rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

Science.gov (United States)

Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

2017-08-01

Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

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Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Datta, Soma [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Bhattacharya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India)]. E-mail: shibnath1@yahoo.co.in

2007-02-15

The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 {mu}M) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.

Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

International Nuclear Information System (INIS)

Ghosh, Debabrata; Datta, Soma; Bhattacharya, Shelley; Mazumder, Shibnath

2007-01-01

The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 μM) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge

In Vitro Experimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells.

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Hagiwara, Masaya; Maruta, Naomichi; Marumoto, Moegi

2017-06-01

Lung branching morphogenesis has been studied for decades, but the underlying developmental mechanisms are still not fully understood. Cellular movements dynamically change during the branching process, but it is difficult to observe long-term cellular dynamics by in vivo or tissue culture experiments. Therefore, developing an in vitro experimental model of bronchial tree would provide an essential tool for developmental biology, pathology, and systems biology. In this study, we succeeded in reconstructing a bronchial tree in vitro by using primary human bronchial epithelial cells. A high concentration gradient of bronchial epithelial cells was required for branching initiation, whereas homogeneously distributed endothelial cells induced the formation of successive branches. Subsequently, the branches grew in size to the order of millimeter. The developed model contains only two types of cells and it facilitates the analysis of lung branching morphogenesis. By taking advantage of our experimental model, we carried out long-term time-lapse observations, which revealed self-assembly, collective migration with leader cells, rotational motion, and spiral motion of epithelial cells in each developmental event. Mathematical simulation was also carried out to analyze the self-assembly process and it revealed simple rules that govern cellular dynamics. Our experimental model has provided many new insights into lung development and it has the potential to accelerate the study of developmental mechanisms, pattern formation, left-right asymmetry, and disease pathogenesis of the human lung.

Assessing long-term effects of demand response policies in wholesale electricity markets

International Nuclear Information System (INIS)

Cepeda, Mauricio; Saguan, Marcelo

2014-05-01

This paper deals with the practical problems related to long-term issues in electricity markets in the presence of demand response development. Different policies have been implemented around the world aiming to develop demand response potential. Externalities, in particular the CO_2 externality, have been one of the key elements in the debate on the effectiveness of different policies regarding demand response development. Policy makers have several options to deal with this externality. The most direct one is to correct the externality by setting a CO_2 price at a level that corresponds to the cost to society of the corresponding CO_2 emissions. One alternative solution could be to subsidize carbon-free technologies as demand response. In this paper we examine potential long-term impacts of these two policies. We rely on a long-term market simulation model that characterizes expansion decisions in a competitive regime. We test for each policy two different scenarios regarding the possibility of internalization of the CO_2 externality. The results show that differences in development policies affect both investments and social costs in the wholesale electricity market and confirm previous findings that a market-driven development of demand response with the internalization of the CO_2 externality is the most efficient approach. (authors)

Facile, Large-Quantity Synthesis of Stable, Tunable-Color Silicon Nanoparticles and Their Application for Long-Term Cellular Imaging.

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Zhong, Yiling; Sun, Xiaotian; Wang, Siyi; Peng, Fei; Bao, Feng; Su, Yuanyuan; Li, Youyong; Lee, Shuit-Tong; He, Yao

2015-06-23

We herein introduce a facile, low-cost photochemical method capable of rapid (nanoparticles (SiNPs) of tunable optical properties (peak emission wavelength in the range of 470-560 nm) under ambient air conditions, by introducing 1,8-naphthalimide as a reducing agent and surface ligands. The as-prepared SiNPs feature robust storage stability and photostability preserving strong and stable fluorescent during long-term (>3 h) high-power UV irradiation, in contrast to the rapid fluorescence quenching within 2 h of conventional organic dyes and II-VI quantum dots under the same conditions. The as-prepared SiNPs serving as photostable nanoprobes are workable for cellular imaging in long-term manners. Our findings provide a powerful method for mild-condition and low-cost, large-quantity production of highly fluorescent and photostable SiNPs for various promising applications.

Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory.

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Sigurdsson, Torfi; Doyère, Valérie; Cain, Christopher K; LeDoux, Joseph E

2007-01-01

Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory.

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.

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

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Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

2016-01-01

Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

Method and Apparatus for a Miniature Bioreactor System for Long-Term Cell Culture

Science.gov (United States)

Kleis, Stanley J. (Inventor); Geffert, Sandra K. (Inventor); Gonda, Steve R. (Inventor)

2015-01-01

A bioreactor and method that permits continuous and simultaneous short, moderate, or long term cell culturing of one or more cell types or tissue in a laminar flow configuration is disclosed, where the bioreactor supports at least two laminar flow zones, which are isolated by laminar flow without the need for physical barriers between the zones. The bioreactors of this invention are ideally suited for studying short, moderate and long term studies of cell cultures and the response of cell cultures to one or more stressors such as pharmaceuticals, hypoxia, pathogens, or any other stressor. The bioreactors of this invention are also ideally suited for short, moderate or long term cell culturing with periodic cell harvesting and/or medium processing for secreted cellular components.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

Science.gov (United States)

Wahie, S; Meggitt, S J

2013-09-01

The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease

Reconstruction of mouse testicular cellular microenvironments in long-term seminiferous tubule culture.

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Juho-Antti Mäkelä

Full Text Available Research on spermatogonia is hampered by complex architecture of the seminiferous tubule, poor viability of testicular tissue ex vivo and lack of physiologically relevant long-term culture systems. Therefore there is a need for an in vitro model that would enable long term survival and propagation of spermatogonia. We aimed at the most simplified approach to enable all different cell types within the seminiferous tubules to contribute to the creation of a niche for spermatogonia. In the present study we describe the establishment of a co-culture of mouse testicular cells that is based on proliferative and migratory activity of seminiferous tubule cells and does not involve separation, purification or differential plating of individual cell populations. The co-culture is composed of the constituents of testicular stem cell niche: Sertoli cells [identified by expression of Wilm's tumour antigen 1 (WT1 and secretion of glial cell line-derived neurotrophic factor, GDNF], peritubular myoid cells (expressing alpha smooth muscle actin, αSMA and spermatogonia [expressing MAGE-B4, PLZF (promyelocytic leukaemia zinc finger, LIN28, Gpr125 (G protein-coupled receptor 125, CD9, c-Kit and Nanog], and can be maintained for at least five weeks. GDNF was found in the medium at a sufficient concentration to support proliferating spermatogonial stem cells (SSCs that were able to start spermatogenic differentiation after transplantation to an experimentally sterile recipient testis. Gdnf mRNA levels were elevated by follicle-stimulating hormone (FSH which shows that the Sertoli cells in the co-culture respond to physiological stimuli. After approximately 2-4 weeks of culture a spontaneous formation of cord-like structures was monitored. These structures can be more than 10 mm in length and branch. They are formed by peritubular myoid cells, Sertoli cells, fibroblasts and spermatogonia as assessed by gene expression profiling. In conclusion, we have managed to

Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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Nesrina eImami

2013-03-01

Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

Determinants of Private Long-Term Care Insurance Purchase in Response to the Partnership Program.

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Lin, Haizhen; Prince, Jeffrey T

2016-04-01

To assess three possible determinants of individuals' response in their private insurance purchases to the availability of the Partnership for Long-Term Care (PLTC) insurance program: bequest motives, financial literacy, and program awareness. The health and retirement study (HRS) merged with data on states' implementation of the PLTC program. Individual-level decision on private long-term care insurance is regressed on whether the PLTC program is being implemented for a given state-year, asset dummies, policy determinant variable, two-way and three-way interactions of these variables, and other controls, using fixed effects panel regression. Analysis used a sample between 50 and 69 years of age from 2002 to 2010, resulting in 12,695 unique individuals with a total of 39,151 observations. We find mild evidence that intent to bequest influences individual purchase of insurance. We also find that program awareness is necessary for response, while financial literacy notably increases responsiveness. Increasing response to the PLTC program among the middle class (the stated target group) requires increased efforts to create awareness of the program's existence and increased education about the program's benefits, and more generally, about long-term care risks and needs. © Health Research and Educational Trust.

Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

Science.gov (United States)

Yiqi Luo; Jerry Melillo; Shuli Niu; Claus Beier; James S. Clark; Aime E.T. Classen; Eric Dividson; Jeffrey S. Dukes; R. Dave Evans; Christopher B. Field; Claudia I. Czimczik; Michael Keller; Bruce A. Kimball; Lara M. Kueppers; Richard J. Norby; Shannon L. Pelini; Elise Pendall; Edward Rastetter; Johan Six; Melinda Smith; Mark G. Tjoelker; Margaret S. Torn

2011-01-01

Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation of nutrient capitals. Understanding and predicting these processes...

Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types.

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Blum, Allison L; Li, Wanhe; Cressy, Mike; Dubnau, Josh

2009-08-25

A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.

Changes in the long-term delayed response of platinum self-powered detector with irradiation

International Nuclear Information System (INIS)

Parent, G.; Serdula, K.J.; Eng, P.

1989-01-01

Two long-term delayed response characteristics have been observed for platinum, Pt, detectors in the Gentilly-2 600 MW(e) CANDU PHWR reactor. The first effect is a dip in the signal two to three hours after a shutdown, due to the (n,beta) interactions of Mn-55 and Ni-64 which exist as impurities in the detector assembly. The second effect is an increase of the delayed fraction of the signal. The low neutron absorption cross-section of Pt-196 combined with the conversion of the Pt-194 and Pt-195 results in build-up of the Pt-196. The long half-lives associated with the beta-emission in the transmutation of Pt-196 to Hg-198 or Hg-199 give rise to the observed long-term delayed response

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

Science.gov (United States)

Finsterwald, Charles; Alberini, Cristina M

2014-07-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

Science.gov (United States)

Finsterwald, Charles; Alberini, Cristina M.

2013-01-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

Long-term potentiation and olfactory memory formation in the carp (Cyprinus carpio L.) olfactory bulb.

Science.gov (United States)

Satou, M; Anzai, S; Huruno, M

2005-05-01

Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract-long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting 1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).

Characterization of the rapid transcriptional response to long-term sensitization training in Aplysia californica.

Science.gov (United States)

Herdegen, Samantha; Holmes, Geraldine; Cyriac, Ashly; Calin-Jageman, Irina E; Calin-Jageman, Robert J

2014-12-01

We used a custom-designed microarray and quantitative PCR to characterize the rapid transcriptional response to long-term sensitization training in the marine mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to one side of the body, a procedure known to induce a long-lasting, transcription-dependent increase in reflex responsiveness that is restricted to the side of training. One hour after training, pleural ganglia from the trained and untrained sides of the body were harvested; these ganglia contain the sensory nociceptors which help mediate the expression of long-term sensitization memory. Microarray analysis from 8 biological replicates suggests that long-term sensitization training rapidly regulates at least 81 transcripts. We used qPCR to test a subset of these transcripts and found that 83% were confirmed in the same samples, and 86% of these were again confirmed in an independent sample. Thus, our new microarray design shows strong convergent and predictive validity for analyzing the transcriptional correlates of memory in Aplysia. Fully validated transcripts include some previously identified as regulated in this paradigm (ApC/EBP and ApEgr) but also include novel findings. Specifically, we show that long-term sensitization training rapidly up-regulates the expression of transcripts which may encode Aplysia homologs of a C/EBPγ transcription factor, a glycine transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36). Copyright © 2014 Elsevier Inc. All rights reserved.

Brief, pre-retrieval stress differentially influences long-term memory depending on sex and corticosteroid response.

Science.gov (United States)

Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Burke, Hanna M; Woelke, Sarah A; Pisansky, Julia M; Talbot, Jeffery N

2014-03-01

Previous work has indicated that stress generally impairs memory retrieval. However, little research has addressed discrepancies that exist in this line of work and the factors that could explain why stress can exert differential effects on retrieval processes. Therefore, we examined the influence of brief, pre-retrieval stress that was administered immediately before testing on long-term memory in males and females. Participants learned a list of 42 words varying in emotional valence and arousal. Following the learning phase, participants were given an immediate free recall test. Twenty-four hours later, participants submerged their non-dominant hand in a bath of ice cold (Stress) or warm (No Stress) water for 3 min. Immediately following this manipulation, participants' memory for the word list was assessed via free recall and recognition tests. We observed no group differences on short-term memory. However, male participants who showed a robust cortisol response to the stress exhibited enhanced long-term recognition memory, while male participants who demonstrated a blunted cortisol response to the stress exhibited impaired long-term recall and recognition memory. These findings suggest that the effects of brief, pre-retrieval stress on long-term memory are sex-specific and mediated by corticosteroid mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

Science.gov (United States)

Jiang, Dong-Bo; Zhang, Jin-Peng; Cheng, Lin-Feng; Zhang, Guan-Wen; Li, Yun; Li, Zi-Chao; Lu, Zhen-Hua; Zhang, Zi-Xin; Lu, Yu-Chen; Zheng, Lian-He; Zhang, Fang-Lin; Yang, Kun

2018-02-01

Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be

Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

Science.gov (United States)

Doronina-Amitonova, L. V.; Fedotov, I. V.; Ivashkina, O. I.; Zots, M. A.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2013-01-01

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli. PMID:24253232

The effects of short-term and long-term learning on the responses of lateral intraparietal neurons to visually presented objects.

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Sigurdardottir, Heida M; Sheinberg, David L

2015-07-01

The lateral intraparietal area (LIP) is thought to play an important role in the guidance of where to look and pay attention. LIP can also respond selectively to differently shaped objects. We sought to understand to what extent short-term and long-term experience with visual orienting determines the responses of LIP to objects of different shapes. We taught monkeys to arbitrarily associate centrally presented objects of various shapes with orienting either toward or away from a preferred spatial location of a neuron. The training could last for less than a single day or for several months. We found that neural responses to objects are affected by such experience, but that the length of the learning period determines how this neural plasticity manifests. Short-term learning affects neural responses to objects, but these effects are only seen relatively late after visual onset; at this time, the responses to newly learned objects resemble those of familiar objects that share their meaning or arbitrary association. Long-term learning affects the earliest bottom-up responses to visual objects. These responses tend to be greater for objects that have been associated with looking toward, rather than away from, LIP neurons' preferred spatial locations. Responses to objects can nonetheless be distinct, although they have been similarly acted on in the past and will lead to the same orienting behavior in the future. Our results therefore indicate that a complete experience-driven override of LIP object responses may be difficult or impossible. We relate these results to behavioral work on visual attention.

Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

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Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

2016-06-01

Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

A single exposure to severe stressors causes long-term desensitisation of the physiological response to the homotypic stressor.

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Armario, Antonio; Vallès, Astrid; Dal-Zotto, Silvina; Márquez, Cristina; Belda, Xavier

2004-09-01

Although some laboratories have reported that a single session of stress is able to induce a long-lasting sensitisation of the hypothalamic-pituitary-adrenal (HPA) response to further exposures to stress, we have found that a single exposure to severe emotional (immobilisation, restraint or shock) or systemic (endotoxin) stressors reduces the responsiveness of the HPA to the same, but not to a novel (heterotypic), stressor, in which case a slight sensitisation was observed. Long-term desensitisation has been found to reduce not only secretion of peripheral HPA hormones (ACTH and corticosterone), but also to reduce responses of central components of the HPA axis (c-fos and CRF gene expression at the level of the paraventricular nucleus of the hypothalamus, PVN). In addition, desensitisation also applies to the impact of the stressor on food intake and, probably, to stress-induced hyperglycaemia. The development of long-term desensitisation of the HPA axis does not appear to be a universal consequence of exposure to severe stressors as it was not observed in response to insulin-induced hypoglycaemia. Whether or not the development of long-term effects of stress depend on the specific pathways activated by particular stressors remains to be tested. The observed desensitisation of the HPA axis in response to the homotypic stressor shows two special features which makes it difficult to be interpreted in terms of an habituation-like process: (a) the effect increased with time (days to weeks) elapsed between the first and second exposure to the stressor, suggesting a progressive maturational process; and (b) the stronger the stressor the greater the long-term desensitisation. Therefore, it is possible that desensitisation of the HPA axis is the sum of two different phenomena: long-term effects and habituation-like processes. The contribution of the former may be more relevant with severe stressors and longer inter-stress intervals, and that of the latter with mild

Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

International Nuclear Information System (INIS)

Thoma, Clemens; Bachy, Veronique; Seaton, Patricia; Green, Nicola K.; Greaves, David R.; Klavinskis, Linda; Seymour, Leonard W.; Morrison, Joanne

2013-01-01

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer

Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Thoma, Clemens, E-mail: c.thoma@oxfordalumni.org [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Bachy, Veronique [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seaton, Patricia [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Green, Nicola K. [Clinical Biomanufacturing Facility, University of Oxford, Old Road, Oxford OX3 7JT (United Kingdom); Greaves, David R. [Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Klavinskis, Linda [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seymour, Leonard W. [Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); Morrison, Joanne [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Department of Obstetrics and Gynaecology, Musgrove Park Hospital, Taunton TA1 5DA (United Kingdom)

2013-12-15

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence

Directory of Open Access Journals (Sweden)

Lauren eChaby

2013-07-01

Full Text Available Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid stress hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g. isolation, crowding, cage tilt were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias (F1,12 = 5.000, P < 0.05, altered coping response (T1,14 = 2.216, P = 0.04, and accelerated decision making (T1,14 = 3.245, P = 0.01. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object (T1,14 = 2.240, P = 0.04; T1,14 = 2.419, P = 0.03, respectively. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions. Stress during adolescence also induced short-term changes in the way animals moved around a novel environment.

Short-term versus long-term contracting for uranium enrichment services

International Nuclear Information System (INIS)

Rudy, G.P.

1990-01-01

The US Department of Energy (US DOE) is the world's largest and most experienced supplier of uranium enrichment services. Through the late 1970s and early 1980s, emerging market forces transformed what was once a monopoly into a highly competitive industry. In the early 1980's the DOE lost market share. But as we enter the 1990s, new market forces have emerged. The US DOE believes a responsible balance between long-term and short-term contracting will be the key to success and the key to assuring the long-term health and reliability of the nuclear fuel industry. The US DOE intends to be in this nuclear business for a long time and will continue to offer reliable and responsive services second to none

Differentiating Visual from Response Sequencing during Long-term Skill Learning.

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Lynch, Brighid; Beukema, Patrick; Verstynen, Timothy

2017-01-01

The dual-system model of sequence learning posits that during early learning there is an advantage for encoding sequences in sensory frames; however, it remains unclear whether this advantage extends to long-term consolidation. Using the serial RT task, we set out to distinguish the dynamics of learning sequential orders of visual cues from learning sequential responses. On each day, most participants learned a new mapping between a set of symbolic cues and responses made with one of four fingers, after which they were exposed to trial blocks of either randomly ordered cues or deterministic ordered cues (12-item sequence). Participants were randomly assigned to one of four groups (n = 15 per group): Visual sequences (same sequence of visual cues across training days), Response sequences (same order of key presses across training days), Combined (same serial order of cues and responses on all training days), and a Control group (a novel sequence each training day). Across 5 days of training, sequence-specific measures of response speed and accuracy improved faster in the Visual group than any of the other three groups, despite no group differences in explicit awareness of the sequence. The two groups that were exposed to the same visual sequence across days showed a marginal improvement in response binding that was not found in the other groups. These results indicate that there is an advantage, in terms of rate of consolidation across multiple days of training, for learning sequences of actions in a sensory representational space, rather than as motoric representations.

Transcriptional regulation of long-term memory in the marine snail Aplysia

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Lee Yong-Seok

2008-06-01

Full Text Available Abstract Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF. The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT, a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT induce a transcription- and translation-dependent long-term facilitation (LTF lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced

Transcriptional regulation of long-term memory in the marine snail Aplysia.

Science.gov (United States)

Lee, Yong-Seok; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

2008-06-17

Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF). The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB) acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription- and translation-dependent long-term facilitation (LTF) lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced by different

Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome

International Nuclear Information System (INIS)

Tao, May L.; Barnes, Patrick D.; Billett, Amy L.; Leong, Traci; Shrieve, Dennis C.; Scott, R. Michael; Tarbell, Nancy J.

1997-01-01

Purpose: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation. Methods and Materials: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients. Results: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients. Conclusions: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence.

Science.gov (United States)

Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

2013-01-01

Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision-making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g., isolation, crowding, cage tilt) were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias [F (1, 12) = 5.000, P chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object [T (1, 14) = 2.240, P = 0.04; T (1, 14) = 2.419, P = 0.03, respectively]. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions.

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.

Extra-auditory responses to long-term intermittent noise stimulation in humans.

Science.gov (United States)

Fruhstorfer, B; Hensel, H

1980-12-01

Respiration, heart rate, cutaneous blood flow, and electroencephalogram (EEG) reactions to long-term intermittent noise exposure were recorded from 13 volunteers (20-29 yr) with normal hearing and vegetative reactivity. They received daily within 1 h 12 noise stimuli (16 s 100 dB (A) white noise) for 10 or 21 days, respectively. Most subjects reported partial subjective adaptation to the noise. Heart rate adapted within a session but did not change considerably during successive days. Vascular responses did not change during one session but diminished mainly during the first 10 days. Noise responses in the EEG remained constant, but a decrease in vigilance occurred during the whole experimental series. Respiration responses were unpredictable and showed no trend within the sessions. It was concluded that certain physiological responses adapt to loud noise but that the time course of adaptation is different. Therefore a general statement about physiological noise adaptation is not possible.

Long-Term Impact of a Cell Phone-Enhanced Parenting Intervention.

Science.gov (United States)

Lefever, Jennifer E Burke; Bigelow, Kathryn M; Carta, Judith J; Borkowski, John G; Grandfield, Elizabeth; McCune, Luke; Irvin, Dwight W; Warren, Steven F

2017-11-01

Home visiting programs support positive parenting in populations at-risk of child maltreatment, but their impact is often limited by poor retention and engagement. The current study assessed whether a cellular phone-supported version (PCI-C) of the Parent-Child Interactions (PCI) intervention improved long-term parenting practices, maternal depression, and children's aggression. Low-income mothers ( n = 371) of preschool-aged children were assigned to one of the three groups: PCI-C, PCI, and a wait-list control (WLC) group. Parenting improved in both intervention groups between baseline and 12-month follow-up compared to the WLC. Children in the PCI-C group were rated to be more cooperative and less aggressive than children in the WLC. The results offer evidence of the long-term effectiveness of PCI and the additional benefits of cellular phone supports for promoting intervention retention and improving children's behavior.

Long-term heat stress induces the inflammatory response in dairy cows revealed by plasma proteome analysis.

Science.gov (United States)

Min, Li; Zheng, Nan; Zhao, Shengguo; Cheng, Jianbo; Yang, Yongxin; Zhang, Yangdong; Yang, Hongjian; Wang, Jiaqi

2016-03-04

In this work we employed a comparative proteomic approach to evaluate seasonal heat stress and investigate proteomic alterations in plasma of dairy cows. Twelve lactating Holstein dairy cows were used and the treatments were: heat stress (n = 6) in hot summer (at the beginning of the moderate heat stress) and no heat stress (n = 6) in spring natural ambient environment, respectively. Subsequently, heat stress treatment lasted 23 days (at the end of the moderate heat stress) to investigate the alterations of plasma proteins, which might be employed as long-term moderate heat stress response in dairy cows. Changes in plasma proteins were analyzed by two-dimensional electrophoresis (2-DE) combined with mass spectrometry. Analysis of the properties of the identified proteins revealed that the alterations of plasma proteins were related to inflammation in long-term moderate heat stress. Furthermore, the increase in plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) directly demonstrated that long-term moderate heat stress caused an inflammatory response in dairy cows. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

Directory of Open Access Journals (Sweden)

Alexander David Bird

2014-01-01

Full Text Available Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modifed during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony setby the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture.

Characterizing heterogeneous cellular responses to perturbations.

Science.gov (United States)

Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

2008-12-09

Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

Science.gov (United States)

Da-Cruz, Alda Maria; Bittar, Rita; Mattos, Marise; Oliveira-Neto, Manuel P.; Nogueira, Ricardo; Pinho-Ribeiro, Vanessa; Azeredo-Coutinho, Rilza Beatriz; Coutinho, Sergio G.

2002-01-01

T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations. PMID:11874860

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

Science.gov (United States)

Kosek, Eva; Rosen, Annelie; Carville, Serena; Choy, Ernest; Gracely, Richard H; Marcus, Hanke; Petzke, Frank; Ingvar, Martin; Jensen, Karin B

2017-07-01

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

Science.gov (United States)

Santini, Emanuela; Huynh, Thu N; Klann, Eric

2014-01-01

The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. © 2014 Elsevier Inc. All rights reserved.

Long term ionization response of several BiCMOS VLSIC technologies

International Nuclear Information System (INIS)

Pease, R.L.; Combs, W.; Clark, S.

1992-01-01

BiCMOS is emerging as a strong competitor to CMOS for gate arrays and memories because of its performance advantages for the same feature size. In this paper, the authors examine the long term ionization response of five BiCMOS technologies by characterizing test structures which emphasize the various failure modes of CMOS and bipolar. The primary failure modes are found to be associated with the recessed field oxide isolation; edge leakage in the n channel MOSFETs and buried layer to buried layer leakage in the bipolar. The ionization failure thresholds for worst case bias were in the range of 5-20 Krad(Si) for both failure modes in all five technologies

Preface: long-term response of a forest watershed ecosystem, clearcutting in the Southern Appalachians

Science.gov (United States)

Wayne Swank; Jackson Webster

2014-01-01

Our North American forests are no longer the wild areas of past centuries; they are an economic and ecological resource undergoing changes from both natural and management disturbances. A watershed-scale and long-term perspective of forest ecosystem responses is requisite to understanding and predicting cause and effect relationships. This book synthesizes...

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.

ERDA's long-term waste management goals and programs

International Nuclear Information System (INIS)

Perge, A.F.; Trice, V.G. Jr.; Walton, R.D. Jr.

1976-01-01

This paper presents an overview of the ERDA's major program for the long-term waste management of radioactive waste and provides a perspective for symposium participants with regard to the interrelationship of specific components of the program that are discussed in detail in other ERDA-sponsored papers. Needs, goals, and plans are reviewed for ERDA's management of the commercially generated wastes which are expected to be delivered to ERDA in accordance with Federal regulations. At present, ERDA responsibilities include long-term management of commercial-level wastes. Possible future regulations may give ERDA responsibility for the long-term management of commercial low-level solid wastes contaminated with transuranic nuclides. Primary planning goals and programs for the development of terminal storage facilities and waste processing technology to produce acceptable waste forms for long-term management are reviewed for each of the waste types identified above. The status of development programs for the long-term management of airborne radionuclides, which may be required at some time in the future, is also reviewed. (author)

OK-432 sclerotherapy in head and neck lymphangiomas: long-term follow-up result.

Science.gov (United States)

Yoo, Jae Chul; Ahn, Youngjin; Lim, Yune Syung; Hah, J Hun; Kwon, Tack-Kyun; Sung, Myung-Whun; Kim, Kwang Hyun

2009-01-01

Nonsurgical treatments, such as sclerotherapy have been attempted for head and neck lymphagiomas. Of the available sclerosing agents, picibanil has shown satisfactory short-term treatment results in many studies, but no study has presented long-term treatment results. Accordingly, in the present study, the authors retrospectively reviewed the long-term treatment results of picibanil sclerotherapy. Fifty-five lymphangioma patients who underwent picibanil sclerotherapy were enrolled. Data about initial and long-term response, recurrence, and excision rate were collected. Initial response rates were 83.5 percent and long-term response rates were 76.3 percent. Initial and the long-term response rate were equally good for lymphangioma.

Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation

Directory of Open Access Journals (Sweden)

Shucai Huang

2018-04-01

Full Text Available Studies utilizing functional magnetic resonance imaging (fMRI cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation.

Science.gov (United States)

Huang, Shucai; Zhang, Zhixue; Dai, Yuanyuan; Zhang, Changcun; Yang, Cheng; Fan, Lidan; Liu, Jun; Hao, Wei; Chen, Hongxian

2018-01-01

Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

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.

Long-term aversive taste memory requires insular and amygdala protein degradation.

Science.gov (United States)

Rodriguez-Ortiz, Carlos J; Balderas, Israela; Saucedo-Alquicira, Fernando; Cruz-Castañeda, Paulina; Bermudez-Rattoni, Federico

2011-03-01

Some reports have shown that the ubiquitin-proteasome system (UPS) is necessary to degrade repressor factors to produce new proteins essential to memory consolidation. Furthermore, recent evidence suggests that memory updating also relies on protein degradation through the UPS. To evaluate whether degradation of proteins is part of the cellular events needed for long-term storage of taste aversion, we injected lactacystin--an UPS inhibitor--into the amygdala and/or insular cortex 30 min before the first or second training trials. The results revealed that degradation of proteins in either the amygdala or insular cortex suffices for long-term stabilization of first-time encounter taste aversion. On the other hand, lactacystin applied in the insula, but not in the amygdala, before the second training prevented long-term storage of updated information. Our results support that degradation of proteins by means of the UPS is required every time taste aversion is to be stored in long-term memory. Copyright © 2010 Elsevier Inc. All rights reserved.

Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

Science.gov (United States)

Sobanski, E; Leppämäki, S; Bushe, C; Berggren, L; Casillas, M; Deberdt, W

2015-11-01

Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Comment and response document for the long-term surveillance plan for the Falls City disposal site, Falls City, Texas

International Nuclear Information System (INIS)

1996-11-01

This is the Comment and Response Document dated November 1996 for the Long-Term Surveillance Plan for the Falls City Disposal Site in Falls City, Texas. The site is part of the U.S. DOE's Uranium Mill Tailings Remedial Action Project (UMTRA). Several comments regarding the hydrology and surface erosion described in the Long-Term Surveillance Plan are addressed in this document

Long-Term Health of Dopaminergic Neuron Transplants in Parkinson's Disease Patients

Directory of Open Access Journals (Sweden)

Penelope J. Hallett

2014-06-01

Full Text Available To determine the long-term health and function of transplanted dopamine neurons in Parkinson’s disease (PD patients, the expression of dopamine transporters (DATs and mitochondrial morphology were examined in human fetal midbrain cellular transplants. DAT was robustly expressed in transplanted dopamine neuron terminals in the reinnervated host putamen and caudate for at least 14 years after transplantation. The transplanted dopamine neurons showed a healthy and nonatrophied morphology at all time points. Labeling of the mitochondrial outer membrane protein Tom20 and α-synuclein showed a typical cellular pathology in the patients’ own substantia nigra, which was not observed in transplanted dopamine neurons. These results show that the vast majority of transplanted neurons remain healthy for the long term in PD patients, consistent with clinical findings that fetal dopamine neuron transplants maintain function for up to 15–18 years in patients. These findings are critically important for the rational development of stem-cell-based dopamine neuronal replacement therapies for PD.

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

The stability of vacuum phototriodes to varying light pulse loads and long term changes in response.

CERN Document Server

Hobson, Peter

2012-01-01

Mesh anode Vacuum Phototriodes (VPTs) are radiation resistant, single gain-stage photomultipliers which are designed to operate in a strong quasi-axial magnetic field. These VPTs are used in the endcap electromagnetic calorimeter of the CMS experiment at the CERN LHC to detect scintillation light from lead tungstate crystals. Short term dynamic response changes occur because of pulse rate variations during normal LHC operation cycles. Over the longer term the effect of increasing integrated charge taken from the photocathode causes an overall degradation of response. We have investigated these effects over time periods exceeding two years of simulated operation and discuss the implications for the long term performance of the VPTs in CMS.

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.

Immune responsiveness and incidence of reticulum cell sarcoma in long-term syngeneic radiation chimeras

International Nuclear Information System (INIS)

Adorini, L.; Gorini, G.; Covelli, V.; Ballardin, E.; di Michele, A.; Bassani, B.; Metalli, P.; Doria, G.

1976-01-01

Long-term syngeneic radiation chimeras displayed a very low incidence of reticulum cell sarcoma as compared with control mice. Immune reactivity of these animals was studied in vivo by anti-dinitrophenyl antibody titer and affinity and in vitro by mitotic responsiveness to phytohemagglutinin, concanavalin A and lipopolysaccharide. Antibody titer and affinity as well as the response to T lectins were found to be increased in chimeras. These results were attributed to increased function of mature T2 cells, which could explain the reduced incidence of reticulum cell sarcoma in chimeras

Imaging windows for long-term intravital imaging

Science.gov (United States)

Alieva, Maria; Ritsma, Laila; Giedt, Randy J; Weissleder, Ralph; van Rheenen, Jacco

2014-01-01

Intravital microscopy is increasingly used to visualize and quantitate dynamic biological processes at the (sub)cellular level in live animals. By visualizing tissues through imaging windows, individual cells (e.g., cancer, host, or stem cells) can be tracked and studied over a time-span of days to months. Several imaging windows have been developed to access tissues including the brain, superficial fascia, mammary glands, liver, kidney, pancreas, and small intestine among others. Here, we review the development of imaging windows and compare the most commonly used long-term imaging windows for cancer biology: the cranial imaging window, the dorsal skin fold chamber, the mammary imaging window, and the abdominal imaging window. Moreover, we provide technical details, considerations, and trouble-shooting tips on the surgical procedures and microscopy setups for each imaging window and explain different strategies to assure imaging of the same area over multiple imaging sessions. This review aims to be a useful resource for establishing the long-term intravital imaging procedure. PMID:28243510

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.

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

Long-term olfactory memories are stabilised via protein synthesis in Camponotus fellah ants

DEFF Research Database (Denmark)

Guerrieri, Fernando Javier; D'Ettorre, Patrizia; Deveaud, J-M.

2011-01-01

-chain hydrocarbons, one paired with sucrose and the other with quinine solution. Differential conditioning leads to the formation of a long-term memory retrievable at least 72¿h after training. Long-term memory consolidation was impaired by the ingestion of cycloheximide, a protein synthesis blocker, prior...... to conditioning. Cycloheximide did not impair acquisition of either short-term memory (10¿min) or early and late mid-term memories (1 or 12¿h). These results show that, upon olfactory learning, ants form different memories with variable molecular bases. While short- and mid-term memories do not require protein...... synthesis, long-term memories are stabilised via protein synthesis. Our behavioural protocol opens interesting research avenues to explore the cellular and molecular bases of olfactory learning and memory in ants....

Determining a functional responsibility allocation between public and private parties in a long-term maintenance contract for waterworks

NARCIS (Netherlands)

Brommet, O.D.; Schoenmaker, R.; Hertogh, M.J.C.M.; Kleijn van Willigen, G.R.; Chen, Y.; Bakker, Jaap; Frangopol, Dan M.; van Breugel, Klaas

2017-01-01

A proper allocation of risks and responsibilities is vital for the success of long-term maintenance contracts. This paper focuses on a method to identify an adequate allocation of responsibilities for the maintenance of waterworks. The Dutch agency recently started outsourcing the maintenance of

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

Science.gov (United States)

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

2015-08-26

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

Long-Term Stewardship Program Science and Technology Requirements

Energy Technology Data Exchange (ETDEWEB)

Joan McDonald

2002-09-01

Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

Implicit short- and long-term memory direct our gaze in visual search.

