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Sample records for signaling enhanced long-term

  1. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    Science.gov (United States)

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

  2. Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.

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    Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen

    2016-02-01

    Fear memory-encoding thalamic input synapses to the lateral amygdala (T-LA) exhibit dynamic efficacy changes that are tightly correlated with fear memory strength. Previous studies have shown that auditory fear conditioning involves strengthening of synaptic strength, and conversely, fear extinction training leads to T-LA synaptic weakening and occlusion of long-term depression (LTD) induction. These findings suggest that the mechanisms governing LTD at T-LA synapses may determine the behavioral outcomes of extinction training. Here, we explored this hypothesis by implementing food deprivation (FD) stress in mice to determine its effects on fear extinction and LTD induction at T-LA synapses. We found that FD increased plasma acylated ghrelin levels and enhanced fear extinction and its retention. Augmentation of fear extinction by FD was blocked by pretreatment with growth hormone secretagogue receptor type-1a antagonist D-Lys(3)-GHRP-6, suggesting an involvement of ghrelin signaling. Confirming previous findings, two distinct forms of LTD coexist at thalamic inputs to LA pyramidal neurons that can be induced by low-frequency stimulation (LFS) or paired-pulse LFS (PP-LFS) paired with postsynaptic depolarization, respectively. Unexpectedly, we found that FD impaired the induction of PP-LFS- and group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD, but not LFS-induced LTD. Ghrelin mimicked the effects of FD to impair the induction of PP-LFS- and DHPG-induced LTD at T-LA synapses, which were blocked by co-application of D-Lys(3)-GHRP-6. The sensitivity of synaptic transmission to 1-naphthyl acetyl spermine was not altered by either FD or ghrelin treatment. These results highlight distinct features of fear extinction and LTD at T-LA synapses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Enhanced long-term fear memory and increased anxiety and depression-like behavior after exposure to an aversive event in mice lacking TIP39 signaling

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    Coutellier, Laurence; Usdin, Ted B.

    2011-01-01

    Exaggerated recall for fear-provoking events leads to abnormal behaviors. We hypothesized that tuberoinfundibular-peptide-of-39-residues (TIP39) modulates fear memory by limiting long-term consequences of aversive experiences. We now show that mice lacking TIP39 signaling display enhanced fear-recall, anxiety and depression-like behavior two weeks after a traumatic event. We suggest that TIP39 modulates long-term fear recall and that mice lacking TIP39 or its receptor are tools for investigating fear-related psychopathologies. PMID:21382418

  4. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

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    Roberto Narcisi

    2015-03-01

    Full Text Available Mesenchymal stem cells (MSCs are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.

  5. Brain-generated estradiol drives long-term optimization of auditory coding to enhance the discrimination of communication signals.

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    Tremere, Liisa A; Pinaud, Raphael

    2011-03-02

    Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species, including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real time, by controlling the strength of inhibitory transmission via a nongenomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homolog of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency, and the neural discrimination of songs. These effects are mediated by estradiol's modulation of both the rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely behaving animals disrupts behavioral responses to songs, but not to other behaviorally relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain.

  6. Long Term 1 Enhanced Surface Water Treatment Rule Documents

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    The Long Term 1 Enhanced Surface Water Treatment Rule (LT1ESWTR) builds on the requirements of the Surface Water Treatment Rule and specifies treatment requirements to address Cryptosporidium m and other microbial contaminants in public water systems.

  7. 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.

  8. Enhanced Polyhydroxybutyrate Production for Long-Term Spaceflight Applications

    Science.gov (United States)

    Putman, Ryan J.; Rahman, Asif; Miller, Charles D.; Hadi, Masood Z.

    2015-01-01

    Synthetic biology holds the promise of advancing long term space fight by the production of medicine, food, materials, and energy. One such application of synthetic biology is the production of biomaterials, specifically polyhydroxyalkanoates (PHAs), using purposed organisms such as Escherichia coli. PHAs are a group of biodegradable bioplastics that are produced by a wide variety of naturally occurring microorganisms, mainly as an energy storage intermediate. PHAs have similar melting point to polypropylene and a Youngs modulus close to polystyrene. Due to limited resources and cost of transportation, large-scale extraction of biologically produced products in situ is extremely cumbersome during space flight. To that end, we are developing a secretion systems for exporting PHA from the cell in order to reduce unit operations. PHAs granules deposited inside bacteria are typically associated with proteins bound to the granule surface. Phasin, a granule bound protein, was targeted for type I secretion by fusion with HlyA signal peptide for indirect secretion of PHAs. In order to validate our secretion strategy, a green fluorescent protein (GFP) was tagged to the PHA polymerase enzyme (phaC), this three part gene cassette consists of phaA and phaB and are required for PHA production. Producing PHAs in situ during space flight or planet colonization will enable mission success by providing a valuable source of biomaterials that can have many potential applications thereby reducing resupply requirements. Biologically produced PHAs can be used in additive manufacturing such as three dimensional (3D) printing to create products that can be made on demand during space flight. After exceeding their lifetime, the PHAs could be melted and recycled back to 3D print other products. We will discuss some of our long term goals of this approach.

  9. Harmonic Enhancement in Low Bitrate Audio Coding Using an Efficient Long-Term Predictor

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    Song Jeongook

    2010-01-01

    Full Text Available This paper proposes audio coding using an efficient long-term prediction method to enhance the perceptual quality of audio codecs to speech input signals at low bit-rates. The MPEG-4 AAC-LTP exploited a similar concept, but its improvement was not significant because of small prediction gain due to long prediction lags and aliased components caused by the transformation with a time-domain aliasing cancelation (TDAC technique. The proposed algorithm increases the prediction gain by employing a deharmonizing predictor and a long-term compensation filter. The look-back memory elements are first constructed by applying the de-harmonizing predictor to the input signal, then the prediction residual is encoded and decoded by transform audio coding. Finally, the long-term compensation filter is applied to the updated look-back memory of the decoded prediction residual to obtain synthesized signals. Experimental results show that the proposed algorithm has much lower spectral distortion and higher perceptual quality than conventional approaches especially for harmonic signals, such as voiced speech.

  10. Harmonic Enhancement in Low Bitrate Audio Coding Using an Efficient Long-Term Predictor

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    Song, Jeongook; Lee, Chang-Heon; Oh, Hyen-O.; Kang, Hong-Goo

    2010-12-01

    This paper proposes audio coding using an efficient long-term prediction method to enhance the perceptual quality of audio codecs to speech input signals at low bit-rates. The MPEG-4 AAC-LTP exploited a similar concept, but its improvement was not significant because of small prediction gain due to long prediction lags and aliased components caused by the transformation with a time-domain aliasing cancelation (TDAC) technique. The proposed algorithm increases the prediction gain by employing a deharmonizing predictor and a long-term compensation filter. The look-back memory elements are first constructed by applying the de-harmonizing predictor to the input signal, then the prediction residual is encoded and decoded by transform audio coding. Finally, the long-term compensation filter is applied to the updated look-back memory of the decoded prediction residual to obtain synthesized signals. Experimental results show that the proposed algorithm has much lower spectral distortion and higher perceptual quality than conventional approaches especially for harmonic signals, such as voiced speech.

  11. Superior Long-Term Synaptic Memory Induced by Combining Dual Pharmacological Activation of PKA and ERK with an Enhanced Training Protocol

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    Liu, Rong-Yu; Neveu, Curtis; Smolen, Paul; Cleary, Leonard J.; Byrne, John H.

    2017-01-01

    Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM).…

  12. PKG-Mediated MAPK Signaling Is Necessary for Long-Term Operant Memory in "Aplysia"

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    Michel, Maximilian; Green, Charity L.; Eskin, Arnold; Lyons, Lisa C.

