (Sweden)

    Emmanuel Njeuhmeli

    Full Text Available Voluntary medical male circumcision (VMMC has been shown to be an effective prevention strategy against HIV infection in males [1-3]. Since 2007, the President's Emergency Plan for AIDS Relief (PEPFAR has supported VMMC programs in 14 priority countries in Africa. Today several of these countries are preparing to transition their VMMC programs from a scale-up and expansion phase to a maintenance phase. As they do so, they must consider the best approaches to sustain high levels of male circumcision in the population. The two alternatives under consideration are circumcising adolescents 10-14 years old over the long term or integrating early infant male circumcision (EIMC into maternal and child health programs. The paper presents an analysis, using the Decision Makers Program Planning Tool, Version 2.0 (DMPPT 2.0, of the estimated cost and impact of introducing EIMC into existing VMMC programs in several countries in eastern and southern Africa. Limited cost data exist for the implementation of EIMC, but preliminary studies, such as the one detailed in Mangenah, et al. [4-5], suggest that the cost of EIMC may be less than that of adolescent and adult male circumcision. If this is the case, then adding EIMC to the VMMC program will increase the number of circumcisions that need to be performed but will not increase the total cost of the program over the long term. In addition, we found that a delayed or slow start-up of EIMC would not substantially reduce the impact of adding it to the program or increase cumulative long-term costs, which should make introduction of EIMC more feasible and attractive to countries contemplating such a program innovation.

  18. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    Science.gov (United States)

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Developing indigenous safeguards capabilities within the MPC ampersand A program: A transition from near-term upgrades to long-term sustainability

    International Nuclear Information System (INIS)

    Robinson, P.W.; Leutters, F.O.; Horton, R.D.; Soo Hoo, M.S.

    1997-01-01

    Approximately five years ago, the United States and countries of ampersand Former Soviet Union (FSU) started the Cooperative Threat Reduction program. The program's purpose was to accelerate reduction of the risk of nuclear proliferation, including such threats as theft, diversion, and unauthorized possession of nuclear materials. This goal would be accomplished through near-term upgrades to strengthen the nuclear material protection, control, and accounting systems within the FSU countries. In addition to this near-term goal, a long-term goal of the U.S. Department of Energy's (DOE) Material Protection, Control, and Accounting (MPC ampersand A) program is to promote a new safeguards culture and to support the establishment of a sustaining MPC ampersand A infrastructure in the FSU. This long-term goal is vital to assuring that the near-term upgrades remain effective for safeguarding nuclear material as these countries experience political and social changes. The MPC ampersand A program is managed by DOE's Russia/Newly Independent States (NIS) Nuclear Materials Security Task Force. A coordinated effort is underway to promote and to help establish a new safeguards culture and a sustaining infrastructure. Elements being implemented at both the national and site levels include system operational performance evaluations, development of MPC ampersand A training, operational procedures, national MPC ampersand A regulations, and adaptation of modern MPC ampersand A methodologies to suit the conditions in the FSU countries. This paper identifies current efforts in several countries that are undergoing transition from near-term upgrades to sustainable MPC ampersand A systems

  20. 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.

  1. 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.

  2. Antifouling coating with controllable and sustained silver release for long-term inhibition of infection and encrustation in urinary catheters.

    Science.gov (United States)

    Wang, Rong; Neoh, Koon Gee; Kang, En-Tang; Tambyah, Paul Anantharajah; Chiong, Edmund

    2015-04-01

    Urinary tract infections constitute a large proportion of nosocomial infections, and the urinary catheter is the most important predisposing factor. Encrustation induced by urease-producing uropathogens like Proteus mirabilis causes further complications. In the present work, a strategy for controllable and sustained release of silver over several weeks has been developed for combating bacterial infection and encrustation in urinary devices. Silver nanoparticles (AgNPs) were first immobilized on polydopamine (PDA) pre-treated silicone catheter surface and this was followed by another PDA coating. The number of AgNP-PDA bilayers could be manipulated to control the amount of silver loaded and its subsequent release. Poly(sulfobetaine methacrylate-co-acrylamide) was then grafted to provide an antifouling outer layer, and to ensure free diffusion of Ag from the surface. The micron-scale combination of an antifouling coating with AgNP-PDA bilayers reduced colonization of the urinary catheter by uropathogens by approximately two orders of magnitude. With one and two AgNP-PDA bilayers, the coated catheter could resist encrustation for 12 and 45 days, respectively, compared with approximately 6 days with the Dover™ silver-coated catheter. Such anti-infective and anti-encrustation catheters can potentially have a large impact on reducing patient morbidity and healthcare expenditure. © 2014 Wiley Periodicals, Inc.

  3. Human-in-the-Loop simulation in support of long-term sustainability of light water reactors

    International Nuclear Information System (INIS)

    Hallbert, Bruce P.

    2014-01-01

    Reliable instrumentation, information, and control systems technologies are essential to ensuring safe and efficient operation of the U.S. light water reactor (LWR) fleet. These technologies affect every aspect of nuclear power plant (NPP) and balance-of-plant operations. In 1997, the National Research Council conducted a study concerning the challenges involved in modernization of digital instrumentation and control systems in NPPs. Their findings identified the need for new II and C technology integration. The NPP owners and operators realize that the traditional analog technology represents a significant challenge to sustaining the operation of the current fleet of NPPs. Beyond control systems, new technologies are needed to monitor and characterize the effects of aging and degradation in critical areas of key structures, systems, and components. The objective of the efforts sponsored by the U.S. Department of Energy is to develop, demonstrate, and deploy new digital technologies for II and C architectures and provide monitoring capabilities to ensure the continued safe, reliable, and economic operation of the nation's NPPs. (author)

  4. Long-term temporal trajectories to enhance restoration efficiency and sustainability on large rivers: an interdisciplinary study

    Science.gov (United States)

    Eschbach, David; Schmitt, Laurent; Imfeld, Gwenaël; May, Jan-Hendrik; Payraudeau, Sylvain; Preusser, Frank; Trauerstein, Mareike; Skupinski, Grzegorz

    2018-05-01

    While the history of a fluvial hydrosystem can provide essential knowledge on present functioning, historical context remains rarely considered in river restoration. Here we show the relevance of an interdisciplinary study for improving restoration within the framework of a European LIFE+ project on the French side of the Upper Rhine (Rohrschollen Island). Investigating the planimetric evolution combined with historical high-flow data enabled us to reconstruct pre-disturbance hydromorphological functioning and major changes that occurred on the reach. A deposition frequency assessment combining vertical evolution of the Rhine thalweg, chronology of deposits in the floodplain, and a hydrological model revealed that the period of incision in the main channel corresponded to high rates of narrowing and lateral channel filling. Analysis of filling processes using Passega diagrams and IRSL dating highlights that periods of engineering works were closely related to fine sediment deposition, which also presents concomitant heavy metal accumulation. In fact, current fluvial forms, processes and sediment chemistry around Rohrschollen Island directly reflect the disturbances that occurred during past correction works, and up to today. Our results underscore the advantage of combining functional restoration with detailed knowledge of the past trajectory to (i) understand the functioning of the hydrosystem prior to anthropogenic disturbances, (ii) characterize the human-driven morphodynamic adjustments during the last 2 centuries, (iii) characterize physico-chemical sediment properties to trace anthropogenic activities and evaluate the potential impact of the restoration on pollutant remobilization, (iv) deduce the post-restoration evolution tendency and (v) evaluate the efficiency and sustainability of the restoration effects. We anticipate our approach will expand the toolbox of decision-makers and help orientate functional restoration actions in the future.

  5. Long-Term Urban Growth and Land Use Efficiency in Southern Europe: Implications for Sustainable Land Management

    Directory of Open Access Journals (Sweden)

    Marco Zitti

    2015-03-01

    Full Text Available The present study illustrates a multidimensional analysis of an indicator of urban land use efficiency (per-capita built-up area, LUE in mainland Attica, a Mediterranean urban region, along different expansion waves (1960–2010: compaction and densification in the 1960s, dispersed growth along the coasts and on Athens’ fringe in the 1970s, fringe consolidation in the 1980s, moderate re-polarization and discontinuous expansion in the 1990s and sprawl in remote areas in the 2000s. The non-linear trend in LUE (a continuous increase up to the 1980s and a moderate decrease in 1990 and 2000 preceding the rise observed over the last decade reflects Athens’ expansion waves. A total of 23 indicators were collected by decade for each municipality of the study area with the aim of identifying the drivers of land use efficiency. In 1960, municipalities with low efficiency in the use of land were concentrated on both coastal areas and Athens’ fringe, while in 2010, the lowest efficiency rate was observed in the most remote, rural areas. Typical urban functions (e.g., mixed land uses, multiple-use buildings, vertical profile are the variables most associated with high efficiency in the use of land. Policies for sustainable land management should consider local and regional factors shaping land use efficiency promoting self-contained expansion and more tightly protecting rural and remote land from dispersed urbanization. LUE is a promising indicator reflecting the increased complexity of growth patterns and may anticipate future urban trends.

  6. Long-term temporal trajectories to enhance restoration efficiency and sustainability on large rivers: an interdisciplinary study

    Directory of Open Access Journals (Sweden)

    D. Eschbach

    2018-05-01

    Full Text Available While the history of a fluvial hydrosystem can provide essential knowledge on present functioning, historical context remains rarely considered in river restoration. Here we show the relevance of an interdisciplinary study for improving restoration within the framework of a European LIFE+ project on the French side of the Upper Rhine (Rohrschollen Island. Investigating the planimetric evolution combined with historical high-flow data enabled us to reconstruct pre-disturbance hydromorphological functioning and major changes that occurred on the reach. A deposition frequency assessment combining vertical evolution of the Rhine thalweg, chronology of deposits in the floodplain, and a hydrological model revealed that the period of incision in the main channel corresponded to high rates of narrowing and lateral channel filling. Analysis of filling processes using Passega diagrams and IRSL dating highlights that periods of engineering works were closely related to fine sediment deposition, which also presents concomitant heavy metal accumulation. In fact, current fluvial forms, processes and sediment chemistry around Rohrschollen Island directly reflect the disturbances that occurred during past correction works, and up to today. Our results underscore the advantage of combining functional restoration with detailed knowledge of the past trajectory to (i understand the functioning of the hydrosystem prior to anthropogenic disturbances, (ii characterize the human-driven morphodynamic adjustments during the last 2 centuries, (iii characterize physico-chemical sediment properties to trace anthropogenic activities and evaluate the potential impact of the restoration on pollutant remobilization, (iv deduce the post-restoration evolution tendency and (v evaluate the efficiency and sustainability of the restoration effects. We anticipate our approach will expand the toolbox of decision-makers and help orientate functional restoration actions in the

  7. Sustainability of the Catalytic Activity of a Silica-Titania Composite (STC) for Long-Term Indoor Air Quality Control

    Science.gov (United States)

    Coutts, Janelle L.; Levine, Lanfang H.; Richards, Jeffrey T.