Science.gov (United States)

Kruijne, Wouter; Meeter, Martijn

2016-04-01

Visual attention is strongly affected by the past: both by recent experience and by long-term regularities in the environment that are encoded in and retrieved from memory. In visual search, intertrial repetition of targets causes speeded response times (short-term priming). Similarly, targets that are presented more often than others may facilitate search, even long after it is no longer present (long-term priming). In this study, we investigate whether such short-term priming and long-term priming depend on dissociable mechanisms. By recording eye movements while participants searched for one of two conjunction targets, we explored at what stages of visual search different forms of priming manifest. We found both long- and short- term priming effects. Long-term priming persisted long after the bias was present, and was again found even in participants who were unaware of a color bias. Short- and long-term priming affected the same stage of the task; both biased eye movements towards targets with the primed color, already starting with the first eye movement. Neither form of priming affected the response phase of a trial, but response repetition did. The results strongly suggest that both long- and short-term memory can implicitly modulate feedforward visual processing.

Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

Science.gov (United States)

Dell’Osso, Bernardo; Buoli, Massimiliano; Riundi, Riccardo; D’Urso, Nazario; Pozzoli, Sara; Bassetti, Roberta; Mundo, Emanuela; Altamura, A Carlo

2009-01-01

Introduction Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset ≤30 years, middle-onset >30–≤45 years, and late-onset >45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features. Results The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032). Conclusions Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset. PMID:19649214

Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures.

Science.gov (United States)

Bastiaansen, John W M; Coster, Albart; Calus, Mario P L; van Arendonk, Johan A M; Bovenhuis, Henk

2012-01-24

Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects. Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations. Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure. The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients

NARCIS (Netherlands)

Wieten, R. W.; Goorhuis, A.; Jonker, E. F. F.; de Bree, G. J.; de Visser, A. W.; van Genderen, P. J. J.; Remmerswaal, E. B. M.; ten Berge, I. J. M.; Visser, L. G.; Grobusch, M. P.; van Leeuwen, E. M. M.

2016-01-01

The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen

Long-term dataset on aquatic responses to concurrent climate change and recovery from acidification

Science.gov (United States)

Leach, Taylor H.; Winslow, Luke A.; Acker, Frank W.; Bloomfield, Jay A.; Boylen, Charles W.; Bukaveckas, Paul A.; Charles, Donald F.; Daniels, Robert A.; Driscoll, Charles T.; Eichler, Lawrence W.; Farrell, Jeremy L.; Funk, Clara S.; Goodrich, Christine A.; Michelena, Toby M.; Nierzwicki-Bauer, Sandra A.; Roy, Karen M.; Shaw, William H.; Sutherland, James W.; Swinton, Mark W.; Winkler, David A.; Rose, Kevin C.

2018-04-01

Concurrent regional and global environmental changes are affecting freshwater ecosystems. Decadal-scale data on lake ecosystems that can describe processes affected by these changes are important as multiple stressors often interact to alter the trajectory of key ecological phenomena in complex ways. Due to the practical challenges associated with long-term data collections, the majority of existing long-term data sets focus on only a small number of lakes or few response variables. Here we present physical, chemical, and biological data from 28 lakes in the Adirondack Mountains of northern New York State. These data span the period from 1994-2012 and harmonize multiple open and as-yet unpublished data sources. The dataset creation is reproducible and transparent; R code and all original files used to create the dataset are provided in an appendix. This dataset will be useful for examining ecological change in lakes undergoing multiple stressors.

Long-term response of the mamane forest to feral herbivore management on Mauna Kea, Hawaii

Science.gov (United States)

E. Reddy; D. H. Van Vuren; P. G. Scowcroft; J. B. Kauffman; L. Perry

2012-01-01

Seven exclosure sites located on Mauna Kea, Hawaii and established in the 1960s and 70s were sampled to characterize long-term response of the mamane (Sophora chrysophylla) forest to protection from feral sheep grazing, and to assess impacts of non-native plant species and recurrent sheep presence on forest recovery. The forest provides essential...

Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response.

Science.gov (United States)

Sominsky, Luba; Ziko, Ilvana; Spencer, Sarah J

2017-01-01

The hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress are exacerbated in adult female but not male rats made obese due to overfeeding in early life. Ghrelin, traditionally known for its role in energy homeostasis, has been recently recognised for its role in coordinating the HPA responses to stress, particularly by acting directly at the anterior pituitary where the growth hormone secretagogue receptor (GHSR), the receptor for acyl ghrelin, is abundantly expressed. We therefore hypothesised that neonatal overfeeding in female rats would compromise pituitary responsiveness to ghrelin, contributing to a hyperactive central stress responsiveness. Unlike in males where hypothalamic ghrelin signalling is compromised by neonatal overfeeding, there was no effect of early life diet on circulating ghrelin or hypothalamic ghrelin signalling in females, indicating hypothalamic feeding and metabolic ghrelin circuitry remains intact. However, neonatal overfeeding did lead to long-term alterations in the pituitary ghrelin system. The neonatally overfed females had increased neonatal and reduced adult expression of GHSR and ghrelin-O-acyl transferase (GOAT) in the pituitary as well as reduced pituitary responsiveness to exogenous acyl ghrelin-induced adrenocorticotropic hormone (ACTH) release in vitro. These data suggest that neonatal overfeeding dysregulates pituitary ghrelin signalling long-term in females, potentially accounting for the hyper-responsive HPA axis in these animals. These findings have implications for how females may respond to stress throughout life, suggesting the way ghrelin modifies the stress response at the level of the pituitary may be less efficient in the neonatally overfed.

Advancing an ethical framework for long-term care.

Science.gov (United States)

Carter, Mary Whelan

2002-02-01

This article represents an effort to formulate an ethical framework for long-term care with the explicit purpose of providing a catalyst to promote further discourse and expand consideration of what an ethic of long-term care might entail. Grounding the discussion, an introduction to traditional ethical philosophy is presented, focusing mainly on the fundamentals of deontological and teleological ethical theories. Attention then shifts to a review of the more frequently cited principles found in the long-term care ethics literature, followed by a critique of the current reliance upon principlism to resolve ethical dilemmas in long-term care. In response to this criticism, an agent-driven ethical framework stressing dignity and respect for personhood, drawn from the philosophy of Immanuel Kant, is advanced.

Interactions between lithology and biology drive the long-term response of stream chemistry to major hurricanes in a tropical landscape

Science.gov (United States)

W.H. McDowell; R.L. Brereton; F.N. Scatena; J.B. Shanley; N.V. Brokaw; A.E. Lugo

2013-01-01

Humid tropical forests play a dominant role in many global biogeochemical cycles, yet long-term records of tropical stream chemistry and its response to disturbance events such as severe storms and droughts are rare. Here we document the long-term variability in chemistry of two streams in the Luquillo Mountains, Puerto Rico over a period of 27 years. Our two focal...

An experimental protocol for the establishment of dogs with long-term cellular immune reactions to Leishmania antigens

Directory of Open Access Journals (Sweden)

Márcia Cristina Aquino Teixeira

2011-03-01

Full Text Available Domestic dogs are considered to be the main reservoirs of zoonotic visceral leishmaniasis. In this work, we evaluated a protocol to induce Leishmania infantum/Leishmania chagasi-specific cellular and humoral immune responses in dogs, which consisted of two injections of Leishmania promastigote lysate followed by a subcutaneous inoculation of viable promastigotes. The primary objective was to establish a canine experimental model to provide positive controls for testing immune responses to Leishmania in laboratory conditions. After inoculation of viable promastigotes, specific proliferative responses of peripheral blood mononuclear cells (PBMCs to either Leishmania lysate or recombinant proteins, the in vitro production of interferon-γ by antigen-stimulated PBMCs and a significant increase in circulating levels of anti-Leishmania antibodies were observed. The immunized dogs also displayed positive delayed-type hypersensitivity reactions to Leishmania crude antigens and to purified recombinant proteins. An important finding that supports the suitability of the dogs as positive controls is that they remained healthy for the entire observation period, i.e., more than seven years after infection. Following the Leishmania antigen lysate injections, the infection of dogs by the subcutaneous route appears to induce a sustained cellular immune response, leading to an asymptomatic infection. This provides a useful model for both the selection of immunogenic Leishmania antigens and for immunobiological studies on their possible immunoprotective activities.

A single low dose of Fe ions can cause long-term biological responses in NL20 human bronchial epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Cao, Qianlin; Wang, Jingdong; Cao, Jianping; Yang, Hongying [Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou, Jiangsu (China); Liu, Wei [Soochow University, Department of Radiotherapy and Oncology, Second Affiliated Hospital, Suzhou, Jiangsu (China)

2018-03-15

Space radiation cancer risk may be a potential obstacle for long-duration spaceflight. Among all types of cancer space radiation may induce, lung cancer has been estimated to be the largest potential risk. Although previous animal study has shown that Fe ions, the most important contributor to the total dose equivalent of space radiation, induced a higher incidence of lung tumorigenesis per dose than X-rays, the underlying mechanisms at cellular level remained unclear. Therefore, in the present study, we investigated long-term biological changes in NL20 human bronchial epithelial cells after exposure to Fe ion or X-ray irradiation. We found that compared with sham control, the progeny of NL20 cells irradiated with 0.1 Gy of Fe ions showed slightly increased micronucleus formation, significantly decreased cell proliferation, disturbed cell cycle distribution, and obviously elevated intracellular ROS levels accompanied by reduced SOD1 and SOD2 expression, but the progeny of NL20 cells irradiated with 0.9 Gy of X-rays did not show any significant changes. More importantly, Fe ion exposure caused much greater soft-agar colony formation than X-rays did in the progeny of irradiated NL20 cells, clearly suggesting higher cell transformation potential of Fe ions compared with X-rays. These data may shed the light on the potential lung tumorigenesis risk from Fe ion exposure. In addition, ATM inhibition by Ku55933 reversed some of the changes in the progeny of Fe ion-irradiated cells but not others such as soft-agar colony formation, suggesting complex processes from DNA damage to carcinogenesis. These data indicate that even a single low dose of Fe ions can induce long-term biological responses such as cell transformation, etc., suggesting unignorable health risk from space radiation to astronauts. (orig.)

Emergency planning and long-term care: least paid, least powerful, most responsible.

Science.gov (United States)

Covan, Eleanor Krassen; Fugate-Whitlock, Elizabeth

2010-11-01

As disasters can occur anywhere, planning to avoid emergencies is an international concern. Our research specifically addresses planning for the needs and safety of a vulnerable population, long-term care residents. Our initial purposes in this evaluation research were to assess the utility of a template to gather emergency management information for individual long-term care communities, to report on how prepared they are to cope with emergencies that have occurred elsewhere in areas like ours, and to assess the effectiveness of employing gerontology students in the planning process. As we began analyzing our data, we realized that it is imperative to consider whether it is possible for long-term care communities to respond effectively to disasters. In our findings we focus on the impact of gender in the planning process, the importance of size with regard to template utility, the positive and negative consequences of student aid, and the fact that gathering plans for individual long-term care communities may have detracted from collaborative community planning.

Modeling long-term dynamics of electricity markets

International Nuclear Information System (INIS)

Olsina, Fernando; Garces, Francisco; Haubrich, H.-J.

2006-01-01

In the last decade, many countries have restructured their electricity industries by introducing competition in their power generation sectors. Although some restructuring has been regarded as successful, the short experience accumulated with liberalized power markets does not allow making any founded assertion about their long-term behavior. Long-term prices and long-term supply reliability are now center of interest. This concerns firms considering investments in generation capacity and regulatory authorities interested in assuring the long-term supply adequacy and the stability of power markets. In order to gain significant insight into the long-term behavior of liberalized power markets, in this paper, a simulation model based on system dynamics is proposed and the underlying mathematical formulations extensively discussed. Unlike classical market models based on the assumption that market outcomes replicate the results of a centrally made optimization, the approach presented here focuses on replicating the system structure of power markets and the logic of relationships among system components in order to derive its dynamical response. The simulations suggest that there might be serious problems to adjust early enough the generation capacity necessary to maintain stable reserve margins, and consequently, stable long-term price levels. Because of feedback loops embedded in the structure of power markets and the existence of some time lags, the long-term market development might exhibit a quite volatile behavior. By varying some exogenous inputs, a sensitivity analysis is carried out to assess the influence of these factors on the long-run market dynamics

Private long-term care insurance and state tax incentives.

Science.gov (United States)

Stevenson, David G; Frank, Richard G; Tau, Jocelyn

2009-01-01

To increase the role of private insurance in financing long-term care, tax incentives for long-term care insurance have been implemented at both the federal and state levels. To date, there has been surprisingly little study of these initiatives. Using a panel of national data, we find that market take-up for long-term care insurance increased over the last decade, but state tax incentives were responsible for only a small portion of this growth. Ultimately, the modest ability of state tax incentives to lower premiums implies that they should be viewed as a small piece of the long-term care financing puzzle.

Grain yield and crop N offtake in response to residual fertilizer N in long-term field experiments

DEFF Research Database (Denmark)

Petersen, Jens; Thomsen, Ingrid Kaag; Mattsson, L.

2010-01-01

in four long-term (>35 yr) field experiments, we measured the response of barley (grain yield and N offtake at crop maturity) to six rates (0, 30, 60, 90, 120 and 150 kg N/ha) of mineral fertilizer N (Nnew) applied in subplots replacing the customary long-term plot treatments of fertilizer inputs (Nprev......). Rates of Nprev above 50-100 kg N/ha had no consistent effect on the soil N content, but this was up to 20% greater than that in unfertilized treatments. Long-term unfertilized plots should not be used as control to test the residual value of N in modern agriculture with large production potentials....... Although the effect of mineral Nprev on grain yield and N offtake could be substituted by Nnew within a range of previous inputs, the value of Nprev was not eliminated irrespective of Nnew rate. Provided a sufficient supply of plant nutrients other than N, the use-efficiency of Nnew did not change...

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: II. Induction DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term islet allograft acceptance.

Science.gov (United States)

Watanabe, Masaaki; Yamashita, Kenichiro; Kamachi, Hirofumi; Kuraya, Daisuke; Koshizuka, Yasuyuki; Shibasaki, Susumu; Asahi, Yoh; Ono, Hitoshi; Emoto, Shin; Ogura, Masaomi; Yoshida, Tadashi; Ozaki, Michitaka; Umezawa, Kazuo; Matsushita, Michiaki; Todo, Satoru

2013-09-15

Long-term graft deterioration remains a major obstacle in the success of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and innate immune responses strengthen subsequent antigen-dependent immunity; further, activation of nuclear factor (NF)-κB plays a key role during these responses. In this study, we tested our hypothesis that, by the inhibition of NF-κB activation, the suppression of these early responses after PITx could facilitate graft acceptance. Full major histocompatibility complex (MHC)-mismatched BALB/c (H-2) mice islets were transplanted into streptozotocin-induced diabetic C57BL/6 (B6: H-2) mice. The NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) was administered for either 3 or 14 days after PITx. To some PITx recipients, tacrolimus was also administered. Islet allograft survival, alloimmune responses, and in vitro effects of DHMEQ on dendritic cells (DCs) were assessed. With a vehicle treatment, 600 islet allografts were promptly rejected after PITx. In contrast, 3-day treatment with DHMEQ, followed by 2-week treatment with tacrolimus, allowed permanent acceptance of islet allografts. The endogenous danger-signaling molecule high mobility group complex 1 (HMGB1) was elevated in sera shortly after PITx, whereas DHMEQ administration abolished this elevation. DHMEQ suppressed HMGB1-driven cellular activation and proinflammatory cytokine secretion in mouse bone marrow-derived DCs and significantly reduced the capacity of DCs to prime allogeneic T-cell proliferation in vitro. Finally, the DHMEQ plus tacrolimus regimen reverted the diabetic state with only 300 islet allografts. Inhibition of NF-κB activation by DHMEQ shortly after PITx suppresses HMGB1, which activates DCs and strengthens the magnitude of alloimmune responses; this permits long-term islet allograft acceptance, even in case of fewer islet allografts.

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.

Non-polarized cytokine profile of a long-term non-progressor HIV infected patient.

Science.gov (United States)

Pina, Ana Flávia; Matos, Vanessa Terezinha Gubert de; Bonin, Camila Mareti; Dal Fabbro, Márcia Maria Ferrairo Janini; Tozetti, Inês Aparecida

The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Programmed cellular response to ionizing radiation damage

International Nuclear Information System (INIS)

Crompton, N.E.A.

1998-01-01

Three forms of radiation response were investigated to evaluate the hypothesis that cellular radiation response is the result of active molecular signaling and not simply a passive physicochemical process. The decision whether or not a cell should respond to radiation-induced damage either by induction of rescue systems, e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g. programmed cell death, appears to be the expression of intricate cellular biochemistry. A cell must recognize damage in its genetic material and then activate the appropriate responses. Cell type is important; the response of a fibroblast to radiation damage is both quantitatively and qualitatively different form that of a lymphocyte. The programmed component of radiation response is significant in radiation oncology and predicted to create unique opportunities for enhanced treatment success. (orig.)

Adaptation to social isolation - Acute and long-term stress responses of growing gilts with different coping characteristics

NARCIS (Netherlands)

Ruis, MAW; te Brake, JHA; Engel, B; Buist, WG; Blokhuis, HJ; Koolhaas, JM

The present experiment studied the acute and long-term stress responses of reactive and proactive prepubertal gilts to social isolation. Gilts with either reactive or proactive features were identified according to behavioral resistance in a backtest at a young age (2-4 days), respectively being low

Short-term versus long-term market opportunities and financial constraints

International Nuclear Information System (INIS)

Ferrari, Angelo

1999-01-01

This presentation discusses gas developments in Europe, the European Gas Directive, short term vs. long term, and Snam's new challenges. The European gas market is characterized by (1) The role of gas in meeting the demand for energy, which varies greatly from one country to another, (2) A growing market, (3) Decreasing role of domestic production, and (4) Increasing imports. Within the European Union, the Gas Directive aims to transform single national markets into one integrated European market by introducing third party access to the network for eligible clients as a means of increasing the competition between operators. The Gas Directive would appear to modify the form of the market rather than its size, and in particular the sharing of responsibility and risk among operators. The market in the future will offer operators the possibility to exploit opportunities deriving mainly from demands for increased flexibility. Opportunities linked to entrepreneurial initiatives require long-term investments characteristic of the gas business. Risks and opportunities must be balanced evenly between different operators. If everyone takes on their own risks and responsibilities, this means a wider distribution of the risks of long-term vs. short-term, currently borne by the gas companies that are integrated, into a market that tends to favour the short-term. A gradual liberalization process should allow incumbent operators to gradually diversify their activities in new gas market areas or enter new business activities. They could move beyond their local and European boundaries in pursuit of an international dimension. The market will have to make the transition from the national to the European dimension: as an example, Snam covers 90% of the Italian market, but its share of an integrated European market will be about 15%

Behavioural and physiological responses of heifer calves to acute stressors : Long-term consistency and relationship with adult reactivity to milking

NARCIS (Netherlands)

Van Reenen, Cornelis G.; Van der Werf, Jozef T. N.; O'Connell, Niamh E.; Heutinck, Leonie F. M.; Spoolder, Hans A. M.; Jones, R. Bryan; Koolhaas, Jaap M.; Blokhuis, Harry J.; O’Connell, Niamh E.

The present study investigated the long-term consistency of individual differences in dairy cattles' responses in tests of behavioural and hypothalamo-pituitary-adrenocortical (HPA) axis reactivity, as well as the relationship between responsiveness in behavioural tests and the reaction to first

Behavioural and physiological responses of heifer calves to acute stressors: Long-term consistency and relationship with adult reactivity to milking

NARCIS (Netherlands)

Reenen, van C.G.; Werf, van der J.T.N.; O'Connell, N.E.; Heutinck, L.F.M.; Spoolder, H.A.M.; Jones, R.B.; Koolhaas, J.M.; Blokhuis, H.J.

2013-01-01

The present study investigated the long-term consistency of individual differences in dairy cattles’ responses in tests of behavioural and hypothalamo–pituitary–adrenocortical (HPA) axis reactivity, as well as the relationship between responsiveness in behavioural tests and the reaction to first

Audit of long-term and short-term liabilities

Directory of Open Access Journals (Sweden)

Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

Assessing Forest Carbon Response to Climate Change and Disturbances Using Long-term Hydro-climatic Observations and Simulations

Science.gov (United States)

Trettin, C.; Dai, Z.; Amatya, D. M.

2014-12-01

Long-term climatic and hydrologic observations on the Santee Experimental Forest in the lower coastal plain of South Carolina were used to estimate long-term changes in hydrology and forest carbon dynamics for a pair of first-order watersheds. Over 70 years of climate data indicated that warming in this forest area in the last decades was faster than the global mean; 35+ years of hydrologic records showed that forest ecosystem succession three years following Hurricane Hugo caused a substantial change in the ratio of runoff to precipitation. The change in this relationship between the paired watersheds was attributed to altered evapotranspiration processes caused by greater abundance of pine in the treatment watershed and regeneration of the mixed hardwood-pine forest on the reference watershed. The long-term records and anomalous observations are highly valuable for reliable calibration and validation of hydrological and biogeochemical models capturing the effects of climate variability. We applied the hydrological model MIKESHE that showed that runoff and water table level are sensitive to global warming, and that the sustained warming trends can be expected to decrease stream discharge and lower the mean water table depth. The spatially-explicit biogeochemical model Forest-DNDC, validated using biomass measurements from the watersheds, was used to assess carbon dynamics in response to high resolution hydrologic observation data and simulation results. The simulations showed that the long-term spatiotemporal carbon dynamics, including biomass and fluxes of soil carbon dioxide and methane were highly regulated by disturbance regimes, climatic conditions and water table depth. The utility of linked-modeling framework demonstrated here to assess biogeochemical responses at the watershed scale suggests applications for assessing the consequences of climate change within an urbanizing forested landscape. The approach may also be applicable for validating large

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

Dynamic response of land use and river nutrient concentration to long-term climatic changes.

Science.gov (United States)

Bussi, Gianbattista; Janes, Victoria; Whitehead, Paul G; Dadson, Simon J; Holman, Ian P

2017-07-15

The combined indirect and direct impacts of land use change and climate change on river water quality were assessed. A land use allocation model was used to evaluate the response of the catchment land use to long-term climatic changes. Its results were used to drive a water quality model and assess the impact of climatic alterations on freshwater nitrate and phosphorus concentrations. Climatic projections were employed to estimate the likelihood of such response. The River Thames catchment (UK) was used as a case-study. If land use is considered as static parameter, according to the model results, climate change alone should reduce the average nitrate concentration, although just by a small amount, by the 2050s in the Lower Thames, due to reduced runoff (and lower export of nitrate from agricultural soils) and increased instream denitrification, and should increase the average phosphorus concentration by 12% by the 2050s in the Lower Thames, due to a reduction of the effluent dilution capacity of the river flow. However, the results of this study also show that these long-term climatic alterations are likely to lead to a reduction in the arable land in the Thames, replaced by improved grassland, due to a decrease in agriculture profitability in the UK. Taking into account the dynamic co-evolution of land use with climate, the average nitrate concentration is expected to be decreased by around 6% by the 2050s in both the upper and the lower Thames, following the model results, and the average phosphorus concentration increased by 13% in the upper Thames and 5% in the lower Thames. On the long term (2080s), nitrate is expected to decrease by 9% and 8% (upper and lower Thames respectively) and phosphorus not to change in the upper thames and increase by 5% in the lower Thames. Copyright © 2017 Elsevier B.V. All rights reserved.

miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

Science.gov (United States)

Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

2014-02-01

Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

Modeling Long Term Corn Yield Response to Nitrogen Rate and Crop Rotation

Directory of Open Access Journals (Sweden)

Laila Alejandra Puntel

2016-11-01

Full Text Available Improved prediction of optimal N fertilizer rates for corn (Zea mays L. can reduce N losses and increase profits. We tested the ability of the Agricultural Production Systems sIMulator (APSIM to simulate corn and soybean (Glycine max L. yields, the economic optimum N rate (EONR using a 16-year field-experiment dataset from central Iowa, USA that included two crop sequences (continuous corn and soybean-corn and five N fertilizer rates (0, 67, 134, 201, and 268 kg N ha-1 applied to corn. Our objectives were to: a quantify model prediction accuracy before and after calibration, and report calibration steps; b compare crop model-based techniques in estimating optimal N rate for corn; and c utilize the calibrated model to explain factors causing year to year variability in yield and optimal N. Results indicated that the model simultaneously simulated well long-term crop yields response to N (relative root mean square error, RRMSE of 19.6% before and 12.3% after calibration, which provided strong evidence that important soil and crop processes were accounted for in the model. The prediction of EONR was more complex and had greater uncertainty than the prediction of crop yield (RRMSE of 44.5% before and 36.6% after calibration. For long-term site mean EONR predictions, both calibrated and uncalibrated versions can be used as the 16-yr mean differences in EONR’s were within the historical N rate error range (40 to 50 kg N ha-1. However, for accurate year-by-year simulation of EONR the calibrated version should be used. Model analysis revealed that higher EONR values in years with above normal spring precipitation were caused by an exponential increase in N loss (denitrification and leaching with precipitation. We concluded that long term experimental data were valuable in testing and refining APSIM predictions. The model can be used as a tool to assist N management guidelines in the US Midwest and we identified five avenues on how the model can add

Modeling Long-Term Corn Yield Response to Nitrogen Rate and Crop Rotation.

Science.gov (United States)

Puntel, Laila A; Sawyer, John E; Barker, Daniel W; Dietzel, Ranae; Poffenbarger, Hanna; Castellano, Michael J; Moore, Kenneth J; Thorburn, Peter; Archontoulis, Sotirios V

2016-01-01

Improved prediction of optimal N fertilizer rates for corn ( Zea mays L. ) can reduce N losses and increase profits. We tested the ability of the Agricultural Production Systems sIMulator (APSIM) to simulate corn and soybean ( Glycine max L. ) yields, the economic optimum N rate (EONR) using a 16-year field-experiment dataset from central Iowa, USA that included two crop sequences (continuous corn and soybean-corn) and five N fertilizer rates (0, 67, 134, 201, and 268 kg N ha -1 ) applied to corn. Our objectives were to: (a) quantify model prediction accuracy before and after calibration, and report calibration steps; (b) compare crop model-based techniques in estimating optimal N rate for corn; and (c) utilize the calibrated model to explain factors causing year to year variability in yield and optimal N. Results indicated that the model simulated well long-term crop yields response to N (relative root mean square error, RRMSE of 19.6% before and 12.3% after calibration), which provided strong evidence that important soil and crop processes were accounted for in the model. The prediction of EONR was more complex and had greater uncertainty than the prediction of crop yield (RRMSE of 44.5% before and 36.6% after calibration). For long-term site mean EONR predictions, both calibrated and uncalibrated versions can be used as the 16-year mean differences in EONR's were within the historical N rate error range (40-50 kg N ha -1 ). However, for accurate year-by-year simulation of EONR the calibrated version should be used. Model analysis revealed that higher EONR values in years with above normal spring precipitation were caused by an exponential increase in N loss (denitrification and leaching) with precipitation. We concluded that long-term experimental data were valuable in testing and refining APSIM predictions. The model can be used as a tool to assist N management guidelines in the US Midwest and we identified five avenues on how the model can add value toward

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

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Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

Dissimilar response of plant and soil biota communities to long-term nutrient adition in grasslands

NARCIS (Netherlands)

Wal, van der A.; Geerts, R.H.E.M.; Korevaar, H.; Schouten, A.J.; Jagers op Akkerhuis, G.A.J.M.; Rutgers, M.; Mulder, C.

2009-01-01

The long-term effect of fertilizers on plant diversity and productivity is well known, but long-term effects on soil biota communities have received relatively little attention. Here, we used an exceptional long-lasting (>40 years) grassland fertilization experiment to investigate the long-term

Structural and functional responses of extremity veins to long-term gravitational loading or unloading—lessons from animal systems

Science.gov (United States)

Monos, Emil; Raffai, Gábor; Dörnyei, Gabriella; Nádasy, György L.; Fehér, Erzsébet

2007-02-01

Long, transparent tubular tilt-cages were developed to maintain experimental rats either in 45∘ head-up (orthostasis model), or in 45∘ head-down body position (antiorthostasis model) for several weeks. In order to study the functional and structural changes in extremity blood vessels, also novel pressure angiograph systems, as well as special quantitative electron microscopic methods were applied. It was found that several adaptive mechanisms are activated in the lower limb superficial veins and microvessels of muscles when an organism is exposed to long-term (1-2 weeks) orthostatic-type gravitational load including a reversible amplification of the pressure-dependent myogenic response, tuning of the myogenic tone by Ca++- and voltage-sensitive K+ channels in humans, augmentation of the intramural sympathetic innervation involving an increased nerve terminal density and synaptic vesicle count with functional remodeling, reorganization of vascular network properties (microvascular rarefaction in muscles, decreased branching angles in superficial veins), and responses of an endothelin and platelet-derived growth factor (PDGF) containing vesicle system in the endothelium. On the other hand, when applying long-term head-down tilting, the effects are dichotomous, e.g. it suppresses significantly the pressure-induced myogenic response, however does not diminish the adventitial sympathetic innervation density.

A basic strategy for financing long term care.

Science.gov (United States)

Greenberg, J A; Leutz, W N

1984-02-01

As pressure mounts to contain Medicaid long term care spending, short-range "quick fixes" must be avoided. Three such false solutions in particular have shortcomings that may actually exacerbate long term care's financial dilemma because they are based on inadequate definitions of the problem. Two of these proposals--legislation to broaden family responsibility toward institutionalized elders on Medicaid and expanded state power to put liens on such elders' real property--err by trying to mandate "caring" and are predicated on a misunderstanding of the "spend-down" problem. The other proposal--to provide tax incentives to family members who care for elders--requires a large administrative apparatus, assumes an elasticity of supply that may not exist, and could disrupt the "gift relationship" on which family exchanges are often based. What is needed is a strategy with short term, intermediate, and long term objectives that move toward an insurance approach. The short term plan should lay the groundwork for intermediate strategy and control costs by changing rate-setting methods and putting limits on facility construction. The intermediate plan should change the problem's definition from one of merely controlling Medicaid long term care expenditures to one of efficiently managing state resources for the elderly through the development of state financing and local delivery systems that target older persons in greatest need. An effective means of doing this is through the creation of social/HMOs, which have five key features: integration of service responsibility and authority; flexibility in organizational design; balanced clientele; pooled prepaid funding; and financial risk for the provider organization. Finally, the long term strategy should transfer much of the long term care financial burden from individuals and state Medicaid agencies to insurance mechanisms. Many individuals would thus avoid impoverishment caused by health care spending and Medicaid would

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

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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.

The Responsive Leadership Intervention: Improving leadership and individualized care in long-term care.

Science.gov (United States)

Caspar, Sienna; Le, Anne; McGilton, Katherine S

The Responsive Leadership Intervention (RLI) is a multi-faceted intervention. We evaluated the influence of the RLI on i) responsive leadership practices by team leaders; ii) health care aides' (HCAs) self-determination; iii) HCAs' perceived ability to provide individualized care. A quasi-experimental repeated measures non-equivalent control group design was used to assess participant outcomes in four long-term care facilities (two control, two intervention) across four time periods. Change from baseline to 1-month post-intervention was greater in the intervention group than control group for Individualized Care (IC) (p = 0.001), but not for Self Determination (p = 0.26). Perceived levels of responsive leadership was greater following the intervention among participants with baseline measures that were less than the median (p = 0.007), but not if greater. At 3-months post-intervention, the intervention group retained 32% of the difference from control in IC, and 49% of the difference from control in responsive leadership; at 6-months post-intervention, 35% and 28%, respectively. The RLI is a feasible method for improving responsive leadership practices and individualized care. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA

Science.gov (United States)

Rakesh Minocha; Swathi A. Turlapati; Stephanie Long; William H. McDowell; Subhash C. Minocha

2015-01-01

We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements...

Biologically-equivalent dose and long-term survival time in radiation treatments

International Nuclear Information System (INIS)

Zaider, Marco; Hanin, Leonid

2007-01-01

Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

Biomechanical, microvascular, and cellular factors promote muscle and bone regeneration.

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Duda, Georg N; Taylor, William R; Winkler, Tobias; Matziolis, Georg; Heller, Markus O; Haas, Norbert P; Perka, Carsten; Schaser, Klaus-D

2008-04-01

It is becoming clear that the long-term outcome of complex bone injuries benefits from approaches that selectively target biomechanical, vascular, and cellular pathways. The typically held view of either biological or mechanical aspects of healing is oversimplified and does not correspond to clinical reality. The fundamental mechanisms of soft tissue regeneration most likely hold the key to understanding healing response.

Cellular response to alkylating agent MNNG is impaired in STAT1-deficients cells.

Science.gov (United States)

Ah-Koon, Laurent; Lesage, Denis; Lemadre, Elodie; Souissi, Inès; Fagard, Remi; Varin-Blank, Nadine; Fabre, Emmanuelle E; Schischmanoff, Olivier

2016-10-01

The SN 1 alkylating agents activate the mismatch repair system leading to delayed G2 /M cell cycle arrest and DNA repair with subsequent survival or cell death. STAT1, an anti-proliferative and pro-apoptotic transcription factor is known to potentiate p53 and to affect DNA-damage cellular response. We studied whether STAT1 may modulate cell fate following activation of the mismatch repair system upon exposure to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Using STAT1-proficient or -deficient cell lines, we found that STAT1 is required for: (i) reduction in the extent of DNA lesions, (ii) rapid phosphorylation of T68-CHK2 and of S15-p53, (iii) progression through the G2 /M checkpoint and (iv) long-term survival following treatment with MNNG. Presence of STAT1 is critical for the formation of a p53-DNA complex comprising: STAT1, c-Abl and MLH1 following exposure to MNNG. Importantly, presence of STAT1 allows recruitment of c-Abl to p53-DNA complex and links c-Abl tyrosine kinase activity to MNNG-toxicity. Thus, our data highlight the important modulatory role of STAT1 in the signalling pathway activated by the mismatch repair system. This ability of STAT1 to favour resistance to MNNG indicates the targeting of STAT1 pathway as a therapeutic option for enhancing the efficacy of SN1 alkylating agent-based chemotherapy. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Local establishment of repetitive long-term potentiation-induced synaptic enhancement in cultured hippocampal slices with divided input pathways.