    2011-01-01

    Signaling pathways necessary for memory formation, such as the mitogen-activated protein kinase (MAPK) pathway, appear highly conserved across species and paradigms. Learning that food is inedible (LFI) represents a robust form of associative, operant learning that induces short- (STM) and long-term memory (LTM) in "Aplysia." We investigated the…

  13. Delayed Dopamine Signaling of Energy Level Builds Appetitive Long-Term Memory in Drosophila

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    Pierre-Yves Musso

    2015-02-01

    Full Text Available Sensory cues relevant to a food source, such as odors, can be associated with post-ingestion signals related either to food energetic value or toxicity. Despite numerous behavioral studies, a global understanding of the mechanisms underlying these long delay associations remains out of reach. Here, we demonstrate in Drosophila that the long-term association between an odor and a nutritious sugar depends on delayed post-ingestion signaling of energy level. We show at the neural circuit level that the activity of two pairs of dopaminergic neurons is necessary and sufficient to signal energy level to the olfactory memory center. Accordingly, we have identified in these dopaminergic neurons a delayed calcium trace that correlates with appetitive long-term memory formation. Altogether, these findings demonstrate that the Drosophila brain remembers food quality through a two-step mechanism that consists of the integration of olfactory and gustatory sensory information and then post-ingestion energetic value.

  14. The psychological contract: enhancing productivity and its implications for long-term care.

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    Flannery, Raymond B

    2002-01-01

    When hired, a new employee is usually given a job description and an explanation of benefits. In addition, the employee will also have a psychological contract with the organization. This contract, often unstated, reflects the main source of the employee's motivation to work hard. This is true of all groups of employees, including long-term care staff. Common examples of psychological contracts for long-term care administrative staff include autonomy, social acceptance, and being in the forefront of cutting-edge research. An awareness of these psychological contracts can result in better "fits" between employee aspirations and relevant long-term care organization tasks so that productivity is enhanced. This article outlines the steps necessary to create these good fits in ways that benefit both the organization and its employees. These recommendations are of particular relevance to administrators and supervisors in long-term carefacilities.

  15. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway

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    Bach, Mary Elizabeth; Barad, Mark; Son, Hyeon; Zhuo, Min; Lu, Yun-Fei; Shih, Robert; Mansuy, Isabelle; Hawkins, Robert D.; Kandel, Eric R.

    1999-01-01

    To study the physiological and molecular mechanisms of age-related memory loss, we assessed spatial memory in C57BL/B6 mice from different age cohorts and then measured in vitro the late phase of hippocampal long-term potentiation (L-LTP). Most young mice acquired the spatial task, whereas only a minority of aged mice did. Aged mice not only made significantly more errors but also exhibited greater individual differences. Slices from the hippocampus of aged mice exhibited significantly reduce...

  16. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

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    Mónica López-Hidalgo

    Full Text Available Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  17. Requirement for nuclear calcium signaling in Drosophila long-term memory.

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    Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

    2013-05-07

    Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

  18. Suicide attempt in young people: a signal for long-term health care and social needs.

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    Goldman-Mellor, Sidra J; Caspi, Avshalom; Harrington, Honalee; Hogan, Sean; Nada-Raja, Shyamala; Poulton, Richie; Moffitt, Terrie E

    2014-02-01

    Suicidal behavior has increased since the onset of the global recession, a trend that may have long-term health and social implications. To test whether suicide attempts among young people signal increased risk for later poor health and social functioning above and beyond a preexisting psychiatric disorder. We followed up a cohort of young people and assessed multiple aspects of their health and social functioning as they approached midlife. Outcomes among individuals who had self-reported a suicide attempt up through age 24 years (young suicide attempters) were compared with those who reported no attempt through age 24 years (nonattempters). Psychiatric history and social class were controlled for. The population-representative Dunedin Multidisciplinary Health and Development Study, which involved 1037 birth cohort members comprising 91 young suicide attempters and 946 nonattempters, 95% of whom were followed up to age 38 years. Outcomes were selected to represent significant individual and societal costs: mental health, physical health, harm toward others, and need for support. As adults approaching midlife, young suicide attempters were significantly more likely to have persistent mental health problems (eg, depression, substance dependence, and additional suicide attempts) compared with nonattempters. They were also more likely to have physical health problems (eg, metabolic syndrome and elevated inflammation). They engaged in more violence (eg, violent crime and intimate partner abuse) and needed more social support (eg, long-term welfare receipt and unemployment). Furthermore, they reported being lonelier and less satisfied with their lives. These associations remained after adjustment for youth psychiatric diagnoses and social class. Many young suicide attempters remain vulnerable to costly health and social problems into midlife. As rates of suicidal behavior rise with the continuing global recession, additional suicide prevention efforts and long-term

  19. Soluble Co-Signaling Molecules Predict Long-Term Graft Outcome in Kidney-Transplanted Patients

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    Melendreras, Susana G.; Martínez-Camblor, Pablo; Menéndez, Aurora; Bravo-Mendoza, Cristina; González-Vidal, Ana; Coto, Eliecer; Díaz-Corte, Carmen; Ruiz-Ortega, Marta; López-Larrea, Carlos; Suárez-Álvarez, Beatriz

    2014-01-01

    Co-signaling molecules are responsible for full T-cell activation after solid organ transplantation. Their increased expression can lead to the release of a soluble form that can modulate the immune response post-transplantation. We analyzed the presence of co-signaling molecules (sCD30, sCD40, sCD137, sCTLA-4, sCD80, sCD28, sCD40L, sPD-1, and sPD-L1) in serum from kidney-transplanted patients (n = 59) obtained at different times (before transplantation, and 15 days, 3 months and 1 year post-transplantation) and their contribution to graft outcome was evaluated using principal component analysis. Before transplantation, high levels of soluble co-signaling molecules (mainly sCD30, sCD137 and sCD40) were detected in all patients. These molecules were modulated soon after receiving an allograft but never attained similar levels to those of healthy controls. A signature based on the determination of six soluble co-stimulatory (sCD30, sCD40, sCD137 and sCD40L) and co-inhibitory (sPD-1 and sPD-L1) molecules at 3 months post-transplantation allowed a group of patients to be identified (27.12%) with a worse long-term graft outcome. Patients with high levels of soluble molecules showed a progressive and gradual deterioration of kidney function (increased creatinine and proteinuria levels and decreased estimated glomerular filtration rate) over time and a higher risk of graft loss at 6 years post-transplantation than patients with low levels of these molecules (62.55% versus 5.14%, pmolecules in kidney-transplanted patients whose quantification at 3 months post-transplantation might be a useful biomarker of immune status and help to predict long-term graft evolution. PMID:25478957

  20. Roles of NO signaling in long-term memory formation in visual learning in an insect.

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    Yukihisa Matsumoto

    Full Text Available Many insects exhibit excellent capability of visual learning, but the molecular and neural mechanisms are poorly understood. This is in contrast to accumulation of information on molecular and neural mechanisms of olfactory learning in insects. In olfactory learning in insects, it has been shown that cyclic AMP (cAMP signaling critically participates in the formation of protein synthesis-dependent long-term memory (LTM and, in some insects, nitric oxide (NO-cyclic GMP (cGMP signaling also plays roles in LTM formation. In this study, we examined the possible contribution of NO-cGMP signaling and cAMP signaling to LTM formation in visual pattern learning in crickets. Crickets that had been subjected to 8-trial conditioning to associate a visual pattern with water reward exhibited memory retention 1 day after conditioning, whereas those subjected to 4-trial conditioning exhibited 30-min memory retention but not 1-day retention. Injection of cycloheximide, a protein synthesis inhibitor, into the hemolymph prior to 8-trial conditioning blocked formation of 1-day memory, whereas it had no effect on 30-min memory formation, indicating that 1-day memory can be characterized as protein synthesis-dependent long-term memory (LTM. Injection of an inhibitor of the enzyme producing an NO or cAMP prior to 8-trial visual conditioning blocked LTM formation, whereas it had no effect on 30-min memory formation. Moreover, injection of an NO donor, cGMP analogue or cAMP analogue prior to 4-trial conditioning induced LTM. Induction of LTM by an NO donor was blocked by DDA, an inhibitor of adenylyl cyclase, an enzyme producing cAMP, but LTM induction by a cAMP analogue was not impaired by L-NAME, an inhibitor of NO synthase. The results indicate that cAMP signaling is downstream of NO signaling for visual LTM formation. We conclude that visual learning and olfactory learning share common biochemical cascades for LTM formation.