    2011-01-01

    TiO2-assisted photocatalytic oxidation (PCO) is an emerging technology for indoor air quality control and is also being evaluated as an alternative trace contaminant control technology for crew habitats in space exploration. Though there exists a vast range of literature on the development of photocatalysts and associated reactor systems, including catalyst performance and performance-influencing factors, the critical question of whether photocatalysts can sustain their initial catalytic activity over an extended period of operation has not been adequately addressed. For a catalyst to effectively serve as an air quality control product, it must be rugged enough to withstand exposure to a multitude of low concentration volatile organic compounds (VOCs) over long periods of time with minimal loss of activity. The objective of this study was to determine the functional lifetime of a promising photocatalyst - the silica-titania composite (STC) from Sol Gel Solutions, LLC in a real-world scenario. A bench-scale STC-packed annular reactor under continuous irradiation by a UV-A fluorescent black-light blue lamp ((lambda)max = 365 nm) was exposed to laboratory air continuously at an apparent contact time of 0.27 sand challenged with a known concentration of ethanol periodically to assess any changes in catalytic activity. Laboratory air was also episodically spiked with halocarbons (e.g., octafluoropropane), organosulfur compounds (e.g., sulfur hexafluoride), and organosilicons (e.g., siloxanes) to simulate accidental releases or leaks of such VOCs. Total organic carbon (TOC) loading and contaminant profiles of the laboratory air were also monitored. Changes in STC photocatalytic performance were evaluated using the ethanol mineralization rate, mineralization efficiency, and oxidation intermediate (acetaldehyde) formation. Results provide insights to any potential catalyst poisoning by trace halocarbons and organosulfur compounds.

  8. 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.

  9. 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...

  10. Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

    Directory of Open Access Journals (Sweden)

    Félix Gutierrez

    Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

  11. Alternative long term strategies for sustainable development: Rapidly increasing electricity consumption in Asian countries and future role of nuclear energy

    International Nuclear Information System (INIS)

    Sagawa, N.

    1997-01-01

    Many people in the world express the concern that global warming will become an increasingly serious problem. A rapid increase in population and demand for energy in the Asian region must be discussed in this context. Despite the forecast of an increase in demand for energy, the Asian region is short of oil and natural gas resources. In addition, only less energy can be supplied by renewable energy sources in the Asian region than in the other regions because of high population density. Nuclear energy is an important energy resource for fulfilling the future increasing energy demand in the Asian region and for contributing to the suppression of carbon dioxide emissions. In the Asian region alone, however, we cannot rely limitlessly on LWR which does not use plutonium. According to a scenario analysis, the total capacity of nuclear power plants in the Asian region would reach large scale and the cumulative amount of demand for natural uranium will increase to about 5 million tons in the Asian region alone. Just the nuclear power plants of this scale in Asia alone will rapidly consume the world's cheap natural uranium resources if we rely only on natural uranium. In the Asian region, few countries have embarked on nuclear power generation and the capacity of equipment is still small. Currently, however, many plans for nuclear power generation are being designed. Many Asian countries obviously consider nuclear power generation as a valid option. Many potential policies must be examined in the light of future uncertainty. In the future, both renewable energy and nuclear energy must be resorted to. When nuclear energy is utilized, the use of plutonium and FBR in the Asian region must be taken into account in order to attain continual growth and development. (author)

  12. 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.

  13. 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.

  14. Systems, strategies, and interventions for sustainable long-term care and protection of children with a history of living outside of family care.

    Science.gov (United States)

    Fluke, John D; Goldman, Philip S; Shriberg, Janet; Hillis, Susan D; Yun, Katherine; Allison, Susannah; Light, Enid

    2012-10-01

    This article reviews the available evidence regarding the efficacy, effectiveness, ethics, and sustainability of approaches to strengthen systems to care for and protect children living outside family care in low- and middle-income countries. For trafficked children, children of and on the street, children of conflict/disaster, and institutionalized children, a systems framework approach was used to organize the topic of sustainable approaches in low- and middle-income countries and addresses the following: legislation, policies, and regulations; system structures and functions (formal and informal); and continuum of care and services. The article draws on the findings of a focal group convened by the U.S. Government Evidence Summit: Protecting Children Outside of Family Care (December 12-13, 2011, Washington, DC), tasked with reviewing the literature on systems, strategies, and interventions for sustainable long-term care and protection of children with a history of living outside of family care in low- and middle-income country contexts. The specific methodology for the review is described in the commentary paper (Higgs, Zlidar, & Balster, 2012) that accompanies these papers. For the most part, the evidence base in support of sustainable long-term care for the populations of interest is relatively weak, with some stronger but unreplicated studies. Some populations have been studied more thoroughly than others, and there are many gaps. Most of the existing studies identify population characteristics, needs, and consequences of a lack of systemic services to promote family-like care. There is some evidence of the effectiveness of laws and policies, as well as some evidence of service effectiveness, in improving outcomes for children outside of family care. Despite the weaknesses and gaps of the existing research, there is a foundation of research for going forward, which should focus on developing and implementing systems for these most vulnerable children. The

  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. Strategic framework for sustainable development in the period of transition towards market economy: Critical overview of the strategy of long-term development of Serbia

    Directory of Open Access Journals (Sweden)

    Hadžić Miroljub

    2005-01-01

    Full Text Available This paper offers a critical analysis of the strategic framework for long-term economic development of Serbia, of the role of strategic development in the success of the transition process, and the consequences of the lack of a development strategy. The strategy of long-term economic development of Serbia, as a programme intended to designate the economic and development policy of the state, is analyzed with the aim of finding an acceptable formulation of development strategy. The authors consider various approaches and propose a strategy for Serbia in the period of transition towards market economy. They also point out that, in the period of transition from a government-planned towards a market economy, strategy should be given greater importance than in periods that do not represent turning points, because of the greater possibility of incorrect policy making, potential conflicts of interest groups, reaching sustainable development, and maximizing prosperity. The authors take into account the advantages and disadvantages of the radical and of the gradualist approach to transition and propose formulating a development strategy that would contain combined elements of plan and market mechanisms. They believe that the process of transition lacks a clear development strategy, and that the quality of the existing development strategy of Serbia until 2010 is such that it cannot be understood as a serious approach to the transition issue. The authors stress the consequences of undergoing transition without a development strategy, that include inappropriate dynamic and sequence of reforms; a lack of coordination between development policy, macroeconomic policy, market reforms, and spatial planning policy; higher costs of transition, insufficient rate of economic growth, etc. They offer proposals for a comprehensive development framework (CDF and for strategic planning of territorial industrial development.

  1. 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.

  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. Human resources for health strategies adopted by providers in resource-limited settings to sustain long-term delivery of ART: a mixed-methods study from Uganda.

    Science.gov (United States)

    Zakumumpa, Henry; Taiwo, Modupe Oladunni; Muganzi, Alex; Ssengooba, Freddie

    2016-10-19

    Human resources for health (HRH) constraints are a major barrier to the sustainability of antiretroviral therapy (ART) scale-up programs in Sub-Saharan Africa. Many prior approaches to HRH constraints have taken a top-down trend of generalized global strategies and policy guidelines. The objective of the study was to examine the human resources for health strategies adopted by front-line providers in Uganda to sustain ART delivery beyond the initial ART scale-up phase between 2004 and 2009. A two-phase mixed-methods approach was adopted. In the first phase, a survey of a nationally representative sample of health facilities (n = 195) across Uganda was conducted. The second phase involved in-depth interviews (n = 36) with ART clinic managers and staff of 6 of the 195 health facilities purposively selected from the first study phase. Quantitative data was analysed based on descriptive statistics, and qualitative data was analysed by coding and thematic analysis. The identified strategies were categorized into five themes: (1) providing monetary and non-monetary incentives to health workers on busy ART clinic days; (2) workload reduction through spacing ART clinic appointments; (3) adopting training workshops in ART management as a motivation strategy for health workers; (4) adopting non-physician-centred staffing models; and (5) devising ART program leadership styles that enhanced health worker commitment. Facility-level strategies for responding to HRH constraints are feasible and can contribute to efforts to increase country ownership of HIV programs in resource-limited settings. Consideration of the human resources for health strategies identified in the study by ART program planners and managers could enhance the long-term sustainment of ART programs by providers in resource-limited settings.

  5. Using QMRAcatch - a stochastic hydrological water quality and infection risk model - to identify sustainable management options for long term drinking water resource planning

    Science.gov (United States)

    Derx, J.; Demeter, K.; Schijven, J. F.; Sommer, R.; Zoufal-Hruza, C. M.; Kromp, H.; Farnleitner, A.; Blaschke, A. P.

    2017-12-01

    River water resources in urban environments play a critical role in sustaining human health and ecosystem services, as they are used for drinking water production, bathing and irrigation. In this study the hydrological water quality model QMRAcatch was used combined with measured concentrations of human enterovirus and human-associated genetic fecal markers. The study area is located at a river/floodplain area along the Danube which is used for drinking water production by river bank filtration and further disinfection. QMRAcatch was previously developed to support long term planning of water resources in accordance with a public infection protection target (Schijven et al., 2015). Derx et al. 2016 previously used QMRAcatch for evaluating the microbiological quality and required virus-reduction targets at the study area for the current and robust future "crisis" scenarios, i.e. for the complete failure of wastewater treatment plants and infection outbreaks. In contrast, the aim of this study was to elaborate future scenarios based on projected climate and population changes in collaboration with urban water managers. The identified scenarios until 2050 include increased wastewater discharge rates due to the projected urban population growth and more frequent storm and overflow events of urban sewer systems following forecasted changes in climate and hydrology. Based on the simulation results for the developed scenarios sustainable requirements of the drinking water treatment system for virus reductions were re-evaluated to achieve the health risk target. The model outcomes are used to guide practical and scientifically sound management options for long term water resource planning. This paper was supported by FWF (Vienna Doctoral Program on Water Resource Systems W1219-N22) and the GWRS project (Vienna Water) as part of the "(New) Danube-Lower Lobau Network Project" funded by the Government of Austria and Vienna, and the European Agricultural Fund for Rural

  6. 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

  7. 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.

  8. 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.

  9. Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNγ responses of hepatic CD8+ memory T cells.

    Science.gov (United States)

    Nganou-Makamdop, Krystelle; van Gemert, Geert-Jan; Arens, Theo; Hermsen, Cornelus C; Sauerwein, Robert W

    2012-01-01

    Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (T(EM)) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ T(EM) cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r(2) = 0.60, pmemory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells.

  10. Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNγ responses of hepatic CD8+ memory T cells.

    Directory of Open Access Journals (Sweden)

    Krystelle Nganou-Makamdop

    Full Text Available Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS, resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (T(EM CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ T(EM cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r(2 = 0.60, p<0.0001. The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells.

  11. 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...

  12. 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.

  13. 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.

  14. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

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    Swee Lin G Chen Yi Mei

    Full Text Available Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR in people with chronic hepatitis C (CHC infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM using transient elastography [FibroScan] were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa or advanced (METAVIR F3-4/ LSM >9.5 kPa. The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2 to advanced fibrosis at follow-up liver fibrosis assessment.131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62 years with median estimated duration of infection 33-years (IQR 29-38. At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17. 109 (83% participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002. The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343. However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F

  15. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Science.gov (United States)

    Chen Yi Mei, Swee Lin G; Thompson, Alexander J; Christensen, Britt; Cunningham, Georgina; McDonald, Lucy; Bell, Sally; Iser, David; Nguyen, Tin; Desmond, Paul V

    2017-01-01

    Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p

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

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    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.