Science.gov (United States)

Oe, Yuki; Tominaga-Yoshino, Keiko; Ogura, Akihiko

2011-09-01

Long-term potentiation (LTP) in the rodent hippocampus is a popular model for synaptic plasticity, which is considered the cellular basis for brain memory. Because most LTP analysis involves acutely prepared brain slices, however, the longevity of single LTP has not been well documented. Using stable hippocampal slice cultures for long-term examination, we previously found that single LTP disappeared within 1 day. In contrast, repeated induction of LTP led to the development of a distinct type of plasticity that lasted for more than 3 weeks and was accompanied by the formation of new synapses. Naming this novel plastic phenomenon repetitive LTP-induced synaptic enhancement (RISE), we proposed it as a model for the cellular processes involved in long-term memory formation. However, because in those experiments LTP was induced pharmacologically in the whole slice, it is not known whether RISE has input-pathway specificity, an essential property for memory. In this study, we divided the input pathway of CA1 pyramidal neurons by a knife cut and induced LTP three times, the third by tetanic stimulation in one of the divided pathways to express RISE specifically. Voltage-sensitive dye imaging and Golgi-staining performed 2 weeks after the three LTP inductions revealed both enhanced synaptic strength and increased dendritic spine density confined to the tetanized region. These results demonstrate that RISE is a feasible cellular model for long-term memory. Copyright © 2011 Wiley-Liss, Inc.

Long Term Recovery in Disaster Response and the Role of Non-Profits

Directory of Open Access Journals (Sweden)

Victor B Flatt

2013-04-01

Full Text Available The Legal Framework of Disaster Response does not deal as well with long term recovery. In particular, the role of non-profits is unexamined. This paper examines the role of non-profits in disaster recovery and argues for a legal framework acknowledging its important role. El marco legal de las respuestas ante desastres no tiene en cuenta la recuperación a largo plazo. En particular, no se analiza el papel de las organizaciones sin ánimo de lucro. Este artículo estudia el papel de las organizaciones sin ánimo de lucro en la recuperación de desastres, y se muestra a favor de establecer un marco legal que reconozca la importancia de su papel.

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.

Quality of life and stress response symptoms in long-term and recent spouses of testicular cancer survivors

NARCIS (Netherlands)

Tuinman, MA; Fleer, J; Hoekstra, HJ; Sleijfer, DT; Hoekstra-Weebers, JEHM

The aim of this study was to gain insight into the quality of life (QoL) and stress response of female spouses of men cured of testicular cancer in the long-term. Time since treatment completion varied from 0.5 to 23.8 years. Two hundred and fifty nine testicular cancer survivors and their spouses

Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.

Science.gov (United States)

Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Obradovic, Zoran; Uversky, Vladimir N

2007-05-01

Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V. N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes approximately 90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes, and coding sequence diversities possessing strong positive and negative correlation with long disordered regions.

Functional Anthology of Intrinsic Disorder. II. Cellular Components, Domains, Technical Terms, Developmental Processes and Coding Sequence Diversities Correlated with Long Disordered Regions

Science.gov (United States)

Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

2008-01-01

Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions. PMID:17391015

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

Physiological and Biochemical Responses of Saltmarsh Plant Spartina alterniflora to Long-term Wave Exposure

Science.gov (United States)

Zhou, W.

2017-12-01

In recent years, ecosystem-based flood defence, i.e., eco-shoreline or living shoreline, that is more sustainable and cost-effective than conventional coastal engineering structures has been brought into large-scale practice. Numerous laboratory experiments have been performed to explore the wave-attenuation effects of saltmarsh plants that are widely used in eco-shoreline, and yet no study has ever been conducted on the physiological and biochemical responses of saltmarsh plants to long-term wave exposure, presumably due to the constraint that traditional wave generator fails to provide long-term stable wave conditions necessary for physiological experiments. In this study, a long-term shallow water wave environment simulator using crank-yoke mechanism was built in the laboratory to address this gap. Experiments using the wave simulator were conducted for 8 weeks in a greenhouse and the temperature was maintained at 24-30°C. 5‰ artificial sea water was filled in the test tank, and the water was changed every week. After being acclimatized, nine S. alterniflora individual plants (initial height 30 cm) were planted in each of the three streamlined cuboid containers (12cm×12cm×20cm), which were partially submerged in a test tank, and undertook horizontal sinusoidal motion imposed by the crank-yoke mechanism to mimic plants exposed to shallow water waves. The substrate filled in the containers were soils collected from the Yellow River Delta, so were the S. alterniflora plants. A realistic stem density of 400 stems/m2 was tested, which corresponded to a grid spacing of 5.0 cm. Shallow water waves with six wave heights (H: 0.041, 0.055, 0.069, 0.033, 0.044 and 0.056m), one plants submerged depth (0.1m) and two wave periods (2s and 3s) were simulated in the experiments. A no wave condition was also tested as control. Key physiological and biochemical parameters, such as stem length, peroxidase activity, catalase, superoxide dismutase, ascorbate peroxidase, etc

Cellular responses to environmental DNA damage

Energy Technology Data Exchange (ETDEWEB)

1994-08-01

This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains.

Science.gov (United States)

Belda, Xavier; Márquez, Cristina; Armario, Antonio

2004-10-05

We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.

Functional diversity of Collembola is reduced in soils subjected to short-term, but not long-term, geothermal warming

DEFF Research Database (Denmark)

Holmstrup, Martin; Ehlers, Bodil K.; Slotsbo, Stine

2018-01-01

the extent of such effects in long-term field-based experiments. In this study we make use of both recent (short-term) and long-term geothermal warming of Icelandic soils to examine the responses of Collembola, an ecologically important group of soil invertebrates, to warming. 2. On the basis of metabolic...

Solar Cycle Response and Long-Term Trends in the Mesospheric Metal Layers

Science.gov (United States)

Dawkins, E. C. M.; Plane, J. M. C.; Chipperfield, M.; Feng, W.; Marsh, D. R.; Hoffner, J.; Janches, D.

2016-01-01

The meteoric metal layers (Na, Fe, and K) which form as a result of the ablation of incoming meteors act as unique tracers for chemical and dynamical processes that occur within the upper mesosphere lower thermosphere region. In this work, we examine whether these metal layers are sensitive Fe indicators of decadal long-term changes within the upper atmosphere. Output from a whole-atmosphere climate model is used to assess the response of the Na, K, and Fe layers across a 50 year period (1955-2005). At short timescales, the K layer has previously been shown to exhibit a very different seasonal behavior compared to the other metals. Here we show that this unusual behavior is also exhibited at longer time scales (both the 11 year solar cycle and 50 year periods), where K displays a much more pronounced response to atmospheric temperature changes than either Na or Fe. The contrasting solar cycle behavior of the K and Na layers predicted by the model is confirmed using satellite and lidar observations for the period 2004-2013.

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.

Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

Science.gov (United States)

CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

[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

Long-term exposure to noise impairs cortical sound processing and attention control.

Science.gov (United States)

Kujala, Teija; Shtyrov, Yury; Winkler, Istvan; Saher, Marieke; Tervaniemi, Mari; Sallinen, Mikael; Teder-Sälejärvi, Wolfgang; Alho, Kimmo; Reinikainen, Kalevi; Näätänen, Risto

2004-11-01

Long-term exposure to noise impairs human health, causing pathological changes in the inner ear as well as other anatomical and physiological deficits. Numerous individuals are daily exposed to excessive noise. However, there is a lack of systematic research on the effects of noise on cortical function. Here we report data showing that long-term exposure to noise has a persistent effect on central auditory processing and leads to concurrent behavioral deficits. We found that speech-sound discrimination was impaired in noise-exposed individuals, as indicated by behavioral responses and the mismatch negativity brain response. Furthermore, irrelevant sounds increased the distractibility of the noise-exposed subjects, which was shown by increased interference in task performance and aberrant brain responses. These results demonstrate that long-term exposure to noise has long-lasting detrimental effects on central auditory processing and attention control.

Long-Term Surveillance and Maintenance Plan for the Gnome-Coach, New Mexico, Site

Energy Technology Data Exchange (ETDEWEB)

Kreie, Ken [USDOE Office of Legacy Management, Grand Junction, CO (United States); Findlay, Rick [Navarro Research and Engineering, Inc., Grand Junction, CO (United States)

2016-06-08

The U.S. Department of Energy (DOE) Office of Legacy Management (LM) prepared this Long-Term Surveillance and Maintenance Plan (LTSMP) for the Gnome-Coach, New Mexico, Site (the Gnome site). The Gnome site is approximately 25 miles east of Carlsbad in Eddy County, New Mexico (Figure 1). The site was the location of a 3-kiloton-yield underground nuclear test and radioisotope groundwater tracer test. The tests resulted in residual contamination and post-detonation features that require long-term oversight. Long-term responsibility for the site was transferred from the DOE National Nuclear Security Administration Nevada Site Office to LM on October 1, 2006. Responsibilities include surveillance, monitoring, and maintenance of institutional controls (ICs) as part of the long-term stewardship of the site. Long-term stewardship is designed to ensure protection of human health and the environment.

Responses of the African catfish Clarias gariepinus to long-term ...

African Journals Online (AJOL)

... environment by pesticides results in a decrease in fish productivity and may elevate concentrations of undesirable chemicals in edible fish tissues. The effects of long-term exposure of Clarias gariepinus juveniles to sublethal concentrations of glyphosate and paraquat, two commonly used herbicides, for eight weeks were ...

The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

Energy Technology Data Exchange (ETDEWEB)

Skjelkvaale, B L; Newell, A D; Raddum, G; Johannessen, M; Hovind, H; Tjomsland, T; Wathne, B M

1994-12-31

This report discusses The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes, which is designed to (1) establish degree and extent of acidification of surface waters, (2) evaluate dose/response relationships and (3) define long-term trends and variations in aquatic chemistry and biota attributable to atmospheric pollution. Data from 200 sites in 14 countries of Europe and North America are available. Dose/response relationships show that the fauna is adapted to different water qualities in different regions, and that critical limits for the fauna must be calculated according to data for the specific region. Long-term trends of water chemistry show decreases in SO{sub 4}{sup 2-} and Ca{sup 2+} at many sites. Nitrate shows no consistent trends. 66 refs., 26 figs., 16 tabs.

Endogenous BDNF Is Required for Long-Term Memory Formation in the Rat Parietal Cortex

Science.gov (United States)

Alonso, Mariana; Bekinschtein, Pedro, Cammarota, Martin; Vianna, Monica R. M.; Izquierdo, Ivan; Medina, Jorge H.

2005-01-01

Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory…

Cellular consequences of sleep deprivation in the brain.

Science.gov (United States)

Cirelli, Chiara

2006-10-01

Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

Cardiovascular responses to orthostasis: methods, assessments, and their association with falls in older adults in long-term care

OpenAIRE

Shaw, Brett Harrison

2013-01-01

Background: Orthostatic hypotension (OH) refers to a significant decline in blood pressure that occurs upon assuming an upright posture and represents an intrinsic risk factor for falls in older adults. Methods: Beat-to-beat blood pressure and cerebral blood flow velocity responses were assessed during a passive seated orthostatic stress test (PSOST). In healthy controls, PSOST responses were compared to head up tilt (the ‘gold-standard’). In a cohort of long-term care residents, data from PS...

Long-term evolution of brainstem electrical evoked responses to sound after restricted ablation of the auditory cortex.

Directory of Open Access Journals (Sweden)

Verónica Lamas

Full Text Available INTRODUCTION: This study aimed to assess the top-down control of sound processing in the auditory brainstem of rats. Short latency evoked responses were analyzed after unilateral or bilateral ablation of auditory cortex. This experimental paradigm was also used towards analyzing the long-term evolution of post-lesion plasticity in the auditory system and its ability to self-repair. METHOD: Auditory cortex lesions were performed in rats by stereotactically guided fine-needle aspiration of the cerebrocortical surface. Auditory Brainstem Responses (ABR were recorded at post-surgery day (PSD 1, 7, 15 and 30. Recordings were performed under closed-field conditions, using click trains at different sound intensity levels, followed by statistical analysis of threshold values and ABR amplitude and latency variables. Subsequently, brains were sectioned and immunostained for GAD and parvalbumin to assess the location and extent of lesions accurately. RESULTS: Alterations in ABR variables depended on the type of lesion and post-surgery time of ABR recordings. Accordingly, bilateral ablations caused a statistically significant increase in thresholds at PSD1 and 7 and a decrease in waves amplitudes at PSD1 that recover at PSD7. No effects on latency were noted at PSD1 and 7, whilst recordings at PSD15 and 30 showed statistically significant decreases in latency. Conversely, unilateral ablations had no effect on auditory thresholds or latencies, while wave amplitudes only decreased at PSD1 strictly in the ipsilateral ear. CONCLUSION: Post-lesion plasticity in the auditory system acts in two time periods: short-term period of decreased sound sensitivity (until PSD7, most likely resulting from axonal degeneration; and a long-term period (up to PSD7, with changes in latency responses and recovery of thresholds and amplitudes values. The cerebral cortex may have a net positive gain on the auditory pathway response to sound.

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...

Pediatric polytrauma : Short-term and long-term outcomes

NARCIS (Netherlands)

vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

Visual long-term memory for spatial frequency?

Science.gov (United States)

Lages, Martin; Paul, Aileen

2006-06-01

It has been suggested that a visual long-term memory based on a sensory representation of the stimulus accounts for discrimination performance when the reference and the test stimuli are separated in time. Decision processes involved in setting response criteria, however, may also contribute to discrimination performance. In the present study, it is shown that under proper control, spatial frequency discrimination thresholds from a group of observers, each performing on a single trial, are significantly higher for a 2-h than for a 5-sec retention interval, whereas thresholds from individual observers performing in repeated trials with a 2-h retention interval are considerably lower. The results suggest that discrimination performance may depend on the retention of task-relevant information, such as a response criterion, rather than on visual memory of the stimulus. It is concluded that it is risky to postulate a high-fidelity long-term visual memory for spatial frequency on the basis of psychophysical group discrimination thresholds.

The role of stress in absenteeism: cortisol responsiveness among patients on long-term sick leave.

Directory of Open Access Journals (Sweden)

Henrik B Jacobsen

Full Text Available OBJECTIVE: This study aimed to (1 See whether increased or decreased variation relate to subjective reports of common somatic and psychological symptoms for a population on long-term sick leave; and (2 See if this pattern in variation is correlated with autonomic activation and psychological appraisal. METHODS: Our participants (n = 87 were referred to a 3.5-week return-to-work rehabilitation program, and had been on paid sick leave >8 weeks due to musculoskeletal pain, fatigue and/or common mental disorders. An extensive survey was completed, addressing socio-demographics, somatic and psychological complaints. In addition, a physician and a psychologist examined the participants, determining baseline heart rate, medication use and SCID-I diagnoses. During the 3.5-week program, the participants completed the Trier Social Stress Test for Groups. Participants wore heart rate monitors and filled out Visual Analogue Scales during the TSST-G. RESULTS: Our participants presented a low cortisol variation, with mixed model analyses showing a maximal increase in free saliva cortisol of 26% (95% CI, 0.21-0.32. Simultaneously, the increase in heart rate and Visual Analogue Scales was substantial, indicating autonomic and psychological activation consistent with intense stress from the Trier Social Stress Test for Groups. CONCLUSIONS: The current findings are the first description of a blunted cortisol response in a heterogeneous group of patients on long-term sick leave. The results suggest lack of cortisol reactivity as a possible biological link involved in the pathway between stress, sustained activation and long-term sick leave.

Endogenous BDNF is required for long-term memory formation in the rat parietal cortex.

Science.gov (United States)

Alonso, Mariana; Bekinschtein, Pedro; Cammarota, Martín; Vianna, Monica R M; Izquierdo, Iván; Medina, Jorge H

2005-01-01

Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory consolidation in the neocortex. Brain-derived neurotrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in hippocampal and cortical neurons. We have recently demonstrated that endogenous BDNF in the hippocampus is involved in memory formation. Here we examined the role of BDNF in the parietal cortex (PCx) in short-term (STM) and long-term memory (LTM) formation of a one-trial fear-motivated learning task in rats. Bilateral infusions of function-blocking anti-BDNF antibody into the PCx impaired both STM and LTM retention scores and decreased the phosphorylation state of cAMP response element-binding protein (CREB). In contrast, intracortical administration of recombinant human BDNF facilitated LTM and increased CREB activation. Moreover, inhibitory avoidance training is associated with a rapid and transient increase in phospho-CREB/total CREB ratio in the PCx. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of inhibitory avoidance learning, possibly involving CREB activation-dependent mechanisms. The present data support the idea that early sensory areas constitute important components of the networks subserving memory formation and that information processing in neocortex plays an important role in memory formation.

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

Science.gov (United States)

Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

Intrahippocampal Glutamine Administration Inhibits mTORC1 Signaling and Impairs Long-Term Memory

Science.gov (United States)

Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; McKenna, James, III.; Moore, Anthony N.; Gambello, Michael J.; Dash, Pramod K.

2015-01-01

The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino…

Short-term and long-term memory in early temporal lobe dysfunction.

Science.gov (United States)

Hershey, T; Craft, S; Glauser, T A; Hale, S

1998-01-01

Following medial temporal damage, mature humans are impaired in retaining new information over long delays but not short delays. The question of whether a similar dissociation occurs in children was addressed by testing children (ages 7-16) with unilateral temporal lobe epilepsy (TLE) and controls on short- and long-term memory tasks, including a spatial delayed response task (SDR). Early-onset TLE did not affect performance on short delays on SDR, but it did impair performance at the longest delay (60 s), similar to adults with unilateral medial temporal damage. In addition, early-onset TLE affected performance on pattern recall, spatial span, and verbal span with rehearsal interference. No differences were found on story recall or on a response inhibition task.

Comment and response document for the long-term surveillance plan for the Bodo Canyon Disposal Site, Durango, Colorado, Revision 0

International Nuclear Information System (INIS)

1995-11-01

This report contains the comment and response document for the Draft Long-Term Surveillance Plan of the Bodo Canyon Site in Durango, California. This is a part of the Uranium Mill Tailings Remedial Action (UMTRA) Project. Questions and comments regarding specific sections or statements in the report are described and then a response to each review comment or question is provided

Numerical simulation of gender differences in a long-term microgravity exposure

Science.gov (United States)

Perez-Poch, Antoni

The objective of this work is to analyse and simulate gender differences when individuals are exposed to long-term microgravity. Risk probability of a health impairment which may put in jeopardy a long-term mission is also evaluated. Computer simulations are becoming a promising research line of work, as physiological models become more and more sophisticated and reliable. Technological advances in state-of-the-art hardware technology and software allow nowadays for better and more accurate simulations of complex phenomena, such as the response of the human cardiovascular system to long-term exposure to microgravity. Experimental data for long-term missions are difficult to achieve and reproduce, therefore the predictions of computer simulations are of a major importance in this field. Our approach is based on a previous model developed and implemented in our laboratory (NELME: Numerical Evaluation of Long-term Microgravity Effects). The software simulates the behaviour of the cardiovascular system and different human organs, has a modular architecture, and allows to introduce perturbations such as physical exercise or countermeasures. The implementation is based on a complex electricallike model of this control system, using inexpensive software development frameworks, and has been tested and validated with the available experimental data. Gender differences have been implemented for this specific work, as an adjustment of a number of parameters that are included in the model. Women versus men physiological differences have been therefore taken into account, based upon estimations from the physiology bibliography. A number of simulations have been carried out for long-term exposure to microgravity. Gravity varying from Earth-based to zero, and time exposure are the two main variables involved in the construction of results, including responses to patterns of physical aerobical exercise, and also thermal stress simulating an extra-vehicular activity. Results show

Modeling long-term host cell-Giardia lamblia interactions in an in vitro co-culture system.

Directory of Open Access Journals (Sweden)

Bridget S Fisher

Full Text Available Globally, there are greater than 700,000 deaths per year associated with diarrheal disease. The flagellated intestinal parasite, Giardia lamblia, is one of the most common intestinal pathogens in both humans and animals throughout the world. While attached to the gastrointestinal epithelium, Giardia induces epithelial cell apoptosis, disrupts tight junctions, and increases intestinal permeability. The underlying cellular and molecular mechanisms of giardiasis, including the role lamina propria immune cells, such as macrophages, play in parasite control or clearance are poorly understood. Thus far, one of the major obstacles in ascertaining the mechanisms of Giardia pathology is the lack of a functionally relevant model for the long-term study of the parasite in vitro. Here we report on the development of an in vitro co-culture model which maintains the basolateral-apical architecture of the small intestine and allows for long-term survival of the parasite. Using transwell inserts, Caco-2 intestinal epithelial cells and IC-21 macrophages are co-cultured in the presence of Giardia trophozoites. Using the developed model, we show that Giardia trophozoites survive over 21 days and proliferate in a combination media of Caco-2 cell and Giardia medium. Giardia induces apoptosis of epithelial cells through caspase-3 activation and macrophages do not abrogate this response. Additionally, macrophages induce Caco-2 cells to secrete the pro-inflammatory cytokines, GRO and IL-8, a response abolished by Giardia indicating parasite induced suppression of the host immune response. The co-culture model provides additional complexity and information when compared to a single-cell model. This model will be a valuable tool for answering long-standing questions on host-parasite biology that may lead to discovery of new therapeutic interventions.

The Long-Term Effects of Youth Unemployment

Science.gov (United States)

Mroz, Thomas A.; Savage, Timothy H.

2006-01-01

Using NLSY data, we examine the long-term effects of youth unemployment on later labor market outcomes. Involuntary unemployment may yield suboptimal investments in human capital in the short run. A theoretical model of dynamic human capital investment predicts a rational "catch-up" response. Using semiparametric techniques to control for the…

Individual decision making in the non-purchase of long-term care insurance.

Science.gov (United States)

Curry, Leslie A; Robison, Julie; Shugrue, Noreen; Keenan, Patricia; Kapp, Marshall B

2009-08-01

Although prior research suggests that economic, behavioral, and psychosocial factors influence decisions not to purchase long-term care insurance, few studies have examined the interplay among these factors in depth and from the consumer's point of view. This study was intended to further illuminate these considerations, generate hypotheses about non-purchasing decisions, and inform the design of policies that are responsive to concerns and preferences of potential purchasers. Qualitative study using 32 in-depth interviews and 6 focus groups, following a grounded theory approach. Five themes characterize decisions not to purchase long-term care insurance: (a) the determination that a policy is "too costly" reflects highly individualized and complex trade-offs not solely economic in nature, (b) non-purchasers are skeptical about the viability and integrity of private insurance companies and seek an unbiased source of information, (c) family dynamics play an important role in insurance decisions, (d) contemplating personal risk for long-term care triggers psychological responses that have implications for decision making, and (e) non-purchasers feel inadequately informed and overwhelmed by the process of deciding whether to purchase long-term care insurance. States are seeking to offset escalating Medicaid long-term care expenditures through a variety of policy mechanisms, including stimulating individual purchase of long-term care insurance. Findings suggest that economic incentives such as lowering premiums will be necessary but not sufficient to attract appropriate candidates. Attention to behavioral and psychosocial factors is essential to designing incentives that are responsive to concerns and preferences of potential purchasers.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Science.gov (United States)

Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

2015-01-01

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Directory of Open Access Journals (Sweden)

Vanessa Manchim Favaro

Full Text Available Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM, fear conditioning and elevated plus maze (EPM performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Long-term nitrogen regulation of forest carbon sequestration

Science.gov (United States)

Yang, Y.; Luo, Y.

2009-12-01

It is well established that nitrogen (N) limits plant production but unclear how N regulates long-term terrestrial carbon (C) sequestration in response to rising atmospheric C dioxide (CO2)(Luo et al., 2004). Most experimental evidence on C-N interactions is primarily derived from short-term CO2 manipulative studies (e.g. Oren et al., 2001; Reich et al., 2006a), which abruptly increase C inputs into ecosystems and N demand from soil while atmospheric CO2 concentration in the real world is gradually increasing over time (Luo & Reynolds, 1999). It is essential to examine long-term N regulations of C sequestration in natural ecosystems. Here we present results of a synthesis of more than 100 studies on long-term C-N interactions during secondary succession. C significantly accumulates in plant, litter and forest floor in most studies, and in mineral soil in one-third studies during stand development. Substantial increases in C stock are tightly coupled with N accretion. The C: N ratio in plant increases with stand age in most cases, but remains relatively constant in litter, forest floor and mineral soil. Our results suggest that natural ecosystems could have the intrinsic capacity to maintain long-term C sequestration through external N accrual, high N use efficiency, and efficient internal N cycling.

Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease.

Science.gov (United States)

Huang, Yuqi; Zhao, Zhe; Wei, Xiaoli; Zheng, Yong; Yu, Jianqiang; Zheng, Jianquan; Wang, Liyun

2016-07-01

Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long-term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved. Male Sprague-Dawley rats (SD) were intraperitoneally injected with THP (0.3 and 1.0 mg/kg) or normal saline (NS) for 7 months. Alterations in cognitive and behavioral performance were assessed using the Morris water maze (MWM) and open field tests. After behavior tests, whole genome oligo microarrays, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence-confocal were used to investigate the global mechanisms underlying THP-induced neuropathology with aging. Compared with NS controls, the MWM test results showed that THP-treated rats exhibited significantly extended mean latencies during the initial 3 months of testing; however, this behavioral deficit was restored between the fourth and sixth month of MWM testing. The same tendencies were confirmed by MWM probe and open field tests. Gene microarray analysis identified 68 (47 %) upregulated and 176 (53 %) downregulated genes in the "THP-aging" vs. "NS-aging" group. The most significant populations of genes downregulated by THP were the immune response-, antigen processing and presentation-, and major histocompatibility complex (MHC)-related genes, as validated by qRT-PCR. The decreased expression of MHC class I in THP-treated aging brains was confirmed by confocal analysis. Notably, long-term THP treatment primed hippocampal and cortical microglia to

Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

DEFF Research Database (Denmark)

Kyte, Jon Amund; Trachsel, Sissel; Risberg, Bente

2009-01-01

Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses...... in long-term survivors after peptide vaccination. There were three main study aims: (1) to characterize the immune response in patients with a possible clinical benefit. (2) To analyze the long-term development of responses and effects of booster vaccination. (3) To investigate whether the Th1/Th2...... display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFbeta receptor II. Cytokine profiling on the long-term survivors demonstrates high IFN gamma/IL10-ratios, favoring immunity over tolerance, and secretion of multiple chemokines likely to mobilize the innate...

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

Directory of Open Access Journals (Sweden)

Iwai Ohbayashi

2018-01-01

Full Text Available The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses.

Science.gov (United States)

Ohbayashi, Iwai; Sugiyama, Munetaka

2017-01-01

The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

Long-term complications in Hodgkin's lymphoma survivors.

Science.gov (United States)

Kilickap, Saadettin; Barista, Ibrahim; Ulger, Sukran; Celik, Ismail; Selek, Ugur; Güllü, Ibrahim; Yildiz, Ferah; Kars, Ayse; Ozisik, Yavuz; Tekuzman, Gülten

2012-01-01

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.

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

Cellular Response to Ionizing Radiation: A MicroRNA Story

Science.gov (United States)

Halimi, Mohammad; Asghari, S. Mohsen; Sariri, Reyhaneh; Moslemi, Dariush; Parsian, Hadi

2012-01-01

MicroRNAs (miRNAs) represent a class of small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They play a crucial role in diverse cellular pathways. Ionizing radiation (IR) is one of the most important treatment protocols for patients that suffer from cancer and affects directly or indirectly cellular integration. Recently it has been discovered that microRNA-mediated gene regulation interferes with radio-related pathways in ionizing radiation. Here, we review the recent discoveries about miRNAs in cellular response to IR. Thoroughly understanding the mechanism of miRNAs in radiation response, it will be possible to design new strategies for improving radiotherapy efficiency and ultimately cancer treatment. PMID:24551775

Near-Term Actions to Address Long-Term Climate Risk

Science.gov (United States)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Dynamic sensorimotor planning during long-term sequence learning: the role of variability, response chunking and planning errors.

Science.gov (United States)

Verstynen, Timothy; Phillips, Jeff; Braun, Emily; Workman, Brett; Schunn, Christian; Schneider, Walter

2012-01-01

Many everyday skills are learned by binding otherwise independent actions into a unified sequence of responses across days or weeks of practice. Here we looked at how the dynamics of action planning and response binding change across such long timescales. Subjects (N = 23) were trained on a bimanual version of the serial reaction time task (32-item sequence) for two weeks (10 days total). Response times and accuracy both showed improvement with time, but appeared to be learned at different rates. Changes in response speed across training were associated with dynamic changes in response time variability, with faster learners expanding their variability during the early training days and then contracting response variability late in training. Using a novel measure of response chunking, we found that individual responses became temporally correlated across trials and asymptoted to set sizes of approximately 7 bound responses at the end of the first week of training. Finally, we used a state-space model of the response planning process to look at how predictive (i.e., response anticipation) and error-corrective (i.e., post-error slowing) processes correlated with learning rates for speed, accuracy and chunking. This analysis yielded non-monotonic association patterns between the state-space model parameters and learning rates, suggesting that different parts of the response planning process are relevant at different stages of long-term learning. These findings highlight the dynamic modulation of response speed, variability, accuracy and chunking as multiple movements become bound together into a larger set of responses during sequence learning.

2003 Long-Term Surveillance and Maintenance Program Report

International Nuclear Information System (INIS)

2004-01-01

are part of long-term site management. In response to post-closure care requirements set forth in UMTRCA, DOE Headquarters established the Long-Term Surveillance and Maintenance (LTS&M) Program in 1988 at the DOE office in Grand Junction, Colorado. The program assumed long-term management responsibility for sites remediated under UMTRCA and other programs. Since its inception, the LTS&M Program has evolved in response to changing stakeholder needs, improvements in technology, and the addition of more DOE sites as remediation is completed. The mission of the LTS&M Program was to fulfill DOE's responsibility to implement all activities necessary to ensure regulatory compliance and to protect the public and the environment from long-lived wastes associated with the nation's nuclear energy, weapons, and research activities. Key components of the LTS&M Program included stakeholder participation, site monitoring and maintenance, records and information management, and research and technology transfer. This report presents summaries of activities conducted in 2003 in fulfillment of the LTS&M Program mission. On December 15, 2003, DOE established the Office of Legacy Management (LM) to allow for optimum management of DOE's legacy responsibilities. Offices are located in Washington, DC, Grand Junction, Colorado, Morgantown, West Virginia, and Pittsburgh, Pennsylvania, to perform long-term site management, land management, site transition support, records management, and other related tasks. All activities formerly conducted under the LTS&M Program have been incorporated into the Office of Land and Site Management (LM-50), as well as management of remedies involving ground water and surface water contaminated by former processing activities

2003 Long-Term Surveillance and Maintenance Program Report

Energy Technology Data Exchange (ETDEWEB)

None

2004-07-01

are part of long-term site management. In response to post-closure care requirements set forth in UMTRCA, DOE Headquarters established the Long-Term Surveillance and Maintenance (LTS&M) Program in 1988 at the DOE office in Grand Junction, Colorado. The program assumed long-term management responsibility for sites remediated under UMTRCA and other programs. Since its inception, the LTS&M Program has evolved in response to changing stakeholder needs, improvements in technology, and the addition of more DOE sites as remediation is completed. The mission of the LTS&M Program was to fulfill DOE’s responsibility to implement all activities necessary to ensure regulatory compliance and to protect the public and the environment from long-lived wastes associated with the nation’s nuclear energy, weapons, and research activities. Key components of the LTS&M Program included stakeholder participation, site monitoring and maintenance, records and information management, and research and technology transfer. This report presents summaries of activities conducted in 2003 in fulfillment of the LTS&M Program mission. On December 15, 2003, DOE established the Office of Legacy Management (LM) to allow for optimum management of DOE’s legacy responsibilities. Offices are located in Washington, DC, Grand Junction, Colorado, Morgantown, West Virginia, and Pittsburgh, Pennsylvania, to perform long-term site management, land management, site transition support, records management, and other related tasks. All activities formerly conducted under the LTS&M Program have been incorporated into the Office of Land and Site Management (LM–50), as well as management of remedies involving ground water and surface water contaminated by former processing activities.

Measurement of long term surface inflation signals at GLISP with two independent tiltmeter systems

Energy Technology Data Exchange (ETDEWEB)

Jones, F.W.; Rogers, J.S.; Ertman, M.E.; Thibault, J.

1989-01-06

Long-term monitoring at an Alberta oil recovery project was conducted to trace the Earth surface tilt response to the steam injection and related water movement through the formations at the site. Attempts were also made to relate the tilt to the various enhancement process activities in order to improve understanding of the long-term recovery process. Field comparisons were made between biaxial mercury-level borehole tiltmeters and biaxial bubble sensor tiltmeters, and some results are presented. It was generally found that the two types of tiltmeters reported similar tilt responses. Examples are shown of tilt response correlated with process activity and of a long-term tilt migration effect. 6 figs.

Integrated response and transit time distributions of watersheds by combining hydrograph separation and long-term transit time modeling

Directory of Open Access Journals (Sweden)

M. C. Roa-García

2010-08-01

Full Text Available We present a new modeling approach analyzing and predicting the Transit Time Distribution (TTD and the Response Time Distribution (RTD from hourly to annual time scales as two distinct hydrological processes. The model integrates Isotope Hydrograph Separation (IHS and the Instantaneous Unit Hydrograph (IUH approach as a tool to provide a more realistic description of transit and response time of water in catchments. Individual event simulations and parameterizations were combined with long-term baseflow simulation and parameterizations; this provides a comprehensive picture of the catchment response for a long time span for the hydraulic and isotopic processes. The proposed method was tested in three Andean headwater catchments to compare the effects of land use on hydrological response and solute transport. Results show that the characteristics of events and antecedent conditions have a significant influence on TTD and RTD, but in general the RTD of the grassland dominated catchment is concentrated in the shorter time spans and has a higher cumulative TTD, while the forest dominated catchment has a relatively higher response distribution and lower cumulative TTD. The catchment where wetlands concentrate shows a flashier response, but wetlands also appear to prolong transit time.

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...

Dissociating Long and Short-term Memory in Three-Month-Old Infants Using the Mismatch Response to Voice Stimuli.