  1. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  2. Reward signal in a recurrent circuit drives appetitive long-term memory formation.

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    Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

    2015-11-17

    Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

  3. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

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    Saïd Kourrich

    2008-01-01

    Full Text Available The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex.

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

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    Dylst, Pieter; Vulto, Arnold; Simoens, Steven

    2015-02-01

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

  5. Hippocampal long-term potentiation is enhanced in urethane-anesthetized RGS2 knockout mice.

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    Hutchison, R Matthew; Chidiac, Peter; Leung, L Stan

    2009-08-01

    RGS2 is a member of the regulator of G-protein signaling (RGS) family and has been implicated in cellular mechanisms associated with neuronal plasticity. Long-term potentiation (LTP) of RGS2 knockout and wild-type mice was examined at the Schaffer collaterals to CA1 pathway in urethane-anesthetized mice in vivo to examine RGS2's possible role in the regulation of potentiation. As compared to wild-type mice, RGS2 knockouts demonstrated much stronger LTP of the extracellular population spikes at the somatic and dendritic layers in CA1 region and more pronounced LTP of the population excitatory postsynaptic current sink. Under baseline conditions, RGS2 knockouts showed lower paired-pulse facilitation of the excitatory postsynaptic potentials and associated current sinks in vivo as compared with wild-type mice. The data show for the first time that RGS2 deficient mice in vivo differ from wild-type mice in both short-term and long-term synaptic plasticity suggesting that RGS2 serves as a negative regulator of long-term synaptic plasticity. Copyright (c) 2009 Wiley-Liss, Inc.

  6. Design Principles and Concepts for Enhancing Long-Term Cap Performance and Confidence

    International Nuclear Information System (INIS)

    Steven J. Piet; Robert P. Breckenridge; Gregory J. White; Jacob J. Jacobson; Hilary I. Inyang

    2005-01-01

    The siting of new landfills is becoming increasing difficult as the public and stakeholders want more confidence of performance for longer times and landfill owners want to store more waste in the least area while knowing and limiting their long-term liabilities. These changes motivate re-examination of long-term performance mechanisms and their implications for cap and barrier designs. Accordingly, in this paper we first consider design principles from the standpoint of long-term performance and management, including the ability to monitor and repair barriers. We then consider some design concepts that may implement these principles, especially evapo-transpiration (ET) caps. We suggest five design principles based on experience in the cap and barrier field as well as other engineering disciplines. These principles are as follows: (1) Establish a clear and defendable design basis. (2) Design for ease of monitoring and repair. (3) Analyze the barrier as a dynamic system, not static. (4) Work with nature, not against. (5) Recognize that increased complexity can reduce, not enhance, net performance. ET caps are an excellent embodiment of these design principles. We apply the design principles to ET caps, as well as variants such as erosion armor, capillary breaks, bio-intrusion layers, and low permeability material layers

  7. Long-term asynchronous decoding of arm motion using electrocorticographic signals in monkey

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    Zenas C Chao

    2010-03-01

    Full Text Available Brain–machine interfaces (BMIs employ the electrical activity generated by cortical neurons directly for controlling external devices and have been conceived as a means for restoring human cognitive or sensory-motor functions. The dominant approach in BMI research has been to decode motor variables based on single-unit activity (SUA. Unfortunately, this approach suffers from poor long-term stability and daily recalibration is normally required to maintain reliable performance. A possible alternative is BMIs based on electrocorticograms (ECoGs, which measure population activity and can provide more durable and stable recording. However, the level of long-term stability that ECoG-based decoding can offer remains unclear. Here we propose a novel ECoG-based decoding paradigm and show that we have successfully decoded hand positions and arm joint angles during an asynchronous food-reaching task in monkeys when explicit cues prompting the onset of movement were not required. Performance using our ECoG-based decoder was comparable to existing SUA-based systems while evincing far superior stability and durability. In addition, the same decoder could be used for months without any drift in accuracy or recalibration. These results were achieved by incorporating the spatio-spectro-temporal integration of activity across multiple cortical areas to compensate for the lower fidelity of ECoG signals. These results show the feasibility of high-performance, chronic and versatile ECoG-based neuroprosthetic devices for real-life applications. This new method provides a stable platform for investigating cortical correlates for understanding motor control, sensory perception, and high-level cognitive processes.

  8. Long-Term Asynchronous Decoding of Arm Motion Using Electrocorticographic Signals in Monkeys

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    Chao, Zenas C.; Nagasaka, Yasuo; Fujii, Naotaka

    2009-01-01

    Brain–machine interfaces (BMIs) employ the electrical activity generated by cortical neurons directly for controlling external devices and have been conceived as a means for restoring human cognitive or sensory-motor functions. The dominant approach in BMI research has been to decode motor variables based on single-unit activity (SUA). Unfortunately, this approach suffers from poor long-term stability and daily recalibration is normally required to maintain reliable performance. A possible alternative is BMIs based on electrocorticograms (ECoGs), which measure population activity and may provide more durable and stable recording. However, the level of long-term stability that ECoG-based decoding can offer remains unclear. Here we propose a novel ECoG-based decoding paradigm and show that we have successfully decoded hand positions and arm joint angles during an asynchronous food-reaching task in monkeys when explicit cues prompting the onset of movement were not required. Performance using our ECoG-based decoder was comparable to existing SUA-based systems while evincing far superior stability and durability. In addition, the same decoder could be used for months without any drift in accuracy or recalibration. These results were achieved by incorporating the spatio-spectro-temporal integration of activity across multiple cortical areas to compensate for the lower fidelity of ECoG signals. These results show the feasibility of high-performance, chronic and versatile ECoG-based neuroprosthetic devices for real-life applications. This new method provides a stable platform for investigating cortical correlates for understanding motor control, sensory perception, and high-level cognitive processes. PMID:20407639

  9. LONG-TERM DEMONSTRATION OF SORBENT ENHANCEMENT ADDITIVE TECHNOLOGY FOR MERCURY CONTROL

    Energy Technology Data Exchange (ETDEWEB)

    Jason D. Laumb; Dennis L. Laudal; Grant E. Dunham; John P. Kay; Christopher L. Martin; Jeffrey S. Thompson; Nicholas B. Lentz; Alexander Azenkeng; Kevin C. Galbreath; Lucinda L. Hamre

    2011-05-27

    Long-term demonstration tests of advanced sorbent enhancement additive (SEA) technologies have been completed at five coal-fired power plants. The targeted removal rate was 90% from baseline conditions at all five stations. The plants included Hawthorn Unit 5, Mill Creek Unit 4, San Miguel Unit 1, Centralia Unit 2, and Hoot Lake Unit 2. The materials tested included powdered activated carbon, treated carbon, scrubber additives, and SEAs. In only one case (San Miguel) was >90% removal not attainable. The reemission of mercury from the scrubber at this facility prevented >90% capture.

  10. Evaluation of Long-term Performance of Enhanced Anaerobic Source Zone Bioremediation using mass flux

    Science.gov (United States)

    Haluska, A.; Cho, J.; Hatzinger, P.; Annable, M. D.