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

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    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.

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

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    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.

  19. 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.

  20. 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.

  1. 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.

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

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    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

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    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.

  8. 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.

  9. 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.

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

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    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Assessing Tourists’ Preferences for Recreational Trips in National and Natural Parks as a Premise for Long-Term Sustainable Management Plans

    Directory of Open Access Journals (Sweden)

    Diana E. Dumitras

    2017-09-01

    Full Text Available Sustainable tourism management plans rely on relevant and consistent information about factors that can influence the decision to visit a protected area. This paper uses the choice experiment method to investigate tourists’ preferences with regard to recreational trip characteristics in national and natural parks in Romania. An on-site survey questionnaire was administered to visitors. The multinomial logit model was employed to investigate the preference orderings of the identified groups of recreational users. Overall, results indicate that tourists gain benefits after visiting the parks. Main preference differences were found for information sources and location of campsites. Visitors who stated that the park was the main trip destination were willing to have access to more information sources, the marks on trails being insufficient. Camping is preferred only in organized places, expressing the concern for environmental protection. The results of this study have management implications, highlighting the importance of assessing tourists’ preferences as a foundation for developing sustainable tourism strategies.

  16. 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.

  17. 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...

  18. 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

  19. 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...

  20. Optimizing Discount Rates: Expressing Preferences for Sustainable Outcomes in Present Value Calculations

    OpenAIRE

    Axelrod, David

    2017-01-01

    This paper describes how the discount rate used in present value calculations expresses the preference for sustainability in decision making, and its implication for sustainable economic growth. In essence, the lower the discount rate, the greater the regard for the future, and the more likely we choose behaviors that lead to long-term sustainability. The theoretical framework combines behavioral economics and holonomics, which involve limitations of regard for the future due to constraints o...

  1. THE GREEN RENOVATION AND EXPANSION OF THE AIKEN CENTER: A SUSTAINABLE GREEN BUILDING DESIGN, COLLABORATIVE PLANNING PROCESS AND LONG-TERM DEMONSTRATION AND RESEARCH PROJECT

    Science.gov (United States)

    One important outcome of this project will be the development of a long-term demonstration program that will provide teaching and research tools for many decades. In addition, we will develop models that will be available for others to use, present our findings to others, and ...

  2. 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

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension.

    Science.gov (United States)

    Fein, Henry G; Vaughan, T Brooks; Kushner, Harvey; Cram, David; Nguyen, Dat

    2015-10-27

    Overweight and obesity are common among patients with Cushing's syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study. Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study). Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 ± 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4-41.9). Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥ 5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost ≥ 10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use. Clinically meaningful weight loss achieved during

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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 .

  20. 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.

  1. 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

  2. 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...

  3. Exploring the possibilities for setting up sustainable energy systems for the long term: two visions for the Dutch energy system in 2050

    International Nuclear Information System (INIS)

    Treffers, D.J.; Faaij, A.P.C.; Spakman, J.; Seebregts, A.

    2005-01-01

    In this paper, two long-term visions of the Dutch future energy system are composed, analysed and evaluated. Both visions were set up to meet the requirement to reduce the GHG emissions with 80% in 2050 in comparison to 1990. The two visions start from very different perspectives and contexts. Quantitative analysis shows that when economic growth and energy use follow a business as usual development, emissions of GreenHouse Gases (GHG) can increase up to 250% of 1990 levels. The two, rather opposing, visions show that it is feasible to combine (strong) economic growth with far going reduction of GHG emissions, provided a number of key options are developed and applied. These options were chosen and discussed during several meetings by stakeholders in a dialogue process, using feedback from scientists, and consist of improvements in energy efficiency in industry, CO 2 neutral feedstocks for transportation, renewable energy and highly insulated buildings in the built environment and improvements in the primary production of the agricultural sector. It is clear that drastic changes in many areas in society are required to obtain the desired GHG-emission levels in 2050. The results also show though, that such a development can be realised in different ways. In other words, there are various ways to implement a low GHG emission economy in the long term

  4. 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 ...

  5. 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)

  6. Maintenance of C sinks sustains enhanced C assimilation during long-term exposure to elevated [CO2] in Mojave Desert shrubs.

    Science.gov (United States)

    Aranjuelo, Iker; Ebbets, Allison L; Evans, R Dave; Tissue, David T; Nogués, Salvador; van Gestel, Natasja; Payton, Paxton; Ebbert, Volker; Adams, Williams W; Nowak, Robert S; Smith, Stanley D

    2011-10-01

    During the first few years of elevated atmospheric [CO(2)] treatment at the Nevada Desert FACE Facility, photosynthetic downregulation was observed in desert shrubs grown under elevated [CO(2)], especially under relatively wet environmental conditions. Nonetheless, those plants maintained increased A (sat) (photosynthetic performance at saturating light and treatment [CO(2)]) under wet conditions, but to a much lesser extent under dry conditions. To determine if plants continued to downregulate during long-term exposure to elevated [CO(2)], responses of photosynthesis to elevated [CO(2)] were examined in two dominant Mojave Desert shrubs, the evergreen Larrea tridentata and the drought-deciduous Ambrosia dumosa, during the eighth full growing season of elevated [CO(2)] treatment at the NDFF. A comprehensive suite of physiological processes were collected. Furthermore, we used C labeling of air to assess carbon allocation and partitioning as measures of C sink activity. Results show that elevated [CO(2)] enhanced photosynthetic performance and plant water status in Larrea, especially during periods of environmental stress, but not in Ambrosia. δ(13)C analyses indicate that Larrea under elevated [CO(2)] allocated a greater proportion of newly assimilated C to C sinks than Ambrosia. Maintenance by Larrea of C sinks during the dry season partially explained the reduced [CO(2)] effect on leaf carbohydrate content during summer, which in turn lessened carbohydrate build-up and feedback inhibition of photosynthesis. δ(13)C results also showed that in a year when plant growth reached the highest rates in 5 years, 4% (Larrea) and 7% (Ambrosia) of C in newly emerging organs were remobilized from C that was assimilated and stored for at least 2 years prior to the current study. Thus, after 8 years of continuous exposure to elevated [CO(2)], both desert perennials maintained their photosynthetic capacities under elevated [CO(2)]. We conclude that C storage, remobilization

  7. 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

  8. Sustained Improvement of Arterial Stiffness and Blood Pressure after Long-Term Rosuvastatin Treatment in Patients with Inflammatory Joint Diseases: Results from the RORA-AS Study.

    Directory of Open Access Journals (Sweden)

    Eirik Ikdahl

    Full Text Available Patients with inflammatory joint diseases (IJD have a high prevalence of hypertension and increased arterial stiffness. The aim of the present study was to evaluate the effect of long-term rosuvastatin treatment on arterial stiffness, measured by augmentation index (AIx and aortic pulse wave velocity (aPWV, and blood pressure (BP in IJD patients with established atherosclerosis.Eighty-nine statin naïve IJD patients with carotid atherosclerotic plaque(s (rheumatoid arthritis n = 55, ankylosing spondylitis n = 23, psoriatic arthritis n = 11 received rosuvastatin for 18 months to achieve low-density lipoprotein cholesterol goal ≤1.8 mmol/L. Change in AIx (ΔAIx, aPWV (ΔaPWV, systolic BP (ΔsBP and diastolic BP (ΔdBP from baseline to study end was assessed by paired samples t-tests. Linear regression was applied to evaluate associations between cardiovascular disease (CVD risk factors, rheumatic disease specific variables and medication, and ΔAIx, ΔaPWV, ΔsBP and ΔdBP.AIx, aPWV, sBP and dBP were significantly reduced from baseline to study end. The mean (95%CI changes were: ΔAIx: -0.34 (-0.03, -0.65% (p = 0.03, ΔaPWV: -1.69 (-0.21, -3.17 m/s2 (p = 0.03, ΔsBP: -5.27 (-1.61, -8.93 mmHg (p = 0.004 and ΔdBP -2.93 (-0.86, -5.00 mmHg (p = 0.01. In linear regression models, ∆aPWV was significantly correlated with ΔsBP and ΔdBP (for all: p<0.001.There is an unmet need of studies evaluating CVD prevention in IJD patients. We have shown for the first time that long-term intensive lipid lowering with rosuvastatin improved arterial stiffness and induced a clinically significant BP reduction in patients with IJD. These improvements were linearly correlated and may represent novel insight into the pleiotropic effects by statins.ClinicalTrials.gov NCT01389388.

  9. Long-Term Sustainability of Evidence-Based Prevention Interventions and Community Coalitions Survival: a Five and One-Half Year Follow-up Study.

    Science.gov (United States)

    Johnson, Knowlton; Collins, David; Shamblen, Steve; Kenworthy, Tara; Wandersman, Abraham

    2017-07-01

    This study examines (1) coalition survival, (2) prevalence of evidence-based prevention interventions (EBPIs) to reduce substance abuse implemented as part of the Tennessee Strategic Prevention Framework (SPF) State Incentive Grant (SIG), (3) EBPI sustainability, and (4) factors that predict EBPI sustainability. Secondary data were collected on 27 SPF SIG-funded coalitions and 88 EBPI and non-EBPI implementations. Primary data were collected by a telephone interview/web survey five and one-half years after the SPF SIG ended. Results from secondary data show that 25 of the 27 coalitions survived beyond the SPF SIG for one to five and one-half years; 19 coalitions (70%) were still active five and one-half years later. Further, 88 EBPIs and non-EBPIs were implemented by 27 county SPF SIG coalitions. Twenty-one (21) of 27 coalitions (78%) implemented one to three EBPIs, totaling 37 EBPI implementations. Based on primary survey data on 29 of the 37 EBPI implementations, 28 EBPIs (97%) were sustained between two and five and one-half years while 22 EBPI implementations (76%) were sustained for five and one-half years. When controlling for variability among coalitions (nesting of EBPIs in coalitions), increases in data resources (availability of five types of prevention data) was a strong predictor of length of EBPI sustainability. Positive change in extramural funding resources and level of expertise during SPF SIG implementation, as well as level of coalition formalization at the end of the SPF SIG predicted EBPI sustainability length. One intervention attribute (trialability) also predicted length of sustainability. Implications are discussed.

  10. SHORT, MEDIUM AND LONG-TERM OPPORTUNITIES AND NEEDS FOR RESEARCH FOR SUSTAINABLE FARM ANIMAL BREEDING AND REPRODUCTION TECHNOLOGY IN EU

    Directory of Open Access Journals (Sweden)

    D. Kompan

    2007-06-01

    Full Text Available The European landscape is characterised by a range of diverse farming systems. These relate not only to varied geographical environments, but also to different social and cultural environments for farming and food production. This diversity is unique to Europe and underlines the importance of European agriculture. Animal breeding is a knowledge intensive sector, and for the future competitiveness of animal breeding and animal production, high level European research is indispensable. The preparation of Strategic Research Agenda were in a full process: opportunities and problems, gaps, short, medium and long term opportunities and needs for research. Each country experts from different group have opportunity to help define his country dimension of animal breeding in its regional and country context, and also in relation to European and global developments. The Farm Animal Breeding and Reproduction European Technology Platform, brings together a wide range of interested parties to produce a vision of how livestock breeding might develop in the next 20 years, and constitutes the first step in achieving that vision.