Science.gov (United States)

Zinke, Katharina; Thöne, Leonie; Bolinger, Elaina M; Born, Jan

2018-01-01

Auditory event-related potentials (ERPs) have been successfully used in adults as well as in newborns to discriminate recall of longer-term and shorter-term memories. Specifically the Mismatch Response (MMR) to deviant stimuli of an oddball paradigm is larger if the deviant stimuli are highly familiar (i.e., retrieved from long-term memory) than if they are unfamiliar, representing an immediate change to the standard stimuli kept in short-term memory. Here, we aimed to extend previous findings indicating a differential MMR to familiar and unfamiliar deviants in newborns (Beauchemin et al., 2011), to 3-month-old infants who are starting to interact more with their social surroundings supposedly based on forming more (social) long-term representations. Using a voice discrimination paradigm, each infant was repeatedly presented with the word "baby" (400 ms, interstimulus interval: 600 ms, 10 min overall duration) pronounced by three different female speakers. One voice that was unfamiliar to the infants served as the frequently presented "standard" stimulus, whereas another unfamiliar voice served as the "unfamiliar deviant" stimulus, and the voice of the infant's mother served as the "familiar deviant." Data collection was successful for 31 infants (mean age = 100 days). The MMR was determined by the difference between the ERP to standard stimuli and the ERP to the unfamiliar and familiar deviant, respectively. The MMR to the familiar deviant (mother's voice) was larger, i.e., more positive, than that to the unfamiliar deviant between 100 and 400 ms post-stimulus over the frontal and central cortex. However, a genuine MMR differentiating, as a positive deflection, between ERPs to familiar deviants and standard stimuli was only found in the 300-400 ms interval. On the other hand, a genuine MMR differentiating, as a negative deflection, between ERPs to unfamiliar deviants from ERPs to standard stimuli was revealed for the 200-300 ms post-stimulus interval. Overall

Assessing the market for long-term care services.

Science.gov (United States)

Rice, J A; Taylor, S

1984-02-01

Traditionally, long-term care services have been used by a diverse marketplace. The chronically ill, developmentally disabled, mentally ill and aging population has looked to long-term care support services as a means of physical and emotional support. Much of the time these services were housed together for the sake of efficiency. The enormous burden these services are creating on the economy, and the growing aging population, have forced the recognition that long-term care service delivery systems must change. Alternate programming for long-term care services that reach out into the community and into individual homes is becoming an attractive approach to meeting the growing demands of the marketplace. Home health, specialized housing and creative funding mechanisms such as HMOs, are examples of initiatives undertaken by healthcare organizations that view diversification as a vehicle for survival. Market research techniques that have been used in other industries are being adapted to the healthcare industry to ensure the proper mix of services that are demanded by older, more knowledgeable consumers. The programs of the future will be market driven, with the ability of the individual to pay for such services playing a significant role. The healthcare provider of today is in a position to serve the community in new ways. By becoming an integral link in the long-term care system and by developing new programs, the organization can serve as a catalyst for change. It is up to the governing bodies and managers of these facilities to become visionaries and to accept responsibility for assessing the market for long-term care services and to guide their organization into the future.

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.

Humoral and cellular immune responses to modified hepatitis B ...

African Journals Online (AJOL)

These findings indicate that the vaccine induced both a humoral and cellular ... Keywords: Hepatitis B virus, Plasmid DNA, Vaccine, Spleen cytokines, Humoral and cellular immune responses ... produced in mice. ... were performed and HBsAg specific IgM and IgG ..... and protection elicited against Plasmodium berghei.

Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability.

Science.gov (United States)

Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

2017-05-15

The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ. © 2017. Published by The Company of Biologists Ltd.

Medium-term and long-term outcomes of interventions for primary psoas tendinopathy.

Science.gov (United States)

Garala, Kanai; Prasad, Vishnu; Jeyapalan, Kanagaratnam; Power, Richard A

2014-05-01

To assess medium- and long-term outcomes of psoas tendinopathy to psoas tenotomy and image-guided steroid injections. This is a 14-year retrospective case-control study to identify the efficacy of psoas tenotomy and image-guided steroid injections. This study was undertaken in a secondary care setting. Patients with confirmed psoas tendinopathy were followed up by postal questionnaire, which included a nonarthritic hip score (NAHS) and a study patient satisfaction questionnaire. Patients underwent image-guided steroid injections. Depending on the analgesic or symptomatic relief, some patients proceeded to psoas tenotomy. Response to steroid injection. Pain relief and symptomatic relief after the surgery. Twenty-three patients were reviewed with a 70% follow-up over a time of 49 months for surgery (range, 13-144 months) and 77 months for injection (range, 14-160 months). Eight patients had a lasting response to injection and required no further intervention, and 15 patients proceeded to psoas tenotomy using a medial Ludloff approach. The average NAHS scores after the surgery and injection were 66.15 and 76.08, respectively. Ten patients reported pain relief after their tenotomy, and 5 patients reported no change in pain. All 8 patients, who only underwent injection, reported lasting pain relief. Local steroid injections can provide long-term relief for patients presenting with psoas tendinopathy. For those patients with only temporary relief from injection, psoas tenotomy can provide good long-term pain relief.

Effects of grasp compatibility on long-term memory for objects.

Science.gov (United States)

Canits, Ivonne; Pecher, Diane; Zeelenberg, René

2018-01-01

Previous studies have shown action potentiation during conceptual processing of manipulable objects. In four experiments, we investigated whether these motor actions also play a role in long-term memory. Participants categorized objects that afforded either a power grasp or a precision grasp as natural or artifact by grasping cylinders with either a power grasp or a precision grasp. In all experiments, responses were faster when the affordance of the object was compatible with the type of grasp response. However, subsequent free recall and recognition memory tasks revealed no better memory for object pictures and object names for which the grasp affordance was compatible with the grasp response. The present results therefore do not support the hypothesis that motor actions play a role in long-term memory. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Circulating sclerostin is elevated in short-term and reduced in long-term SCI.

Science.gov (United States)

Battaglino, Ricardo A; Sudhakar, Supreetha; Lazzari, Antonio A; Garshick, Eric; Zafonte, Ross; Morse, Leslie R

2012-09-01

Spinal cord injury (SCI) causes profound bone loss due to muscle paralysis resulting in the inability to walk. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have demonstrated increased sclerostin in response to mechanical unloading that is reversed with reloading. Although sclerostin inhibition has been proposed as a potential therapy for bone loss, it is not known if sclerostin levels vary with duration of SCI in humans. We analyzed circulating sclerostin in 155 men with varying degrees of SCI who were 1 year or more post-injury. We report that sclerostin levels are greatest in subjects with short-term SCI (≤5 years post-injury) and decrease significantly over the first 5 years post-injury. There was no association between sclerostin and injury duration in subjects with long-term SCI (>5 years post-injury). In subjects with long-term SCI, sclerostin levels were positively associated with lower extremity bone density and bone mineral content. These data suggest that sclerostin levels are initially increased after SCI in response to mechanical unloading. This response is time-limited and as bone loss progresses, circulating sclerostin is lowest in subjects with severe osteoporosis. These findings support a dual role for sclerostin after SCI: a therapeutic target in acute SCI, and a biomarker of osteoporosis severity in chronic SCI. Copyright © 2012 Elsevier Inc. All rights reserved.

Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

Directory of Open Access Journals (Sweden)

Hong Qin

2010-01-01

Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

Characterization of the long-term immune response to vaccination against Mycobacterium avium subsp. paratuberculosis in Danish dairy cows

DEFF Research Database (Denmark)

Thomsen, Vibeke Thulstrup; Nielsen, Søren Saxmose; Thakur, Aneesh

2012-01-01

including 895 vaccinated and 2526 non-vaccinated dairy cows in 9 Danish dairy herds aiming at characterizing the long-term antibody-response to vaccination; and (2) a cross-sectional study of responses in the IFN-γ assay carried out in 140 vaccinated animals in two herds to evaluate the effect....... The prevalence of antibody responses of the vaccinated animals was relatively constant from 2 to 6years of age, but decreased in older animals. Among the 140 vaccinated animals 88% tested positive with the IFN-γ test to johnin PPD and 50% responded to PPDb with IFN-γ production above a similar cut-off. Although...

Employer, insurance, and health system response to long-term sick leave in the public sector: policy implications.

Science.gov (United States)

Heijbel, Bodil; Josephson, Malin; Jensen, Irene; Vingård, Eva

2005-06-01

This study has been conducted to describe the situation of long-term sick-listed persons employed in the public sector regarding the medical reasons of their sick leave, the duration of their problems, the duration of the actual sick leave, rehabilitation support, rehabilitation measures, and the persons expectations of the future. Response rate of a postal questionnaire, where 484 women and 51 men on long-term sick leave answered, was 69%. The study-group consisted of 90% women with a median age of 50 years. The most common reasons for sick listing were long-lasting musculoskeletal problems, especially neck/shoulder pain, low back pain and osteoarthritis or other joint problems and mental problems, especially depression and burn-out syndromes. Forty-seven procent of the men and 57% of the women had been on the sick list for more than a year. Only half of them had been subjected to the legally required rehabilitation investigation of the employer This half got access to rehabilitation programs and/or vocational rehabilitation to a greater extent than those who not had been subjected to rehabilitation investigation. Less than half had been in contact with the workplace-connected rehabilitation actors, the Occupational Health Service or the Trade Union. In spite of this the sick-listed persons had a positive view of their future return to work. For long-term sick-listed persons in the public sector, there is a great potential for improvements of the rehabilitation at the workplace arena, in the involvement and cooperation between the already existing rehabilitation actors, in order to promote return to work.

Long-term selection experiment with Afrikaner cattle

African Journals Online (AJOL)

Mario Beffa

Long-term selection experiment with Afrikaner cattle. 3. Selection applied and response in calf growth traits. L.M. Beffa. 1,2,3. , J.B. van Wyk. 1# and G.J. Erasmus. 1. 1 University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa. 2 Matopos Research Station, P. Bag K5137, Bulawayo, Zimbabwe ...

Wnt Signaling Is Required for Long-Term Memory Formation

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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.

Spirally-patterned pinhole arrays for long-term fluorescence cell imaging.

Science.gov (United States)

Koo, Bon Ung; Kang, YooNa; Moon, SangJun; Lee, Won Gu

2015-11-07

Fluorescence cell imaging using a fluorescence microscope is an extensively used technique to examine the cell nucleus, internal structures, and other cellular molecules with fluorescence response time and intensity. However, it is difficult to perform high resolution cell imaging for a long period of time with this technique due to necrosis and apoptosis depending on the type and subcellular location of the damage caused by phototoxicity. A large number of studies have been performed to resolve this problem, but researchers have struggled to meet the challenge between cellular viability and image resolution. In this study, we employ a specially designed disc to reduce cell damage by controlling total fluorescence exposure time without deterioration of the image resolution. This approach has many advantages such as, the apparatus is simple, cost-effective, and easily integrated into the optical pathway through a conventional fluorescence microscope.

The role of nuclear factor κB in the cellular response to different radiation qualities

International Nuclear Information System (INIS)

Koch, Kristina

2013-01-01

Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

The role of nuclear factor κB in the cellular response to different radiation qualities

Energy Technology Data Exchange (ETDEWEB)

Koch, Kristina

2013-04-11

Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

Science.gov (United States)

White, André O.; Wood, Marcelo A.

2013-01-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. PMID:24149059

Genomic counter-stress changes induced by the relaxation response.

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Jeffery A Dusek

2008-07-01

Full Text Available Mind-body practices that elicit the relaxation response (RR have been used worldwide for millennia to prevent and treat disease. The RR is characterized by decreased oxygen consumption, increased exhaled nitric oxide, and reduced psychological distress. It is believed to be the counterpart of the stress response that exhibits a distinct pattern of physiology and transcriptional profile. We hypothesized that RR elicitation results in characteristic gene expression changes that can be used to measure physiological responses elicited by the RR in an unbiased fashion.We assessed whole blood transcriptional profiles in 19 healthy, long-term practitioners of daily RR practice (group M, 19 healthy controls (group N(1, and 20 N(1 individuals who completed 8 weeks of RR training (group N(2. 2209 genes were differentially expressed in group M relative to group N(1 (p<0.05 and 1561 genes in group N(2 compared to group N(1 (p<0.05. Importantly, 433 (p<10(-10 of 2209 and 1561 differentially expressed genes were shared among long-term (M and short-term practitioners (N(2. Gene ontology and gene set enrichment analyses revealed significant alterations in cellular metabolism, oxidative phosphorylation, generation of reactive oxygen species and response to oxidative stress in long-term and short-term practitioners of daily RR practice that may counteract cellular damage related to chronic psychological stress. A significant number of genes and pathways were confirmed in an independent validation set containing 5 N(1 controls, 5 N(2 short-term and 6 M long-term practitioners.This study provides the first compelling evidence that the RR elicits specific gene expression changes in short-term and long-term practitioners. Our results suggest consistent and constitutive changes in gene expression resulting from RR may relate to long term physiological effects. Our study may stimulate new investigations into applying transcriptional profiling for accurately measuring

Nursing Assistants for Long-Term Care. Performance-Based Instructional Materials.

Science.gov (United States)

Indiana Univ., Bloomington. Vocational Education Services.

This guide is intended to assist students enrolled in programs to train nursing assistants for employment in an Indiana long-term health care facility. The first part discusses human development (growth, aging, and dying); communication with residents; sexuality; legal, ethical, and professional responsibilities of nursing assistants in long-term…

Two Pairs of Mushroom Body Efferent Neurons Are Required for Appetitive Long-Term Memory Retrieval in Drosophila

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Pierre-Yves Plaçais

2013-11-01

Full Text Available One of the challenges facing memory research is to combine network- and cellular-level descriptions of memory encoding. In this context, Drosophila offers the opportunity to decipher, down to single-cell resolution, memory-relevant circuits in connection with the mushroom bodies (MBs, prominent structures for olfactory learning and memory. Although the MB-afferent circuits involved in appetitive learning were recently described, the circuits underlying appetitive memory retrieval remain unknown. We identified two pairs of cholinergic neurons efferent from the MB α vertical lobes, named MB-V3, that are necessary for the retrieval of appetitive long-term memory (LTM. Furthermore, LTM retrieval was correlated to an enhanced response to the rewarded odor in these neurons. Strikingly, though, silencing the MB-V3 neurons did not affect short-term memory (STM retrieval. This finding supports a scheme of parallel appetitive STM and LTM processing.

Carica Papaya Seed Extract Enhances Cellular Response to Stress ...

African Journals Online (AJOL)

Therefore, the present study was carried out to investigate the role of Carica papaya seed (CPS) extract that contains, Benzyl Isothiocyanates, one of the inducers of phase II enzymes in the regulation of cellular stress. The cellular responses were observed in U937 cells (human monocyte/macrophage cell line) at the ...

Cadmium toxicity studies under long term-low level exposure (LLE) conditions. I

International Nuclear Information System (INIS)

Sabbioni, E.; Marafante, E.; Amantini, L.; Ubertalli, L.; Pietra, R.

1978-01-01

A long term-low level exposure (LLE) experiment was conducted on rats to determine the metabolic patterns for realistic dietary levels of cadmium. Male rats fed with 61 ppb of cadmium ad libitum, 50 labelled with 109 Cd radiotracer as cadmium chloride via drinking mineral water and 11 unlabelled via food for 2 years. The diet was characterized in its metal content by neutron activation analysis to obtain the total dietary intake of different elements. The kidney was found to be the tissue with the major concentration of cadmium which accumulated continuously during the experiment. The variation of the accumulation pattern of Cd concentration in the liver and intestine indicated an initial rapid increase of Cd during the first 100 days. After this period an apparent equilibrium was attained in both these tissues until the end of the study. The intracellular distribution of cadmium in kidneys, liver, intestine and pancreas were similar, the cytosol fractions containing about 80% of the cellular cadmium. Dialysis experiments indicated that significant amounts of cadmium were able to be associated with cellular organelles, the mitochondria representing the most important organelle capable of binding cadmium. The cytoplasmatic Cd-profiles obtained at various stages of the experiment showed that the metal was only bound to a low-molecular-weight component, cadmium-binding protein (CdBP), which represents the specific cellular-binding component for cadmium under the long term-low level exposure (LLE) conditions. No significant variations in the concentrations of the elements in different organs were observed in animals supplemented with 109 Cd in respect to 109 Cd untreated controls. (Auth.)

Long-term capital planning considering nuclear plant life-cycle management

International Nuclear Information System (INIS)

Negin, C.A.; Simpson, J.M.; Hostetler, D.R.

1992-09-01

The creation of a Life Cycle Management (LCM) group at utilities to evaluate the long term capital refurbishment needs is gaining favor. Among the functions of such groups can be the responsibility for recommending long term capital planning projects based on results of evaluations of systems, structures, and components that are not only essential to achieving the full current license term of operation, but also to extend the service life of the plant. Making such recommendations, in content and timing, requires the ability to view all recommendations in the context of an overall capital budget and long range outage impacts. This report illustrates an approach for creating a Long-Term Capital Plan with methods for deciding on, compiling, integrating, and presenting projects from the perspective of an LCM program for a nuclear power plant. It also addresses a rationale for capitalization of LCM program activities that would not be allowed under current accounting treatment

Long-term care: the family, post-modernity, and conflicting moral life-worlds.

Science.gov (United States)

Engelhardt, H Tristram

2007-01-01

Long-term care is controversial because it involves foundational disputes. Some are moral-economic, bearing on whether the individual, the family, or the state is primarily responsible for long-term care, as well as on how one can establish a morally and financially sustainable long-term-care policy, given the moral hazard of people over-using entitlements once established, the political hazard of media democracies promising unfundable entitlements, the demographic hazard of relatively fewer workers to support those in need of long-term care, the moral hazard to responsibility of shifting accountability to third parties, and the bureaucratic hazard of moving from individual and family choice to bureaucratic oversight. These disputes are compounded by controversies regarding the nature of the family (Is it to be regarded primarily as a socio-biological category, a fundamental ontological category of social reality, or a construct resulting from the consent of the participants?), as well as its legal and moral autonomy and authority over its members. As the disputes show, there is no common understanding of respect and human dignity that will easily lead out of these disputes. The reflections on long-term care in this issue underscore the plurality of moralities defining bioethics.

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.

Adrenocortical and Adipose Responses to High-Altitude-Induced, Long-Term Hypoxia in the Ovine Fetus

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Dean A. Myers

2012-01-01

Full Text Available By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m, long-term hypoxia (LTH in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN, anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress.

Physiological and Molecular Processes Associated with Long Duration of ABA Treatment

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Mei Wang

2018-02-01

Full Text Available Plants need to respond to various environmental stresses such as abiotic stress for proper development and growth. The responses to abiotic stress can be biochemically demanding, resulting in a trade-off that negatively affects plant growth and development. Thus, plant stress responses must be fine-tuned depending on the stress severity and duration. Abscisic acid, a phytohormone, plays a key role in responses to abiotic stress. Here, we investigated time-dependent physiological and molecular responses to long-term ABA treatment in Arabidopsis as an approach to gain insight into the plant responses to long-term abiotic stress. Upon ABA treatment, the amount of cellular ABA increased to higher levels, reaching to a peak at 24 h after treatment (HAT, and then gradually decreased with time whereas ABA-GE was maintained at lower levels until 24 HAT and then abruptly increased to higher levels at 48 HAT followed by a gradual decline at later time points. Many genes involved in dehydration stress responses, ABA metabolism, chloroplast biogenesis, and chlorophyll degradation were strongly expressed at early time points with a peak at 24 or 48 HAT followed by gradual decreases in induction fold or even suppression at later time points. At the physiological level, long-term ABA treatment caused leaf yellowing, reduced chlorophyll levels, and inhibited chloroplast division in addition to the growth suppression whereas short-term ABA treatment did not affect chlorophyll levels. Our results indicate that the duration of ABA treatment is a crucial factor in determining the mode of ABA-mediated signaling and plant responses: active mobilization of cellular resources at early time points and suppressive responses at later time points.

Behavioural and physiological responses of shelter dogs to long-term confinement

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Paolo Dalla Villa

2013-06-01

Full Text Available In Italy, National Law (281/1991 prohibits euthanasia of shelter dogs if they are not dangerous or suffering seriously. Adoption rates in rescue shelters are often lower than entrance rates, leading inevitably to overcrowded facilities where animals are likely to spend the rest of their lives in kennels. In this situation, housing conditions (i.e. space provided, environmental, and social stimulation may have an impact on canine welfare. In this research project, the effects of two different forms of housing (group- and pair housing on long-term shelter dogs were compared using behavioural and physiological parameters. Observational data and saliva samples were collected from dogs exposed to both experimental settings; behaviour and cortisol concentration levels were used as welfare indicators. Pair housing offered fewer social and environmental stimuli and behavioural analysis showed a significant decrease in locomotor, exploratory, and social behaviour. Cortisol levels show that this parameter varied independently of housing conditions. Although this study found no evidence suggesting that one form of confinement reduced animal welfare more than the other (e.g. in terms of abnormal behaviour, or higher cortisol concentrations, the type of confinement did affect the expression of a variety of behaviours and these variations should not be ignored with respect to housing decisions for long-term shelter dogs.

SHORT-TERM STRESS ENHANCES CELLULAR IMMUNITY AND INCREASES EARLY RESISTANCE TO SQUAMOUS CELL CARCINOMA

OpenAIRE

Dhabhar, Firdaus S.; Saul, Alison N.; Daugherty, Christine; Holmes, Tyson H.; Bouley, Donna M.; Oberyszyn, Tatiana M.

2009-01-01

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposu...

Predicting long-term temperature increase for time-dependent SAR levels with a single short-term temperature response.

Science.gov (United States)

Carluccio, Giuseppe; Bruno, Mary; Collins, Christopher M

2016-05-01

Present a novel method for rapid prediction of temperature in vivo for a series of pulse sequences with differing levels and distributions of specific energy absorption rate (SAR). After the temperature response to a brief period of heating is characterized, a rapid estimate of temperature during a series of periods at different heating levels is made using a linear heat equation and impulse-response (IR) concepts. Here the initial characterization and long-term prediction for a complete spine exam are made with the Pennes' bioheat equation where, at first, core body temperature is allowed to increase and local perfusion is not. Then corrections through time allowing variation in local perfusion are introduced. The fast IR-based method predicted maximum temperature increase within 1% of that with a full finite difference simulation, but required less than 3.5% of the computation time. Even higher accelerations are possible depending on the time step size chosen, with loss in temporal resolution. Correction for temperature-dependent perfusion requires negligible additional time and can be adjusted to be more or less conservative than the corresponding finite difference simulation. With appropriate methods, it is possible to rapidly predict temperature increase throughout the body for actual MR examinations. © 2015 Wiley Periodicals, Inc.

Effects of long-term high CO2 exposure on two species of coccolithophores

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K. G. Schulz

2010-03-01

Full Text Available The physiological performance of two coccolithophore species, Emiliania huxleyi and Coccolithus braarudii, was investigated during long-term exposure to elevated pCO2 levels. Mono-specific cultures were grown over 152 (E. huxleyi and 65 (C. braarudii generations while pCO2 was gradually increased to maximum levels of 1150 μatm (E. huxleyi and 930 μatm (C. braarudii and kept constant thereafter. Rates of cell growth and cell quotas of particulate organic carbon (POC, particulate inorganic carbon (PIC and total particulate nitrogen (TPN were determined repeatedly throughout the incubation period. Increasing pCO2 caused a decrease in cell growth rate of 9% and 29% in E. huxleyi and C. braarudii, respectively. In both species cellular PIC:TPN and PIC:POC ratios decreased in response to rising pCO2, whereas no change was observed in the POC:TPN ratios of E. huxleyi and C. braarudii. These results are consistent with those obtained in shorter-term high CO2 exposure experiments following abrupt pertubations of the seawater carbonate system and indicate that for the strains tested here a gradual CO2 increase does not alleviate CO2/pH sensitivity.

Distinct cerebellar engrams in short-term and long-term motor learning.

Science.gov (United States)

Wang, Wen; Nakadate, Kazuhiko; Masugi-Tokita, Miwako; Shutoh, Fumihiro; Aziz, Wajeeha; Tarusawa, Etsuko; Lorincz, Andrea; Molnár, Elek; Kesaf, Sebnem; Li, Yun-Qing; Fukazawa, Yugo; Nagao, Soichi; Shigemoto, Ryuichi

2014-01-07

Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-term adaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.

Guidance for implementing the UMTRA Project long-term surveillance program

International Nuclear Information System (INIS)

1992-09-01

The US Nuclear Regulatory Commission (NRC) has issued a general license for the custody and long-term care of US Department of Energy (DOE) Uranium Mill Tailings Remedial Action (UMTRA) Project permanent disposal sites. The purpose of this general license is to ensure that the UMTRA disposal sites will be cared for in such a manner as to protect the public health and safety and the environment upon completion of remedial actions. The general license will be in effect for a disposal site when NRC accepts the disposal site long-term surveillance plan (LTSP) that meets the requirements of 10 CFR 40.27. The site LTSP describes in detail the long-term surveillance program, including any monitoring, maintenance, and emergency measures necessary to fulfill the conditions of the general license. This guidance document provides (1) instructions for preparing the disposal site LTSPs and (2) instructions for carrying out the UMTRA Project long-term surveillance program, including any monitoring that may be required. The information provided in this document also is in accordance with the regulatory requirements set forth in 40 CFR 192. On January 5, 1985, the US Tenth Circuit Court of Appeals remanded the groundwater standards, 40 CFR 192.02. Proposed groundwater standards were issued for comment on September 24, 1987 (52 FR 3600). When the groundwater standards become final, this document will be revised, as appropriate. This document also will be updated in response to any changes to 10 CFR 40, or in response to changes in the manner in which the long-term care of the licensed disposal sites is carried out

ESBWR long term containment response to loss of coolant accidents

International Nuclear Information System (INIS)

Alamgir, M. D.; Marquino, W.; Diaz-Quiroz, J.; Tucker, L.

2010-01-01

ESBWR is a 4500 MWt generation III+ natural circulation reactor with an array of robust passive safety systems to keep the reactor safe during postulated transients and accidents. With the submittal of the latest revision of the Design Control Document (DCD) to US Nuclear Regulatory Commission, ESBWR is nearing the completion of the US certification process. This paper focuses on the bounding licensing analysis of the long-term (30-day) response of the ESBWR containment to limiting Loss of Coolant Accident (LOCA) performed with the TRACG code. It is shown that using only passive systems available during the first 72 hours after the limiting Main Steam Line Break LOCA, the predicted peak containment pressure in the ESBWR containment remain well below the design limits with good margin. After 72 hours of LOCA initiation, PCCS Vent Fans (non-safety system) become available that remove non-condensable gases from, and further enhance the effectiveness of, PCCS heat exchangers to reduce the containment pressure and temperature to values substantially below the design limits. During the post- 72 hour period, the beneficial effects of the Vent Fan operation, combined with the available operator action to refill of PCCS pools, continue to maintain the containment pressure to about 30% below the design limit at 30 days after a limiting ESBWR LOCA. (authors)

Dissociating Long and Short-term Memory in Three-Month-Old Infants Using the Mismatch Response to Voice Stimuli

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Katharina Zinke

2018-01-01

Full Text Available Auditory event-related potentials (ERPs have been successfully used in adults as well as in newborns to discriminate recall of longer-term and shorter-term memories. Specifically the Mismatch Response (MMR to deviant stimuli of an oddball paradigm is larger if the deviant stimuli are highly familiar (i.e., retrieved from long-term memory than if they are unfamiliar, representing an immediate change to the standard stimuli kept in short-term memory. Here, we aimed to extend previous findings indicating a differential MMR to familiar and unfamiliar deviants in newborns (Beauchemin et al., 2011, to 3-month-old infants who are starting to interact more with their social surroundings supposedly based on forming more (social long-term representations. Using a voice discrimination paradigm, each infant was repeatedly presented with the word “baby” (400 ms, interstimulus interval: 600 ms, 10 min overall duration pronounced by three different female speakers. One voice that was unfamiliar to the infants served as the frequently presented “standard” stimulus, whereas another unfamiliar voice served as the “unfamiliar deviant” stimulus, and the voice of the infant’s mother served as the “familiar deviant.” Data collection was successful for 31 infants (mean age = 100 days. The MMR was determined by the difference between the ERP to standard stimuli and the ERP to the unfamiliar and familiar deviant, respectively. The MMR to the familiar deviant (mother’s voice was larger, i.e., more positive, than that to the unfamiliar deviant between 100 and 400 ms post-stimulus over the frontal and central cortex. However, a genuine MMR differentiating, as a positive deflection, between ERPs to familiar deviants and standard stimuli was only found in the 300–400 ms interval. On the other hand, a genuine MMR differentiating, as a negative deflection, between ERPs to unfamiliar deviants from ERPs to standard stimuli was revealed for the 200–300 ms

Immunization of mice with the nef gene from Human Immunodeficiency Virus type 1: Study of immunological memory and long-term toxicology

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Engström Gunnel

2007-07-01

Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 regulatory protein, Nef, is an attractive vaccine target because it is involved in viral pathogenesis, is expressed early in the viral life cycle and harbors many T and B cell epitopes. Several clinical trials include gene-based vaccines encoding this protein. However, Nef has been shown to transform certain cell types in vitro. Based on these findings we performed a long-term toxicity and immunogenicity study of Nef, encoded either by Modified Vaccinia virus Ankara or by plasmid DNA. BALB/c mice were primed twice with either DNA or MVA encoding Nef and received a homologous or heterologous boost ten months later. In the meantime, the Nef-specific immune responses were monitored and at the time of sacrifice an extensive toxicological evaluation was performed, where presence of tumors and other pathological changes were assessed. Results The toxicological evaluation showed that immunization with MVAnef is safe and does not cause cellular transformation or other toxicity in somatic organs. Both DNAnef and MVAnef immunized animals developed potent Nef-specific cellular responses that declined to undetectable levels over time, and could readily be boosted after almost one year. This is of particular interest since it shows that plasmid DNA vaccine can also be used as a potent late booster of primed immune responses. We observed qualitative differences between the T cell responses induced by the two different vectors: DNA-encoded nef induced long-lasting CD8+ T cell memory responses, whereas MVA-encoded nef induced CD4+ T cell memory responses. In terms of the humoral immune responses, we show that two injections of MVAnef induce significant anti-Nef titers, while repeated injections of DNAnef do not. A single boost with MVAnef could enhance the antibody response following DNAnef prime to the same level as that observed in animals immunized repeatedly with MVAnef. We also demonstrate

Long-Term Research in Ecology and Evolution (LTREE): 2015 survey data.

Science.gov (United States)

Bradford, Mark A; Leiserowitz, Anthony; Feinberg, Geoffrey; Rosenthal, Seth A; Lau, Jennifer A

2017-11-01

To systematically assess views on contributions and future activities for long-term research in ecology and evolution (LTREE), we conducted and here provide data responses and associated metadata for a survey of ecological and evolutionary scientists. The survey objectives were to: (1) Identify and prioritize research questions that are important to address through long-term, ecological field experiments; and (2) understand the role that these experiments might play in generating and applying ecological and evolutionary knowledge. The survey was developed adhering to the standards of the American Association for Public Opinion Research. It was administered online using Qualtrics Survey Software. Survey creation was a multi-step process, with questions and format developed and then revised with, for example, input from an external advisory committee comprising senior and junior ecological and evolutionary researchers. The final questionnaire was released to ~100 colleagues to ensure functionality and then fielded 2 d later (January 7 th , 2015). Two professional societies distributed it to their membership, including the Ecological Society of America, and it was posted to three list serves. The questionnaire was available through February 8th 2015 and completed by 1,179 respondents. The distribution approach targeted practicing ecologists and evolutionary biologists in the U.S. Quantitative (both ordinal and categorical) closed-ended questions used a predefined set of response categories, facilitating direct comparison across all respondents. Qualitative, open-ended questions, provided respondents the opportunity to develop their own answers. We employed quantitative questions to score views on the extent to which long-term experimental research has contributed to understanding in ecology and evolutionary biology; its role compared to other approaches (e.g., short-term experiments); justifications for and caveats to long-term experiments; and the relative importance

Long-term associative learning predicts verbal short-term memory performance.

Science.gov (United States)

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

Change of exposure response over time and long-term risk of silicosis among a cohort of Chinese pottery workers.

Science.gov (United States)

Sun, Yi; Bochmann, Frank; Morfeld, Peter; Ulm, Kurt; Liu, Yuewei; Wang, Heijiao; Yang, Lei; Chen, Weihong

2011-07-01

An analysis was conducted on a cohort of Chinese pottery workers to estimate the exposure-response relationship between respirable crystalline silica dust exposure and the incidence of radiographically diagnosed silicosis, and to estimate the long-term risk of developing silicosis until the age of 65. The cohort comprised 3,250 employees with a median follow-up duration of around 37 years. Incident cases of silicosis were identified via silicosis registries (Chinese X-ray stage I, similar to International Labor Organisation classification scheme profusion category 1/1). Individual exposure to respirable crystalline silica dust was estimated based on over 100,000 historical dust measurements. The association between dust exposure, incidence and long-time risk of silicosis was quantified by Poisson regression analysis adjusted for age and smoking. The risk of silicosis depended not only on the cumulative respirable crystalline silica dust exposures, but also on the time-dependent respirable crystalline silica dust exposure pattern (long-term average concentration, highest annual concentration ever experienced and time since first exposure). A long-term "excess" risk of silicosis of approximately 1.5/1,000 was estimated among workers with all annual respirable crystalline silica dust concentration estimates less than 0.1 mg/m(3), using the German measurement strategy. This study indicates the importance of proper consideration of exposure information in risk quantification in epidemiological studies.

Change of Exposure Response over Time and Long-Term Risk of Silicosis among a Cohort of Chinese Pottery Workers

Directory of Open Access Journals (Sweden)

Yuewei Liu

2011-07-01

Full Text Available An analysis was conducted on a cohort of Chinese pottery workers to estimate the exposure-response relationship between respirable crystalline silica dust exposure and the incidence of radiographically diagnosed silicosis, and to estimate the long-term risk of developing silicosis until the age of 65. The cohort comprised 3,250 employees with a median follow-up duration of around 37 years. Incident cases of silicosis were identified via silicosis registries (Chinese X-ray stage I, similar to International Labor Organisation classification scheme profusion category 1/1. Individual exposure to respirable crystalline silica dust was estimated based on over 100,000 historical dust measurements. The association between dust exposure, incidence and long-time risk of silicosis was quantified by Poisson regression analysis adjusted for age and smoking. The risk of silicosis depended not only on the cumulative respirable crystalline silica dust exposures, but also on the time-dependent respirable crystalline silica dust exposure pattern (long-term average concentration, highest annual concentration ever experienced and time since first exposure. A long-term “excess” risk of silicosis of approximately 1.5/1,000 was estimated among workers with all annual respirable crystalline silica dust concentration estimates less than 0.1 mg/m3, using the German measurement strategy. This study indicates the importance of proper consideration of exposure information in risk quantification in epidemiological studies.