    2017-12-01

    Chlorinated ethene DNAPL source zones in groundwater act as potential long term sources of contamination as they dissolve yielding concentrations well above MCLs, posing an on-going public health risk. Enhanced bioremediation has been applied to treat many source zones with significant promise, but long-term sustainability of this technology has not been thoroughly assessed. This study evaluated the long-term effectiveness of enhanced anaerobic source zone bioremediation at chloroethene contaminated sites to determine if the treatment prevented contaminant rebound and removed NAPL from the source zone. Long-term performance was evaluated based on achieving MCL-based contaminant mass fluxes in parent compound concentrations during different monitoring periods. Groundwater concertation versus time data was compiled for 6-sites and post-remedial contaminant mass flux data was then measured using passive flux meters at wells both within and down-gradient of the source zone. Post-remedial mass flux data was then combined with pre-remedial water quality data to estimate pre-remedial mass flux. This information was used to characterize a DNAPL dissolution source strength function, such as the Power Law Model and the Equilibrium Stream tube model. The six-sites characterized for this study were (1) Former Charleston Air Force Base, Charleston, SC; (2) Dover Air Force Base, Dover, DE; (3) Treasure Island Naval Station, San Francisco, CA; (4) Former Raritan Arsenal, Edison, NJ; (5) Naval Air Station, Jacksonville, FL; and, (6) Former Naval Air Station, Alameda, CA. Contaminant mass fluxes decreased for all the sites by the end of the post-treatment monitoring period and rebound was limited within the source zone. Post remedial source strength function estimates suggest that decreases in contaminant mass flux will continue to occur at these sites, but a mass flux based on MCL levels may never be exceeded. Thus, site clean-up goals should be evaluated as order

  11. A Methodology for Long-Term Analysis of Innovative Signalling Systems on Regional Rail Lines

    Directory of Open Access Journals (Sweden)

    Luca D'Acierno

    2016-10-01

    Full Text Available A rail system may be considered a useful tool for reducing vehicular flows on a road system (i.e. cars and trucks, especially in high-density contexts such as urban and metropolitan areas where greenhouse gas emissions need to be abated. In particular, since travellers maximise their own utility, variations in mobility choices can be induced only by significantly improving the level-of-service of public transport. Our specific proposal is to identify the economic and environmental effects of implementing an innovative signalling system (which would reduce passenger waiting times by performing a cost-benefit analysis based on a feasibility threshold approach. Hence, it is necessary to calculate long-term benefits and compare them with intervention costs. In this context, a key factor to be considered is travel demand estimation in current and future conditions. This approach was tested on a regional rail line in southern Italy to show the feasibility and utility of the proposed methodology.

  12. River networks dampen long-term hydrological signals of climate change

    Science.gov (United States)

    Chezik, K. A.; Anderson, S. C.; Moore, J. W.

    2017-07-01

    River networks may dampen local hydrologic signals of climate change through the aggregation of upstream climate portfolio assets. Here we examine this hypothesis using flow and climate trend estimates (1970-2007) at 55 hydrometric gauge stations and across their contributing watersheds' within the Fraser River basin in British Columbia, Canada. Using a null hypothesis framework, we compared our observed attenuation of river flow trends as a function of increasing area and climate trend diversity, with null-simulated estimates to gauge the likelihood and strength of our observations. We found the Fraser River reduced variability in downstream long-term discharge by >91%, with >3.1 times the attenuation than would be expected under null simulation. Although the strength of dampening varied seasonally, our findings indicate that large free-flowing rivers offer a powerful and largely unappreciated process of climate change mitigation. River networks that integrate a diverse climate portfolio can dampen local extremes and offer climate change relief to riverine biota.

  13. Enhancing long-term memory with stimulation tunes visual attention in one trial.

    Science.gov (United States)

    Reinhart, Robert M G; Woodman, Geoffrey F

    2015-01-13

    Scientists have long proposed that memory representations control the mechanisms of attention that focus processing on the task-relevant objects in our visual field. Modern theories specifically propose that we rely on working memory to store the object representations that provide top-down control over attentional selection. Here, we show that the tuning of perceptual attention can be sharply accelerated after 20 min of noninvasive brain stimulation over medial-frontal cortex. Contrary to prevailing theories of attention, these improvements did not appear to be caused by changes in the nature of the working memory representations of the search targets. Instead, improvements in attentional tuning were accompanied by changes in an electrophysiological signal hypothesized to index long-term memory. We found that this pattern of effects was reliably observed when we stimulated medial-frontal cortex, but when we stimulated posterior parietal cortex, we found that stimulation directly affected the perceptual processing of the search array elements, not the memory representations providing top-down control. Our findings appear to challenge dominant theories of attention by demonstrating that changes in the storage of target representations in long-term memory may underlie rapid changes in the efficiency with which humans can find targets in arrays of objects.

  14. Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

    Directory of Open Access Journals (Sweden)

    Jun Il Kang

    Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

  15. Novel environments enhance the induction and maintenance of long-term potentiation in the dentate gyrus.

    Science.gov (United States)

    Davis, Cyndy D; Jones, Floretta L; Derrick, Brian E

    2004-07-21

    The induction of long-term potentiation (LTP) in the hippocampal formation can be modulated by different behavioral states. However, few studies have addressed modulation of LTP during behavioral states in which the animal is likely acquiring new information. Here, we demonstrate that both the induction and the longevity of LTP in the dentate gyrus are enhanced when LTP is induced during the initial exploration of a novel environment. These effects are independent from locomotor activity, changes in brain temperature, and theta rhythm. Previous exposure to the novel environment attenuated this enhancement, suggesting that the effects of novelty habituate with familiarity. LTP longevity also was enhanced when induced in familiar environments containing novel objects. Together, these data indicate that both LTP induction and maintenance are enhanced when LTP is induced while rats investigate novel stimuli. We suggest that novelty initiates a transition of the hippocampal formation to a mode that is particularly conducive to synaptic plasticity, a process that could allow for new learning while preserving the stability of previously stored information. In addition, LTP induced in novel environments elicited a sustained late LTP. This suggests that a single synaptic population can display distinct profiles of LTP maintenance and that this depends on the animal's behavioral state during its induction. Furthermore, the duration of LTP enhanced by novelty parallels the time period during which the hippocampal formation is thought necessary for memory, consistent with the view that dentate LTP is of a duration sufficient to sustain memory in the hippocampal formation.

  16. Long-term growth enhancement of baldcypress (Taxodium distichum) from municipal wastewater application

    Science.gov (United States)

    Hesse, I.D.; Day, J.W.; Doyle, T.W.

    1998-01-01

    Tree ring analysis was used to document the long-term effects of municipal wastewater on the growth rate of baldcypress (Taxodium distichum (L.) Rich.]. The study site, a swamp in St. Martin Parish, Louisiana, has received municipal wastewater for the last 40 years. Growth chronologies from 1920 to 1992 were developed from cross-dated tree core samples taken from treated and control sites with similar size and age classes. Mean diameter increment (DINC) and mean basal area increment (BAI) chronologies were constructed separately for each stand. These chronologies were then summarized by tree and stand into seven nine-year intervals resulting in three pretreatment intervals from 1926 to 1952 and four treatment intervals from 1953 to 1988. Significant differences in growth response between sites showed a consistent pattern of growth enhancement in the treated site coincident with the onset of effluent discharge. The ratio of treated to control baldcypress growth rates (computed from DINC) averaged 0.74 during the pretreatment period and 1.53 during the treatment period. Over the period of study, control DINC decreased from 77 mm to 29 mm/nine-year interval, while treatment DINC increased slightly from 40 mm to 47 mm/nine-year interval. Control BAI did not increase significantly and averaged 192 cm2/nine-year interval. There was a significant increase in treatment BAI from 129 to 333 cm2/nine-year interval over the period of record. These results clearly demonstrate sustained long-term baldcypress growth enhancement throughout 40 years of municipal effluent discharge.

  17. Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway.