  11. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance

    DEFF Research Database (Denmark)

    Arciero, Paul J; Edmonds, Rohan; He, Feng

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in ob......Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein....../day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P......-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men...

  12. 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

  13. 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...

  14. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

    Science.gov (United States)

    Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

    2016-07-30

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p 50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet.

  15. Long-term structural canopy changes sustain net photosynthesis per ground area in high arctic Vaccinium uliginosum exposed to changes in near-ambient UV-B levels.

    Science.gov (United States)

    Boesgaard, Kristine S; Albert, Kristian R; Ro-Poulsen, Helge; Michelsen, Anders; Mikkelsen, Teis N; Schmidt, Niels M

    2012-08-01

    Full recovery of the ozone layer is not expected for several decades and consequently, the incoming level of solar ultraviolet-B (UV-B) will only slowly be reduced. Therefore to investigate the structural and photosynthetic responses to changes in solar UV-B we conducted a 5-year UV-B exclusion study in high arctic Greenland. During the growing season, the gas exchange (H₂O and CO₂) and chlorophyll-a fluorescence were measured in Vaccinium uliginosum. The leaf dry weight, carbon, nitrogen, stable carbon isotope ratio, chlorophyll and carotenoid content were determined from a late season harvest. The net photosynthesis per leaf area was on average 22% higher in 61% reduced UV-B treatment across the season, but per ground area photosynthesis was unchanged. The leaf level increase in photosynthesis was accompanied by increased leaf nitrogen, higher stomatal conductance and F(v)/F(m). There was no change in total leaf biomass, but reduction in total leaf area caused a pronounced reduction of specific leaf area and leaf area index in reduced UV-B. This demonstrates the structural changes to counterbalance the reduced plant carbon uptake seen per leaf area in ambient UV-B as the resulting plant carbon uptake per ground area was not affected. Thus, our understanding of long-term responses to UV-B reduction must take into account both leaf level processes as well as structural changes to understand the apparent robustness of plant carbon uptake per ground area. In this perspective, V. uliginosum seems able to adjust plant carbon uptake to the present amount of solar UV-B radiation in the High Arctic. Copyright © Physiologia Plantarum 2011.

  16. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Oscar eHerreras

    2012-10-01

    Full Text Available Long term potentiation (LTP is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes difficult estimating the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. These indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  17. Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

    Directory of Open Access Journals (Sweden)

    Samantha J Westrop

    Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

  18. The Long-Term Impact of an Education for Sustainability Course on Israeli Science and Technology Teachers' Pro-Environment Awareness, Commitment and Behaviour

    Science.gov (United States)

    Abramovich, Anat; Loria, Yahavit

    2015-01-01

    The impact of an Education for Sustainability (EfS) course for science and technology junior high school teachers on the intentional and actual environmental behaviour of participants was studied by researching the EfS implementation of 13 science and technology teachers within their family, community, and work environment. The research was…

  19. Nurses' Experiences of End-of-life Care in Long-term Care Hospitals in Japan: Balancing Improving the Quality of Life and Sustaining the Lives of Patients Dying at Hospitals

    Directory of Open Access Journals (Sweden)

    Ryo Odachi, RN, MA

    2017-09-01

    Full Text Available Summary: Purpose: In Japan, about 80% of deaths occur in hospitals, especially long-term care beds. The purpose of this study was to clarify the nursing practices used for such older patients at the end-of-life stage in long-termcare wards via the modified grounded theory approach (M-GTA. Methods: Data were obtained through semi-structured interviews of nineteen nurses working in cooperating long-term care wards, acute care wards, or hospice services (to allow for constant comparison between these types of wards in western Japan in 2014. We analyzed the transcribed data using M-GTA. Results: The core category that emerged from the analysis was “Balancing enhancement of patients' daily life quality and life-sustaining care in the face of uncertainty about the patients' character.” Eleven categories emerged, such as Seeking older patients' character with their family, Supporting families' decision making, Rebuilding patients' daily life in the ward, and Sustaining patients' life span through medical care. Conclusions: Nurses experienced uncertainty about the care needs of older patients, the ethical problems of Enhancing the patients' QOL by using risky care, and the evaluation criteria used to judge their own nursing care after the patients' death. All nurses had the goal of ensuring a natural death for all patients. Nurses' acceptance and evaluation of their own care was critically influenced by the patient's family's responses to their care after patients' death. Further research is necessary to develop evaluation criteria and educational programs for end-of-life nursing care of older adults. Keywords: terminal care, aged, long-term care, qualitative research

  20. 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

  1. 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.

  2. Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

    Science.gov (United States)

    Hutchings, Elizabeth J.; Waller, Jennifer L.

    2013-01-01

    A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15–60 and 84–320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non–match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility. PMID:24042161

  3. Differential long-term effects of haloperidol and risperidone on the acquisition and performance of tasks of spatial working and short-term memory and sustained attention in rats.

    Science.gov (United States)

    Hutchings, Elizabeth J; Waller, Jennifer L; Terry, Alvin V

    2013-12-01

    A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non-match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility.

  4. Sustained safety and efficacy of extended-shelf-life {sup 90}Y glass microspheres: long-term follow-up in a 134-patient cohort

    Energy Technology Data Exchange (ETDEWEB)

    Lewandowski, Robert J.; Minocha, Jeet; Memon, Khairuddin; Riaz, Ahsun; Gates, Vanessa L.; Ryu, Robert K.; Sato, Kent T.; Omary, Reed; Salem, Riad [Northwestern University, Department of Radiology, Chicago, IL (United States)

    2014-03-15

    To validate our initial pilot study and confirm sustained safety and tumor response of extended-shelf-life {sup 90}Y glass microspheres. We hypothesized that for the same planned tissue dose, the increase in number of glass microspheres (decayed to the second week of their allowable shelf-life) administered for the same absorbed dose would result in better tumor distribution of the microspheres without causing additional adverse events. Between June 2007 and January 2010, 134 patients underwent radioembolization with extended-shelf-life {sup 90}Y glass microspheres; data from 84 new patients were combined with data from our 50-patient pilot study cohort. Baseline and follow-up imaging and laboratory data were obtained 1 and 3 months after therapy and every 3 months thereafter. Clinical and biochemical toxicities were prospectively captured and categorized according to the Common Terminology Criteria. Response in the index lesion was assessed using WHO and EASL guidelines. The mean delivered radiation dose was 123 Gy to the target liver tissue. The mean increase in number of microspheres with this approach compared to standard {sup 90}Y glass microsphere dosimetry was 103 %, corresponding to an increase from 3.84 to 7.78 million microspheres. Clinical toxicities included fatigue (89 patients, 66 %), abdominal pain (49 patients, 36.6 %), and nausea/vomiting (25 patients, 18.7 %). Grade 3/4 bilirubin toxicity was seen in three patients (2 %). Two (1 %) of the initial 50-patient cohort showed gastroduodenal ulcers; gastroduodenal ulcers were not seen in any of the subsequent 84 patients. According to WHO and EASL guidelines, response rates were 48 % and 57 %, respectively, and 21 % demonstrated a complete EASL response. This study showed sustained safety and efficacy of extended-shelf-life {sup 90}Y glass microspheres in a larger, 134-patient cohort. The increase in number of microspheres administered theoretically resulted in better tumor distribution of the

  5. Long term remediation of highly polluted acid mine drainage: A sustainable approach to restore the environmental quality of the Odiel river basin

    Energy Technology Data Exchange (ETDEWEB)

    Caraballo, Manuel A., E-mail: manuel.caraballo@dgeo.uhu.es [Geology Department, University of Huelva, Avenida 3 de Marzo s/n, Campus ' El Carmen' , E-21071 Huelva (Spain); Macias, Francisco [Geology Department, University of Huelva, Avenida 3 de Marzo s/n, Campus ' El Carmen' , E-21071 Huelva (Spain); Roetting, Tobias S. [Technical University of Catalonia (UPC), Hydrogeology Group, E-08034 Barcelona (Spain); Nieto, Jose Miguel [Geology Department, University of Huelva, Avenida 3 de Marzo s/n, Campus ' El Carmen' , E-21071 Huelva (Spain); Ayora, Carlos [Institute of Environmental Assessment and Water Research, IDAEA - CSIC, Jordi Girona 18, 08034 Barcelona (Spain)

    2011-12-15

    During 20 months of proper operation the full scale passive treatment in Mina Esperanza (SW Spain) produced around 100 mg/L of ferric iron in the aeration cascades, removing an average net acidity up to 1500 mg/L as CaCO{sub 3} and not having any significant clogging problem. Complete Al, As, Cd, Cr, Cu, Ti and V removal from the water was accomplished through almost the entire operation time while Fe removal ranged between 170 and 620 mg/L. The system operated at a mean inflow rate of 43 m{sup 3}/day achieving an acid load reduction of 597 g.(m{sup 2} day){sup -1}, more than 10 times higher than the generally accepted 40 g.(m{sup 2} day){sup -1} value commonly used as a passive treatment system designing criteria. The high performance achieved by the passive treatment system at Mina Esperanza demonstrates that this innovative treatment design is a simple, efficient and long lasting remediation option to treat highly polluted acid mine drainage. - Highlights: > Novel reactive mixture enable 20 month of high hydraulic conductivity. > Acid load reduction improved 10 times comparing to vertical flow wetland. > High biotic and abiotic iron oxidation and removal. > Complete Al, As, Cd, Cr, Cu, Ti and V water removal. - A high permeable alkaline reactive substrate offers a sustainable option to remediate severely polluted acid mine drainage in the Odiel basin

  6. Identifying breakthrough technologies for the production of basic chemicals. A long term view on the sustainable production of ammonia, olefins and aromatics in the European region

    Energy Technology Data Exchange (ETDEWEB)

    Benner, J.; Van Lieshout, M.; Croezen, H.

    2012-01-15

    The European Commission's Roadmap for a competitive and low carbon economy in 2050 indicates that greenhouse gas emissions (GHG) in all sectors should be significantly reduced to meet the European Union (EU) objective of 80 to 95% greenhouse gas emission reductions by 2050 compared to 1990 levels. The European Commission indicated in the Roadmap that the EU's industrial sectors should reduce emissions by 83 to 87% domestically by 2050 compared to 1990 levels. The objective of this study is to explore breakthrough abatement technologies in three processes in the European chemical industry that can considerably contribute to achieving the required greenhouse gas emission reductions. In this context we have assessed the processes for the production of: (1) Ammonia; (2) Olefins; (3) Aromatics (BTX). For all three processes possible breakthrough abatement technologies were found, allowing for reductions in GHG emissions varying between 50 and 100% compared to the conventional processes. Our finding regarding the chemical industry and our earlier findings regarding options in the steel, cement and pulp and paper industries show that promising breakthrough abatement technologies are available for European energy-intensive industries to contribute to a low-carbon economy. However, large scale deployment requires an integrated EU industry and energy policy allowing for a resource efficient and sustainable use of available biomass, CCS storage capacity and renewable energy capacity.