Response of aerobic granular sludge to the long-term presence to nanosilver in sequencing batch reactors: Reactor performance, sludge property, microbial activity and community

Energy Technology Data Exchange (ETDEWEB)

Quan, Xiangchun, E-mail: xchquan@bnu.edu.cn; Cen, Yan; Lu, Fang; Gu, Lingyun; Ma, Jingyun

2015-02-15

The increasing use of silver nanoparticles (Ag NPs) raises concerns about their potential toxic effects on the environment. Granular shape sludge is a special type of microbial aggregate. The response of aerobic granular sludge (AGS) to the long-term presence of Ag NPs has not been well studied. In this study, AGS was exposed to 5 and 50 mg/L Ag NPs in sequence batch reactors (SBRs) for 69 days, and its response was evaluated based on the sludge properties, microbial activity and community, and reactor performance. The results showed that Ag NPs caused inhibition to microbial activities of AGS from Day 35. At the end of 69 days of Ag NPs exposure, the microbial activity of AGS was significantly inhibited in terms of inhibitions of the ammonia oxidizing rate (33.0%), respiration rate (17.7% and 45.6%) and denitrification rate (6.8%), as well as decreases in the ammonia mono-oxygenase and nitrate reductase activities. During the long-term exposure, the AGS maintained its granular shape and large granule size (approximately 900 μm); the microbial community of AGS slightly changed, but the dominant microbial population remained. Overall, the AGS tolerated the toxicity of Ag NPs well, but a long-term exposure may produce chronic toxicity to the AGS, which is concerning. - Highlights: • AGS demonstrated a good tolerance to the long-term presence of Ag NPs. • Ag NPs did not produce acute toxicity but cause chronic toxicity to AGS. • AGS maintained granular shape, granule size and good settling ability. • The microbial community of AGS slightly changed after long-term Ag NPs exposure.

Response of aerobic granular sludge to the long-term presence to nanosilver in sequencing batch reactors: Reactor performance, sludge property, microbial activity and community

International Nuclear Information System (INIS)

Quan, Xiangchun; Cen, Yan; Lu, Fang; Gu, Lingyun; Ma, Jingyun

2015-01-01

The increasing use of silver nanoparticles (Ag NPs) raises concerns about their potential toxic effects on the environment. Granular shape sludge is a special type of microbial aggregate. The response of aerobic granular sludge (AGS) to the long-term presence of Ag NPs has not been well studied. In this study, AGS was exposed to 5 and 50 mg/L Ag NPs in sequence batch reactors (SBRs) for 69 days, and its response was evaluated based on the sludge properties, microbial activity and community, and reactor performance. The results showed that Ag NPs caused inhibition to microbial activities of AGS from Day 35. At the end of 69 days of Ag NPs exposure, the microbial activity of AGS was significantly inhibited in terms of inhibitions of the ammonia oxidizing rate (33.0%), respiration rate (17.7% and 45.6%) and denitrification rate (6.8%), as well as decreases in the ammonia mono-oxygenase and nitrate reductase activities. During the long-term exposure, the AGS maintained its granular shape and large granule size (approximately 900 μm); the microbial community of AGS slightly changed, but the dominant microbial population remained. Overall, the AGS tolerated the toxicity of Ag NPs well, but a long-term exposure may produce chronic toxicity to the AGS, which is concerning. - Highlights: • AGS demonstrated a good tolerance to the long-term presence of Ag NPs. • Ag NPs did not produce acute toxicity but cause chronic toxicity to AGS. • AGS maintained granular shape, granule size and good settling ability. • The microbial community of AGS slightly changed after long-term Ag NPs exposure

Long-Term Sensitization Training Primes "Aplysia" for Further Learning

Science.gov (United States)

Cleary, Leonard J.; Byrne, John H.; Antzoulatos, Evangelos G.; Wainwright, Marcy L.

2006-01-01

Repetitive, unilateral stimulation of "Aplysia" induces long-term sensitization (LTS) of ipsilaterally elicited siphon-withdrawal responses. Whereas some morphological effects of training appear only on ipsilateral sensory neurons, others appear bilaterally. We tested the possibility that contralateral morphological modifications may have…

Improving simulated long-term responses of vegetation to temperature and precipitation extremes using the ACME land model

Science.gov (United States)

Ricciuto, D. M.; Warren, J.; Guha, A.

2017-12-01

While carbon and energy fluxes in current Earth system models generally have reasonable instantaneous responses to extreme temperature and precipitation events, they often do not adequately represent the long-term impacts of these events. For example, simulated net primary productivity (NPP) may decrease during an extreme heat wave or drought, but may recover rapidly to pre-event levels following the conclusion of the extreme event. However, field measurements indicate that long-lasting damage to leaves and other plant components often occur, potentially affecting the carbon and energy balance for months after the extreme event. The duration and frequency of such extreme conditions is likely to shift in the future, and therefore it is critical for Earth system models to better represent these processes for more accurate predictions of future vegetation productivity and land-atmosphere feedbacks. Here we modify the structure of the Accelerated Climate Model for Energy (ACME) land surface model to represent long-term impacts and test the improved model against observations from experiments that applied extreme conditions in growth chambers. Additionally, we test the model against eddy covariance measurements that followed extreme conditions at selected locations in North America, and against satellite-measured vegetation indices following regional extreme events.

Cellular biomarker responses of bagrid catfish, Chrysichthys ...

African Journals Online (AJOL)

An assessment of the pollution status of Agboyi creek, a water body associated with various anthropogenic activities was carried out in order to determine responses induced in Catfishes, Chrysichthys nigrodigitatus inhabiting it. Cellular biomarkers of stress including the antioxidative stress enzyme, catalase (CAT), lipid ...

Short-Term and Working Memory Impairments in Early-Implanted, Long-Term Cochlear Implant Users Are Independent of Audibility and Speech Production.

Science.gov (United States)

AuBuchon, Angela M; Pisoni, David B; Kronenberger, William G

2015-01-01

To determine whether early-implanted, long-term cochlear implant (CI) users display delays in verbal short-term and working memory capacity when processes related to audibility and speech production are eliminated. Twenty-three long-term CI users and 23 normal-hearing controls each completed forward and backward digit span tasks under testing conditions that differed in presentation modality (auditory or visual) and response output (spoken recall or manual pointing). Normal-hearing controls reproduced more lists of digits than the CI users, even when the test items were presented visually and the responses were made manually via touchscreen response. Short-term and working memory delays observed in CI users are not due to greater demands from peripheral sensory processes such as audibility or from overt speech-motor planning and response output organization. Instead, CI users are less efficient at encoding and maintaining phonological representations in verbal short-term memory using phonological and linguistic strategies during memory tasks.

Long-Term Photometry of Very Slow Novae

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Chochol D.

2003-12-01

Full Text Available Long-term photographic, photoelectric and recent CCD photometry of the classical nova V723 Cas and symbiotic novae V1329 Cyg, PU Vul, V1016 Cyg and HM Sge were used to find their orbital periods. The arguments in favor of the presence of the third components in these systems are given. Physical processes, responsible for the brightness variations, are discussed.

Radiosurgery of craniopharyngiomas. Results of long-term follow-up

International Nuclear Information System (INIS)

Kida, Yoshihisa; Hasegawa, Toshinori; Yoshimoto, Masayuki; Koike, Johzi; Kobayashi, Tatsuya

2007-01-01

Long-term follow-up results of craniopharyngiomas after radiosurgery are reported. Among 125 cases of craniopharyngioma, long-term follow-up more than 6 months is obtained in 108 cases. Majority of the cases have had surgical excision before radiosurgery. The tumors, 19 mm in mean diameter were treated with the mean maximum dose of 22.1 Gy and with the marginal dose of 11.6 Gy. The final radiological outcomes during 63 months of mean follow-up showed 9 complete responses (CRs), 61 partial responses (PRs), 1 minor response (MR), 19 no changes (NCs) and 18 PGs, indicating the response rate of 65% and the control rate of 83% respectively. Neurological and endocrinological signs were improved in 18%, unchanged in 53% and worsened in 15% of cases, meanwhile 8% of the patients were dead. Small and solid tumors were the best indication for radiosurgery due to excellent tumor control as well as no adverse effects. They may have a good chance for complete remission. In conclusion a sufficient tumor resection with microsurgery is required and subsequent radiosurgery is most adequate for treating craniopharyngiomas. (author)

Antioxidant responses and cellular adjustments to oxidative stress.

Science.gov (United States)

Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

2015-12-01

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. Copyright © 2015. Published by Elsevier B.V.

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

Science.gov (United States)

White, André O; Wood, Marcelo A

2014-07-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-term periodontal response to orthodontic treatment of palatally impacted maxillary canines.

Science.gov (United States)

Caprioglio, Alberto; Vanni, Arianna; Bolamperti, Laura

2013-06-01

One of the most important aspects to take into consideration when evaluating the outcome of treatment of impacted maxillary canines is the final periodontal status. The aim of the present study was to evaluate the long-term periodontal response of palatally impacted maxillary canines aligned using a codified procedure and the 'Easy Cuspid' compared with contralateral spontaneously erupted teeth. The periodontal conditions of the adjacent teeth were also considered. From an initial sample of 124 patients, 33 patients (24 females and 9 males) were selected. All patients who had undergone surgical orthodontic treatment conducted in accordance with a standardized protocol were recalled for follow-up at an average of 4.6 years after the end of treatment. The average treatment time was 29 months and the mean eruption time of the previously impacted tooth was 3.1 months. The average probing depth values showed no significant clinical differences. Probing depths recorded at the vestibular surface of the lateral incisor (P alignment of palatally impacted canines without damage to the periodontium.

Fluoroscopically guided caudal epidural steroid injection for management of degenerative lumbar spinal stenosis: short-term and long-term results

Energy Technology Data Exchange (ETDEWEB)

Lee, Joon Woo; Myung, Jae Sung; Kang, Heung Sik [Seoul National University Bundang Hospital, Department of Radiology, Seong Nam, Gyeongi-do (Korea); Park, Kun Woo; Yeom, Jin S. [Seoul National University Bundang Hospital, Department of Orthopaedic Surgery, Seong Nam, Gyeongi-do (Korea); Kim, Ki-Jeong; Kim, Hyun-Jib [Seoul National University Bundang Hospital, Department of Neurosurgery, Seong Nam, Gyeongi-do (Korea)

2010-07-15

To evaluate the short-term and long-term effects of fluoroscopically guided caudal epidural steroid injection (ESI) for the management of degenerative lumbar spinal stenosis (DLSS) and to analyze outcome predictors. All patients who underwent caudal ESI in 2006 for DLSS were included in the study. Response was based on chart documentation (aggravated, no change, slightly improved, much improved, no pain). In June 2009 telephone interviews were conducted, using formatted questions including the North American Spine Society (NASS) patient satisfaction scale. For short-term and long-term effects, age difference was evaluated by the Mann-Whitney U test, and gender, duration of symptoms, level of DLSS, spondylolisthesis, and previous operations were evaluated by Fisher's exact test. Two hundred and sixteen patients (male: female = 75:141; mean age 69.2 years; range 48{proportional_to}91 years) were included in the study. Improvements (slightly improved, much improved, no pain) were seen in 185 patients (85.6%) after an initial caudal ESI and in 189 patients (87.5%) after a series of caudal ESIs. Half of the patients (89/179, 49.8%) replied positively to the NASS patient satisfaction scale (1 or 2). There were no significant outcome predictors for either the short-term or the long-term responses. Fluoroscopically guided caudal ESI was effective for the management of DLSS (especially central canal stenosis) with excellent short-term and good long-term results, without significant outcome predictors. (orig.)

Medium- and long-term consequences of pollution on labor supply: evidence from Indonesia

Directory of Open Access Journals (Sweden)

Younoh Kim

2017-04-01

Full Text Available Abstract We use a natural experiment in Indonesia to study the medium- and long-term effects of air pollution on labor supply. We find that exposure to air pollution reduces hours worked and while the medium-term effects are larger in magnitude, some effects do persist in the long term. More interestingly, we are able to provide some insight regarding the underlying channels that contribute to the reduced labor supply. Own health seems to be the only responsible channel in the long term, while in the medium term, a different channel based on dependent caregiving is the most important. JEL Classification: J22, Q53

Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

International Nuclear Information System (INIS)

Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

1997-01-01

Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

SKI and SSI's recommendations to the government concerning long-term responsibility after closure of a repository for spent nuclear fuel

International Nuclear Information System (INIS)

Paeivioe Jonsson, Josefin

2008-01-01

Many activities will cease at the closure of a repository, but not responsibilities. The candidate municipalities in Sweden expressed concern about who will take over after the implementer is released from responsibility for the facility. The government thus commissioned SKI (Swedish Nuclear Power Inspectorate) and SSI (Swedish Radiation Protection Authority) to review the legal obligations of institutional players as laid out today in legislation in Sweden. After closure of the repository in about 100 years there will be post-closure monitoring, possibly for a few hundred years. This will be a part of the conditions on SKB (Swedish Nuclear Fuel and Waste Management Company) which will be set out at the time. Some activities will end at the closure of the facility but monitoring and safeguards obligations may continue. The exact nature of this monitoring and safeguard work needs to be discussed and agreed upon. With the proposed approach most of the liabilities rest with the state in the long term, the waste producers only have liabilities in the short term but their decisions could have big impacts on long term liabilities

Emergency Response and Long Term Planning: Two sides of the Coin for Managing Water Resources

Science.gov (United States)

Metchis, K.; Beller-Simms, N.

2014-12-01

As projected by the US National Climate Assessment and the IPCC, extreme climate and weather events are occurring more frequently and with more intensity across the nation. Communities - and the water resource managers that serve them - are facing difficult choices to increase emergency preparedness, recover from costly impacts, and increase long term resilience. The presentation is based on a recent set of case studies about what happened in six communities that experienced one or more extreme events, focusing on water resource management. Two of the case studies will be presented, revealing that building climate resilience is not just about long term planning - it is also about taking the steps to be prepared for - and to be able to recover from - emergency events. The results of this study have implications for educating local officials on ways to think about resilience to balance both long-term and short-term preparedness.

The effect of heat and mass transfer on the cellular plastic insulation and the long-term aging

Energy Technology Data Exchange (ETDEWEB)

Fan Youchen [VTT Building Technology, Espoo (Finland). Building Physics, Building Services and Fire Technology

1997-12-31

To produce environmental-friendly products, foamed plastic industries are facing the challenge to replace the traditional blowing agents chlorofluorocarbons (CFCs) with zero ozone depletion potential (ODP) alternatives. After a series of studies were completed, more understandings and new findings have been achieved with respect to the rigid closed-cell cellular plastic insulations or foamed plastic insulations (FPIs). The mechanism of heat transfer within the FPIs was examined. A new formula for calculating the solid polymer matrix thermal conductivity has been deduced based on the law of energy conservation and Fourier equation of heat conduction. All the parameters involved in this formula can be easily measured. By comparing the simulation results with measurements, the Brokaw equation is recommended for the prediction of the thermal conductivity of a cell-gas mixture. The foamed plastic deformation was also discussed. A new model has been established for predicting the elastic modulus of the foamed plastics. In comparison to the published measurements, it was found that the new model gives fairly good results. A diffusion chamber has been designed and constructed for measuring the gaseous transport properties within the FPIs. To overcome the difficulties of the traditional method, a new measurement procedure and post test data treatment have been suggested. The measurement accuracy is equivalent to the traditional method with an exception of much short time being required. The diffusion coefficients of CO{sub 2}, O{sub 2}, and N{sub 2} within five n-pentane/CO{sub 2} based polyurethane (PUR) foams have been obtained from the diffusion chamber tests. Measurements showed that the relationship between the gaseous diffusion coefficients within FPIs and temperature follows the Arrhenius type. No identical relationship between diffusion coefficients and foam density was reached. To predict the long-term aging property of CFC-free foamed plastic insulations, a two

Evidence from Individual Inference for High-Dimensional Coexistence: Long-Term Experiments on Recruitment Response

Science.gov (United States)

Clark, James S.; Soltoff, Benjamin D.; Powell, Amanda S.; Read, Quentin D.

2012-01-01

Background For competing species to coexist, individuals must compete more with others of the same species than with those of other species. Ecologists search for tradeoffs in how species might partition the environment. The negative correlations among competing species that would be indicative of tradeoffs are rarely observed. A recent analysis showed that evidence for partitioning the environment is available when responses are disaggregated to the individual scale, in terms of the covariance structure of responses to environmental variation. That study did not relate that variation to the variables to which individuals were responding. To understand how this pattern of variation is related to niche variables, we analyzed responses to canopy gaps, long viewed as a key variable responsible for species coexistence. Methodology/Principal Findings A longitudinal intervention analysis of individual responses to experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment responses showed that species-level responses are positively correlated – species that grow fast on average in the understory also grow fast on average in response to gap formation. In other words, there is no tradeoff. However, the joint distribution of individual responses to understory and gap showed a negative correlation – species having individuals that respond most to gaps when previously growing slowly also have individuals that respond least to gaps when previously growing rapidly (e.g., Morus rubra), and vice versa (e.g., Quercus prinus). Conclusions/Significance Because competition occurs at the individual scale, not the species scale, aggregated species-level parameters and correlations hide the species-level differences needed for coexistence. By disaggregating models to the scale at which the interaction occurs we show that individual variation provides insight for species differences. PMID:22393349

Evidence from individual inference for high-dimensional coexistence: long-term experiments on recruitment response.

Directory of Open Access Journals (Sweden)

James S Clark

Full Text Available BACKGROUND: For competing species to coexist, individuals must compete more with others of the same species than with those of other species. Ecologists search for tradeoffs in how species might partition the environment. The negative correlations among competing species that would be indicative of tradeoffs are rarely observed. A recent analysis showed that evidence for partitioning the environment is available when responses are disaggregated to the individual scale, in terms of the covariance structure of responses to environmental variation. That study did not relate that variation to the variables to which individuals were responding. To understand how this pattern of variation is related to niche variables, we analyzed responses to canopy gaps, long viewed as a key variable responsible for species coexistence. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal intervention analysis of individual responses to experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment responses showed that species-level responses are positively correlated--species that grow fast on average in the understory also grow fast on average in response to gap formation. In other words, there is no tradeoff. However, the joint distribution of individual responses to understory and gap showed a negative correlation--species having individuals that respond most to gaps when previously growing slowly also have individuals that respond least to gaps when previously growing rapidly (e.g., Morus rubra, and vice versa (e.g., Quercus prinus. CONCLUSIONS/SIGNIFICANCE: Because competition occurs at the individual scale, not the species scale, aggregated species-level parameters and correlations hide the species-level differences needed for coexistence. By disaggregating models to the scale at which the interaction occurs we show that individual variation provides insight for species differences.

Micro patterned surfaces: an effective tool for long term digital holographic microscopy cell imaging

Science.gov (United States)

Mues, Sarah; Lilge, Inga; Schönherr, Holger; Kemper, Björn; Schnekenburger, Jürgen

2017-02-01

The major problem of Digital Holographic Microscopy (DHM) long term live cell imaging is that over time most of the tracked cells move out of the image area and other ones move in. Therefore, most of the cells are lost for the evaluation of individual cellular processes. Here, we present an effective solution for this crucial problem of long-term microscopic live cell analysis. We have generated functionalized slides containing areas of 250 μm per 200 μm. These micropatterned biointerfaces consist of passivating polyaclrylamide brushes (PAAm). Inner areas are backfilled with octadecanthiol (ODT), which allows cell attachment. The fouling properties of these surfaces are highly controllable and therefore the defined areas designed for the size our microscopic image areas were effective in keeping all cells inside the rectangles over the selected imaging period.

Imaging windows for long-term intravital imaging: General overview and technical insights.

Science.gov (United States)

Alieva, Maria; Ritsma, Laila; Giedt, Randy J; Weissleder, Ralph; van Rheenen, Jacco

2014-01-01

Intravital microscopy is increasingly used to visualize and quantitate dynamic biological processes at the (sub)cellular level in live animals. By visualizing tissues through imaging windows, individual cells (e.g., cancer, host, or stem cells) can be tracked and studied over a time-span of days to months. Several imaging windows have been developed to access tissues including the brain, superficial fascia, mammary glands, liver, kidney, pancreas, and small intestine among others. Here, we review the development of imaging windows and compare the most commonly used long-term imaging windows for cancer biology: the cranial imaging window, the dorsal skin fold chamber, the mammary imaging window, and the abdominal imaging window. Moreover, we provide technical details, considerations, and trouble-shooting tips on the surgical procedures and microscopy setups for each imaging window and explain different strategies to assure imaging of the same area over multiple imaging sessions. This review aims to be a useful resource for establishing the long-term intravital imaging procedure.

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Science.gov (United States)

McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

2014-01-01

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to

Penetration of sulfur hexafluoride into cellular polypropylene films and its effect on the electric charging and electromechanical response of ferroelectrets

International Nuclear Information System (INIS)

Qiu Xunlin; Wegener, Michael; Wirges, Werner; Zhang Xiaoqing; Hillenbrand, Joachim; Xia Zhongfu; Gerhard-Multhaupt, Reimund; Sessler, Gerhard M

2005-01-01

Cellular polypropylene (PP) films were treated with sulfur hexafluoride (SF 6 ) gas in order to study the SF 6 penetration behaviour and optimize the electric charging conditions. There were differences in the penetration of SF 6 for different cellular PP materials, depending on the microscopic properties, which manifest themselves in the voided structure as well as in the mechanical stiffnesses of the cellular films. The penetration of SF 6 after long-term pressure treatment is confirmed in strongly inflated cellular PP films with a low mechanical stiffness of about 1 MPa. No SF 6 penetration occurs for slightly inflated cellular PP films with smaller void sizes and higher mechanical stiffnesses of around 5.8 MPa. The observed thickness variations, the higher charging fields during corona charging because of SF 6 penetration and the SF 6 environment, as well as the resulting electromechanical properties are discussed

Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome

International Nuclear Information System (INIS)

Avallone, Antonio; Casaretti, Rossana; Montano, Massimo; Silvestro, Lucrezia; Aloj, Luigi; Caraco, Corradina; Di Gennaro, Francesca; Lastoria, Secondo; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Scott, Nigel; Budillon, Alfredo

2012-01-01

The aim of the present study is to prospectively evaluate the prognostic value of previously defined [ 18 F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up. Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin, raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy. FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy (CRT) treatment. Total mesorectal excision (TME) was carried out 8 weeks after completion of CRT. A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG standardized uptake value (SUV mean ) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade (TRG) and survival. Twenty-two metabolic responders showed complete (TRG1) or subtotal tumour regression (TRG2) and demonstrated a statistically significantly higher 5-year relapse-free survival (RFS) compared with the 20 non-responders (86 vs 55 %, p =.014) who showed TRG3 and TRG4 pathologic responses. A multivariate analysis demonstrated that early ∇SUV mean was the only pre-surgical parameter correlated to the likelihood of recurrence (p =.05). This study is the first prospective long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool. Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC. (orig.)

Reforming Long-Term Care Funding in Alberta.

Science.gov (United States)

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

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

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

Liabilities identification and long-term management - Review of French situation

International Nuclear Information System (INIS)

2003-01-01

In France, long term liabilities due to nuclear activities concern four main operators: Electricite de France (EDF), AREVA (an industrial group created on September 3, 2001 and covering the entire fuel cycle from ore extraction and transformation to the recycling of spent fuel), the Atomic Energy Commission (CEA, the French public research organism in the nuclear sector) and the French Agency for radioactive waste management (ANDRA, in charge with the long term operation of radioactive waste installations). Long term liabilities are due to the financing of both decommissioning of nuclear installations and radioactive waste long term management. In the current French organisational scheme, the different operators must take the responsibility of these long term liabilities. The setting of national policies and the establishment of the legislation are carried out at a national level by the French state. These include the supervision of the three operators through different Ministries and the regulatory control of safety trough the Nuclear Safety Authority (ASN). EDF, AREVA, CEA and ANDRA are responsible for all aspects of the decommissioning (from a technical and financial point of view). Within a safety regulatory frame, they have their own initiative concerning future expenses, based on estimated costs and the expected operational lifetime of the installations. They are responsible of the definition and implementation of the technical options. Through its supervision activities, the French State regularly requires updating studies of these estimated costs, which are conducted by the operators. A general review of the management of these long-term liabilities is also carried out on a four years basis by the French Court of Accounts. Operators are due to constitute provisions during the life cycle of their installations. Provisions are calculated for each installation on the basis of the decommissioning expenses and of the reasonably estimated lifetime. They are re

Long-term power generation expansion planning with short-term demand response: Model, algorithms, implementation, and electricity policies

Science.gov (United States)

Lohmann, Timo

Electric sector models are powerful tools that guide policy makers and stakeholders. Long-term power generation expansion planning models are a prominent example and determine a capacity expansion for an existing power system over a long planning horizon. With the changes in the power industry away from monopolies and regulation, the focus of these models has shifted to competing electric companies maximizing their profit in a deregulated electricity market. In recent years, consumers have started to participate in demand response programs, actively influencing electricity load and price in the power system. We introduce a model that features investment and retirement decisions over a long planning horizon of more than 20 years, as well as an hourly representation of day-ahead electricity markets in which sellers of electricity face buyers. This combination makes our model both unique and challenging to solve. Decomposition algorithms, and especially Benders decomposition, can exploit the model structure. We present a novel method that can be seen as an alternative to generalized Benders decomposition and relies on dynamic linear overestimation. We prove its finite convergence and present computational results, demonstrating its superiority over traditional approaches. In certain special cases of our model, all necessary solution values in the decomposition algorithms can be directly calculated and solving mathematical programming problems becomes entirely obsolete. This leads to highly efficient algorithms that drastically outperform their programming problem-based counterparts. Furthermore, we discuss the implementation of all tailored algorithms and the challenges from a modeling software developer's standpoint, providing an insider's look into the modeling language GAMS. Finally, we apply our model to the Texas power system and design two electricity policies motivated by the U.S. Environment Protection Agency's recently proposed CO2 emissions targets for the

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Science.gov (United States)

Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

2006-01-01

Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders. PMID:17050681

Thermo-hydro-mechanical coupling in long-term sedimentary rock response

Science.gov (United States)

Makhnenko, R. Y.; Podladchikov, Y.

2017-12-01

Storage of nuclear waste or CO2 affects the state of stress and pore pressure in the subsurface and may induce large thermal gradients in the rock formations. In general, the associated coupled thermo-hydro-mechanical effect on long-term rock deformation and fluid flow have to be studied. Principles behind mathematical models for poroviscoelastic response are reviewed, and poroviscous model parameter, the bulk viscosity, is included in the constitutive equations. Time-dependent response (creep) of fluid-filled sedimentary rocks is experimentally quantified at isotropic stress states. Three poroelastic parameters are measured by drained, undrained, and unjacketed geomechanical tests for quartz-rich Berea sandstone, calcite-rich Apulian limestone, and clay-rich Jurassic shale. The bulk viscosity is calculated from the measurements of pore pressure growth under undrained conditions, which requires time scales 104 s. The bulk viscosity is reported to be on the order of 1015 Pa•s for the sandstone, limestone, and shale. It is found to be decreasing with the increase of pore pressure despite corresponding decrease in the effective stress. Additionally, increase of temperature (from 24 ºC to 40 ºC) enhances creep, where the most pronounced effect is reported for the shale with bulk viscosity decrease by a factor of 3. Viscous compaction of fluid-filled porous media allows a generation of a special type of fluid flow instability that leads to formation of high-porosity, high-permeability domains that are able to self-propagate upwards due to interplay between buoyancy and viscous resistance of the deforming porous matrix. This instability is known as "porosity wave" and its formation is possible under conditions applicable to deep CO2 storage in reservoirs and explains creation of high-porosity channels and chimneys. The reported experiments show that the formation of high-permeability pathways is most likely to occur in low-permeable clay-rich materials (caprock

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...

Long-term associative learning predicts verbal short-term memory performance

OpenAIRE

Jones, Gary; Macken, Bill

2017-01-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term...

Long-Term Care Insurance: Does Experience Matter?*

Science.gov (United States)

Coe, Norma B.; Skira, Meghan M.; Van Houtven, Courtney Harold

2015-01-01

We examine whether long-term care (LTC) experience helps explain the low demand for long-term care insurance (LTCI). We test if expectations about future informal care receipt, expectations about inheritance receipt, and LTCI purchase decisions vary between individuals whose parents or in-laws have used LTC versus those who have not. We find parental use of a nursing home decreases expectations that one’s children will provide informal care, consistent with the demonstration effect. Nursing home use by in-laws does not have the same impact, suggesting that individuals are responding to information gained about their own aging trajectory. Nursing home use by either a parent or in-law increases LTCI purchase probability by 0.8 percentage points, with no significant difference in response between parents’ and in-laws’ use. The estimated increase in purchase probability from experience with LTC is about half the previously estimated increase from tax policy-induced price decreases. PMID:25647006

Long-term care insurance: Does experience matter?

Science.gov (United States)

Coe, Norma B; Skira, Meghan M; Van Houtven, Courtney Harold

2015-03-01

We examine whether long-term care (LTC) experience helps explain the low demand for long-term care insurance (LTCI). We test if expectations about future informal care receipt, expectations about inheritance receipt, and LTCI purchase decisions vary between individuals whose parents or in-laws have used LTC versus those who have not. We find parental use of a nursing home decreases expectations that one's children will provide informal care, consistent with the demonstration effect. Nursing home use by in-laws does not have the same impact, suggesting that individuals are responding to information gained about their own aging trajectory. Nursing home use by either a parent or in-law increases LTCI purchase probability by 0.8 percentage points, with no significant difference in response between parents' and in-laws' use. The estimated increase in purchase probability from experience with LTC is about half the previously estimated increase from tax policy-induced price decreases. Copyright © 2015 Elsevier B.V. All rights reserved.

Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

Science.gov (United States)

Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

2006-10-01

Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity.

Science.gov (United States)

Hu, Jiang-Yuan; Schacher, Samuel

2014-04-02

Short-term and long-term synaptic plasticity are cellular correlates of learning and memory of different durations. Little is known, however, how these two forms of plasticity interact at the same synaptic connection. We examined the reciprocal impact of short-term heterosynaptic or homosynaptic plasticity at sensorimotor synapses of Aplysia in cell culture when expressing persistent long-term facilitation (P-LTF) evoked by serotonin [5-hydroxytryptamine (5-HT)]. Short-term heterosynaptic plasticity induced by 5-HT (facilitation) or the neuropeptide FMRFa (depression) and short-term homosynaptic plasticity induced by tetanus [post-tetanic potentiation (PTP)] or low-frequency stimulation [homosynaptic depression (HSD)] of the sensory neuron were expressed in both control synapses and synapses expressing P-LTF in the absence or presence of protein synthesis inhibitors. All forms of short-term plasticity failed to significantly affect ongoing P-LTF in the absence of protein synthesis inhibitors. However, P-LTF reversed to control levels when either 5-HT or FMRFa was applied in the presence of rapamycin. In contrast, P-LTF was unaffected when either PTP or HSD was evoked in the presence of either rapamycin or anisomycin. These results indicate that synapses expressing persistent plasticity acquire a "new" baseline and functionally express short-term changes as naive synapses, but the new baseline becomes labile following selective activations-heterosynaptic stimuli that evoke opposite forms of plasticity-such that when presented in the presence of protein synthesis inhibitors produce a rapid reversal of the persistent plasticity. Activity-selective induction of a labile state at synapses expressing persistent plasticity may facilitate the development of therapies for reversing inappropriate memories.

Friction transfer of polytetrafluoroethylene (PTFE) to produce nanoscale features and influence cellular response in vitro.

Science.gov (United States)

Kearns, V R; Doherty, P J; Beamson, G; Martin, N; Williams, R L

2010-07-01

A large number of cell types are known to respond to chemical and topographical patterning of substrates. Friction transfer of polytetrafluoroethylene (PTFE) onto substrates has been shown to produce continuous, straight, parallel nanofibres. Ammonia plasma treatment can be used to defluorinate the PTFE, decreasing the dynamic contact angle. Fibroblast and epithelial cells were elongated and oriented with their long axis parallel to the fibres, both individually and in clusters. The fibres restricted cell migration. Cell alignment was slightly reduced on the plasma-treated fibres. These results indicated that although surface topography can affect cellular response, surface chemistry also mediates the extent of this response.

Response to Intervention as a Predictor of Long-Term Reading Outcomes in Children with Dyslexia.

Science.gov (United States)

van der Kleij, Sanne W; Segers, Eliane; Groen, Margriet A; Verhoeven, Ludo

2017-08-01

The goal of this study was to investigate how growth during a phonics-based intervention, as well as reading levels at baseline testing, predicted long-term reading outcomes of children with dyslexia. Eighty Dutch children with dyslexia who had completed a 50-week phonics-based intervention in grade 4 were tested in grade 5 on both word and pseudoword (following regular Dutch orthographic patterns) reading efficiency and compared to 93 typical readers. In grade 5 the children with dyslexia were still significantly slower in word and pseudoword reading than their typically developing peers. Results showed that long-term pseudoword reading in the group with dyslexia was predicted by pseudoword reading at pretest and growth in pseudoword reading during the intervention, which was itself predicted by pseudoword reading at pretest. This was not the case for word reading. We found that long-term word reading was directly predicted from pretest word reading, and indirectly via pretest pseudoword reading, via growth in pseudoword and word reading. It can be concluded that pseudoword reading is not only a good indicator of severity of reading difficulties in children with dyslexia, it is also an indicator of who will profit from intervention in the long-term. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

Science.gov (United States)

Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

2017-09-01

Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

Taking into account the long term dimension associated with radioactive waste management

International Nuclear Information System (INIS)

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

2008-01-01

Radioactive waste introduces a new time dimension in the field of risk management. This is why, for more than 10 years, there have been reflections on the societal and organisational mechanisms allowing a responsible management over the long term of the risk associated with radioactive waste. These reflections lead one to ask questions regarding interactions between what is at stake for societal and radiation protection criteria, demanding a multidisciplinary approach to the problem. Within the framework of the European project C.O.W.A.M. 2, dedicated to the improvement of governance of radioactive waste management in Europe, a working group involving experts, authorities, waste managers, locally elected representatives and N.G.O.s, discussed the stakes associated with the long term dimension. This article presents the main results of this working group, organised around four themes: meaning of the long term and what is at stake, the ethical dimension regarding long term issues, continuity and sustainability of the surveillance and control of radioactive waste facilities, effectiveness of financing schemes for the long term management of radioactive waste. (authors)

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

Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

Science.gov (United States)

Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

2014-01-01

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

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.

An integrated stochastic multi-regional long-term energy planning model incorporating autonomous power systems and demand response

International Nuclear Information System (INIS)

Koltsaklis, Nikolaos E.; Liu, Pei; Georgiadis, Michael C.