    Science.gov (United States)

    Xu, Guang; Takashi, En; Kudo, Mitsuhiro; Ishiwata, Toshiyuki; Naito, Zenya

    2004-02-01

    Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction, there is disagreement about the sensitivity of ischemic injury of an infarcted myocardium in experimental studies. The present study evaluated the influences of different durations of hyperglycemia on ischemic and reperfusion injuries of the myocardium, and focused on extracellular signal-regulated kinase 1/2 (ERK1/2), which plays an important role in the intracellular signaling pathway and is reported to be associated with myocardial protection against heart injury. Short- and long-term hyperglycemias were induced in rats by streptozotocin (STZ) injection and the rats were examined 4 (4WDM) and 20 weeks (20WDM) after the treatment. Ischemia and reperfusion were induced by occlusion and reperfusion (I/R) of the left coronary artery (LCA). I/R-induced infarct size was determined using triphenyltetrazolium chloride (TTC) staining. After 20 weeks of STZ treatment (20WDM+I/R), the infarct size in the rat heart increased by 65.2 +/- 4.3%, whereas after 4 weeks of STZ treatment (4WDM+I/R), the infarct size decreased compared with the time-matched I/R group (43.1 +/- 3.6% and 59.5 +/- 5.6%, respectively). The number of dead myocytes including necrotic and apoptotic cells was determined using horseradish peroxidase (HRP) and terminal deoxynucleotide nick-end labeling (TUNEL) methods. The number of dead myocytes decreased in the 4WDM+I/R group, while the number of dead myocytes increased markedly in the 20WDM+I/R group, compared with the time-matched I/R group. The increment of ERK1/2 phosphorylation in the 4WDM group and the slight enhancement of this phosphorylation by I/R treatment were observed by western blotting. However, in the 20WDM group, the level of ERK1/2 phosphorylation reduced by approximately 1/3 compared with the time-matched control group; moreover, I/R treatment did not enhance the phosphorylation level. This study demonstrated that short- and long-term

  18. Price-signals and long term equilibrium. Reconsidering the organisation of electricity markets

    International Nuclear Information System (INIS)

    Finon, Dominique; Defeuilley, Christophe; Marty, Frederic

    2009-11-01

    The purpose of this article is to show that the reform of the electricity sector, based on a framework of interpretation in which the short-term/long-term articulation is made by the market price, does not result in an efficient result in terms of investment. After a presentation of a bibliographical review on investment in an uncertain context, the authors present a model of decentralised electricity markets which backs reforms. They highlight issues related to production investment which remain unresolved, and which may result in socially inefficient choices on the long term. They report an analysis of two solutions of industrial organisations, long term contracts and vertical and horizontal integration, which could solve these problems

  19. A novel whole-cell mechanism for long-term memory enhancement.

    Directory of Open Access Journals (Sweden)

    Iris Reuveni

    Full Text Available Olfactory-discrimination learning was shown to induce a profound long-lasting enhancement in the strength of excitatory and inhibitory synapses of pyramidal neurons in the piriform cortex. Notably, such enhancement was mostly pronounced in a sub-group of neurons, entailing about a quarter of the cell population. Here we first show that the prominent enhancement in the subset of cells is due to a process in which all excitatory synapses doubled their strength and that this increase was mediated by a single process in which the AMPA channel conductance was doubled. Moreover, using a neuronal-network model, we show how such a multiplicative whole-cell synaptic strengthening in a sub-group of cells that form a memory pattern, sub-serves a profound selective enhancement of this memory. Network modeling further predicts that synaptic inhibition should be modified by complex learning in a manner that much resembles synaptic excitation. Indeed, in a subset of neurons all GABAA-receptors mediated inhibitory synapses also doubled their strength after learning. Like synaptic excitation, Synaptic inhibition is also enhanced by two-fold increase of the single channel conductance. These findings suggest that crucial learning induces a multiplicative increase in strength of all excitatory and inhibitory synapses in a subset of cells, and that such an increase can serve as a long-term whole-cell mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism does not act as synaptic plasticity mechanism that underlies memory formation but rather enhances the response of already existing memory. This mechanism is cell-specific rather than synapse-specific; it modifies the channel conductance rather than the number of channels and thus has the potential to be readily induced and un-induced by whole-cell transduction mechanisms.

  20. Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats

    International Nuclear Information System (INIS)

    Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

    2014-01-01

    Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl 3 ) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle–box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus

  1. Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats.

    Science.gov (United States)

    Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

    2014-09-02

    Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle-box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus. Copyright

  2. Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.

    Directory of Open Access Journals (Sweden)

    Mark P DeAndrade

    Full Text Available Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS, a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.

  3. Long-term academic stress enhances early processing of facial expressions.

    Science.gov (United States)

    Zhang, Liang; Qin, Shaozheng; Yao, Zhuxi; Zhang, Kan; Wu, Jianhui

    2016-11-01

    Exposure to long-term stress can lead to a variety of emotional and behavioral problems. Although widely investigated, the neural basis of how long-term stress impacts emotional processing in humans remains largely elusive. Using event-related brain potentials (ERPs), we investigated the effects of long-term stress on the neural dynamics of emotionally facial expression processing. Thirty-nine male college students undergoing preparation for a major examination and twenty-one matched controls performed a gender discrimination task for faces displaying angry, happy, and neutral expressions. The results of the Perceived Stress Scale showed that participants in the stress group perceived higher levels of long-term stress relative to the control group. ERP analyses revealed differential effects of long-term stress on two early stages of facial expression processing: 1) long-term stress generally augmented posterior P1 amplitudes to facial stimuli irrespective of expression valence, suggesting that stress can increase sensitization to visual inputs in general, and 2) long-term stress selectively augmented fronto-central P2 amplitudes for angry but not for neutral or positive facial expressions, suggesting that stress may lead to increased attentional prioritization to processing negative emotional stimuli. Together, our findings suggest that long-term stress has profound impacts on the early stages of facial expression processing, with an increase at the very early stage of general information inputs and a subsequent attentional bias toward processing emotionally negative stimuli. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Fatty-acid binding proteins modulate sleep and enhance long-term memory consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason R Gerstner

    2011-01-01

    Full Text Available Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7 on sleep and long-term memory (LTM formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation "window" that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.

  5. Negative emotion enhances mnemonic precision and subjective feelings of remembering in visual long-term memory.

    Science.gov (United States)

    Xie, Weizhen; Zhang, Weiwei

    2017-09-01

    Negative emotion sometimes enhances memory (higher accuracy and/or vividness, e.g., flashbulb memories). The present study investigates whether it is the qualitative (precision) or quantitative (the probability of successful retrieval) aspect of memory that drives these effects. In a visual long-term memory task, observers memorized colors (Experiment 1a) or orientations (Experiment 1b) of sequentially presented everyday objects under negative, neutral, or positive emotions induced with International Affective Picture System images. In a subsequent test phase, observers reconstructed objects' colors or orientations using the method of adjustment. We found that mnemonic precision was enhanced under the negative condition relative to the neutral and positive conditions. In contrast, the probability of successful retrieval was comparable across the emotion conditions. Furthermore, the boost in memory precision was associated with elevated subjective feelings of remembering (vividness and confidence) and metacognitive sensitivity in Experiment 2. Altogether, these findings suggest a novel precision-based account for emotional memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

    Directory of Open Access Journals (Sweden)

    Guilherme T Silva

    2009-06-01

    Full Text Available A single intra-peritoneal injection of valproic acid (VPA on embryonic day (ED 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm. In the present study, we explored whether Long Term Microcircuit Plasticity (LTMP was altered in this animal model. We performed multi-neuron patch-clamp recordings on clusters of layer V pyramidal cells in somatosensory cortex brain slices (PN 12-15, mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.

  7. Corticosterone enhances the potency of ethanol against hippocampal long-term potentiation via local neurosteroid synthesis

    Directory of Open Access Journals (Sweden)

    Yukitoshi eIzumi

    2015-07-01

    Full Text Available Corticosterone is known to accumulate in brain after various stressors including alcohol intoxication. Just as severe alcohol intoxication is typically required to impair memory formation only high concentrations of ethanol (60mM acutely inhibit long-term potentiation (LTP, a cellular memory mechanism, in naïve hippocampal slices. This LTP inhibition involves synthesis of neurosteroids, including allopregnanolone, and appears to involve a form of cellular stress. In the CA1 region of rat hippocampal slices, we examined whether a lower concentration of ethanol (20 mM inhibits LTP in the presence of corticosterone, a stress-related modulator, and whether corticosterone stimulates local neurosteroid synthesis. Although low micromolar corticosterone alone did not inhibit LTP induction, we found that 20 mM ethanol inhibited LTP in the presence of corticosterone. At 20 mM, ethanol alone did not stimulate neurosteroid synthesis or inhibit LTP. LTP inhibition by corticosterone plus ethanol was blocked by finasteride, an inhibitor of 5α-reductase, suggesting a role for neurosteroid synthesis. We also found that corticosterone alone enhanced neurosteroid immunostaining in CA1 pyramidal neurons and that this immunostaining was further augmented by 20 mM ethanol. The enhanced neurosteroid staining was blocked by finasteride and the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate (APV. These results indicate that corticosterone promotes neurosteroid synthesis in hippocampal pyramidal neurons and can participate in ethanol-mediated synaptic dysfunction even at moderate ethanol levels. These effects may contribute to the influence of stress on alcohol-induced cognitive impairment.