  7. Identifying breakthrough technologies for the production of basic chemicals. A long term view on the sustainable production of ammonia, olefins and aromatics in the European region

    Energy Technology Data Exchange (ETDEWEB)

    Benner, J.; Van Lieshout, M.; Croezen, H.

    2012-01-15

    The European Commission's Roadmap for a competitive and low carbon economy in 2050 indicates that greenhouse gas emissions (GHG) in all sectors should be significantly reduced to meet the European Union (EU) objective of 80 to 95% greenhouse gas emission reductions by 2050 compared to 1990 levels. The European Commission indicated in the Roadmap that the EU's industrial sectors should reduce emissions by 83 to 87% domestically by 2050 compared to 1990 levels. The objective of this study is to explore breakthrough abatement technologies in three processes in the European chemical industry that can considerably contribute to achieving the required greenhouse gas emission reductions. In this context we have assessed the processes for the production of: (1) Ammonia; (2) Olefins; (3) Aromatics (BTX). For all three processes possible breakthrough abatement technologies were found, allowing for reductions in GHG emissions varying between 50 and 100% compared to the conventional processes. Our finding regarding the chemical industry and our earlier findings regarding options in the steel, cement and pulp and paper industries show that promising breakthrough abatement technologies are available for European energy-intensive industries to contribute to a low-carbon economy. However, large scale deployment requires an integrated EU industry and energy policy allowing for a resource efficient and sustainable use of available biomass, CCS storage capacity and renewable energy capacity.

  8. Long term remediation of highly polluted acid mine drainage: A sustainable approach to restore the environmental quality of the Odiel river basin

    International Nuclear Information System (INIS)

    Caraballo, Manuel A.; Macias, Francisco; Roetting, Tobias S.; Nieto, Jose Miguel; Ayora, Carlos

    2011-01-01

    During 20 months of proper operation the full scale passive treatment in Mina Esperanza (SW Spain) produced around 100 mg/L of ferric iron in the aeration cascades, removing an average net acidity up to 1500 mg/L as CaCO 3 and not having any significant clogging problem. Complete Al, As, Cd, Cr, Cu, Ti and V removal from the water was accomplished through almost the entire operation time while Fe removal ranged between 170 and 620 mg/L. The system operated at a mean inflow rate of 43 m 3 /day achieving an acid load reduction of 597 g.(m 2 day) -1 , more than 10 times higher than the generally accepted 40 g.(m 2 day) -1 value commonly used as a passive treatment system designing criteria. The high performance achieved by the passive treatment system at Mina Esperanza demonstrates that this innovative treatment design is a simple, efficient and long lasting remediation option to treat highly polluted acid mine drainage. - Highlights: → Novel reactive mixture enable 20 month of high hydraulic conductivity. → Acid load reduction improved 10 times comparing to vertical flow wetland. → High biotic and abiotic iron oxidation and removal. → Complete Al, As, Cd, Cr, Cu, Ti and V water removal. - A high permeable alkaline reactive substrate offers a sustainable option to remediate severely polluted acid mine drainage in the Odiel basin

  9. Long-term trends in tourism climate index scores for 40 stations across Iran: the role of climate change and influence on tourism sustainability.

    Science.gov (United States)

    Roshan, Gholamreza; Yousefi, Robabe; Fitchett, Jennifer M

    2016-01-01

    Tourism is a rapidly growing international sector and relies intrinsically on an amenable climate to attract visitors. Climate change is likely to influence the locations preferred by tourists and the time of year of peak travel. This study investigates the effect of climate change on the Tourism Climate Index (TCI) for Iran. The paper first calculates the monthly TCI for 40 cities across Iran for each year from 1961 to 2010. Changes in the TCI over the study period for each of the cities are then explored. Increases in TCI are observed for at least one station in each month, whilst for some months no decreases occurred. For October, the maximum of 45% of stations demonstrated significant changes in TCI, whilst for December only 10% of stations demonstrated change. The stations Kashan, Orumiyeh, Shahrekord, Tabriz, Torbat-e-Heidarieh and Zahedan experienced significant increases in TCI for over 6 months. The beginning of the change in TCI is calculated to have occurred from 1970 to 1980 for all stations. Given the economic dependence on oil exports, the development of sustainable tourism in Iran is of importance. This critically requires the identification of locations most suitable for tourism, now and in the future, to guide strategic investment.

  10. 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 ...

  11. Long-term River Trajectories to Enhance Restoration Efficiency and Sustainability on the Upper Rhine: an Interdisciplinary Study (Rohrschollen Island, France)

    Science.gov (United States)

    Eschbach, D.; Laurent, S.; May, J. H.; Imfeld, G.; Payraudeau, S.; Preusser, F.

    2017-12-01

    While the history of a fluvial hydrosystem can provide essential knowledge on present functioning, historical context remains rarely considered in river restoration. Here we show the relevance of an interdisciplinary historical study for improving restoration within the framework of a European LIFE+ project on the French side of the Upper-Rhine (Rohrschollen Island). Planimetric evolution combined with historical high flow data enabled to reconstruct pre-disturbance hydromorphological functioning and major changes that occurred on the reach. A deposition frequency assessment combining vertical evolution of the Rhine thalweg, chronology of deposits in the floodplain and a hydrological model revealed that the period of vertical incision in the main channel corresponded to high rates of narrowing and lateral channel filling. The analysis of filling processes by Passega diagram and IRLS dating highlight that periods of engineering works were closely related to fine sediment deposition, which present also concomitant heavy metal accumulation. In fact, current fluvial forms, processes and sediment chemistry around the Rohrschollen Island directly reflect the disturbances that occurred during past correction works, and up to today. Our results underscore the advantage of combining functional restoration with detailed knowledge of past-trajectory to: (i) understand the functioning of the hydrosystem prior anthropogenic disturbances, (ii) characterize the human-driven morphodynamic adjustments during the two last centuries, (iii) characterize physio-chemical sediment properties to trace anthropogenic activities and evaluate the potential impact of the restoration on pollutant remobilization, (iv) deduce post-restoration evolution and (v) evaluate efficiency and sustainability of the restoration effects. We anticipate our approach to expand the toolbox of decision-makers and help orientating functional restoration actions in the future.

  12. What makes a sustainability tool valuable, practical and useful in real-world healthcare practice? A mixed-methods study on the development of the Long Term Success Tool in Northwest London.

    Science.gov (United States)

    Lennox, Laura; Doyle, Cathal; Reed, Julie E; Bell, Derek

    2017-09-24

    Although improvement initiatives show benefits to patient care, they often fail to sustain. Models and frameworks exist to address this challenge, but issues with design, clarity and usability have been barriers to use in healthcare settings. This work aimed to collaborate with stakeholders to develop a sustainability tool relevant to people in healthcare settings and practical for use in improvement initiatives. Tool development was conducted in six stages. A scoping literature review, group discussions and a stakeholder engagement event explored literature findings and their resonance with stakeholders in healthcare settings. Interviews, small-scale trialling and piloting explored the design and tested the practicality of the tool in improvement initiatives. National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London (CLAHRC NWL). CLAHRC NWL improvement initiative teams and staff. The iterative design process and engagement of stakeholders informed the articulation of the sustainability factors identified from the literature and guided tool design for practical application. Key iterations of factors and tool design are discussed. From the development process, the Long Term Success Tool (LTST) has been designed. The Tool supports those implementing improvements to reflect on 12 sustainability factors to identify risks to increase chances of achieving sustainability over time. The Tool is designed to provide a platform for improvement teams to share their own views on sustainability as well as learn about the different views held within their team to prompt discussion and actions. The development of the LTST has reinforced the importance of working with stakeholders to design strategies which respond to their needs and preferences and can practically be implemented in real-world settings. Further research is required to study the use and effectiveness of the tool in practice and assess engagement with

  13. [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

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.)

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Long term agro-ecosystem research: The Southern Plains partnership

    Science.gov (United States)

    The USDA Agricultural Research Service (ARS) is coordinating ten well-established research sites as a Long Term Agro-ecosystem Research (LTAR) Network. The goal of the LTAR is to sustain a land-based infrastructure for research, environmental management testing, and education, that enables understan...

  2. Introduction: Long term economic development

    DEFF Research Database (Denmark)

    Pyka, Andreas; Andersen, Esben Sloth

    2012-01-01

    The general theme of the 13th International Joseph A. Schumpeter Society Conference, held during June 21st–24th, 2010 at Aalborg University in Denmark, was the exploration of the interrelated phenomena of innovation, organization, sustainability and crises. By addressing these phenomena an attemp...... was made to confront some of the underexplored parts the Schumpeterian legacy, but there was also room for new results concerning more well-developed parts of evolutionary economics....

  3. Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity.

    Science.gov (United States)

    Hu, Jiangyuan; Adler, Kerry; Farah, Carole Abi; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel

    2017-03-08

    Multiple kinase activations contribute to long-term synaptic plasticity, a cellular mechanism mediating long-term memory. The sensorimotor synapse of Aplysia expresses different forms of long-term facilitation (LTF)-nonassociative and associative LTF-that require the timely activation of kinases, including protein kinase C (PKC). It is not known which PKC isoforms in the sensory neuron or motor neuron L7 are required to sustain each form of LTF. We show that different PKMs, the constitutively active isoforms of PKCs generated by calpain cleavage, in the sensory neuron and L7 are required to maintain each form of LTF. Different PKMs or calpain isoforms were blocked by overexpressing specific dominant-negative constructs in either presynaptic or postsynaptic neurons. Blocking either PKM Apl I in L7, or PKM Apl II or PKM Apl III in the sensory neuron 2 d after 5-hydroxytryptamine (5-HT) treatment reversed persistent nonassociative LTF. In contrast, blocking either PKM Apl II or PKM Apl III in L7, or PKM Apl II in the sensory neuron 2 d after paired stimuli reversed persistent associative LTF. Blocking either classical calpain or atypical small optic lobe (SOL) calpain 2 d after 5-HT treatment or paired stimuli did not disrupt the maintenance of persistent LTF. Soon after 5-HT treatment or paired stimuli, however, blocking classical calpain inhibited the expression of persistent associative LTF, while blocking SOL calpain inhibited the expression of persistent nonassociative LTF. Our data suggest that different stimuli activate different calpains that generate specific sets of PKMs in each neuron whose constitutive activities sustain long-term synaptic plasticity. SIGNIFICANCE STATEMENT Persistent synaptic plasticity contributes to the maintenance of long-term memory. Although various kinases such as protein kinase C (PKC) contribute to the expression of long-term plasticity, little is known about how constitutive activation of specific kinase isoforms sustains long-term

  4. 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.

  5. Long term governance for radioactive waste management. Final report of Cowan2 - work package 4

    International Nuclear Information System (INIS)

    Schneider, Th.; Schieber, C.; Lavele, S.