2015-01-01

The power sector faces a rapid transformation worldwide from a dominant fossil-fueled towards a low carbon electricity generation mix. Renewable energy technologies (RES) are steadily becoming a greater part of the global energy mix, in particular in regions that have put in place policies and measures to promote their utilization. This paper presents an optimization-based approach to address the generation expansion planning (GEP) problem of a large-scale, central power system in a highly uncertain and volatile electricity industry environment. A multi-regional, multi-period linear mixed-integer linear programming (MILP) model is presented, combining optimization techniques with a Monte Carlo (MCA) method and demand response concepts. The optimization goal concerns the minimization of the total discounted cost by determining optimal power capacity additions per time interval and region, and the power generation mix per technology and time period. The model is evaluated on the Greek power system (GPS), taking also into consideration the scheduled interconnection of the mainland power system with those of selected autonomous islands (Cyclades and Crete), and aims at providing full insight into the composition of the long-term energy roadmap at a national level. - Highlights: • A spatial, multi-period, long-term generation expansion planning model is presented. • A Monte-Carlo method along with a demand response mechanism are incorporated. • Autonomous power systems interconnection is considered. • Electricity and CO 2 emission trade are taken into account. • Lignite, natural gas and wind power comprise the dominant power technologies

The Erlangen Dose Optimization Trial for radiotherapy of benign painful shoulder syndrome. Long-term results

International Nuclear Information System (INIS)

Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R.

2014-01-01

To evaluate the long-term efficacy of pain reduction by two dose-fractionation schedules for radiotherapy of painful shoulder syndrome. Between February 2006 and February 2010, 312 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). Median follow-up was 35 months (range 11-57). The overall early, delayed and long-term response rates for all patients were 83, 85 and 82%, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 56.8±23.7 and 53.2±21.8 (p=0.16); 38.2±36.1 and 34.0±24.5 (p=0.19); 33.0±27.2 and 23.7±22.7 (p=0.04) and 27.9±25.8 and 32.1±26.9 (p=0.25), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 9.7±3.0 and 9.5±2.7 (p=0.31); 6.1±3.6 and 5.4±3.6 (p=0.10); 5.3±3.7 and 4.1±3.7 (p=0.05) and 4.0±3.9 and 5.3±4.4 (p=0.05), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p=0.28). Radiotherapy is an effective treatment for the management of benign painful shoulder syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy. (orig.)

WOOD CELLULAR DENDROCLIMATOLOGY: TESTING NEW PROXIES IN GREAT BASIN BRISTLECONE PINE

Directory of Open Access Journals (Sweden)

Emanuele Ziaco

2016-10-01

adaptations to external stressors. Integrating xylem cellular features with ring-width chronologies can widen our understanding of past climatic variability (including annual extreme events and improve the evaluation of long-term plant response to drought, especially in connection with future warming scenarios.

Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects.

Science.gov (United States)

Rath, Judith J G; Tavy, Dénes L J; Wertenbroek, Agnes A A C M; van Woerkom, Theodoor C A M; de Bruijn, Sebastiaan F T M

2010-08-01

To determine the short-term and long-term treatment-effects of botulinum toxin type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with simple motor tics that were treated every 3 months with injections of BTX-A. Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and last 2 (if treated 5 times or more) treatments were recorded, as well as latency of response, changes of premonitory urges (PMUs) and possible side effects. Total number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16 of 18 tics (89%) short-term efficacy was reported successful (good or moderate). Long-term efficacy was reported in 12 tics of which 11 showed similar or even increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A permanent remission of the treated tic was seen in 3 patients with a maximum follow-up of 10 years. BTX-A appears a safe and effective treatment for simple motor tics and retains its efficacy after long-term treatment. BTX may also induce permanent remission of the treated tics and effects of BTX are not restricted to merely motor behaviour.

Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus

DEFF Research Database (Denmark)

Christensen, Jan Pravsgaard; Doherty, P C

1999-01-01

The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first...... in the mediastinal lymph nodes and then in the cervical lymph nodes and the spleen. The numbers of MHV-68-specific CD4(+) T cells generated in congenic mice homozygous for disruption of the beta2-microglobulin gene tended to be higher, indicating that the absence of the CD8(+) set in this group resulted...... in a compensatory response. The peak frequency within the splenic CD4(+) T-cell population may reach 1:50 in the acute response; it then drops to 1:400 to 1:500 within 4 months and stays at that level in the very long term. Sorting for L-selectin (CD62L) expression established that all virus-specific CD4(+) T cells...

Implicit short- and long-term memory direct our gaze in visual search

NARCIS (Netherlands)

Kruijne, Wouter; Meeter, Martijn

2016-01-01

Visual attention is strongly affected by the past: both by recent experience and by long-term regularities in the environment that are encoded in and retrieved from memory. In visual search, intertrial repetition of targets causes speeded response times (short-term priming). Similarly, targets that

The value of short-term pain relief in predicting the long-term outcome of 'indirect' cervical epidural steroid injections.

Science.gov (United States)

Joswig, Holger; Neff, Armin; Ruppert, Christina; Hildebrandt, Gerhard; Stienen, Martin Nikolaus

2018-05-01

The predictive value of short-term arm pain relief after 'indirect' cervical epidural steroid injection (ESI) for the 1-month treatment response has been previously demonstrated. It remained to be answered whether the long-term response could be estimated by the early post-interventional pain course as well. Prospective observational study, following a cohort of n = 45 patients for a period of 24 months after 'indirect' ESI for radiculopathy secondary to a single-level cervical disk herniation (CDH). Arm and neck pain on the visual analog scale (VAS), health-related quality of life with the Short Form-12 (SF-12), and functional outcome with the Neck Pain and Disability (NPAD) Scale were assessed. Any additional invasive treatment after a single injection (second injection or surgery) defined treatment outcome as 'non-response'. At 24 months, n = 30 (66.7%) patients were responders and n = 15 (33.3%) were non-responders. Non-responders exited the follow-up at 1 month (n = 10), at 3 months (n = 4), and at 6 months (n = 1). No patients were injected again or operated on between the 6- and 24-month follow-up. Patients with favorable treatment response at 24 months had significantly lower VAS arm pain (p  50% short term pain reduction was not a reliable predictor of the 24-month responder status. SF-12 and NPAD scores were better among treatment responders in the long term. Patients who require a second injection or surgery after 'indirect' cervical ESI for a symptomatic CDH do so within the first 6 months. Short-term pain relief cannot reliably predict the long-term outcome.

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Science.gov (United States)

Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

2004-03-01

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

Science.gov (United States)

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Long-term storage of Greater-Than-Class C Low-Level Waste

International Nuclear Information System (INIS)

Magleby, M.T.

1990-01-01

Under Federal law, the Department of Energy (DOE) is responsible for safe disposal of Greater-Than-Class C Low-Level Waste (GTCC LLW) generated by licenses of the Nuclear Regulatory commission (NRC) or Agreement States. Such waste must be disposed of in a facility licensed by the NRC. It is unlikely that licensed disposal of GTCC LLW will be available prior to the year 2010. Pending availability of disposal capacity, DOE is assessing the need for collective, long-term storage of GTCC LLW. Potential risks to public health and safety caused by long-term storage of GTCC LLW at the place of generation will be evaluated to determine if alternative facilities are warranted. If warranted, several options will be investigated to determine the preferred alternative for long-term storage. These options include modification of an existing DOE facility, development of a new DOE facility, or development of a facility by the private sector with or without DOE support. Reasonable costs for long-term storage would be borne by the waste generators. 5 refs., 1 fig

Induction of a specific strong polyantigenic cellular immune response after short-term chemotherapy controls bacillary reactivation in murine and guinea pig experimental models of tuberculosis.

Science.gov (United States)

Guirado, Evelyn; Gil, Olga; Cáceres, Neus; Singh, Mahavir; Vilaplana, Cristina; Cardona, Pere-Joan

2008-08-01

RUTI is a therapeutic vaccine that is generated from detoxified and liposomed Mycobacterium tuberculosis cell fragments that has demonstrated its efficacy in the control of bacillus reactivation after short-term chemotherapy. The aim of this study was to characterize the cellular immune response generated after the therapeutic administration of RUTI and to corroborate the lack of toxicity of the vaccine. Mouse and guinea pig experimental models were infected with a low-dose M. tuberculosis aerosol. RUTI-treated animals showed the lowest bacillary load in both experimental models. RUTI also decreased the percentage of pulmonary granulomatous infiltration in the mouse and guinea pig models. This was not the case after Mycobacterium bovis BCG treatment. Cellular immunity was studied through the characterization of the intracellular gamma interferon (IFN-gamma)-producing cells after the splenocytes' stimulation with M. tuberculosis-specific structural and growth-related antigens. Our data show that the difference between the therapeutic administration of BCG and RUTI resides mainly in the stronger activation of IFN-gamma(+) CD4(+) cells and CD8(+) cells against tuberculin purified protein derivative, ESAT-6, and Ag85B that RUTI generates. Both vaccines also triggered a specific immune response against the M. tuberculosis structural antigens Ag16kDa and Ag38kDa and a marked mRNA expression of IFN-gamma, tumor necrosis factor, interleukin-12, inducible nitric oxide synthase, and RANTES in the lung. The results show that RUTI's therapeutic effect is linked not only to the induction of a Th1 response but also to the stimulation of a quicker and stronger specific immunity against structural and growth-related antigens that reduces both the bacillary load and the pulmonary pathology.

Protein quality control in protection against systolic overload cardiomyopathy: the long term role of small heat shock proteins.

Science.gov (United States)

Kumarapeli, Asangi R K; Horak, Kathleen; Wang, Xuejun

2010-07-21

Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short-term protection against various insults and injuries. Previously, we reported that the small HSP alphaB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressingtransgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overex-pression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload.

Research into care quality criteria for long-term care institutions.

Science.gov (United States)

Wang, Wen-Liang; Chang, Hong-Jer; Liu, An-Chi; Chen, Yu-Wen

2007-12-01

The purpose of this paper was to determine the criteria that reflect the quality of care provided by long-term care institutions. Research was conducted using a two-step procedure that first utilized the SERVQUAL model with Fuzzy Delphi Method to establish the proper criteria by which service quality could be measured. A total of 200 questionnaires were mailed to expert respondents, of which 89 were returned and 77 deemed valid for use in this study. We then applied the Multi-Criteria Decision Making Process to determine the degree of importance of each criterion to long-term care institution service quality planning work. Secondly, 200 questionnaires were distributed and 74 valid responses were returned. Based on the 5 SERVQUAL model constructs, this study found 17 of the 28 criteria, to be pertinent to nursing care quality, with those in the Responsiveness and Empathy domains being the ones most critical.

Reduction on OFF-responses of Electroretinogram in Monkeys with Long-term High Intraocular Pressure

Directory of Open Access Journals (Sweden)

Ke-Gao Liu

2017-01-01

Conclusions: Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.

Principles of exercise physiology: responses to acute exercise and long-term adaptations to training.

Science.gov (United States)

Rivera-Brown, Anita M; Frontera, Walter R

2012-11-01

Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Long-term Studies of Marine Halogen Release

Science.gov (United States)

Tschritter, J.; Holla, R.; Frieß, U.; Platt, U.

2009-04-01

Institute of Enviromental Physics, Heidelberg, Germany. Long term measurements of atmospheric trace gases using multi-axis DOAS instruments are pursued at the new SOLAS observatory on the island of Sao Vicente, (Cape Verde). This research is part of the SOPRAN (Surface Ocean Processes in the ANthropocene) project (Fördernummer:03F0462F). Reactive halogen species (RHS) such as bromine- and iodine- containing species play major roles in the chemistry of ozone in both the troposphere and lower stratosphere and thus possibly influence the ozone budget on a global scale. In addition iodine-species emitted from the ocean surface have been shown to be responsible for the production of new atmospheric particles in the marine boundary layer. This may have an effect on cloud formation and radiation transfer on local and global scales. Long term measurements of RHS abundances will help to identify their key regions and processes for formation. A new long term Multi-MAX-DOAS instrument has been installed at the SOLAS observatory on the island of Sao Vicente, (Cape Verde). The main focus of these unique measurements is the investigation of reactive halogen chemistry in the subtropical marine boundary layer based on measurements of BrO, IO, and possibly OIO. Because of its wide spectral range also the use for O4-retrievals to gain aerosol profiles is possible. IO has been detected with mixing ratios up to 1.3 ppt. For BrO an upper limit of 2 ppt could be determined.

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...

HIV-related politics in long-term perspective.

Science.gov (United States)

Friedman, S R

1998-06-01

Some long-term, large-scale socio-economic changes may affect the politics of HIV and other emerging viruses such as hepatitis C. It is useful to ask why the potential peace dividend of the early 1990s failed to provide adequate resources for HIV-related social and medical service delivery in developed or developing nations. This failure can be understood by looking at long-term global economic trends and the pressures they put on governments and corporations. They have produced a period in which fundamental issues of political and economic structure are at stake and, often, the response is a divide-and-rule politics to promote stability. National politics differ in terms of the extent to which such a 'politics of scapegoating' is institutionalized and in terms of which groups are scapegoated. Groups such as drug injectors, gay and bisexual men and sex traders are particularly likely to be targeted both by the scapegoaters and by HIV. Given this framework, how should public health professionals and activists engaged in HIV-related issues respond? Under what circumstances should we orient efforts upwards towards corporate, political or bureaucratic leaders? Under what circumstances, and how, should we orient towards popular forces? Relatedly, we need to consider an issue we often ignore: What do we have to offer potential allies? That is, in terms of their goals, philosophies and needs, why should they ally with us?

Long-Term Sensitization Training in "Aplysia" Decreases the Excitability of a Decision-Making Neuron through a Sodium-Dependent Mechanism

Science.gov (United States)

Hernandez, John S.; Wainwright, Marcy L.; Mozzachiodi, Riccardo

2017-01-01

In "Aplysia," long-term sensitization (LTS) occurs concurrently with a suppression of feeding. At the cellular level, the suppression of feeding is accompanied by decreased excitability of decision-making neuron B51. We examined the contribution of voltage-gated Na[superscript +] and K[superscript +] channels to B51 decreased…

Differences in health status between long-term and short-term benzodiazepine users.

NARCIS (Netherlands)

Zandstra, S.M.; Furer, J.W.; Lisdonk, E.H. van de; Bor, J.H.J.; Zitman, F.G.; Weel, C. van

2002-01-01

BACKGROUND: Despite generally accepted advice to keep treatment short, benzodiazepines are often prescibed for more than six months. Prevention of long-term benzodiazepine use could be facilitated by the utilisation of risk indicators for long-term use. However, the characteristics of long-term

Dryland ecosystem responses to precipitation extremes and wildfire at a long-term rainfall manipulation experiment

Science.gov (United States)

Brown, R. F.; Collins, S. L.

2017-12-01

Climate is becoming increasingly more variable due to global environmental change, which is evidenced by fewer, but more extreme precipitation events, changes in precipitation seasonality, and longer, higher severity droughts. These changes, combined with a rising incidence of wildfire, have the potential to strongly impact net primary production (NPP) and key biogeochemical cycles, particularly in dryland ecosystems where NPP is sequentially limited by water and nutrient availability. Here we utilize a ten-year dataset from an ongoing long-term field experiment established in 2007 in which we experimentally altered monsoon rainfall variability to examine how our manipulations, along with naturally occurring events, affect NPP and associated biogeochemical cycles in a semi-arid grassland in central New Mexico, USA. Using long-term regional averages, we identified extremely wet monsoon years (242.8 mm, 2013), and extremely dry monsoon years (86.0 mm, 2011; 80.0 mm, 2015) and water years (117.0 mm, 2011). We examined how changes in precipitation variability and extreme events affected ecosystem processes and function particularly in the context of ecosystem recovery following a 2009 wildfire. Response variables included above- and below-ground plant biomass (ANPP & BNPP) and abundance, soil nitrogen availability, and soil CO2 efflux. Mean ANPP ranged from 3.6 g m-2 in 2011 to 254.5 g m-2 in 2013, while BNPP ranged from 23.5 g m-2 in 2015 to 194.2 g m-2 in 2013, demonstrating NPP in our semi-arid grassland is directly linked to extremes in both seasonal and annual precipitation. We also show increased nitrogen deposition positively affects NPP in unburned grassland, but has no significant impact on NPP post-fire except during extremely wet monsoon years. While soil respiration rates reflect lower ANPP post-fire, patterns in CO2 efflux have not been shown to change significantly in that efflux is greatest following large precipitation events preceded by longer drying

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

Science.gov (United States)

Gosz, J.

2001-12-01

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

Long-term memory traces for language sounds are highly context-sensitive: an MEG/ERF study

DEFF Research Database (Denmark)

Nielsen, Andreas Højlund; Gebauer, Line; Mcgregor, William

impact on the proposed long-term memory traces for native phonological categories. In order to generate different MMF responses to the same language sound contrast depending on the phonetic context, these long-term memory traces must thus be context-sensitive themselves or exist as separate traces...

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

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

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.

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.

Repair and mutagenesis in procaryotes as cellular responses to ambiental agents

International Nuclear Information System (INIS)

Gomes, R.A.

1982-01-01

The correct and incorrect mechanisms of DNA repair are discussed, as well as the cellular responses induced by the DNA lesions; the reductone mollecular effects; the cellular interactions among irradiated populations of microorganisms and the utilization of microbial assays for the detection of oncogenic activities of chemicals. (M.A.) [pt

The return of the family? Welfare state retrenchment and client autonomy in long-term care

NARCIS (Netherlands)

Grootegoed, E.; van Dijk, D.

2012-01-01

European welfare states are cutting back their responsibilities for long-term care, emphasising ‘self-reliance’ and replacing care as an entitlement of citizenship with targeted services. But we do not know how former long-term care recipients cope with retrenchment and if they are able to negotiate

Quantifying long-term responses of crop yield and nitrate leaching in an intensive farmland using agro-eco-environmental model.

Science.gov (United States)

Sun, Mei; Huo, Zailin; Zheng, Yanxia; Dai, Xiaoqin; Feng, Shaoyuan; Mao, Xiaomin

2018-02-01

Quantitatively ascertaining and analyzing long-term responses of crop yield and nitrate leaching on varying irrigation and fertilization treatments are focal points for guaranteeing crop yield and reducing nitrogen loss. The calibrated agricultural-hydrological RZWQM2 model was used to explore the long-term (2003-2013) transport processes of water and nitrogen and the nitrate leaching amount into groundwater in summer maize and winter wheat rotation field in typical intensive plant area in the North China Plain, Daxing district of Beijing. Simulation results showed that application rates of irrigation and nitrogen fertilizer have couple effects on crop yields and nitrogen leaching of root zone. When both the irrigation and fertilizer for summer maize and winter wheat were 400mm and 400kgNha -1 , respectively, nitrate leaching into groundwater accounted for 47.9% of application amount of nitrogen fertilizer. When application amount of irrigation is 200mm and fertilization is 200kgNha -1 , NUPE (nitrogen uptake efficiency), NUE (nitrogen use efficiency), NPFP (nitrogen partial factor productivity), and W pi (irrigation water productive efficiency) were in general higher than that under other irrigation and fertilization condition (irrigation from 104-400mm, fertilizer 104-400kgNha -1 ). Irrigation bigger than 200mm could shorten the response time of nitrate leaching in deeper soil layer in different irrigation treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term use of metformin and colorectal cancer risk in type II diabetics

DEFF Research Database (Denmark)

Cardel, Majken; Jensen, S. M.; Pottegård, Anton

2014-01-01

of prescriptions for a cumulative dose of 2000 g within 5 years prior to the index date. To control for potential confounders, we used unconditional logistic regression. We generated adjusted odds ratios (OR) for the association between metformin and CRC and performed subanalyses for selected subgroups...... and for the dose-response relation. We identified 2088 cases and 9060 controls during the study period. The association between long-term metformin use and CRC gave an adjusted OR at 0.83 (95% CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.......99 for men). There was a significant dose-response association of metformin use > 250 defined daily dose (DDD) and for the duration of metformin use > 1 year. We found an indication of a protective effect of long-term metformin use against CRC in type II diabetics, although this effect was only seen in women....

Confidence in delegation and leadership of registered nurses in long-term-care hospitals.

Science.gov (United States)

Yoon, Jungmin; Kim, Miyoung; Shin, Juhhyun

2016-07-01

Effective delegation improves job satisfaction, responsibility, productivity and development. The ageing population demands more nurses in long-term-care hospitals. Delegation and leadership promote cooperation among nursing staff. However, little research describes nursing delegation and leadership style. We investigated the relationship between registered nurses' delegation confidence and leadership in Korean long-term-care hospitals. Our descriptive correlational design sampled 199 registered nurses from 13 long-term-care hospitals in Korea. Instruments were the Confidence and Intent to Delegate Scale and Multifactor Leadership Questionnaire. Confidence in delegation significantly aligned with current-unit clinical experience, length of total clinical-nursing experience, delegation-training experience and leadership. Transformational leadership was the most statistically significant factor influencing delegation confidence. When effective delegation integrates with efficient leadership, staff can deliver optimal care to long-term-care patients. © 2016 John Wiley & Sons Ltd.

PKMζ inhibition prevents the metaplastic change induced by conditioned taste aversion on insular cortex long-term potentiation in vivo.

Science.gov (United States)

Ángeles-Durán, Sandybel; Ramos-Languren, Laura E; Escobar, Martha L

2012-01-01

The activity history of a given neuron or pathway has been suggested to influence its future responses to synaptic inputs. In particular, training in several learning tasks produces a metaplastic change, that is, a change in the ability to induce subsequent synaptic plasticity. Experimental evidence shows that the maintenance of long term memory and long-term potentiation (LTP) requires the persistent action of the atypical protein kinase Cisoform, protein kinase M ζ (PKM ζ ). Recent work has demonstrated that the inactivation of PKM ζ in the insular cortex (IC) abolishes conditioned taste aversion (CTA) long term memory. Our previous studies in the IC have demonstrated that the induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to CTA training enhances the retention of this task. Moreover, recently, we have observed that CTA training blocks the subsequent induction of LTP in the Bla-IC projection. The aim of the present study was to investigate the participation of PKM ζon the CTA-dependent modification of the ability to induce subsequent LTP in the Bla-IC projection in vivo . Thus, we have delivered high-frequency stimulation in the Bla-IC projection in order to induce in vivo IC-LTP in the rats that underwent or did not have an impairment of CTA retention due to the intracortical administration of the selective PKM ζ pseudosubstrate inhibitory peptide, ZIP. Our results show that the microinfusion of ZIP into the IC of the behaving rats impairs long-term memory of CTA and prevents its effects on IC-LTP. These results indicate that PKM ζ is a key component of the cellular mechanisms necessary for the persistence of lasting memory traces as well as for those underlying metaplastic changes in neocortex, contributing to the persistence of aversive memories.

Competitive short-term and long-term memory processes in spatial habituation.

Science.gov (United States)

Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Modelling the long-term deployment of electricity storage in the global energy system

International Nuclear Information System (INIS)

Despres, Jacques

2015-01-01

The current development of wind and solar power sources calls for an improvement of long-term energy models. Indeed, high shares of variable wind and solar productions have short- and long-term impacts on the power system, requiring the development of flexibility options: fast-reacting power plants, demand response, grid enhancement or electricity storage. Our first main contribution is the modelling of electricity storage and grid expansion in the POLES model (Prospective Outlook on Long-term Energy Systems). We set up new investment mechanisms, where storage development is based on several combined economic values. After categorising the long-term energy models and the power sector modelling tools in a common typology, we showed the need for a better integration of both approaches. Therefore, the second major contribution of our work is the yearly coupling of POLES to a short-term optimisation of the power sector operation, with the European Unit Commitment and Dispatch model (EUCAD). The two-way data exchange allows the long-term coherent scenarios of POLES to be directly backed by the short-term technical detail of EUCAD. Our results forecast a strong and rather quick development of the cheapest flexibility options: grid interconnections, pumped hydro storage and demand response programs, including electric vehicle charging optimisation and vehicle-to-grid storage. The more expensive battery storage presumably finds enough system value in the second half of the century. A sensitivity analysis shows that improving the fixed costs of batteries impacts more the investments than improving their efficiency. We also show the explicit dependency between storage and variable renewable energy sources. (author) [fr

Cellular composition of long-standing gingivitis and periodontitis lesions.

Science.gov (United States)

Thorbert-Mros, S; Larsson, L; Berglundh, T

2015-08-01

Insufficient information on the cellular composition of long-standing gingivitis lesions without signs of attachment loss makes an understanding of differences in cellular composition between "destructive" and "nondestructive" periodontal lesions difficult. The aim of the current study was to analyze differences in cell characteristics between lesions representing long-standing gingivitis and severe periodontitis. Two groups of patients were recruited. One group consisted of 36 patients, 33-67 years of age, with severe generalized periodontitis (periodontitis group). The second group consisted of 28 patients, 41-70 years of age, with overt signs of gingival inflammation but no attachment loss (gingivitis group). From each patient a gingival biopsy was obtained from one selected diseased site and prepared for immunohistochemical analysis. Periodontitis lesions were twice as large and contained significantly larger proportions, numbers and densities of cells positive for CD138 (plasma cells) and CD68 (macrophages) than did gingivitis lesions. The proportion of B cells that expressed the additional CD5 marker (B-1a cells) was significantly larger in periodontitis lesions than in gingivitis lesions. The densities of T cells and B cells did not differ between periodontitis lesions and gingivitis lesions. T cells were not the dominating cell type in gingivitis lesions, as B cells together with their subset plasma cells comprised a larger number and proportion than T cells. Periodontitis lesions at teeth with advanced attachment and bone loss exhibit quantitative and qualitative differences in relation to gingivitis lesions at teeth with no attachment and bone loss. It is suggested that the large number and high density of plasma cells are the hallmarks of advanced periodontitis lesions and the most conspicuous difference in relation to long-standing gingivitis lesions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long term liquidity analysis of the firm

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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.

The Long-term Impact of Early Life Pain On Adult Responses to Anxiety and Stress: Historical Perspectives and Empirical Evidence

Science.gov (United States)

Victoria, Nicole C.; Murphy, Anne Z.

2016-01-01

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10–18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. PMID:26210872

Long-term changes in river system hydrology in Texas

Directory of Open Access Journals (Sweden)

Y. Zhang

2018-06-01

Full Text Available Climate change and human actives are recognized as a topical issue that change long-term water budget, flow-frequency, and storage-frequency characteristics of different river systems. Texas is characterized by extreme hydrologic variability both spatially and temporally. Meanwhile, population and economic growth and accompanying water resources development projects have greatly impacted river flows throughout Texas. The relative effects of climate change, water resources development, water use, and other factors on long-term changes in river flow, reservoir storage, evaporation, water use, and other components of the water budgets of different river basins of Texas have been simulated in this research using the monthly version of the Water Rights Analysis Package (WRAP modelling system with input databases sets from the Texas Commission on Environmental Quality (TCEQ and Texas Water Development Board (TWDB. The results show that long-term changes are minimal from analysis monthly precipitation depths. Evaporation rates vary greatly seasonally and for much of the state appear to have a gradually upward trend. River/reservoir system water budgets and river flow characteristics have changed significantly during the past 75 years in response to water resources development and use.

Tritium: a model for low level long-term ionizing radiation exposure

International Nuclear Information System (INIS)

Carsten, A.L.

1984-01-01

The somatic, cytogenetic and genetic effects of single and chronic tritiated water (HTO) ingestion in mice was investigated. This study serves not only as an evaluation of tritium toxicity (TRITOX) but due to its design involving long-term low concentration ingestion of HTO may serve as a model for low level long-term ionizing radiation exposure in general. Long-term studies involved animals maintained on HTO at concentrations of 0.3 μCi/ml, 1.0 μCi/ml, 3.0 μCi/ml or depth dose equivalent chronic external exposures to 137 Cs gamma rays. Maintenance on 3.0 μCi/ml resulted in no effect on growth, life-time shortening or bone marrow cellularity, but did result in a reduction of bone marrow stem cells, an increase in DLM's in second generation animals maintained on this regimen and cytogenetic effects as indicated by increased sister chromatid exchanges (SCE's) in bone marrow cells, increased chromosome aberrations in the regenerating liver and an increase in micronuclei in red blood cells. Biochemical and microdosimetry studies showed that animals placed on the HTO regimen reached tritium equilibrium in the body water in approximately 17 to 21 days with a more gradual increase in bound tritium. When animals maintained for 180 days on 3.0 μCi/ml HTO were placed on a tap water regimen, the tritium level in tissue dropped from the equilibrium value of 2.02 μCi/ml before withdrawal to 0.001 μCi/ml at 28 days. 18 references

NUMO's approach for long-term safety assessment - 59404

International Nuclear Information System (INIS)

Ebashi, Takeshi; Kaku, Kenichi; Ishiguro, Katsuhiko

2012-01-01

One of NUMO's policies for ensuring safety is staged and flexible project implementation and decision-making based on iterative confirmation of safety. The safety assessment takes the central role in multiple lines of reasoning and argumentation by providing a quantitative evaluation of long-term safety; a key aspect is uncertainty management. This paper presents NUMO's basic strategies for long-term safety assessment based on the above policy. NUMO's approach considering Japanese boundary conditions is demonstrated as a starting-point for evaluating the long-term safety of an actual site. In Japan, the Act on Final Disposal of Specified Radioactive Waste states that the siting process shall consist of three stages. The Nuclear Waste Management Organization of Japan (NUMO) is responsible for geological disposal of vitrified high-level waste and some types of TRU waste. NUMO has chosen to implement a volunteer approach to siting. NUMO decided to prepare the so-called 2010 technical report, which sets out three safety policies, one of which is staged project implementation and decision-making based on iterative confirmation of safety. Based on this policy, NUMO will gradually integrate relevant interdisciplinary knowledge to build a safety case when a formal volunteer application is received that would allow site investigations to be initiated. The safety assessment takes the central role in multiple lines of reasoning and argumentation by providing a quantitative evaluation of long-term safety; one of a key aspect is uncertainty management. This paper presents the basic strategies for NUMO's long-term safety assessment based on the above policy. In concrete terms, the common procedures involved in safety assessment are applied in a stepwise manner, based on integration of knowledge obtained from site investigations/evaluations and engineered measures. The results of the safety assessment are then reflected in the planning of site investigations and engineered

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...

A Methodology to Infer Crop Yield Response to Climate Variability and Change Using Long-Term Observations

Directory of Open Access Journals (Sweden)

Manfred A. Lange

2013-11-01

Full Text Available A new methodology to extract crop yield response to climate variability and change from long-term crop yield observations is presented in this study. In contrast to the existing first-difference approach (FDA, the proposed methodology considers that the difference in value between crop yields of two consecutive years reflects necessarily the contributions of climate and management conditions, especially at large spatial scales where both conditions may vary significantly from one year to the next. Our approach was applied to remove the effect of non-climatic factors on crop yield and, hence, to isolate the effect of the observed climate change between 1961 and 2006 on three widely crops grown in three Mediterranean countries—namely wheat, corn and potato—using national-level crop yield observations’ time-series. Obtained results show that the proposed methodology provides us with a ground basis to improve substantially our understanding of crop yield response to climate change at a scale that is relevant to large-scale estimations of agricultural production and to food security analyses; and therefore to reduce uncertainties in estimations of potential climate change effects on agricultural production. Furthermore, a comparison of outputs of our methodology and FDA outputs yielded a difference in terms of maize production in Egypt, for example, that exceeds the production of some neighbouring countries.

Linking physiological and cellular responses to thermal stress: β-adrenergic blockade reduces the heat shock response in fish.

Science.gov (United States)

Templeman, Nicole M; LeBlanc, Sacha; Perry, Steve F; Currie, Suzanne

2014-08-01

When faced with stress, animals use physiological and cellular strategies to preserve homeostasis. We were interested in how these high-level stress responses are integrated at the level of the whole animal. Here, we investigated the capacity of the physiological stress response, and specifically the β-adrenergic response, to affect the induction of the cellular heat shock proteins, HSPs, following a thermal stress in vivo. We predicted that blocking β-adrenergic stimulation during an acute heat stress in the whole animal would result in reduced levels of HSPs in red blood cells (RBCs) of rainbow trout compared to animals where adrenergic signaling remained intact. We first determined that a 1 h heat shock at 25 °C in trout acclimated to 13 °C resulted in RBC adrenergic stimulation as determined by a significant increase in cell swelling, a hallmark of the β-adrenergic response. A whole animal injection with the β2-adrenergic antagonist, ICI-118,551, successfully reduced this heat-induced RBC swelling. The acute heat shock caused a significant induction of HSP70 in RBCs of 13 °C-acclimated trout as well as a significant increase in plasma catecholamines. When heat-shocked fish were treated with ICI-118,551, we observed a significant attenuation of the HSP70 response. We conclude that circulating catecholamines influence the cellular heat shock response in rainbow trout RBCs, demonstrating physiological/hormonal control of the cellular stress response.

Nuclear and cytoplasmic signalling in the cellular response to ionising radiation

International Nuclear Information System (INIS)

Szumiel, Irena

2001-01-01

DNA is the universal primary target for ionising radiation; however, the cellular response is highly diversified not only by differential DNA repair ability. The monitoring system for the ionising radiation-inflicted DNA damage consists of 3 apparently independently acting enzymes which are activated by DNA breaks: two protein kinases, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and a poly(ADP-ribose) polymerase, PARP-1. These 3 enzymes are the source of alarm signals, which affect to various extents DNA repair, progression through the cell cycle and eventually the pathway to cell death. Their functions probably are partly overlapping. On the side of DNA repair their role consists in recruiting and/or activating the repair enzymes, as well as preventing illegitimate recombination of the damaged sites. A large part of the nuclear signalling pathway, including the integrating role of TP53 has been revealed. Two main signalling pathways start at the plasma membrane: the MAPK/ERK (mitogen and extracellular signal regulated protein kinase family) 'survival pathway' and the SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase) 'cell death pathway'. The balance between them is likely to determine the cell's fate. An additional important 'survival pathway' starts at the insulin-like growth factor type I receptor (IGF-IR), involves phosphoinositide- 3 kinase and Akt kinase and is targeted at inactivation of the pro-apoptotic BAD protein. Interestingly, over-expression of IGF-IR almost entirely abrogates the extreme radiation sensitivity of ataxia telangiectasia cells. When DNA break rejoining is impaired, the cell is unconditionally radiation sensitive. The fate of a repair-competent cell is determined by the time factor: the cell cycle arrest should be long enough to ensure the completion of repair. Incomplete repair or misrepair may be tolerated, when generation of the death signal is prevented. So, the character and timing

Long-Term Persistency of Abnormal Heart Rate Variability following Long NICU Stay and Surgery at Birth

Directory of Open Access Journals (Sweden)

Mélanie Morin

2014-01-01

Full Text Available Preterm birth is associated with painful procedures during the neonatal intensive care unit (NICU stay. Full-term newborns can also experience pain, following surgery. These procedures can have long-lasting consequences. It has been shown that children born preterm show pain responses and cardiac alterations. This study aimed to explore the heart rate reactivity to pain in 107 subjects born either preterm or full-term who were between 7 and 25 years old at testing. We also evaluated the effect of pain experienced at birth, as represented by a longer NICU stay, time under ventilation, and surgery at birth. Participants were asked to immerse their right forearm in 10°C water for 2 minutes. Electrocardiograms were recorded at baseline and during the immersion procedure. Full-term subjects showed a stable increase in heart rate throughout the procedure, whereas preterm ones showed a strong increase at the beginning, which decreased over time. Also, preterm and full-term subjects who experienced pain at birth showed higher resting heart rate, stronger sympathetic activity, and lower cardiac vagal activity. Our study demonstrated a long-term impact of a long NICU stay and surgery at birth on cardiac autonomic activity. This could lead to impaired reactions to pain or stress in later life.