  8. Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming.

    Science.gov (United States)

    Feng, Wenting; Liang, Junyi; Hale, Lauren E; Jung, Chang Gyo; Chen, Ji; Zhou, Jizhong; Xu, Minggang; Yuan, Mengting; Wu, Liyou; Bracho, Rosvel; Pegoraro, Elaine; Schuur, Edward A G; Luo, Yiqi

    2017-11-01

    Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon-climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming. Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the

  9. Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness.

    Science.gov (United States)

    Hoggatt, Jonathan; Mohammad, Khalid S; Singh, Pratibha; Pelus, Louis M

    2013-10-24

    Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for malignant and nonmalignant hematologic diseases and metabolic disorders. Although successful, hematopoietic transplantation can be hindered by inadequate stem cell number or poor engrafting efficiency. To overcome these deficits, we and others have previously reported the HSC-enhancing ability of a short-term exposure of prostaglandin E2 (PGE2); this strategy has now progressed to phase 1 clinical trials in double cord blood transplantation. To further analyze the short- and long-term effects of HSC exposure to PGE2, we followed the repopulation kinetics of PGE2-treated hematopoietic grafts through 5 serial transplantations and compared inherent long-term competitiveness in a HSC head-to-head secondary transplantation model. Treatment with PGE2 did not result in a long-term increase in HSC competitiveness, lineage bias, or enhanced proliferative potential, demonstrating that pulse exposure to PGE2 results in transient increases in HSC homing and engraftment potential.

  10. Long-term health-enhancing physical activity in rheumatoid arthritis - the PARA 2010 study

    Directory of Open Access Journals (Sweden)

    Nordgren Birgitta

    2012-07-01

    Full Text Available Abstract Background People with rheumatoid arthritis (RA suffer increased risk of disability andpremature mortality. Health-enhancing physical activity (HEPA could be one importantfactor to reduce this risk. Rising health care costs call for the development and evaluation ofnew modes of rehabilitation, including physical activity in settings outside the health caresystem. Methods/Design This cohort study targets 450 patients with RA that do not currently meet HEPA recommendations, recruited from six hospitals reporting to the Swedish Rheumatology Quality Registers (SRQ. We have developed a two-year real-life intervention program including a minimum of twice-weekly circuit training, moderately intense physical activity the remaining days of the week and group meetings to support behavior change every other week. Our hypothesis is that increased physical activity and exercise will improve perceived health, reduce pain and fatigue, increase muscle function and aerobic capacity, impact psychosocial factors and prevent future cardiovascular events. Research questions regard outcomes, retention rates, dose–response matters and the exploration of responder characteristics. This protocol outlines recruitment procedure, design, assessment methods and the intervention program of the study. Discussion The PARA 2010 project is designed to expand the knowledge on HEPA in RA by a progressive approach regarding population, setting, intervention, time frames and outcome measures. To our knowledge this is the first long-term HEPA program based on Social Cognitive Theory, and performed in a real life environment to demonstrate if this new setting can promote increased and maintained physical activity in people with RA. Trial registration number ISRCTN25539102

  11. Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

    Science.gov (United States)

    Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

    2015-01-01

    The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

  12. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation

    NARCIS (Netherlands)

    B.J. van Beugen (Boeke); X. Qiao (Xin); D.H. Simmons (Dana H.); C.I. de Zeeuw (Chris); C.R.W. Hansel (Christian)

    2014-01-01

    textabstractAmpakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of

  13. Enhanced AMPA Receptor Function Promotes Cerebellar Long-Term Depression Rather than Potentiation

    Science.gov (United States)

    van Beugen, Boeke J.; Qiao, Xin; Simmons, Dana H.; De Zeeuw, Chris I.; Hansel, Christian

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar…

  14. Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking delphilin

    NARCIS (Netherlands)

    T. Takeuchi (Tomonori); G. Ohtsuki (Gen); T. Yoshida (Takashi); M. Fukaya (Masahiro); T. Wainai (Tasuku); M. Yamashita (Manami); Y. Yamazaki (Yoshito); H. Mori (Hisashi); K. Sakimura (Kenji); S. Kawamoto (Susumu); M. Watanabe (Masahiko); T. Hirano (Tomoo); M. Mishina (Masayoshi)

    2008-01-01

    textabstractIn the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) δ2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring,

  15. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation

    NARCIS (Netherlands)

    van Beugen, Boeke J; Qiao, Xin; Simmons, Dana H; De Zeeuw, Chris I; Hansel, Christian

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory

  16. Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans

    Science.gov (United States)

    Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah

    2011-01-01

    Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…

  17. Long-Term In Vitro Expansion of Salivary Gland Stem Cells Driven by Wnt Signals

    Directory of Open Access Journals (Sweden)

    Martti Maimets

    2016-01-01

    Full Text Available Adult stem cells are the ultimate source for replenishment of salivary gland (SG tissue. Self-renewal ability of stem cells is dependent on extrinsic niche signals that have not been unraveled for the SG. The ductal compartment in SG has been identified as the location harboring stem cells. Here, we report that rare SG ductal EpCAM+ cells express nuclear β-catenin, indicating active Wnt signaling. In cell culture experiments, EpCAMhigh cells respond potently to Wnt signals stimulating self-renewal and long-term expansion of SG organoids, containing all differentiated SG cell types. Conversely, Wnt inhibition ablated long-term organoid cultures. Finally, transplantation of cells pre-treated with Wnt agonists into submandibular glands of irradiated mice successfully and robustly restored saliva secretion and increased the number of functional acini in vivo. Collectively, these results identify Wnt signaling as a key driver of adult SG stem cells, allowing extensive in vitro expansion and enabling restoration of SG function upon transplantation.

  18. Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior.

    Science.gov (United States)

    Janak, Patricia H; Bowers, M Scott; Corbit, Laura H

    2012-03-01

    Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies.

  19. Analysis of Spanish generic medicines retail market: recommendations to enhance long-term sustainability.

    Science.gov (United States)

    Dylst, Pieter; Vulto, Arnold G; Simoens, Steven

    2014-06-01

    The use of generic medicines in Spain is traditionally low compared to other European countries, despite efforts of the Spanish government in the past. This paper provides a perspective on the Spanish generic medicines retail market and how the current policy environment may affect the long-term sustainability. The Spanish government's focus on prices of generic medicines (e.g., mandatory price cuts, reference price set at the lowest level) have made them amongst the lowest in Europe. In our opinion, this combination of continuous pressure on prices and limited diffusion of generic medicines may undermine the long-term sustainability of the Spanish generic medicines retail market. The unique experience in Spain shows the impact of demand-side policies on the use of generic medicines. Because a sustainable generic medicines retail market is important to maintain future competition in the off-patent medicines market, this perspective paper rounds off with recommendations to increase its sustainability.

  20. 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.

  1. Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

    OpenAIRE

    Guilherme T Silva; Guilherme T Silva; Jean-Vincent Le Bé; Imad Riachi; Tania Rinaldi; Kamila Markram; Henry Markram

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm). In the present study, we explored whether Long Term Microcircuit ...

  2. 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.