    2006-12-01

    This report aims at identifying key features for the long term governance of radioactive waste. It is proposed by the COWAN2 Work Package 4 the purpose of which was to identify, discuss and analyse the institutional, ethical, economic and legal considerations raised by long term radioactive waste storage or disposal on the three interrelated issues of: responsibility and ownership of radioactive waste on the long term, continuity of local dialogue between stakeholders and monitoring of radioactive waste management facilities, and compensation and sustainable development. The aim is also to propose guidelines in order to better address long term issues in decision-making processes and start long term governance

  6. Long term governance for radioactive waste management. Final report of Cowan2 - work package 4

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Th.; Schieber, C.; Lavele, S.

    2006-12-15

    This report aims at identifying key features for the long term governance of radioactive waste. It is proposed by the COWAN2 Work Package 4 the purpose of which was to identify, discuss and analyse the institutional, ethical, economic and legal considerations raised by long term radioactive waste storage or disposal on the three interrelated issues of: responsibility and ownership of radioactive waste on the long term, continuity of local dialogue between stakeholders and monitoring of radioactive waste management facilities, and compensation and sustainable development. The aim is also to propose guidelines in order to better address long term issues in decision-making processes and start long term governance

  7. 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.

  8. 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

  9. p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice

    Directory of Open Access Journals (Sweden)

    Lu Lu

    2016-06-01

    Full Text Available Senescent hematopoietic stem cells (HSCs accumulate with age and exposure to stress, such as total-body irradiation (TBI, which may cause long-term myelosuppression in the clinic. However, the methods available for long-term myelosuppression remain limited. Previous studies have demonstrated that sustained p38 mitogen-activated protein kinases (p38 MAPK activation in HSCs following exposure to TBI in mice and the administration of its inhibitor twenty-four hours after TBI may partially prevent long-term myelosuppression. However, long-term myelosuppression is latent and identified long after the administration of radiation. In this study, we investigated the effects of SB203580 (a small molecule inhibitor of p38 MAPK on long-term myelosuppression induced by TBI. Mice with hematopoietic injury were injected intraperitoneally with SB203580 every other day five times beginning 70 days after 6 Gy of 137Cs γ ray TBI. Our results at 80 days demonstrated that SB203580 did not significantly improve the TBI-induced long-term reduction of peripheral blood cell and bone marrow nucleated cell (BMNC counts, or defects in hematopoietic progenitor cells (HPCs and HSC clonogenic function. SB203580 reduced reactive oxygen species (ROS production and p-p38 expression; however, SB203580 had no effect on p16 expression in the HSCs of mice. In conclusion, these findings suggest that treatment with SB203580 70 days after TBI in mice inhibits the ROS-p38 oxidative stress pathway; however, it has no therapeutic effect on long-term myelosuppression induced by TBI.

  10. 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...

  11. 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…

  12. 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.

  13. 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

  14. Defining a communication system for the long term

    International Nuclear Information System (INIS)

    Mitropoulou, Eleni

    2015-01-01

    Prof. Eleni Mitropoulou presented an ongoing study, undertaken on behalf of Andra, on long-term communication. The speaker highlighted that it is not so much the marking that needs to be sustainable, but above all what the marking communicates. She highlighted the importance of sustainable human action to produce memory and, thus, the need to reconcile the passive character of geological disposal and the active character of memory keeping. Focusing on semiotics, the interaction between the short, medium and long term was pointed out, highlighting the need to create a relay system. A multidimensional message was proposed, for the purposes of information ('storage site here'), interpellation (to warn, prevent or alert) and integration (with regard to the surrounding environment). This corresponds to the systemic approach of the RK and M initiative, which is based on a variety of RK and M transmission mechanisms that are integrated with and/or complement one another

  15. Immediate and persistent transcriptional correlates of long-term sensitization training at different CNS loci in Aplysia californica.

    Directory of Open Access Journals (Sweden)

    Samantha Herdegen

    Full Text Available Repeated noxious stimulation produces long-term sensitization of defensive withdrawal reflexes in Aplysia californica, a form of long-term memory that requires changes in both transcription and translation. Previous work has identified 10 transcripts which are rapidly up-regulated after long-term sensitization training in the pleural ganglia. Here we use quantitative PCR to begin examining how these transcriptional changes are expressed in different CNS loci related to defensive withdrawal reflexes at 1 and 24 hours after long-term sensitization training. Specifically, we sample from a the sensory wedge of the pleural ganglia, which exclusively contains the VC nociceptor cell bodies that help mediate input to defensive withdrawal circuits, b the remaining pleural ganglia, which contain withdrawal interneurons, and c the pedal ganglia, which contain many motor neurons. Results from the VC cluster show different temporal patterns of regulation: 1 rapid but transient up-regulation of Aplysia homologs of C/EBP, C/EBPγ, and CREB1, 2 delayed but sustained up-regulation of BiP, Tolloid/BMP-1, and sensorin, 3 rapid and sustained up-regulation of Egr, GlyT2, VPS36, and an uncharacterized protein (LOC101862095, and 4 an unexpected lack of regulation of Aplysia homologs of calmodulin (CaM and reductase-related protein (RRP. Changes in the remaining pleural ganglia mirror those found in the VC cluster at 1 hour but with an attenuated level of regulation. Because these samples had almost no expression of the VC-specific transcript sensorin, our data suggests that sensitization training likely induces transcriptional changes in either defensive withdrawal interneurons or neurons unrelated to defensive withdrawal. In the pedal ganglia, we observed only a rapid but transient increase in Egr expression, indicating that long-term sensitization training is likely to induce transcriptional changes in motor neurons but raising the possibility of different

  16. 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.

  17. The uranium industry: long term planning for short term competition

    International Nuclear Information System (INIS)

    Vottero, X.

    2000-01-01

    Today, uranium producers face new challenges in terms of both production (new regulatory, environmental and social constraints) and market conditions (new sources of uranium supply, very low prices and tough competition). In such a context, long-term planning is not just a prerequisite to survive in the nuclear fuel cycle industry. In fact, it also contributes to sustaining nuclear electricity generation facing fierce competition from other energy sources in increasingly deregulated markets. (authors)

  18. Debt Maturity: Is Long-Term Debt Optimal?

    OpenAIRE

    Laura Alfaro; Fabio Kanczuk

    2007-01-01

    We model and calibrate the arguments in favor and against short-term and long-term debt. These arguments broadly include: maturity premium, sustainability, and service smoothing. We use a dynamic equilibrium model with tax distortions and government outlays uncertainty, and model maturity as the fraction of debt that needs to be rolled over every period. In the model, the benefits of defaulting are tempered by higher future interest rates. We then calibrate our artificial economy and solve fo...

  19. 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

  20. 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

  1. 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...

  2. 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 ...

  3. 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)

  4. 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.

  5. 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...

  6. 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...

  7. Factors influencing long-term adherence to two previously implemented hospital guidelines

    NARCIS (Netherlands)

    Knops, A. M.; Storm-Versloot, M. N.; Mank, A. P. M.; Ubbink, D. T.; Vermeulen, H.; Bossuyt, P. M. M.; Goossens, A.

    2010-01-01

    After successful implementation, adherence to hospital guidelines should be sustained. Long-term adherence to two hospital guidelines was audited. The overall aim was to explore factors accounting for their long-term adherence or non-adherence. A fluid balance guideline (FBG) and body temperature

  8. Long-term effects of HIV treatment in sub-Saharan Africa: from access to quality

    NARCIS (Netherlands)

    Boender, T.S.

    2016-01-01

    As HIV treatment programs in sub-Saharan Africa mature, there are rising concerns about the long-term sustainability and quality of these programs. Increasing levels of HIV drug resistance have been measured in sub-Saharan Africa, and could jeopardize long-term treatment success. This thesis

  9. Long Term Monitoring of Microbial Induced Soil Strengthening Processes

    Science.gov (United States)

    Saneiyan, S.; Ntarlagiannis, D.; Werkema, D. D., Jr.; Colwell, F. S.; Ohan, J.

    2016-12-01

    Soil strengthening/stabilization processes are used to address some of soil quality issues. Microbial induced calcite precipitation (MICP) is a promising soil stabilization process that could offer long term solution by overcoming problems of commonly used methods (e.g. injecting cement slurry). MICP can be applied in larger spatial scales, allowing the enhanced soils to be maintained in an economic sustainable and environmental friendly way. Methods are sought for the long term monitoring of MICP enhanced soils. The spectral induced polarization (SIP) method is one promising method due to sensitivity on such processes and the ability for long term, even autonomous, operation as well as cost effectiveness. Previous laboratory tests showed the sensitivity of the SIP method on soil strengthening as a result of abiotic calcite precipitation. We extended this work to biotic calcite precipitation through MICP. Early results suggest that the MICP formed calcite is denser and could provide improved strengthening capabilities. Our results are supported by geophysical (SIP and shear-wave velocity), geo-chemical and microbiological monitoring. Destructive analysis and visualization (scanning electron imaging - SEM) is expected to provide conclusive evidence on the MICP long term effectiveness.

  10. Issues for the long term management of radioactive waste

    International Nuclear Information System (INIS)

    Schneider, T.; Schieber, C.; Lavelle, S.

    2006-01-01

    High-level radioactive waste are currently managed in interim storage installations, providing an adequate protection of the public and the workers for the short term period. However, the long-term persistence of the radioactivity of the waste gives a new timescale dimension, never experimented by the society for the development of protection systems. In the framework of the European Commission research project 'COWAM-2' (COmmunity WAste Management) dedicated to the governance of radioactive waste management, the issues of 'long term governance' have been addressed by exploring the elements which can contribute to a better integration of the technical and societal time dimensions, taking into account technical, ethical, economic and organizational considerations. The originality of this project is to address the various issues within working groups involving stakeholders from different origins and European countries together with a research team. After a discussion on the time dimensions to be taken into account from the technical and societal perspective, this paper presents, mainly based on the findings of the COWAM-2 project, a brief analysis of the ethical criteria to be considered when future generations are concerned as well as some performance criteria regarding long term governance. Finally, it proposes a discussion on the interest for the radiation protection experts to engage a process with stakeholders concerned by radioactive waste management in order to favour the emergence of a sustainable management responding to the issues at stake and including radiation protection considerations for long term periods. (authors)

  11. Issues for the long term management of radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, T.; Schieber, C. [CEPN, 92 - Fontenay-aux-Roses (France); Lavelle, S. [ICAM, 59 - Lille (France)

    2006-07-01

    High-level radioactive waste are currently managed in interim storage installations, providing an adequate protection of the public and the workers for the short term period. However, the long-term persistence of the radioactivity of the waste gives a new timescale dimension, never experimented by the society for the development of protection systems. In the framework of the European Commission research project 'COWAM-2' (COmmunity WAste Management) dedicated to the governance of radioactive waste management, the issues of 'long term governance' have been addressed by exploring the elements which can contribute to a better integration of the technical and societal time dimensions, taking into account technical, ethical, economic and organizational considerations. The originality of this project is to address the various issues within working groups involving stakeholders from different origins and European countries together with a research team. After a discussion on the time dimensions to be taken into account from the technical and societal perspective, this paper presents, mainly based on the findings of the COWAM-2 project, a brief analysis of the ethical criteria to be considered when future generations are concerned as well as some performance criteria regarding long term governance. Finally, it proposes a discussion on the interest for the radiation protection experts to engage a process with stakeholders concerned by radioactive waste management in order to favour the emergence of a sustainable management responding to the issues at stake and including radiation protection considerations for long term periods. (authors)

  12. Neural correlates of long-term intense romantic love.

    Science.gov (United States)

    Acevedo, Bianca P; Aron, Arthur; Fisher, Helen E; Brown, Lucy L

    2012-02-01

    The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system, such as the ventral tegmental area (VTA) and dorsal striatum, consistent with results from early-stage romantic love studies; and (ii) several regions implicated in maternal attachment, such as the globus pallidus (GP), substantia nigra, Raphe nucleus, thalamus, insular cortex, anterior cingulate and posterior cingulate. Correlations of neural activity in regions of interest with widely used questionnaires showed: (i) VTA and caudate responses correlated with romantic love scores and inclusion of other in the self; (ii) GP responses correlated with friendship-based love scores; (iii) hypothalamus and posterior hippocampus responses correlated with sexual frequency; and (iv) caudate, septum/fornix, posterior cingulate and posterior hippocampus responses correlated with obsession. Overall, results suggest that for some individuals the reward-value associated with a long-term partner may be sustained, similar to new love, but also involves brain systems implicated in attachment and pair-bonding.