Compensating for non-response in a study estimating the incidence of mental disorders in long-term sickness absence by a two-phased design

DEFF Research Database (Denmark)

Søgaard, Hans Jørgen; Bech, Per

2010-01-01

AIMS: The study compensates for the non-response that was observed in a previous study that estimated the frequencies of mental disorders in long-term sickness absence (LSA) (more than eight weeks of continuous sickness absence). In this study, the frequency of any mental disorder was estimated a...

Long-term contracts vs. short-term trade of natural gas - a European perspective

International Nuclear Information System (INIS)

Neuhoff, Karsten; Hirschhausen, Christian von

2005-01-01

This paper analyses the economics of long-term gas contracts under changing institutional conditions, mainly gas sector liberalisation. The paper is motivated by the increasingly tense debate in continental Europe, UK and the US on the security of long-term gas supply. We discuss the main issues regarding long-term contracts, i.e. the changing role of the flexibility clause, the effect of abandoning the destination clause, and the strategic behaviour of producers between long-term sales and spot-sales. The literature suggests consumers and producers benefit from risk hedging through long-term contracts. Furthermore long-term contracts may reduce exercise of market power. Our analysis adds an additional benefit if the long-run demand elasticity is significantly lower than the short-run elasticity, both strategic producers and consumers benefit from lower prices and larger market volume. Some policy implications of the findings are also discussed. (Author)

The uranium industry: long-term planning for short-term competition

International Nuclear Information System (INIS)

Vottero, X.; Georges Capus, G.

2001-01-01

Long term planning for short term competition 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. Firstly, the risk of investing in new mining projects in western countries is growing because, on the one hand, of very erratic market conditions and, on the other hand, of increasingly lengthy, complex and unpredictable regulatory conditions. Secondly, the supply of other sources of uranium (uranium derived from nuclear weapons, uranium produced in CIS countries, ...) involve other risks, mainly related to politics and commercial restrictions. Consequently, competitive uranium supply requires not only technical competence but also financial strength and good marketing capabilities in order to anticipate long-term market trends, in terms of both demand and supply. It also requires taking into account new parameters such as politics, environment, regulations, etc. Today, a supplier dedicated to the sustainable production of nuclear electricity must manage a broad range of long-term risks inherent to the procurement of uranium. Taking into account all these parameters in a context of short-term, fast-changing market is a great challenge for the future generation. World Uranium Civilian Supply and Demand. (authors)

Long-term strain response of polymer optical fiber FBG sensors

DEFF Research Database (Denmark)

Bundalo, Ivan-Lazar; Nielsen, Kristian; Woyessa, Getinet

2017-01-01

We report on the viscoelastic response of PMMA microstructured polymer optical fibers (mPOFs) when exposed to long periods of strain and relaxation, with the strain period ranging from 0.5 min to 50 min. The behavior of the fibers was monitored by inscribing a fiber Bragg grating (FBG) in them...... and tracking the reflection peak. We demonstrate that the fiber, when relaxing from strains of up to 0.9%, has a two-phase recovery: initially linear (elastic driven) and subsequently nonlinear (viscoelastic driven) contraction. The linear (elastic) relaxation wavelength range depends both on the strain level...

Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities

International Nuclear Information System (INIS)

Lim, Seong-Rin; Schoenung, Julie M.

2010-01-01

Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones.

Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities.

Science.gov (United States)

Lim, Seong-Rin; Schoenung, Julie M

2010-01-01

Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones. 2010 Elsevier Ltd. All rights reserved.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

Science.gov (United States)

Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

2013-11-11

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

Science.gov (United States)

2013-01-01

Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

Short-term memory and long-term memory are still different.

Science.gov (United States)

Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genetic variation in the cellular response of Daphnia magna (Crustacea: Cladocera) to its bacterial parasite.

Science.gov (United States)

Auld, Stuart K J R; Scholefield, Jennifer A; Little, Tom J

2010-11-07

Linking measures of immune function with infection, and ultimately, host and parasite fitness is a major goal in the field of ecological immunology. In this study, we tested for the presence and timing of a cellular immune response in the crustacean Daphnia magna following exposure to its sterilizing endoparasite Pasteuria ramosa. We found that D. magna possesses two cell types circulating in the haemolymph: a spherical one, which we call a granulocyte and an irregular-shaped amoeboid cell first described by Metchnikoff over 125 years ago. Daphnia magna mounts a strong cellular response (of the amoeboid cells) just a few hours after parasite exposure. We further tested for, and found, considerable genetic variation for the magnitude of this cellular response. These data fostered a heuristic model of resistance in this naturally coevolving host-parasite interaction. Specifically, the strongest cellular responses were found in the most susceptible hosts, indicating resistance is not always borne from a response that destroys invading parasites, but rather stems from mechanisms that prevent their initial entry. Thus, D. magna may have a two-stage defence--a genetically determined barrier to parasite establishment and a cellular response once establishment has begun.

Long-term follow-up in dogs with idiopathic eosinophilic bronchopneumopathy treated with inhaled steroid therapy.

Science.gov (United States)

Canonne, A M; Bolen, G; Peeters, D; Billen, F; Clercx, C

2016-10-01

Treatment of canine idiopathic eosinophilic bronchopneumopathy mainly consists of long-term oral corticosteroid therapy. To avoid side effects, inhaled steroid therapy has been increasingly used but long-term clinical response and potential side effects are sparsely described. Description of clinical response and side effects with long-term fluticasone in dogs with eosinophilic bronchopneumopathy. Case series of dogs with eosinophilic bronchopneumopathy and treated with fluticasone monotherapy for at least 6 months. Clinical response and side effects assessed by physical examination, standardised questionnaire and ACTH (corticotropin) stimulation test. Eight dogs were treated for between 6 months and 5 years. Cough initially improved in all dogs; two dogs remained free of clinical signs, three were well controlled, but three showed severe relapse. Pituitary-adrenal axis inhibition occurred in two dogs treated with fluticasone monotherapy for more than 2 years; only one dog had clinical signs of iatrogenic hyperadrenocorticism. Fluticasone monotherapy allows initial improvement or remission in the majority of dogs but long-term treatment fails to resolve the cough in some individuals. In addition, such therapy may induce pituitary-adrenal axis inhibition. Prospective larger and randomised studies including both fluticasone and orally-treated dogs are needed to define the optimal treatment. © 2016 British Small Animal Veterinary Association.

The cellular adaptive response the role in life organisms

International Nuclear Information System (INIS)

Smith, H.

1998-01-01

Exposure of living cells to ionizing radiation may cause DNA damage that are generally harmful to the organism. This paper discuss the cellular adaptive response which may be seen when cells which have already been exposed to low concentration radiation doses are subsequently exposed to high concentration doses. It also discusses evidence of the adaptive response in laboratory animals and from limited epidemiological studies. (Author)

A model integrating longshore and cross-shore processes for predicting long-term shoreline response to climate change

Science.gov (United States)

Vitousek, Sean; Barnard, Patrick; Limber, Patrick W.; Erikson, Li; Cole, Blake

2017-01-01

We present a shoreline change model for coastal hazard assessment and management planning. The model, CoSMoS-COAST (Coastal One-line Assimilated Simulation Tool), is a transect-based, one-line model that predicts short-term and long-term shoreline response to climate change in the 21st century. The proposed model represents a novel, modular synthesis of process-based models of coastline evolution due to longshore and cross-shore transport by waves and sea-level rise. Additionally, the model uses an extended Kalman filter for data assimilation of historical shoreline positions to improve estimates of model parameters and thereby improve confidence in long-term predictions. We apply CoSMoS-COAST to simulate sandy shoreline evolution along 500 km of coastline in Southern California, which hosts complex mixtures of beach settings variably backed by dunes, bluffs, cliffs, estuaries, river mouths, and urban infrastructure, providing applicability of the model to virtually any coastal setting. Aided by data assimilation, the model is able to reproduce the observed signal of seasonal shoreline change for the hindcast period of 1995-2010, showing excellent agreement between modeled and observed beach states. The skill of the model during the hindcast period improves confidence in the model's predictive capability when applied to the forecast period (2010-2100) driven by GCM-projected wave and sea-level conditions. Predictions of shoreline change with limited human intervention indicate that 31% to 67% of Southern California beaches may become completely eroded by 2100 under sea-level rise scenarios of 0.93 to 2.0 m.

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.

The role of thiols in cellular response to radiation and drugs

International Nuclear Information System (INIS)

Biaglow, J.E.; Varnes, M.E.; Clark, E.P.; Epp, E.R.

1983-01-01

Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme A. GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Some nitroheterocyclic radiosensitizing drugs also deplete cellular thiols under aerobic conditions. Such reactivity may be the reason that they show anomalous radiation sensitization (i.e., better than predicted on the basis of electron affinity). Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole

Global exponential stability of fuzzy cellular neural networks with delays and reaction-diffusion terms

International Nuclear Information System (INIS)

Wang Jian; Lu Junguo

2008-01-01

In this paper, we study the global exponential stability of fuzzy cellular neural networks with delays and reaction-diffusion terms. By constructing a suitable Lyapunov functional and utilizing some inequality techniques, we obtain a sufficient condition for the uniqueness and global exponential stability of the equilibrium solution for a class of fuzzy cellular neural networks with delays and reaction-diffusion terms. The result imposes constraint conditions on the network parameters independently of the delay parameter. The result is also easy to check and plays an important role in the design and application of globally exponentially stable fuzzy neural circuits

Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic salmon anterior kidney T-cells: Indications of short- and long-term immunomodulation

International Nuclear Information System (INIS)

Iwanowicz, Luke R.; Lerner, Darren T.; Blazer, Vicki S.; McCormick, Stephen D.

2005-01-01

Polychlorinated biphenyls (PCBs) exist as persistent organic pollutants in numerous river systems in the United States. Unfortunately, some of these rivers are sites of active Atlantic salmon restoration programs, and polychlorinated biphenyls have been implicated as ancillary factors contributing to failed salmon restoration. Here, we investigate the immediate and chronic effects of intermediate duration aqueous PCB exposure (1 or 10 μg L -1 Aroclor 1254) on the mitogen-stimulated lymphoproliferative response of Atlantic salmon anterior kidney leukocytes (AKLs). A short-term study was designed to examine immunomodulation in Atlantic salmon smolts immediately following 21 days of aqueous exposure, while a long-term study evaluated chronic impacts in the mitogen response in parr 15 months post-exposure as larvae. The proliferative response of AKLs to the mitogens concanavalin A (CON A), phytohemaglutinnin-P (PHA-P), pokeweed mitogen (PWM), and lipopolysaccharide were used as an indice of immunomodulation. The proliferative response to the T-cell mitogens CON A and PHA-P was significantly increased in the 10 μg L -1 group (n = 10; P = 0.043 and 0.002, respectively) immediately following exposure of smolts. Additionally, The PHA-P response was significantly increased in the 1 μg L -1 exposure group (n = 10, P = 0.036). In fish treated as larvae and tested 15 months later, the PHA-P sensitive populations exhibited elevated proliferation in the 1 and 10 μg L -1 groups (n = 12, P -1 treated groups. These results demonstrate an immunomodulatory effect of PCBs on T-cell mitogen sensitive populations of lymphocytes in Atlantic salmon as well as long-term immunomodulation in PHA-P and PWM sensitive populations

Long-Term IgG Response to Porcine Neu5Gc Antigens without Transmission of PERV in Burn Patients Treated with Porcine Skin Xenografts

Czech Academy of Sciences Publication Activity Database

Scobie, L.; Padler-Karavani, V.; Les Bas-Bernardet, S.; Crossan, C.; Bláha, J.; Matoušková, Magda; Hector, R.D.; Cozzi, E.; Vanhove, B.; Charreau, B.; Blancho, G.; Bourdais, L.; Tallacchini, M.; Ribes, J.; Yu, H.; Chen, X.; Kracíková, J.; Brož, L.; Hejnar, Jiří; Veselý, Pavel; Takeuchi, Y.; Varki, A.; Soulillou, J.P.

2013-01-01

Roč. 191, č. 6 (2013), s. 2907-2915 ISSN 0022-1767 Grant - others:EK(XE) LSHB-CT-2006-037377 Source of funding: R - rámcový projekt EK Keywords : PERV transmission * xenotransplantation * long-term immune response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.362, year: 2013

Local Government Implementation of Long-Term Stewardship at Two DOE Facilities

Energy Technology Data Exchange (ETDEWEB)

John Pendergrass; Roman Czebiniak; Kelly Mott; Seth Kirshenberg; Audrey Eidelman; Zachary Lamb; Erica Pencak; Wendy Sandoz

2003-08-13

The Department of Energy (DOE) is responsible for cleaning up the radioactive and chemical contamination that resulted from the production of nuclear weapons. At more than one hundred sites throughout the country DOE will leave some contamination in place after the cleanup is complete. In order to protect human health and the environment from the remaining contamination DOE, U.S. Environmental Protection Agency (EPA), state environmental regulatory agencies, local governments, citizens and other entities will need to undertake long-term stewardship of such sites. Long-term stewardship includes a wide range of actions needed to protect human health in the environment for as long as the risk from the contamination remains above acceptable levels, such as barriers, caps, and other engineering controls and land use controls, signs, notices, records, and other institutional controls. In this report the Environmental Law Institute (ELI) and the Energy Communities Alliance (ECA) examine how local governments, state environmental agencies, and real property professionals implement long-term stewardship at two DOE facilities, Losa Alamos National Laboratory and Oak Ridge Reservation.

Modulation of Long-term Potentiation of Cortico-amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

Directory of Open Access Journals (Sweden)

Daisuke Yamada

2016-08-01

Full Text Available Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala. However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP of optogenetically–evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed a diet with a high ω3 to ω6 PUFA ratio (0.97, compared with mice fed a diet with a low ω3 to ω6 PUFA ratio (0.14. Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol, in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.

Narp regulates long-term aversive effects of morphine withdrawal

Science.gov (United States)

Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

2008-01-01

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic salmon anterior kidney T-cells: indications of short- and long-term immunomodulation.

Science.gov (United States)

Iwanowicz, Luke R; Lerner, Darren T; Blazer, Vicki S; McCormick, Stephen D

2005-05-15

Polychlorinated biphenyls (PCBs) exist as persistent organic pollutants in numerous river systems in the United States. Unfortunately, some of these rivers are sites of active Atlantic salmon restoration programs, and polychlorinated biphenyls have been implicated as ancillary factors contributing to failed salmon restoration. Here, we investigate the immediate and chronic effects of intermediate duration aqueous PCB exposure (1 or 10 microgL-1 Aroclor 1254) on the mitogen-stimulated lymphoproliferative response of Atlantic salmon anterior kidney leukocytes (AKLs). A short-term study was designed to examine immunomodulation in Atlantic salmon smolts immediately following 21 days of aqueous exposure, while a long-term study evaluated chronic impacts in the mitogen response in parr 15 months post-exposure as larvae. The proliferative response of AKLs to the mitogens concanavalin A (CON A), phytohemaglutinnin-P (PHA-P), pokeweed mitogen (PWM), and lipopolysaccharide were used as an indice of immunomodulation. The proliferative response to the T-cell mitogens CON A and PHA-P was significantly increased in the 10 microgL-1 group (n=10; P=0.043 and 0.002, respectively) immediately following exposure of smolts. Additionally, The PHA-P response was significantly increased in the 1 microgL-1 exposure group (n=10, P=0.036). In fish treated as larvae and tested 15 months later, the PHA-P sensitive populations exhibited elevated proliferation in the 1 and 10 microgL-1 groups (n=12, P<0.04) relative to the vehicle control while the PWM response was significantly increased (n=12, P=0.036) only in the 10 microgL-1 treated groups. These results demonstrate an immunomodulatory effect of PCBs on T-cell mitogen sensitive populations of lymphocytes in Atlantic salmon as well as long-term immunomodulation in PHA-P and PWM sensitive populations.

Accelerated long-term forgetting in aging and intra-sleep awakenings

Directory of Open Access Journals (Sweden)

Alison eMary

2013-10-01

Full Text Available The architecture of sleep and the functional neuroanatomical networks subtending memory consolidation processes are both modified with aging, possibly leading to accelerated forgetting in long-term memory. We investigated associative learning and declarative memory consolidation processes in 16 young (18–30 years and 16 older (65–75 years healthy adults. Performance was tested using a cued recall procedure at the end of learning (immediate recall, and 30 minutes and 7 days later. A delayed recognition test was also administered on day 7. Daily sleep diaries were completed during the entire experiment. Results revealed a similar percentage of correct responses at immediate and 30-minute recall in young and older participants. However, recall was significantly decreased 7 days later, with an increased forgetting in older participants. Additionally, intra-sleep awakenings were more frequent in older participants than young adults during the 7 nights, and were negatively correlated with delayed recall performance on day 7 in the older group. Altogether, our results suggest a decline in verbal declarative memory consolidation processes with aging, eventually leading to accelerated long-term forgetting indicating that increased sleep fragmentation due to more frequent intra-sleep awakenings in older participants contribute to the reported age-related decline in long-term memory retrieval. Our results highlight the sensitivity of long-term forgetting measures to evidence consolidation deficits in healthy aging.

Long-Term Memory Performance in Adult ADHD.

Science.gov (United States)

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Sea level anomaly in the North Atlantic and seas around Europe: Long-term variability and response to North Atlantic teleconnection patterns.

Science.gov (United States)

Iglesias, Isabel; Lorenzo, M Nieves; Lázaro, Clara; Fernandes, M Joana; Bastos, Luísa

2017-12-31

Sea level anomaly (SLA), provided globally by satellite altimetry, is considered a valuable proxy for detecting long-term changes of the global ocean, as well as short-term and annual variations. In this manuscript, monthly sea level anomaly grids for the period 1993-2013 are used to characterise the North Atlantic Ocean variability at inter-annual timescales and its response to the North Atlantic main patterns of atmospheric circulation variability (North Atlantic Oscillation, Eastern Atlantic, Eastern Atlantic/Western Russia, Scandinavian and Polar/Eurasia) and main driven factors as sea level pressure, sea surface temperature and wind fields. SLA variability and long-term trends are analysed for the North Atlantic Ocean and several sub-regions (North, Baltic and Mediterranean and Black seas, Bay of Biscay extended to the west coast of the Iberian Peninsula, and the northern North Atlantic Ocean), depicting the SLA fluctuations at basin and sub-basin scales, aiming at representing the regions of maximum sea level variability. A significant correlation between SLA and the different phases of the teleconnection patterns due to the generated winds, sea level pressure and sea surface temperature anomalies, with a strong variability on temporal and spatial scales, has been identified. Long-term analysis reveals the existence of non-stationary inter-annual SLA fluctuations in terms of the temporal scale. Spectral density analysis has shown the existence of long-period signals in the SLA inter-annual component, with periods of ~10, 5, 4 and 2years, depending on the analysed sub-region. Also, a non-uniform increase in sea level since 1993 is identified for all sub-regions, with trend values between 2.05mm/year, for the Bay of Biscay region, and 3.98mm/year for the Baltic Sea (no GIA correction considered). The obtained results demonstrated a strong link between the atmospheric patterns and SLA, as well as strong long-period fluctuations of this variable in spatial and

Health-related quality of life in long-term survivors of testicular cancer

DEFF Research Database (Denmark)

Rossen, Philip Blach; Pedersen, Anette Fischer; Zachariae, Robert

2009-01-01

PURPOSE: A growing number of patients with testicular cancer (TC) become long-term survivors. As a consequence, quality-of-life (QOL) issues become increasingly important. The objective of this study was to investigate QOL among Danish TC survivors. METHODS: A long-term follow-up assessment of all...... patients with TC treated at Aarhus University Hospital in Denmark between 1990 and 2000 was conducted. A total of 401 survivors (response rate, 66%) completed questionnaires concerning QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), depression (Beck...

Long-term leaf production response to elevated atmospheric carbon dioxide and tropospheric ozone

Science.gov (United States)

Alan F. Talhelm; Kurt S. Pregitzer; Christian P. Giardina

2011-01-01

Elevated concentrations of atmospheric CO2 and tropospheric O3 will profoundly influence future forest productivity, but our understanding of these influences over the long-term is poor. Leaves are key indicators of productivity and we measured the mass, area, and nitrogen concentration of leaves collected in litter traps...

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...

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…

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...

Effects of long- and short-term management on the functional structure of meadows through species turnover and intraspecific trait variability.

Science.gov (United States)

Volf, Martin; Redmond, Conor; Albert, Ágnes J; Le Bagousse-Pinguet, Yoann; Biella, Paolo; Götzenberger, Lars; Hrázský, Záboj; Janeček, Štěpán; Klimešová, Jitka; Lepš, Jan; Šebelíková, Lenka; Vlasatá, Tereza; de Bello, Francesco

2016-04-01

The functional structures of communities respond to environmental changes by both species replacement (turnover) and within-species variation (intraspecific trait variability; ITV). Evidence is lacking on the relative importance of these two components, particularly in response to both short- and long-term environmental disturbance. We hypothesized that such short- and long-term perturbations would induce changes in community functional structure primarily via ITV and turnover, respectively. To test this we applied an experimental design across long-term mown and abandoned meadows, with each plot containing a further level of short-term management treatments: mowing, grazing and abandonment. Within each plot, species composition and trait values [height, shoot biomass, and specific leaf area (SLA)] were recorded on up to five individuals per species. Positive covariations between the contribution of species turnover and ITV occurred for height and shoot biomass in response to both short- and long-term management, indicating that species turnover and intraspecific adjustments selected for similar trait values. Positive covariations also occurred for SLA, but only in response to long-term management. The contributions of turnover and ITV changed depending on both the trait and management trajectory. As expected, communities responded to short-term disturbances mostly through changes in intraspecific trait variability, particularly for height and biomass. Interestingly, for SLA they responded to long-term disturbances by both species turnover and intraspecific adjustments. These findings highlight the importance of both ITV and species turnover in adjusting grassland functional trait response to environmental perturbation, and show that the response is trait specific and affected by disturbance regime history.

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

Science.gov (United States)

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

KAUST Repository

Gao, Virginia; Suzuki, Akinobu; Magistretti, Pierre J.; Lengacher, Sylvain; Pollonini, Gabriella; Steinman, Michael Q.; Alberini, Cristina M.

2016-01-01

Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

KAUST Repository

Gao, Virginia

2016-07-12

Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

Numerical simulation of long-term radiation effects for MOSFETs

International Nuclear Information System (INIS)

Wei Yuan; Xie Honggang; Gong Ding; Zhu Jinhui; Niu Shengli; Huang Liuxing

2013-01-01

A coupled algorithm is introduced to simulate the long-term radiation effects of MOSFETs, which combines particle transport with semiconductor governing equations. The former is dealt with Monte-Carlo method, and the latter is solved by finite-volume method. The trapped charge in SiO 2 and the free charge in Si are both described by the drift-diffusion model, and the deposited energy by incident particles can be coupled with the continuous equations of charge, acting as a source item. The discrete form of governing equations is obtained using the finite-volume method, and the numerical solutions of these equations are the long-term radiation response result of MOSFETs. The threshold voltage shift and off-state leakage current of an irradiated MOSFET are simulated with the coupled algorithm respectively, showing a good accordance with results by other calculations. (authors)

The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence.

Science.gov (United States)

Victoria, Nicole C; Murphy, Anne Z

2016-01-01

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Huntingtin is critical both pre- and postsynaptically for long-term learning-related synaptic plasticity in Aplysia.

Directory of Open Access Journals (Sweden)

Yun-Beom Choi

Full Text Available Patients with Huntington's disease exhibit memory and cognitive deficits many years before manifesting motor disturbances. Similarly, several studies have shown that deficits in long-term synaptic plasticity, a cellular basis of memory formation and storage, occur well before motor disturbances in the hippocampus of the transgenic mouse models of Huntington's disease. The autosomal dominant inheritance pattern of Huntington's disease suggests the importance of the mutant protein, huntingtin, in pathogenesis of Huntington's disease, but wild type huntingtin also has been shown to be important for neuronal functions such as axonal transport. Yet, the role of wild type huntingtin in long-term synaptic plasticity has not been investigated in detail. We identified a huntingtin homolog in the marine snail Aplysia, and find that similar to the expression pattern in mammalian brain, huntingtin is widely expressed in neurons and glial cells. Importantly the expression of mRNAs of huntingtin is upregulated by repeated applications of serotonin, a modulatory transmitter released during learning in Aplysia. Furthermore, we find that huntingtin expression levels are critical, not only in presynaptic sensory neurons, but also in the postsynaptic motor neurons for serotonin-induced long-term facilitation at the sensory-to-motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest a key role for huntingtin in long-term memory storage.

Long-Term Stewardship Baseline Report and Transition Guidance

Energy Technology Data Exchange (ETDEWEB)

Kristofferson, Keith

2001-11-01

Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

The long Tramp from Cellular Pathology to Molecular Pathology

Directory of Open Access Journals (Sweden)

Hans Guski

2017-05-01

Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules might be responsible for changes that are visible ‘in larger elements’ (at cellular level.  The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

Legal, administrative and financial aspects of the long-term management of radioactive waste

International Nuclear Information System (INIS)

Strohl, P.; Reyners, P.

1984-01-01

The paper describes the principal features of a study undertaken by the OECD Nuclear Energy Agency on the institutional problems raised by the long-term management of radioactive waste. The purpose of this study is to provide the competent national authorities with a common approach based on experience. All management operations which may extend over periods of more than 50 years are covered by the study, which analyses the control measures or other institutional measures that must be taken with regard to such operations. It distinguishes between ''active'' and ''passive'' control measures and describes their application ''before closure'' and ''after closure'' of the disposal or storage sites. An attempt is made to evaluate the lifetime of such institutional control measures and it is proposed, on this basis, that a period of several centuries, at most 300 years, should be considered reasonable in view of the need to avoid imposing an excessive burden on future generations. The study also provides a description of relations between governments and industry, stressing the increased responsibility of governments in the context of long-term management of radioactive waste. Specific questions of financing and responsibility for civil nuclear activities which relate to long-term management are also analysed. The general conclusion arrived at is that a long-term management strategy must be based on a viable combination of technological methods and institutional measures. (author)

Gastrointestinal Symptoms in Celiac Disease Patients on a Long-Term Gluten-Free Diet.

Science.gov (United States)

Laurikka, Pilvi; Salmi, Teea; Collin, Pekka; Huhtala, Heini; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle

2016-07-14

Experience suggests that many celiac patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD). We investigated the prevalence and severity of these symptoms in patients with variable duration of GFD. Altogether, 856 patients were classified into untreated (n = 128), short-term GFD (1-2 years, n = 93) and long-term GFD (≥3 years, n = 635) groups. Analyses were made of clinical and histological data and dietary adherence. Symptoms were evaluated by the validated GSRS questionnaire. One-hundred-sixty healthy subjects comprised the control group. Further, the severity of symptoms was compared with that in peptic ulcer, reflux disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Altogether, 93% of the short-term and 94% of the long-term treated patients had a strict GFD and recovered mucosa. Untreated patients had more diarrhea, indigestion and abdominal pain than those on GFD and controls. There were no differences in symptoms between the short- and long-term GFD groups, but both yielded poorer GSRS total score than controls (p = 0.03 and p = 0.05, respectively). Furthermore, patients treated 1-2 years had more diarrhea (p = 0.03) and those treated >10 years more reflux (p = 0.04) than controls. Long-term treated celiac patients showed relatively mild symptoms compared with other gastrointestinal diseases. Based on our results, good response to GFD sustained in long-term follow-up, but not all patients reach the level of healthy individuals.

Cognitive, physical, and mental health outcomes between long-term cannabis and tobacco users.

Science.gov (United States)

Lovell, M E; Bruno, R; Johnston, J; Matthews, A; McGregor, I; Allsop, D J; Lintzeris, N

2018-04-01

Cannabis intoxication adversely affects health, yet persistent effects following short-term abstinence in long-term cannabis users are unclear. This matched-subjects, cross-sectional study compared health outcomes of long-term cannabis and long-term tobacco-only users, relative to population norms. Nineteen long-term (mean 32.3years of use, mean age 55.7years), abstinent (mean 15h) cannabis users and 16 long-term tobacco users (mean 37.1years of use, mean age 52.9years), matched for age, educational attainment, and lifetime tobacco consumption, were compared on measures of learning and memory, response inhibition, information-processing, sustained attention, executive control, and mental and physical health. Cannabis users exhibited poorer overall learning and delayed recall and greater interference and forgetting than tobacco users, and exhibited poorer recall than norms. Inhibition and executive control were similar between groups, but cannabis users had slower reaction times during information processing and sustained attention tasks. Cannabis users had superior health satisfaction and psychological, somatic, and general health than tobacco users and had similar mental and physical health to norms whilst tobacco users had greater stress, role limitations from emotional problems, and poorer health satisfaction. Long-term cannabis users may exhibit deficits in some cognitive domains despite short-term abstinence and may therefore benefit from interventions to improve cognitive performance. Tobacco alone may contribute to adverse mental and physical health outcomes, which requires appropriate control in future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

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Renata eToth

2015-10-01

Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

C. elegans positive butanone learning, short-term, and long-term associative memory assays.

Science.gov (United States)

Kauffman, Amanda; Parsons, Lance; Stein, Geneva; Wills, Airon; Kaletsky, Rachel; Murphy, Coleen

2011-03-11

The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans navigates its environment through neuron-specific detection of food and chemical odors, and can associate nutritive states with chemical odors, temperature, and the pathogenicity of a food source. Here, we describe assays of C. elegans associative learning and short- and long-term associative memory. We modified an aversive olfactory learning paradigm to instead produce a positive response; the assay involves starving ~400 worms, then feeding the worms in the presence of the AWC neuron-sensed volatile chemoattractant butanone at a concentration that elicits a low chemotactic index (similar to Toroyama et al.). A standard population chemotaxis assay1 tests the worms' attraction to the odorant immediately or minutes to hours after conditioning. After conditioning, wild-type animals' chemotaxis to butanone increases ~0.6 Chemotaxis Index units, its "Learning Index". Associative learning is dependent on the presence of both food and butanone during training. Pairing food and butanone for a single conditioning period ("massed training") produces short-term associative memory that lasts ~2 hours. Multiple conditioning periods with rest periods between ("spaced training") yields long-term associative memory (long-term memory across species. Our protocol also includes image analysis methods for quick and accurate determination of chemotaxis indices. High-contrast images of animals on chemotaxis assay plates are captured and analyzed by worm counting software in MatLab. The software corrects for uneven background using a morphological tophat transformation. Otsu's method is then used to determine a threshold to separate worms from the background. Very small particles are removed automatically and larger non-worm regions (plate edges or agar punches) are removed by manual selection. The software then estimates the size of single worm by ignoring

Non-alcoholic fatty liver disease and impaired proinsulin conversion as newly identified predictors of the long-term non-response to a lifestyle intervention for diabetes prevention: results from the TULIP study.

Science.gov (United States)

Schmid, Vera; Wagner, Robert; Sailer, Corinna; Fritsche, Louise; Kantartzis, Konstantinos; Peter, Andreas; Heni, Martin; Häring, Hans-Ulrich; Stefan, Norbert; Fritsche, Andreas

2017-12-01

Lifestyle intervention is effective to prevent type 2 diabetes. However, a considerable long-term non-response occurs to a standard lifestyle intervention. We investigated which risk phenotypes at baseline and their changes during the lifestyle intervention predict long-term glycaemic non-response to the intervention. Of 300 participants at high risk for type 2 diabetes who participated in a 24 month lifestyle intervention with diet modification and increased physical activity, 190 participants could be re-examined after 8.7 ± 1.6 years. All individuals underwent a five-point 75 g OGTT and measurements of body fat compartments and liver fat content with MRI and spectroscopy at baseline, 9 and 24 months during the lifestyle intervention, and at long-term follow-up. Fasting proinsulin to insulin conversion (PI/I ratio) and insulin sensitivity and secretion were calculated from the OGTT. Non-response to lifestyle intervention was defined as no decrease in glycaemia, i.e. no decrease in AUC for glucose at 0-120 min during OGTT (AUCglucose 0-120 min ). Before the lifestyle intervention, 56% of participants had normal glucose regulation and 44% individuals had impaired fasting glucose and/or impaired glucose tolerance. At long-term follow-up, 11% had developed diabetes. Multivariable regression analysis with adjustment for age, sex, BMI and change in BMI during the lifestyle intervention revealed that baseline insulin secretion and insulin sensitivity, as well as change in insulin sensitivity during the lifestyle intervention, predicted long-term glycaemic control after 9 years. In addition, increased hepatic lipid content as well as impaired fasting proinsulin conversion at baseline were newly detected phenotypes that independently predicted long-term glycaemic control. Increased hepatic lipid content and impaired proinsulin conversion are new predictors, independent of change in body weight, for non-response to lifestyle intervention in addition to the

Long-term monitoring of the Italian forests

Directory of Open Access Journals (Sweden)

Pompei E

2014-02-01

Full Text Available Long-term monitoring of the Italian forests. The long-term monitoring is an essential tool for the study of the state of health of European forest ecosystems over time, especially in relation to the adaptation strategies adopted in response to changes in climate. In 2008, at the European level, there was a need to review the various existing monitoring networks in the various States in order to plan an integration and a more rational use of the information from each detected. The Project for the integration of monitoring networks was carried out using the instrument of the European LIFE+ funding. The fundamental objective of the project was the renovation and expansion of the main European Networks Monitoring of Forests, improving its representativeness, effectiveness and harmonization between them. In addition, in the period 2009/2010 was carried out the extensive and intensive monitoring of forest ecosystems in Europe. The project, approved and co-financed by the European Commission, has been coordinated at the international level by Johann Heinrich von Thunen-Institute, Germany, and saw the participation of 24 EU member states and 38 partners.