  3. Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation

    NARCIS (Netherlands)

    B.J. van Beugen (Boeke); R.Y. Nagaraja (Raghavendra); C.R.W. Hansel (Christian)

    2006-01-01

    textabstractEndocannabinoid signaling has been demonstrated to mediate depolarization-induced suppression of excitation at climbing fiber (CF) and parallel fiber (PF) synapses onto cerebellar Purkinje cells. Here, we show that CF-evoked release of cannabinoids (CBs) additionally suppresses a

  4. Infarction of Uterine Fibroids After Embolization: Relationship Between Postprocedural Enhanced MRI Findings and Long-Term Clinical Outcomes

    International Nuclear Information System (INIS)

    Katsumori, Tetsuya; Kasahara, Toshiyuki; Kin, Yoko; Nozaki, Taiki

    2008-01-01

    Purpose. To retrospectively evaluate the relationship between the degree of infarction of uterine fibroids on enhanced MRI after embolization and long-term clinical outcomes. Methods. During 92 months, 290 consecutive patients with symptomatic uterine fibroids were treated with embolization; 221 who underwent enhanced MRI before embolization and 1 week after embolization were included in this study. The infarction rates of all fibroid tissue were assessed using enhanced MRI after embolization. Patients were divided into three groups according to the infarction rates: group A (100% infarction, n 142), group B (90-99% infarction, n = 74), group C (<90% infarction, n = 5). The cumulative rates of clinical outcomes were compared among groups using the Kaplan-Meier limited method. Results. Group A had a significantly higher rate of symptom control than groups B and C. The cumulative rates of symptom control at 5 years were 93%, 71%, and 60% in groups A, B, and C, respectively. Group A had a significantly lower rate of gynecologic intervention after embolization than groups B and C. The cumulative rates of additional gynecologic intervention at 5 years were 3%, 15%, and 20% in groups A, B, and C, respectively. Conclusions. The degree of infarction of uterine fibroids after embolization on enhanced MRI was related to long-term clinical outcomes. Complete infarction of all fibroid tissue can induce a higher rate of symptom control, with a lower rate of additional gynecologic intervention in the long term compared with incomplete infarction of fibroid tissue

  5. Amplitude calibration of an acoustic backscattered signal from a bottom-moored ADCP based on long-term measurement series

    Science.gov (United States)

    Piotukh, V. B.; Zatsepin, A. G.; Kuklev, S. B.

    2017-05-01

    A possible approach to, and preliminary results of, amplitude calibration of acoustic signals backscattered from an ADCP moored at the bottom of the near-shelf zone of the Black Sea is considered. The aim of this work is to obtain vertical profiles of acoustic scattering signal levels, showing the real characteristics of the volume content of suspended sediments in sea water in units of conventional acoustic turbidity for a given signal frequency. In this case, the assumption about the intervals of maximum acoustic transparency and vertical homogeneity of the marine environment in long-term series of ADCP measurements is used. According to this hypothesis, the intervals of the least values of acoustic backscattered signals are detected, an empirical transfer function of the ADCP reception path is constructed, and it is calibrated. Normalized sets of acoustic backscattered signals relative to a signal from a level of conventionally clear water are obtained. New features in the behavior of vertical profiles of an acoustic echo-signal are revealed due to the calibration. The results of this work will be used in subsequent analysis of the vertical and time variations in suspended sediment content in the near-shelf zone of the Black Sea.

  6. Long-term music training tunes how the brain temporally binds signals from multiple senses

    OpenAIRE

    Lee, HweeLing; Noppeney, Uta

    2011-01-01

    Practicing a musical instrument is a rich multisensory experience involving the integration of visual, auditory, and tactile inputs with motor responses. This combined psychophysics–fMRI study used the musician's brain to investigate how sensory-motor experience molds temporal binding of auditory and visual signals. Behaviorally, musicians exhibited a narrower temporal integration window than nonmusicians for music but not for speech. At the neural level, musicians showed increased audiovisua...

  7. Long-term music training tunes how the brain temporally binds signals from multiple senses.

    Science.gov (United States)

    Lee, Hweeling; Noppeney, Uta

    2011-12-20

    Practicing a musical instrument is a rich multisensory experience involving the integration of visual, auditory, and tactile inputs with motor responses. This combined psychophysics-fMRI study used the musician's brain to investigate how sensory-motor experience molds temporal binding of auditory and visual signals. Behaviorally, musicians exhibited a narrower temporal integration window than nonmusicians for music but not for speech. At the neural level, musicians showed increased audiovisual asynchrony responses and effective connectivity selectively for music in a superior temporal sulcus-premotor-cerebellar circuitry. Critically, the premotor asynchrony effects predicted musicians' perceptual sensitivity to audiovisual asynchrony. Our results suggest that piano practicing fine tunes an internal forward model mapping from action plans of piano playing onto visible finger movements and sounds. This internal forward model furnishes more precise estimates of the relative audiovisual timings and hence, stronger prediction error signals specifically for asynchronous music in a premotor-cerebellar circuitry. Our findings show intimate links between action production and audiovisual temporal binding in perception.

  8. Long-term electroacupuncture stimulation prevents osteoporosis in ovariectomised osteopaenic rats through multiple signalling pathways.

    Science.gov (United States)

    Zheng, Xuefeng; Nie, Yan; Sun, Chengtao; Wu, Guangwen; Cai, Qiaoyan; Huang, Shu; Lin, Yanping

    2018-04-06

    The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone. Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group).Bone turnover markers osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured in serum, and bone mineral density (BMD) of the lumbar vertebrae and histomorphology of the femur were evaluated. Moreover, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) was detected by ELISA. The expression of lipoprotein receptor-related protein (LRP) 5, β-catenin, runt-related transcription factor (Runx) 2 involving Wnt/β-catenin signalling and p38, c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 involving mitogen-activated protein kinase signalling were determined by Western blotting. The two EA-treated groups demonstrated increased levels of OC and the BMD of lumbar vertebrae, decreased levels of TRACP 5b and improved bone microstructure in the femur, compared with the untreated OVX group (P<0.05). Histomorphology analysis showed that EA treatment significantly increased the values of the trabeculae (µm), trabecular area (%) and trabecular bone number (per mm) and reduced trabecular separation (mm), compared with the OVX group. In addition, the ratio of OPG to RANKL and LRP5, β-catenin and Runx2 expression were significantly upregulated, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in EA-treated groups compared with the OVX group. EA

  9. Long term variations of chlorine-36 input signal to groundwater as recorded in deep unsaturated zones, south-east Australia

    International Nuclear Information System (INIS)

    Le Gal La Salle, C.; Herczeg, A.L.; Leaney, F.W.; Fifield, L.K.; Cresswell, R.G.; Kellet, J.

    1997-01-01

    The use of chlorine-36 is increasing in hydrology as its long half-life (3x10 5 a), allows useful long-term investigations into groundwater systems. Because chloride is very hydrophillic, the chlorine-36 signal should not be affected by geochemical processes in most aquatic systems. Nevertheless, over long periods of time, the chlorine-36 input to groundwater systems may vary due to factors such as: changes of production of chlorine-36 and/or changes of its distribution in the atmosphere. For instance the production of chlorine-36 might be governed by long-term terrestrial magnetic dipole strength variations as suggested for other radiogenic isotopes. Variations of the input signal of chlorine-36 should be recorded in pore waters of deep unsaturated zones. In this system, the time scale is approximated by the cumulative chloride content with depth assuming a constant input of chloride. Long-term records of chloride and chlorine-36 in two deep unsaturated-zone profiles, situated in the semi-arid Murray Basin in Australia, are presented. The two profiles record periods of approximately 20±1 to 27±2 ka and 100±5 to 220±10 ka respectively. The range of variation of the recorded time at each site is related to the estimated range of chloride deposition rate. The recharge rates are constant in both profiles with values approximating 0.4 and less than 0.1 mm.a -1 respectively. The linear relationship between chlorine-36 and stable chloride indicates that variations of chlorine-36 are governed by evapotranspiration, with a concentration factor of up to 2. Therefore the chlorine-36 is normalised to chloride to take account of the evapotranspiration process. In the soil profile at Kaniva, Western Victoria, 36 Cl/Cl'- ratio shows an increase of approximately 20% down profile. The second profile at Boree Plains, Wester, NSW, shows variations of 36 Cl/Cl'- ratio of 40% with a decreasing trend down profile. The input signal of chlorine-36/chloride is calculated by correction

  10. [Further enhance the long-term myopia control efficacy and safety of orthokeratology].