  13. Neural correlates of long-term intense romantic love

    Science.gov (United States)

    Aron, Arthur; Fisher, Helen E.; Brown, Lucy L.

    2012-01-01

    The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system, such as the ventral tegmental area (VTA) and dorsal striatum, consistent with results from early-stage romantic love studies; and (ii) several regions implicated in maternal attachment, such as the globus pallidus (GP), substantia nigra, Raphe nucleus, thalamus, insular cortex, anterior cingulate and posterior cingulate. Correlations of neural activity in regions of interest with widely used questionnaires showed: (i) VTA and caudate responses correlated with romantic love scores and inclusion of other in the self; (ii) GP responses correlated with friendship-based love scores; (iii) hypothalamus and posterior hippocampus responses correlated with sexual frequency; and (iv) caudate, septum/fornix, posterior cingulate and posterior hippocampus responses correlated with obsession. Overall, results suggest that for some individuals the reward-value associated with a long-term partner may be sustained, similar to new love, but also involves brain systems implicated in attachment and pair-bonding. PMID:21208991

  14. 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

  15. 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.

  16. 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.

  17. GIS Operations at the U.S. Department of Energy’s Hanford Site: A Review of the Current Status and a Proposed Action to Ensure Long-Term Data Sustainability

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, Andre M.; Webber, William D.

    2005-07-27

    This paper provides a current state of spatial data collections, use, management, and challenges at the Hanford Site through the use and development of a Spatial Data Infrastructure. Recommendations designed to ensure data quality, usability and sustainability now and into the future are presented.

  18. 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...

  19. 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.

  20. Samish Indian Nation Long-Term Strategic Energy Plan

    Energy Technology Data Exchange (ETDEWEB)

    Christine Woodward; B. Beckley; K. Hagen

    2005-06-30

    The Tribes strategic energy planning effort is divided into three phases: (1) Completing an Energy Resource Assessment; (2) Developing a Long-Term Strategic Energy Plan; and (3) Preparing a Strategic Energy Implementation Plan for the Samish Homelands. The Samish Indian Nation developed a comprehensive Strategic Energy plan to set policy for future development on tribal land that consists of a long-term, integrated, systems approach to providing a framework under which the Samish Community can use resources efficiently, create energy-efficient infrastructures, and protect and enhance quality of life. Development of the Strategic Energy plan will help the Samish Nation create a healthy community that will sustain current and future generations by addressing economic, environmental, and social issues while respecting the Samish Indian Nation culture and traditions.

  1. 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)

  2. 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.

  3. 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.

  4. 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...

  5. 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.)

  6. 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.

  7. 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...

  8. 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

  9. 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....

  10. 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

  11. 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

  12. 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

  13. 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…

  14. 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

  15. 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

  16. 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

  17. 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...

  18. 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

  19. 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

  20. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

    Science.gov (United States)

    Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

    2016-01-01

    Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

  1. CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells

    Science.gov (United States)

    Kim, Jiyeon; Seandel, Marco; Falciatori, Ilaria; Wen, Duancheng; Rafii, Shahin

    2010-01-01

    Stem cells reside in specialized microenvironments created by supporting stromal cells that orchestrate self-renewal and lineage-specific differentiation. However, the precise identity of the cellular and molecular pathways that support self-renewal of stem cells is not known. For example, long-term culture of prototypical stem cells, such as adult spermatogonial stem and progenitor cells (SPCs), in vitro has been impeded by the lack of an optimal stromal cell line that initiates and sustains proliferation of these cells. Indeed, current methods, including the use of mouse embryonic fibroblasts (MEFs), have not been efficient and have generally led to inconsistent results. Here, we report the establishment of a novel CD34-positive cell line, referred to as JK1, derived from mouse testicular stromal cells that not only facilitated long-term SPC culture but also allowed faithful generation of SPCs and multipotent stem cells. SPCs generated on JK1 maintained key features of germ line stem cells, including expression of PLZF, DAZL, and GCNA. Furthermore, these feeders also promoted the long-term cultivation of other types of primitive cells including multi-potent adult spermatogonial-derived stem cells, pluripotent murine embryonic stem cells, and embryonic germ cells derived from primordial germ cells. Stem cells could be passaged serially and still maintained expression of characteristic markers such as OCT4 and NANOG in vitro, as well as the ability to generate all three germ layers in vivo. These results indicate that the JK1 cell line is capable of promoting long-term culture of primitive cells. As such, this cell line allows for identification of stromal-derived factors that support long-term proliferation of various types of stem cells and constitutes a convenient alternative to other types of feeder layers. PMID:18669907

  2. Antimicrobial stewardship in long term care facilities: what is effective?

    Science.gov (United States)

    Nicolle, Lindsay E

    2014-02-12

    Intense antimicrobial use in long term care facilities promotes the emergence and persistence of antimicrobial resistant organisms and leads to adverse effects such as C. difficile colitis. Guidelines recommend development of antimicrobial stewardship programs for these facilities to promote optimal antimicrobial use. However, the effectiveness of these programs or the contribution of any specific program component is not known. For this review, publications describing evaluation of antimicrobial stewardship programs for long term care facilities were identified through a systematic literature search. Interventions included education, guidelines development, feedback to practitioners, and infectious disease consultation. The studies reviewed varied in types of facilities, interventions used, implementation, and evaluation. Comprehensive programs addressing all infections were reported to have improved antimicrobial use for at least some outcomes. Targeted programs for treatment of pneumonia were minimally effective, and only for indicators of uncertain relevance for stewardship. Programs focusing on specific aspects of treatment of urinary infection - limiting treatment of asymptomatic bacteriuria or prophylaxis of urinary infection - were reported to be effective. There were no reports of cost-effectiveness, and the sustainability of most of the programs is unclear. There is a need for further evaluation to characterize effective antimicrobial stewardship for long term care facilities.

  3. Designing indicators of long-term energy supply security

    International Nuclear Information System (INIS)

    Jansen, J.C.; Van Arkel, W.G.; Boots, M.G.

    2004-01-01

    To our knowledge, so far amazingly little research work has been undertaken to construct meaningful indicators of long-run energy supply security for a particular nation or region. Currently, in addressing energy supply security, policy makers tend to emphasise short-term supply disruptions. In contrast, this pre-study accords with the broader Sustainability Outlook in considering the long-term perspective. This report starts with taking stock, in a concise way, of the official EU energy outlook and issues related to the opportunities to administer changes in the energy mix at the level of major energy use categories. Then a brief survey of relevant literature is made on long-term strategies to ensure survival of systems - be it biological, social, etc. - in an environment largely characterised by high uncertainty and a lot of unchartered territory. We found the work of Andrew Stirling very inspiring in this context. Based on his work and considering the limitations of the present research activity, we retained the Shannon index as the best 'simple' indicator of diversity. In the core of the report, the Shannon index is elaborated into four indicators of long-term energy supply security. Stepwise, additional aspects of long-term energy supply security are introduced. These aspects are: Diversification of energy sources in energy supply; Diversification of imports with respect to imported energy sources; Long-term political stability in regions of origin; The resource base in regions of origin, including the home region/country itself. After small adjustments to allow for data availability, these indicators were applied to the reference year 2030 of four long-term scenarios with data of base year 1995 and projections for underlying variables provided by the Netherlands Environmental Assessment Agency (MNP). Preliminary interpretation of the results suggests the usefulness of the indicators presented in this report. A second activity undertaken in this report was

  4. Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.

    Science.gov (United States)

    Hullinger, Rikki; O'Riordan, Kenneth; Burger, Corinna

    2015-11-01

    Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 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.

  6. 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)

  7. 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.

  8. 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...

  9. 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.

  10. 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.)

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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)

  16. 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...

  17. 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...

  18. 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....

  19. 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,...

  20. 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.

  1. 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

  2. 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)

  3. 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.

  4. Long-term deflection and flexural behavior of reinforced concrete beams with recycled aggregate

    International Nuclear Information System (INIS)

    Choi, Won-Chang; Yun, Hyun-Do

    2013-01-01

    Highlights: • Long-term deformation of recycled aggregate concrete beams was examined. • Three beams were monitored for over 380 days. • Influence of recycled aggregate on the long-term performance. • Comparison of that between normal and recycled aggregate concrete beams. - Abstract: This paper presents experimental results on the long-term deformations of recycled aggregate concrete (RAC) beams for over 1 year (380 days) and flexural behavior of RAC beams after exposure to sustained loading. Three reinforced concrete (RC) beam specimens were fabricated with replacement percentage of aggregate (100% natural aggregate, 100% recycled coarse aggregate, and 50% recycled fine aggregate) and subjected to sustained loading that is 50% of the nominal flexural capacity. During the sustained loading period (380 days), the long-term deflection due to creep and shrinkage was recorded and compared with predicted behavior that was determined based on current specifications (ACI 318 Code). After measuring the long-term deflection for 380 days, four-point bending tests were conducted to investigate the flexural behavior of RC beams after exposure to sustained loading and determine any reduction in flexural capacity. A modified equation to predict the long-term deflection values for RC beams with recycled aggregate is proposed, and the experimental results are compared with the predictions calculated using the ACI 318 Code provisions

  5. 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...

  6. Long-term Agroecosystem Research in the Northern Great Plains.

    Science.gov (United States)

    Schmer, M.; Sanderson, M.; Liebig, M. A.; Wienhold, B.; Awada, T.; Papiernik, S.; Osborne, S.; Kemp, W.; Okalebo, J. A.; Riedall, W.