Spatial coding of ordinal information in short- and long-term memory

Directory of Open Access Journals (Sweden)

Veronique eGinsburg

2015-01-01

Full Text Available The processing of numerical information induces a spatial response bias: Faster responses to small numbers with the left hand and faster responses to large numbers with the right hand. Most theories agree that long-term representations underlie this so called SNARC effect (Spatial Numerical Association of Response Codes; Dehaene, Bossini, & Giraux, 1993. However, a spatial response bias was also observed with the activation of temporary position-space associations in working memory (ordinal position effect; van Dijck & Fias, 2011. Items belonging to the beginning of a memorized sequence are responded to faster with the left hand side while items at the end of the sequence are responded to faster with the right hand side. The theoretical possibility was put forward that the SNARC effect is an instance of the ordinal position effect, with the empirical consequence that the SNARC effect and the ordinal position effect cannot be observed simultaneously. In two experiments we falsify this claim by demonstrating that the SNARC effect and the ordinal position effect are not mutually exclusive. Consequently, this suggests that the SNARC effect and the ordinal position effect result from the activation of different representations. We conclude that spatial response biases can result from the activation of both pre-existing positions in long-term memory and from temporary space associations in working memory at the same time.

Spatial coding of ordinal information in short- and long-term memory.

Science.gov (United States)

Ginsburg, Véronique; Gevers, Wim

2015-01-01

The processing of numerical information induces a spatial response bias: Faster responses to small numbers with the left hand and faster responses to large numbers with the right hand. Most theories agree that long-term representations underlie this so called SNARC effect (Spatial Numerical Association of Response Codes; Dehaene et al., 1993). However, a spatial response bias was also observed with the activation of temporary position-space associations in working memory (ordinal position effect; van Dijck and Fias, 2011). Items belonging to the beginning of a memorized sequence are responded to faster with the left hand side while items at the end of the sequence are responded to faster with the right hand side. The theoretical possibility was put forward that the SNARC effect is an instance of the ordinal position effect, with the empirical consequence that the SNARC effect and the ordinal position effect cannot be observed simultaneously. In two experiments we falsify this claim by demonstrating that the SNARC effect and the ordinal position effect are not mutually exclusive. Consequently, this suggests that the SNARC effect and the ordinal position effect result from the activation of different representations. We conclude that spatial response biases can result from the activation of both pre-existing positions in long-term memory and from temporary space associations in working memory at the same time.

Spatial coding of ordinal information in short- and long-term memory

Science.gov (United States)

Ginsburg, Véronique; Gevers, Wim

2015-01-01

The processing of numerical information induces a spatial response bias: Faster responses to small numbers with the left hand and faster responses to large numbers with the right hand. Most theories agree that long-term representations underlie this so called SNARC effect (Spatial Numerical Association of Response Codes; Dehaene et al., 1993). However, a spatial response bias was also observed with the activation of temporary position-space associations in working memory (ordinal position effect; van Dijck and Fias, 2011). Items belonging to the beginning of a memorized sequence are responded to faster with the left hand side while items at the end of the sequence are responded to faster with the right hand side. The theoretical possibility was put forward that the SNARC effect is an instance of the ordinal position effect, with the empirical consequence that the SNARC effect and the ordinal position effect cannot be observed simultaneously. In two experiments we falsify this claim by demonstrating that the SNARC effect and the ordinal position effect are not mutually exclusive. Consequently, this suggests that the SNARC effect and the ordinal position effect result from the activation of different representations. We conclude that spatial response biases can result from the activation of both pre-existing positions in long-term memory and from temporary space associations in working memory at the same time. PMID:25688199

Effect of partially purified fumonisins on cellular immune response in ...

African Journals Online (AJOL)

After 7 days, cellular immune response was evaluated by delayed-type hypersensitivity (DTH) and lymphoproliferative assays (LA) using spleen cells. Nitric oxide (NO) production by spleen cells was also evaluated. The specific LA response to Pb antigen was higher in group PB than in FB and CTR groups (p< 0.05) but not ...

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

Science.gov (United States)

Durando, Xavier; Thivat, Emilie; D'Incan, Michel; Sinsard, Anne; Madelmont, Jean-Claude; Chollet, Philippe

2005-11-15

Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

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...

Long-term dependence in exchange rates

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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.

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning.

Science.gov (United States)

Månsson, K N T; Frick, A; Boraxbekk, C-J; Marquand, A F; Williams, S C R; Carlbring, P; Andersson, G; Furmark, T

2015-03-17

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2-97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale-Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC-amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC-amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

Collagen Type III and VI Turnover in Response to Long-Term Immobilization.

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Shu Sun

Full Text Available Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization.In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage.Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization.The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.

Role of thiols in cellular response to radiation and drugs. Symposium: thiols

International Nuclear Information System (INIS)

Biaglow, J.E.; Varnes, M.E.; Clark, E.P.; Epp, E.R.

1983-01-01

Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme. A GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole. In conclusion, we propose an altered thiol model which includes a mechanism for thiol involvement in the aerobic radiation response of cells

The cellular response of Saccharomyces cerevisiae to multi-walled carbon nanotubes (MWCNTs

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Chantelle L. Phillips

2015-03-01

Full Text Available Nanoparticles (NPs especially those of carbon nanotubes (CNTs have remarkable properties that are very desirable in various biological and biomedical applications. This has necessitated the rapid study of CNT toxicities, to augment their safe use, particularly, in yeast cells. The yeast cell; Saccharomyces cerevisiae is a widely used industrial and biological organism with very limited data regarding their cellular behaviour in NPs. The current study examines the cellular response of S. cerevisiae to MWCNTs. The CNTs were produced by the swirled floating catalytic chemical vapour deposition (SFCCVD method and covalently functionalised using 1,3-dipolar cycloaddition. The CNT properties such as size, surface area, quality and surface vibrations were characterized using TEM, SEM, BET, TGA and Raman spectroscopy, respectively. The cellular uptake was confirmed with a FITC functionalised MWCNTs using 1H NMR, SEM and TEM. The CNT concentrations of 2–40 μg/ml were used to determine the cellular response through cell growth phases and cell viability characteristics. The TEM and SEM analyses showed the production of MWCNTs with an average diameter of 53 ± 12 nm and a length of 2.5 ± 0.5 μm. The cellular uptake of FITC-MWCNTs showed 100% internalisation in the yeast cells. The growth curve responses to the MWCNT doses showed no significant differences at P > 0.05 on the growth rate and viability of the S. cerevisiae cells.

Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

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John Wikswo

2009-03-01

Full Text Available Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

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Flavia Indrio

2017-08-01

Full Text Available Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects.

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

Science.gov (United States)

Indrio, Flavia; Martini, Silvia; Francavilla, Ruggiero; Corvaglia, Luigi; Cristofori, Fernanda; Mastrolia, Salvatore Andrea; Neu, Josef; Rautava, Samuli; Russo Spena, Giovanna; Raimondi, Francesco; Loverro, Giuseppe

2017-01-01

Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects. PMID:28879172

Stability analysis of impulsive fuzzy cellular neural networks with distributed delays and reaction-diffusion terms

International Nuclear Information System (INIS)

Li Zuoan; Li Kelin

2009-01-01

In this paper, we investigate a class of impulsive fuzzy cellular neural networks with distributed delays and reaction-diffusion terms. By employing the delay differential inequality with impulsive initial conditions and M-matrix theory, we find some sufficient conditions ensuring the existence, uniqueness and global exponential stability of equilibrium point for impulsive fuzzy cellular neural networks with distributed delays and reaction-diffusion terms. In particular, the estimate of the exponential converging index is also provided, which depends on the system parameters. An example is given to show the effectiveness of the results obtained here.

Final programmatic environmental impact statement for alternative strategies for the long-term management and use of depleted uranium hexafluoride. Volume 3: Responses to public comments

International Nuclear Information System (INIS)

1999-04-01

This PEIS assesses the potential impacts of alternative management strategies for depleted uranium hexafluoride (UF 6 ) currently stored at three DOE sites: Paducah site near Paducah, Kentucky, Portsmouth site near Portsmouth, Ohio; and K-25 site on the Oak Ridge Reservation, Oak Ridge, Tennessee. The alternatives analyzed in the PEIS include no action, long-term storage as UF 6 , long-term storage as uranium oxide, use as uranium oxide, use as uranium metal, and disposal. DOE's preferred alternative is to begin conversion of the depleted UF 6 inventory as soon as possible, either to uranium oxide, uranium metal, or a combination of both, while allowing for use of as much of this inventory as possible. This volume of the Final PEIS contains the comments and DOE's responses to comments received during the comment period. Chapter 2 contains photocopies of written submissions received by DOE on the Draft PEIS; DOE's responses to those comments are listed in Chapter 3. Chapter 4 provides the oral comments received at the public hearings and DOE's responses. Chapter 5 provides indices to comments and responses arranged by commentor name and by comment number

Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

Science.gov (United States)

Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

2013-11-01

We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival

Long-Term Dynamics of Autonomous Fractional Differential Equations

Science.gov (United States)

Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

Directory of Open Access Journals (Sweden)

Ravi Goyal

Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

Human dendritic cells sequentially matured with CD4(+) T cells as a secondary signal favor CTL and long-term T memory cell responses.

Science.gov (United States)

Simon, Thomas; Tanguy-Royer, Séverine; Royer, Pierre-Joseph; Boisgerault, Nicolas; Frikeche, Jihane; Fonteneau, Jean-François; Grégoire, Marc

2012-01-01

Dendritic cells (DCs) are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL) responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

Surface coal mine land reclamation using a dry flue gas desulfurization product: Short-term and long-term water responses.

Science.gov (United States)

Chen, Liming; Stehouwer, Richard; Tong, Xiaogang; Kost, Dave; Bigham, Jerry M; Dick, Warren A

2015-09-01

Abandoned coal-mined lands are a worldwide concern due to their potential negative environmental impacts, including erosion and development of acid mine drainage. A field study investigated the use of a dry flue gas desulfurization product for reclamation of abandoned coal mined land in USA. Treatments included flue gas desulfurization product at a rate of 280 Mg ha(-1) (FGD), FGD at the same rate plus 112 Mg ha(-1) yard waste compost (FGD/C), and conventional reclamation that included 20 cm of re-soil material plus 157 Mg ha(-1) of agricultural limestone (SOIL). A grass-legume sward was planted after treatment applications. Chemical properties of surface runoff and tile water (collected from a depth of 1.2m below the ground surface) were measured over both short-term (1-4 yr) and long-term (14-20 yr) periods following reclamation. The pH of surface runoff water was increased from approximately 3, and then sustained at 7 or higher by all treatments for up to 20 yr, and the pH of tile flow water was also increased and sustained above 5 for 20 yr. Compared with SOIL, concentrations of Ca, S and B in surface runoff and tile flow water were generally increased by the treatments with FGD product in both short- and long-term measurements and concentrations of the trace elements were generally not statistically increased in surface runoff and tile flow water over the 20-yr period. However, concentrations of As, Ba, Cr and Hg were occasionally elevated. These results suggest the use of FGD product for remediating acidic surface coal mined sites can provide effective, long-term reclamation. Copyright © 2015. Published by Elsevier Ltd.

pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

Directory of Open Access Journals (Sweden)

Eiji Yuba

2017-11-01

Full Text Available (1 Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2 Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3 Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4 Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

Science.gov (United States)

Older Women's League, Washington, DC.

Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

Multiresolution with Hierarchical Modulations for Long Term Evolution of UMTS

Directory of Open Access Journals (Sweden)

Soares Armando

2009-01-01

Full Text Available In the Long Term Evolution (LTE of UMTS the Interactive Mobile TV scenario is expected to be a popular service. By using multiresolution with hierarchical modulations this service is expected to be broadcasted to larger groups achieving significant reduction in power transmission or increasing the average throughput. Interactivity in the uplink direction will not be affected by multiresolution in the downlink channels, since it will be supported by dedicated uplink channels. The presence of interactivity will allow for a certain amount of link quality feedback for groups or individuals. As a result, an optimization of the achieved throughput will be possible. In this paper system level simulations of multi-cellular networks considering broadcast/multicast transmissions using the OFDM/OFDMA based LTE technology are presented to evaluate the capacity, in terms of number of TV channels with given bit rates or total spectral efficiency and coverage. multiresolution with hierarchical modulations is presented to evaluate the achievable throughput gain compared to single resolution systems of Multimedia Broadcast/Multicast Service (MBMS standardised in Release 6.

Immunomodulatory effect of ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice.

Science.gov (United States)

Shi, Yali; Cai, Dehua; Wang, Xiaojie; Liu, Xinshen

2012-12-01

Long-term heavy-load exercise can lead to a decrease in the organism's immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

Self-reported Occupational Skin Exposure and Risk of Physician-certified Long-term Sick Leave

DEFF Research Database (Denmark)

Alfonso, Jose H; Tynes, Tore; Thyssen, Jacob P

2016-01-01

Little is known about the contribution of occupational skin exposure as a risk factor for physician-certified long-term sick leave in the general working population of Norway. This study drew a cohort (n = 12,255; response at baseline 69.9%) randomly from the general population of Norway. Occupat......Little is known about the contribution of occupational skin exposure as a risk factor for physician-certified long-term sick leave in the general working population of Norway. This study drew a cohort (n = 12,255; response at baseline 69.9%) randomly from the general population of Norway....... Occupational skin exposure (in 2009) was measured based on 5 items. The outcome of interest was physician-certified long-term sick leave ≥ 16 days during 2010. Statistical adjustment for psychosocial and mechanical occupational exposures was performed. Long-term sick leave was predicted by occupational skin...... exposure to cleaning products (odds ratio (OR) 1.7; 95% confidence interval (95% CI) 1.1-2.5) and waste (OR 2.1; 95% CI 1.1-3.7) among men, and occupational skin exposure to water (OR 1.3; 95% CI 1.0-1.6) among women. The estimated population attributable risk for occupational skin exposure was 14...

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

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...

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...

Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

NARCIS (Netherlands)

Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

2003-01-01

textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

Visual recognition memory, manifest as long-term habituation, requires synaptic plasticity in V1

Science.gov (United States)

Cooke, Sam F.; Komorowski, Robert W.; Kaplan, Eitan S.; Gavornik, Jeffrey P.; Bear, Mark F.

2015-01-01

Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioural habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioural habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behaviour in an open arena, and in a stereotyped motor response to visual stimuli in head-restrained mice. We show that the latter behavioural response, termed a vidget, requires V1. Parallel electrophysiological recordings in V1 reveal that plasticity, in the form of stimulus-selective response potentiation (SRP), occurs in layer 4 of V1 as OSH develops. Local manipulations of V1 that prevent and reverse electrophysiological modifications likewise prevent and reverse memory demonstrated behaviourally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex. PMID:25599221

Visual recognition memory, manifested as long-term habituation, requires synaptic plasticity in V1.

Science.gov (United States)

Cooke, Sam F; Komorowski, Robert W; Kaplan, Eitan S; Gavornik, Jeffrey P; Bear, Mark F

2015-02-01

Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioral habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioral habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behavior in an open arena and in a stereotyped motor response to visual stimuli in head-restrained mice. We found that the latter behavioral response, termed a 'vidget', requires V1. Parallel electrophysiological recordings in V1 revealed that plasticity, in the form of stimulus-selective response potentiation (SRP), occurred in layer 4 of V1 as OSH developed. Local manipulations of V1 that prevented and reversed electrophysiological modifications likewise prevented and reversed memory demonstrated behaviorally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

Science.gov (United States)

Trautmann, Agnes; Schnaidt, Sven; Lipska-Ziętkiewicz, Beata S; Bodria, Monica; Ozaltin, Fatih; Emma, Francesco; Anarat, Ali; Melk, Anette; Azocar, Marta; Oh, Jun; Saeed, Bassam; Gheisari, Alaleh; Caliskan, Salim; Gellermann, Jutta; Higuita, Lina Maria Serna; Jankauskiene, Augustina; Drozdz, Dorota; Mir, Sevgi; Balat, Ayse; Szczepanska, Maria; Paripovic, Dusan; Zurowska, Alexandra; Bogdanovic, Radovan; Yilmaz, Alev; Ranchin, Bruno; Baskin, Esra; Erdogan, Ozlem; Remuzzi, Giuseppe; Firszt-Adamczyk, Agnieszka; Kuzma-Mroczkowska, Elzbieta; Litwin, Mieczyslaw; Murer, Luisa; Tkaczyk, Marcin; Jardim, Helena; Wasilewska, Anna; Printza, Nikoleta; Fidan, Kibriya; Simkova, Eva; Borzecka, Halina; Staude, Hagen; Hees, Katharina; Schaefer, Franz

2017-10-01

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established. Copyright © 2017 by the American Society of Nephrology.

The Christian Schools Campaign: What Were Its Long-Term Consequences?

Science.gov (United States)

Baker, Sylvia

2009-01-01

This article looks at the long-term consequences of a political campaign that was influential in Britain between 1988 and 1992, the Christian Schools Campaign. The campaign was a response to the need for funding of a group of small independent Christian schools. The article brings up to date the direct outcomes of the campaign in two areas. The…

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

OpenAIRE

Clemens Kiecker; Anthony Graham; Malcolm Logan

2016-01-01

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in compete...

Long term Suboxone™ emotional reactivity as measured by automatic detection in speech.

Directory of Open Access Journals (Sweden)

Edward Hill

Full Text Available Addictions to illicit drugs are among the nation's most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states ("true ground emotionality" in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of "true" emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP and 33 members of Alcoholics Anonymous (AA. Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate "true ground" emotionality in long-term buprenorphine/naloxone combination (Suboxone™. We found in long-term SUBX patients a significantly flat affect (p<0.01, and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.

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.

Changing incentives for long-term gas contracts

International Nuclear Information System (INIS)

Bohi, D.R.

1992-01-01

There is much concern about the absence of long-term gas contracts with fixed price and quantity conditions, which until recent years was the standard way of doing business in the gas industry. These types of contracts performed a valuable service in the development of the gas industry, and there comparative absence today is sometimes thought to be one reason for the current malaise in the industry. One hears the argument that there must be some kind of 'market failure' that prevents buyers and sellers from entering into these long term arrangements, and recent changes in state and federal regulations are often cited as the cause of the problem. The purpose of the author's remarks is to argue that what is taken as a breakdown in the market may be simply a reaction to a decline in economic incentives to enter into long-term contracts with rigid price and quantity terms. This is, in other words, simply one more aspect of change in the gas business that Frank Heintz referred to in his opening remarks this morning. The author starts by giving a brief description of the motives for engaging in long-term contracts, and then describes how incentives to use long-term contracts have declined for both gas buyers and gas sellers. He concludes that the decline in the use of long-term contracts is not cause for regulatory concern, but a result of the continuing transformation of the gas business to one that more closely resembles other commodity markets

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

Energy Technology Data Exchange (ETDEWEB)

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

2000-02-02

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

Cellular response to DNA damage. Link between p53 and DNA-PK

International Nuclear Information System (INIS)

Salles-Passador, I.; Fotedar, R.; Fotedar, A.

1999-01-01

Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to ionizing radiation and display an inability to repair double-strand DNA breaks. DNA-PK is a member of a protein kinase family that includes ATR and ATM which have strong homology in their carboxy-terminal kinase domain with Pl-3 kinase. ATM has been proposed to act upstream of p53 in cellular response to ionizing radiation. DNA-PK may similarly interact with p53 in cellular growth control and in mediation of the response to ionizing radiation. (author)

Opening remarks for a panel discussion on short-term vs long-term procurement

International Nuclear Information System (INIS)

Courtenay, R.H.

1990-01-01

Long-term contracting in the late 1970's and early 1980's is blamed for some of the inequities that plague the uranium industry today. Utilities are obliged to pay prices far above prevailing levels and relatively low cost producers are forced to shut down while watching less efficient suppliers stay in business thanks to their long term supply agreements. Furthermore, it is argued that long-term contracts have contributed to supply instability by forcing the buildup of surplus inventories and by supporting excess incremental production by suppliers who have a baseload of long-term contracts. The depressed prices resulting from this oversupply are in turn jeopardizing future resource development and damaging supply reliability. In summary, the author's argument is that supply reliability will be greatly enhanced by the assurance of adequate primary supply from traditional sources such as Canada. This will not happen without long-term contracts. This conclusion may not be expected coming from a representative of Canada's largest uranium producer. But the final comment is less self serving. Many of the critics of long term contracts apparently expect a continuing and plentiful supply of East Bloc uranium to the spot market. A further question is to what extent East Bloc suppliers will eventually require long-term contracts in order to maintain production facilitates in economies that are no longer centrally planned, and where there is open competition for capital. Ultimately, reliability of supply from the non-traditional suppliers may also depend on long-term contracts

Challenges in long-term operation of nuclear power plants - Implications for regulatory bodies

International Nuclear Information System (INIS)

Soda, Kunihisa; Van Wonterghem, Frederik; Khouaja, Hatem; Vilpas, Martti; Osouf, Nicolas; Harikumar, S.; Ishigaki, Hiroki; Osaki, Toru; Yamada, Tomoho; Carlsson, Lennart; Shepherd, David; Galloway, Melanie; Liszka, Ervin; Svab, Miroslav; Pereira, Ken; Huerta, Alejandro

2012-01-01

Nuclear power reactors have become a major source of electricity supply in many countries in the past half a century. Based on this experience, many operators have sought and have received authorisation for long-term operation, whereby plant operation continues beyond the period considered in the design of the plant. Acceptance of a nuclear power plant for extended service should be based on assurance of the fitness of the plant and the operator for safe and reliable operation over the entire period considered for long-term operation. This assurance may be obtained by establishment of appropriate regulatory requirements, specification of goals and safety levels and regulatory assessment and oversight of the operator's programme for long-term operation. The operators and regulators should ensure that operating experience continues to be evaluated during long-term operation to ensure that any relevant lessons are effectively applied. Other considerations for assurance of safe operation are effective management of ageing, possible need for safety improvements, application of lessons learnt from operating experience, evaluation of environmental impacts, adequate staff resources and performance, review of security at the plant, action in response to emerging issues, and openness and transparency in the transition to long-term operation. Even though most of these considerations are addressed under the regulatory framework that applies to the initial operating period, additional regulatory activities in these areas may be necessary for long-term operation. Although there can be significant differences in regulatory approaches used by different countries for evaluating acceptability of long-term operation, there is general agreement on the purposes and goals of the regulatory reviews. An authorisation of long-term operation could involve a licence renewal or a periodic safety review or an approach that melds elements of both. This report presents guidance that is intended

Characterization of humoral and cellular immune responses in patients with human papilloma virus

International Nuclear Information System (INIS)

Clares Pochet, Maria del Carmen; Ferrer Cosme, Belkis Maria; Dominguez Cardosa, Magda

2012-01-01

A descriptive and cross-sectional study was carried out in 30 females infected with the human papilloma virus, attended in the office of Immunology of the Specialty Polyclinic belonging to 'Saturnino Lora' Provincial Clinical Surgical Teaching Hospital in Santiago de Cuba, from June 2009 to June 2010, in order to characterize them according to immune response. To evaluate the humoral and cellular immune response rosetting assay and quantification of immunoglobulins were used respectively. Women between 25-36 years of age (40 %) infected with this virus, especially those coming from urban areas, prevailed in the series, and a significant decrease of the cellular response as compared to the humoral response was evidenced

Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein.

Directory of Open Access Journals (Sweden)

Karishma T Mody

Full Text Available Bovine Viral Diarrhoea Virus (BVDV is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2 antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3 g(-1 have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg/SV-140 (500 μg and FD oE2 (100 μg/SV-140 (500 μg to induce long-term immunity was compared to immunisation with oE2 (100 μg together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications.

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

Directory of Open Access Journals (Sweden)

Sinsard Anne

2005-11-01

Full Text Available Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU (60 or 90 mg/m2. Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

Elderly and long-term care trends and policy in Taiwan: Challenges and opportunities for health care professionals

Directory of Open Access Journals (Sweden)

Hsiu-Hung Wang

2012-09-01

Full Text Available The purpose of this article is to address the trends and policy of elderly and long-term care in Taiwan. In response to the increasing demand of an aging society, healthcare professionals play crucial roles in elderly and long-term care and quality assurance of services. This article focuses on the current situation of elderly health care, demands of long-term care, long-term care policy in Taiwan, draft of the Long-term Care Services Act, and draft of the Long-term Care Insurance Act. After the 10-year long-term care project was proposed by the Taiwan government, the supply of health care services and demand for long-term care have created many challenges and opportunities for innovative health professional development. Challenges consist of low old dependency ratio caused by low birth rate, lack of elderly and long-term care related manpower, services and education reform related to long-term care for the future society, and interprofessional collaboration and team work of long-term care. Opportunities include expanding the roles and the career pathways of healthcare professionals, promoting the concepts of active aging and good quality of life, and developing industrial cooperation related to long-term care services. Under these circumstances, healthcare professonals are actively involved in practice, education and research of long-term care services that ensure elderly and disabled people can live a healthier and better life.

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.

Long-term risks of kidney living donation

DEFF Research Database (Denmark)

Maggiore, Umberto; Budde, Klemens; Heemann, Uwe

2017-01-01

Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science...... and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information...... to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors...

Effects of long-term elevated temperature on covering, sheltering and righting behaviors of the sea urchin Strongylocentrotus intermedius

Science.gov (United States)

Zhang, Lisheng; Zhang, Lingling; Shi, Dongtao; Wei, Jing; Chang, Yaqing

2017-01-01

Increases in ocean temperature due to climate change are predicted to change the behaviors of marine invertebrates. Altered behaviors of keystone ecosystem engineers such as echinoderms will have consequences for the fitness of individuals, which are expected to flow on to the local ecosystem. Relatively few studies have investigated the behavioral responses of echinoderms to long-term elevated temperature. We investigated the effects of exposure to long-term (∼31 weeks) elevated temperature (∼3 °C above the ambient water temperature) on covering, sheltering and righting behaviors of the sea urchin Strongylocentrotus intermedius. Long-term elevated temperature showed different effects on the three behaviors. It significantly decreased covering behavior, including both covering behavior reaction (time to first covering) and ability (number of covered sea urchins and number of shells used for covering). Conversely, exposure to long-term elevated temperature significantly increased sheltering behavior. Righting response in S. intermedius was not significantly different between temperature treatments. The results provide new information into behavioral responses of echinoderms to ocean warming. PMID:28348933

Partnership insurance: an innovation to meet long-term care financing needs in an era of federal minimalism.

Science.gov (United States)

Meiners, Mark R; McKay, Hunter L; Mahoney, Kevin J

2002-01-01

In the case of long-term care financing, federal minimalism is not new news. Long-term care has long played a weak "third fiddle" to national health reform concerns about the uninsured and catastrophic expenditures on prescription drugs. The states have been left to struggle with the issue of long-term financing as part of their responsibilities in funding and administering the means-tested Medicaid program. Recently, the environment has become even more challenging. Much of what is on the national agenda for health and welfare reform has been delegated to the states. This "devolution" of responsibilities has created many competing priorities for both the attention and resources of states. This context of evolving federal minimalism calls for creative solutions that balance competing points of view. In this article, we provide some background and insights from one such effort: a collaboration between state governments and private insurers to put into operation an insurance-based approach to long-term care financing that uses Medicaid as an incentive to encourage potential purchasers.

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.)

Sensitive and long-term monitoring of intracellular microRNAs using a non-integrating cytoplasmic RNA vector.

Science.gov (United States)

Sano, Masayuki; Ohtaka, Manami; Iijima, Minoru; Nakasu, Asako; Kato, Yoshio; Nakanishi, Mahito

2017-10-04

MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression at the post-transcriptional level. Different types of cells express unique sets of miRNAs that can be exploited as potential molecular markers to identify specific cell types. Among the variety of miRNA detection methods, a fluorescence-based imaging system that utilises a fluorescent-reporter gene regulated by a target miRNA offers a major advantage for long-term tracking of the miRNA in living cells. In this study, we developed a novel fluorescence-based miRNA-monitoring system using a non-integrating cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp). Because SeVdp vectors robustly and stably express transgenes, this system enabled sensitive monitoring of miRNAs by fluorescence microscopy. By applying this system for cellular reprogramming, we found that miR-124, but not miR-9, was significantly upregulated during direct neuronal conversion. Additionally, we were able to isolate integration-free human induced pluripotent stem cells by long-term tracking of let-7 expression. Notably, this system was easily expandable to allow detection of multiple miRNAs separately and simultaneously. Our findings provide insight into a powerful tool for evaluating miRNA expression during the cellular reprogramming process and for isolating reprogrammed cells potentially useful for medical applications.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

Science.gov (United States)

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Long-term injury in B-lymphocyte precursor cells in repeatedly-irradiated mice

International Nuclear Information System (INIS)

Hendry, J.H.; Clarke, D.; Testa, N.; Kimber, J.

1984-01-01

Mice irradiated with 4 doses of 4,5 Gy X-rays at 3-week intervals, demonstrated long-term proliferative defects in B lymphocytes. There was a reduced mitogenic response to bacterial polysaccharide (30%), a lower concentration (35%) of B-lymphocyte colony-forming cells (BL-CFC) in agar with an increased proportion of clusters (x2), and a reduced concentration (30%) of plaque-forming cells. Grafts of thymocytes were able to restore the levels of BL-CFC in the short term, but in the long term large grafts of femoral marrow cells were much better in restoring the numbers of BL-CFC. The reduced mitogenesis (25%) of splenocytes by concanavalin A and the diminished number of plaque-forming cells, may suggest persistent injury in T-B cell cooperation

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...

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...

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

What are the differences between long-term, short-term, and working memory?

OpenAIRE

Cowan, Nelson

2008-01-01

In the recent literature there has been considerable confusion about the three types of memory: long-term, short-term, and working memory. This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory. Long- and short-term memory could differ in two fundamental ways, with only short-term memory demonstrating (1) temporal decay and (2) chunk capacity limits. Both properties of short-term memory are still controversial but the current literature is rath...

Accessing forgotten memory traces from long-term memory via visual movements

Directory of Open Access Journals (Sweden)

Estela eCamara

2014-11-01

Full Text Available Because memory retrieval often requires overt responses, it is difficult to determine to what extend forgetting occurs as a problem in explicit accessing of long-term memory traces. In this study, we used eye-tracking measures in combination with a behavioural task that favoured high forgetting rates to investigate the existence of memory traces from long-term memory in spite of failure in accessing them consciously. In 2 experiments, participants were encouraged to encode a large set of sound-picture-location associations. In a later test, sounds were presented and participants were instructed to visually scan, before a verbal memory report, for the correct location of the associated pictures in an empty screen. We found the reactivation of associated memories by sound cues at test biased oculomotor behaviour towards locations congruent with memory representations, even when participants failed to consciously provide a memory report of it. These findings reveal the emergence of a memory-guided behaviour that can be used to map internal representations of forgotten memories from long-term memory.

Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy

International Nuclear Information System (INIS)

Murayama, Masanori; Yasuda, Keigo; Minamori, Yoshiaki; Mercado-Asis, L.B.; Morita, Hiroyuki; Miura, Kiyoshi; Yamakita, Noriyoshi.

1994-01-01

Subtotal adrenalectomy was given to 10 adult patients with Cushing's disease, concurrently with or following therapeutic regimen by long term reserpine administration and pituitary irradiation. In the present study, we describe long term follow-up results. Two patients died after the operation due to acute adrenal crisis and pneumonia, respectively. The other 8 patients achieved clinical and biochemical remissions and were followed for long term. Three patients relapsed 9, 14 or 17 years after achieving remission, two patients developed hypopituitarism 12 or 20 years after and one died of cerebral vascular accident at 64 years, 5 years after the remission. The remaining 2 patients maintained remission for 10 or 18 years, respectively. During the remission periods of 0.5 to 20 years with a mean of 10.1±6.7 years, 6 of 7 patients examined by 1 mg overnight dexamethasone test showed normal suppressibility of plasma cortisol. Provocative tests of plasma GH by 1-arginine infusion and/or insulin-induced hypoglycemia were performed in 6 patients in the early remission period. All of 5 patients in the arginine infusion test and 3 of 5 in the insulin-induced hypoglycemia test showed normal responses. Furthermore, to facilitate prediction of long term response or failure to our therapeutic regimen, long term reserpine administration and pituitary irradiation, pretreatment clinical and biochemical characteristics were analyzed retrospectively in 3 divided groups; the present 10 patients treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy, 11 patients achieving long term remission treated by our regimen alone, and 7 patients failed with our regimen alone. There were no significant factors predictive of response to our regimen. (author)

Long-term repetition priming with symmetrical polygons and words.

Science.gov (United States)

Kersteen-Tucker, Z

1991-01-01

In two different tasks, subjects were asked to make lexical decisions (word or nonword) and symmetry judgments (symmetrical or nonsymmetrical) about two-dimensional polygons. In both tasks, every stimulus was repeated at one of four lags (0, 1, 4, or 8 items interposed between the first and second stimulus presentations). This paradigm, known as repetition priming, revealed comparable short-term priming (Lag 0) and long-term priming (Lags 1, 4, and 8) both for symmetrical polygons and for words. A shorter term component (Lags 0 and 1) of priming was observed for nonwords, and only very short-term priming (Lag 0) was observed for nonsymmetrical polygons. These results indicate that response facilitation accruing from repeated exposure can be observed for stimuli that have no preexisting memory representations and suggest that perceptual factors contribute to repetition-priming effects.

Long-term complications of splenectomy in adult immune thrombocytopenia.

Science.gov (United States)

Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

2016-11-01

The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

Science.gov (United States)

Gur, Rotem; Tendler, Alex; Wagner, Shlomo

2014-09-01

Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-term hearing preservation in vestibular schwannoma

DEFF Research Database (Denmark)

Stangerup, Sven-Eric; Thomsen, Jens; Tos, Mirko

2010-01-01

The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas.......The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas....

Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

International Nuclear Information System (INIS)

Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

2004-01-01

The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

Long-term neuroendocrine and behavioural effects of a single exposure to stress in adult animals.

Science.gov (United States)

Armario, Antonio; Escorihuela, Rosa M; Nadal, Roser

2008-08-01

There is now considerable evidence for long-lasting sequels of stress. A single exposure to high intensity predominantly emotional stressors such as immobilisation in wooden-boards (IMO) induces long-term (days to weeks) desensitization of the hypothalamic-pituitary-adrenal (HPA) response to the same (homotypic) stressor, whereas the response to novel (heterotypic) stressors was enhanced. In addition, long-lasting changes in behaviour have been described after a single exposure to brief or more prolonged sessions of shocks, predator, predator odour, underwater stress or a combination of three stressors on 1 day. The most consistent changes are reduced entries into the open arms of the elevated plus-maze and enhanced acoustic startle response, both reflecting enhanced anxiety. However, it is unclear whether there is any relationship between the intensity of the stressors, as evaluated by the main physiological indexes of stress (e.g. HPA axis), the putative traumatic experience they represent and their long-term behavioural consequences. This is particularly critical when trying to model post-traumatic stress disorders (PTSD), which demands a great effort to validate such putative models.