    2015-12-01

    The Northern Great Plains is the bread basket of the United States, accounting for a substantial portion of U.S. agricultural production. This region faces critical challenges regarding balancing food needs, resource conservation (e.g Ogallala aquifer), environmental concerns, and rural economy development. Developing transformative, multifunctional systems will require equally imaginative and efficient tools to help farmers manage complex agroecosystems in a rapidly changing climate. The Northern Plains long-term agroecosystem research (LTAR) site at Mandan, ND and the Platte River High Plains LTAR (ARS/University of Nebraska-Lincoln) at Lincoln, NE in collaboration with USDA-ARS research units in Brookings, SD and Fargo, ND are collaborating to address the grand challenge of providing and sustaining multiple service provisions from Northern Great Plains agroecosystems. We propose to attain these goals through sustainable intensification based on the adoption of conservation agriculture principles including reduced soil disturbance, livestock integration, and greater complexity and diversity in the cropping system. Here, we summarize new concepts these locations have pioneered in dynamic cropping systems, resource use efficiency, and agricultural management technologies. As part of the LTAR network, we will conduct long-term cross-site research to design and assess new agricultural practices and systems aimed at improving our understanding of decision making processes and outcomes across an array of agricultural systems.

  7. Resuming growth in Latin America: short and long term policies

    Directory of Open Access Journals (Sweden)

    Julio Lopez G.

    2008-09-01

    Full Text Available The authors of this paper assert that the paralysis of the state generated by the crises of the 1970s and 1980s deprived the economies of the region of an important lever to resume and sustain growth. They thus maintain that to overcome stagnation it will be necessary to reconstruct the state's capacity to implement pro-growth policies. Following Keynes and Kalecki's ideas, but also classical development economists, the authors argue, first, that short-term macroeconomic policies, to reduce unemployment and to increase the degree of capacity utilization, should be used to promote the generation of profits to firms and to wake up entrepreneurs' animal spirits. Short-term expansionary policies should be coupled with measures to improve competitiveness and avoid balance of payments problems. They also claim that alternatives to the liberal programme will fail unless a pro-growth strategy is adopted which includes both short- and long-term policies. They thus propose that long-term policies must complete the package, signaling: a sustained increases of effective demand in the future; and b investment priorities to ensure that capacities will be created in strategic sectors and branches of the economy.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Effective Moment Of Inertia And Deflections Of Reinforced Concrete Beams Under Long-Term Loading

    OpenAIRE

    Mahmood, Khalid M.; Ashour, Samir A.; Al-Noury, Soliman I.

    1995-01-01

    The paper presents a method for estimating long-term deflections of reinforced concrete beams by considering creep and shrinkage effects separately. Based on equilibrium and compatibility conditions a method is developed for investigating the properties of a cracked transformed section under sustained load. The concept of effective moment of inertia is extended to predict initial-plus-creep deflections. Long-term deflections computed by the proposed method are compared with the experimental r...

  13. A study on shear behavior of R/C beams subjected to long-term heating

    International Nuclear Information System (INIS)

    Maruta, M.; Yamazaki, M.

    1993-01-01

    In nuclear power plants, many structural members are subjected to long term heating. There are few experimental data available on the behavior especially in shear of reinforced concrete (R/C) members subjected to long term heating. This paper describes a study aimed at experimentally determining the shear behavior of R/C members in nuclear power plant facilities following sustained heating at high temperatures

  14. 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.

  15. 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)

  16. 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.

  17. 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...

  18. 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...

  19. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    Science.gov (United States)

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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.)

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.)

  8. 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.

  9. 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

  10. 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.

  11. Sustainable Software Decisions for Long-term Projects (Invited)

    Science.gov (United States)

    Shepherd, A.; Groman, R. C.; Chandler, C. L.; Gaylord, D.; Sun, M.

    2013-12-01

    Adopting new, emerging technologies can be difficult for established projects that are positioned to exist for years to come. In some cases the challenge lies in the pre-existing software architecture. In others, the challenge lies in the fluctuation of resources like people, time and funding. The Biological and Chemical Oceanography Data Management Office (BCO-DMO) was created in late 2006 by combining the data management offices for the U.S. GLOBEC and U.S. JGOFS programs to publish data for researchers funded by the National Science Foundation (NSF). Since its inception, BCO-DMO has been supporting access and discovery of these data through web-accessible software systems, and the office has worked through many of the challenges of incorporating new technologies into its software systems. From migrating human readable, flat file metadata storage into a relational database, and now, into a content management system (Drupal) to incorporating controlled vocabularies, new technologies can radically affect the existing software architecture. However, through the use of science-driven use cases, effective resource management, and loosely coupled software components, BCO-DMO has been able to adapt its existing software architecture to adopt new technologies. One of the latest efforts at BCO-DMO revolves around applying metadata semantics for publishing linked data in support of data discovery. This effort primarily affects the metadata web interface software at http://bco-dmo.org and the geospatial interface software at http://mapservice.bco-dmo.org/. With guidance from science-driven use cases and consideration of our resources, implementation decisions are made using a strategy to loosely couple the existing software systems to the new technologies. The results of this process led to the use of REST web services and a combination of contributed and custom Drupal modules for publishing BCO-DMO's content using the Resource Description Framework (RDF) via an instance of the Virtuoso Open-Source triplestore.

  12. Long-term outcomes of vertebroplasty for osteoporotic compression fractures

    International Nuclear Information System (INIS)

    Thillainadesan, G.; Schlaphoff, G.; Gibson, K.A.; Hassett, G.M.; McNeil, H.P.

    2010-01-01

    This study aimed to determine outcomes of percutaneous vertebroplasty for osteoporotic vertebral compression fractures (VCFs). Prospective assessment of short-term (≤6 weeks), medium-term (6 months) and long-term (29 months) outcomes of vertebroplasty, followed by a retrospective long-term follow-up of patients treated with vertebroplasty compared with conservative therapy. Outcomes measured were visual analogue scale pain scores, analgesic use, disability scores using the Roland Morris Disability questionnaire and a number of new VCFs. In 27 patients with acute VCFs followed prospectively, vertebroplasty resulted in significant reductions in pain levels (56-mm reduction on a 100-mm scale) and disability scores (11.8-point reduction on a 24-point scale) at all follow-up points up to a mean of 29 months compared with pre-vertebroplasty levels (P < 0.001). Analgesic use was significantly less intense in the short and medium term after vertebroplasty (P < 0.005). In 25 patients who had vertebroplasty for VCF, a sustained reduction in all outcomes was demonstrated at a mean follow-up of 30 months, with less pain, significantly lower disability scores (P < 0.05) and less analgesic use (P < 0.05) compared with nine conservatively treated subjects. During the follow-up period, six new VCFs occurred in 4/25 vertebroplasty patients compared with four new VCFs in 2/9 control subjects. Vertebroplasty provides significant and clinically meaningful reductions in pain, analgesic use, and disability in the short, medium and long term. Compared with conservative therapy, vertebroplasty provides significantly greater functional improvement and reduction in analgesic use. The procedure is relatively safe with no clearly increased risk of new vertebral fractures.

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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.)

  20. 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

  1. 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.

  2. 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...

  3. 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....

  4. 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...

  5. 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

  6. 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

  7. Long-term bioventing performance in low-permeability soils

    International Nuclear Information System (INIS)

    Phelps, M.B.; Stanin, F.T.; Downey, D.C.

    1995-01-01

    Short-term and long-term bioventing treatability testing has shown that in situ air injection and extraction is a practical method for sustaining increased oxygen levels and enhancing aerobic biodegradation of petroleum hydrocarbons in low-permeability soils. At several test sites, initial physical parameter analysis of soils and air permeability tests indicated that impacted soils (fine sandy silts and clays) had low air permeabilities. Measurements of depleted soil-gas oxygen levels and increased soil-gas carbon dioxide levels indicated that the natural process of aerobic biodegradation of petroleum hydrocarbons was oxygen-limited. Initial treatability testing consisted of air permeability tests to measure the permeability of the soils to air and in situ respiration tests to measure the rates at which native microorganisms could biodegrade the contaminants when provided with sufficient oxygen. During the long-term treatment period, active air injection or extraction systems were operated for 1 year or longer. Soil gas was periodically monitored within the treatment zone to evaluate the success of the bioventing systems in increasing soil-gas oxygen levels in the low-permeability soils. Follow-up respiration tests and soil and soil-gas sampling were conducted to evaluate changes in respiration rates and contaminant concentrations with time

  8. [The Development of Long-Term Care Policies and the Impact on Nursing].

    Science.gov (United States)

    Wu, Shiao-Chi; Tsai, Yin-Yin; Yeh, Shin-Ting

    2015-10-01

    The government must reform and enhance current medical and long-term care services in order to respond effectively to societal ageing and labor shortage trends and to ensure sustainable operations. The post-acute care system should be reoriented on the home and community instead of the hospital. The Long Term Care Service Act integrates long-term care services that were previously dispersed amongst different departments, sets up a long-term care development fund, and improves the quality and allocation of long-term care services. Moreover, the Long Term Care Insurance Act will implement a bundle payment system to assist disabled families. The integration of automation and information technology will make long-term care more efficient. Although nurses are more skilled at elderly care and counseling than other community care professionals, nurses generally lack training in business management. Home and community-based services thus require better-trained manpower, opportunities to set care agents, and opportunities to offer flexible caring jobs. Therefore, nurses should strengthen their capabilities in post-acute care, business management, cooperation, and coordination.

  9. 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.

  10. Is there an upward long term trend in Danish real house prices?

    DEFF Research Database (Denmark)

    Skak, Morten

    2012-01-01

    In Denmark, like in other countries, there is no agreement on the fundamental long term path of real house prices and the sustainability of the present price level. The paper presents Danish house price indices and discusses the question of quality correction of the indices. Subsequently, factors...... behind the long term trend in real house prices and its sustainability are discussed. The paper finds an annual real growth trend around 1.5 per cent for Danish single family house prices likely for the coming ten years....

  11. Effect of long-term selenium supplementation on mortality

    DEFF Research Database (Denmark)

    Rayman, Margaret P.; Winther, Kristian Hillert; Pastor-Barriuso, Roberto

    2018-01-01

    Background: Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ∼ 125 μg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained...... concentrations higher than this are beneficial, or indeed detrimental, is unknown. Objective: In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels. Design: The Denmark PRECISE study was a single...... for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 μg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were followed up for mortality for a further 10 years (through March 31, 2015...

  12. The environment in the Netherlands in the long-term

    International Nuclear Information System (INIS)

    Wieringa, K.; Maas, R.

    1992-01-01

    The environmental problem is one of the central elements in the newest long-term scenarios of the CPB (Dutch Central Planning Bureau). Will the environmental problems limit the economic growth for the next 25 years? Or can growth of production and consumption be combined with the environmental aims as formulated in the National Environmental Policy (NMP in Dutch). Being a preliminary study on the third National Environmental Outlook (to be published in 1993) the governmental institute for public health and environmental hygiene (RIVM) calculated the environmental impacts in the scenarios developed by the CPB. In particular attention is paid to the costs of the planned environmental policy. The scenarios discussed are Balanced Growth, characterized by a strong economic growth, sustainable economic development, and a dynamic technological development, the Global Shift scenario, characterized by a very dynamic technological development, and the European Renaissance scenario with a less dynamic development. 2 figs., 1 tab

  13. 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

  14. 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...

  15. 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....

  16. 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.

  17. [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.

  18. 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)

  19. 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.

  20. 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