    Science.gov (United States)

    Xie, Peiying

    2014-01-01

    Strategies and methods of myopia prevention and control has been more and more. In recent years optical correction method is focusing on promoting the retinal mid-peripheral myopic defocus, improving the visual quality and promoting the accommodative function. Among the all, orthokeratology is the most notable optometry technology. This article will combine research progress both local and international achievements, the present situation of the domestic popularized the technique, and the existing problems. From the realistic approach, keep improving, the pursuit of stability, the pursuit of harmony and eliminate the false five aspects, to discuss how to promote orthokeratology for the myopia control with long-term stably efficacy and safety. How to promote the harmony and cooperation between doctors, patients and manufactures. And how to correctly guide the orthokeratology Having both specification and continued development.

  11. Long-term Autophagy and Nrf2 Signaling in the Hippocampi of Developing Mice after Carbon Ion Exposure

    Science.gov (United States)

    Ye, Fei; Zhao, Ting; Liu, Xiongxiong; Jin, Xiaodong; Liu, Xinguo; Wang, Tieshan; Li, Qiang

    2015-12-01

    To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi. Secondary X-ray insult was adopted to amplify potential damages. Long-term behavioral changes were observed in high-LET carbon ion-irradiated mice. There were no differences in the rates of LC3-II induction and p62/SQSTM1 degradation compared to the control group regardless of whether the mice received the secondary X-ray insult. A high nuclear Nrf2 content and low apoptosis level in hippocampal cells subjected to secondary X-rays were observed for the mice exposed to relatively low-LET carbon ions. Therefore, carbon ion exposure in the immature mouse led to an LET-dependent behavioral change after maturation. Although autophagy was intact, the persistently high nuclear Nrf2 content in the hippocampus might account for the unchanged behavioral pattern in mice exposed to the relatively low-LET carbon ions and the subsequent increased radioresistance of the hippocampus.

  12. Long-term no-tillage and organic input management enhanced the diversity and stability of soil microbial community.

    Science.gov (United States)

    Wang, Yi; Li, Chunyue; Tu, Cong; Hoyt, Greg D; DeForest, Jared L; Hu, Shuijin

    2017-12-31

    Intensive tillage and high inputs of chemicals are frequently used in conventional agriculture management, which critically depresses soil properties and causes soil erosion and nonpoint source pollution. Conservation practices, such as no-tillage and organic farming, have potential to enhance soil health. However, the long-term impact of no-tillage and organic practices on soil microbial diversity and community structure has not been fully understood, particularly in humid, warm climate regions such as the southeast USA. We hypothesized that organic inputs will lead to greater microbial diversity and a more stable microbial community, and that the combination of no-tillage and organic inputs will maximize soil microbial diversity. We conducted a long-term experiment in the southern Appalachian mountains of North Carolina, USA to test these hypotheses. The results showed that soil microbial diversity and community structure diverged under different management regimes after long term continuous treatments. Organic input dominated the effect of management practices on soil microbial properties, although no-tillage practice also exerted significant impacts. Both no-tillage and organic inputs significantly promoted soil microbial diversity and community stability. The combination of no-tillage and organic management increased soil microbial diversity over the conventional tillage and led to a microbial community structure more similar to the one in an adjacent grassland. These results indicate that effective management through reducing tillage and increasing organic C inputs can enhance soil microbial diversity and community stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Life’s Critical Role in the Long-term Carbon Cycle: the Biotic Enhancement of Weathering

    Directory of Open Access Journals (Sweden)

    David W. Schwartzman

    2017-06-01

    Full Text Available The biotic enhancement of weathering (BEW has important implications for the long-term carbon cycle, in particular as a driver of climatic cooling. The BEW factor is defined as how much faster the silicate weathering carbon sink is under biotic conditions than under abiotic conditions at the same atmospheric pCO2 level and surface temperature. The BEW factor and its evolution over geological time can potentially be inferred from consideration of empirical and theoretical weathering studies. Estimates of the global magnitude of the BEW are presented, drawing from laboratory, field, watershed data and models of the long-term carbon cycle, with values ranging from one to two orders of magnitude.

  14. Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways.

    Science.gov (United States)

    Huang, Chen; Zhang, Pei; Wang, Wei; Xu, Yongsheng; Wang, Minshu; Chen, Xiaoyong; Dong, Xuran

    2014-06-01

    The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly understood. In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure significantly reduced cell viability in a time-dependent manner and induced apoptosis and necrosis in RGC-5 cells. Long-term blue light exposure marked an increase in the expression of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down-regulation, and displayed features of the mitochondria-dependent apoptosis pathway. Blue light exposure also increased the generation of reactive oxygen species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, blue light exposure constitutively activated p38 mitogen-activated protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the phosphorylation of extracellular signal-regulated kinase in the early phase, in blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was further enhanced after RGC-5 cells were exposed to blue light. Taken together, these findings indicated that blue light induced RGC-5 cell line death in dependence upon exposure duration. The potential mechanisms for this phenomenon might be via activated mitochondria-dependent apoptosis, increased ROS production and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling pathways.

  15. Enhancing AP1000 reactor accident management capabilities for long term accidents

    International Nuclear Information System (INIS)

    Jiang Pingting; Liu Mengying; Duan Chengjie; Liao Yehong

    2015-01-01

    Passive safety actions are considered as main measures under severe accident in AP1000 power plant. However, risk is still existed. According to PSA, several probable scenarios for AP1000 nuclear power plant are analyzed in this paper with MAAP the severe accident analysis code. According to the analysis results, several deficiencies of AP1000 severe accident management are found. The long term cooling and containment depressurization capability for AP1000 power plant appear to be most important factors under such accidents. Then, several temporary strategies for AP1000 power plant are suggested, including PCCWST temporary water supply strategy after 72h, temporary injection strategy for IRWST, hydrogen relief action in fuel building, which would improve the safety of AP1000 power plant. At last, assessments of effectiveness for these strategies are performed, and the results are compared with analysis without these strategies. The comparisons showed that correct actions of these strategies would effectively prevent the accident process of AP1000 power plant. (author)

  16. Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients

    Science.gov (United States)

    Lefebvre, S.; Laloux, P.; Peeters, A.; Desfontaines, P.; Jamart, J.; Vandermeeren, Y.

    2013-01-01

    Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p dual-tDCS (n = 10) than after sham (n = 3). More importantly, 1 week later, online enhancement under dual-tDCS had translated into superior long-term retention (+44%) compared to sham (+4%). The improvement generalized to a new untrained circuit and to digital dexterity. Conclusion: A single-session of dual-tDCS, applied while stroke patients trained with the paretic hand significantly enhanced online motor skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation. PMID:23316151

  17. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

    2007-01-01

    Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...... as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes...

  18. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

    Science.gov (United States)

    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

  19. Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber–Purkinje cell synapses via cannabinoid signaling

    Science.gov (United States)

    Rinaldo, Lorenzo; Hansel, Christian

    2013-01-01

    Muscarinic acetylcholine receptors (mAChRs) are known to modulate synaptic plasticity in various brain areas. A signaling pathway triggered by mAChR activation is the production and release of endocannabinoids that bind to type 1 cannabinoid receptors (CB1R) located on synaptic terminals. Using whole-cell patch-clamp recordings from rat cerebellar slices, we have demonstrated that the muscarinic agonist oxotremorine-m (oxo-m) blocks the induction of presynaptic long-term potentiation (LTP) at parallel fiber (PF)–Purkinje cell synapses in a CB1R-dependent manner. Under control conditions, LTP was induced by delivering 120 PF stimuli at 8 Hz. In contrast, no LTP was observed when oxo-m was present during tetanization. PF-LTP was restored when the CB1R antagonist N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251) was coapplied with oxo-m. Furthermore, the suppressive effect of oxo-m on PF-LTP was abrogated by the GDP analog GDP-β-S (applied intracellularly), the phospholipase C inhibitor U-73122, and the diacylglycerol lipase inhibitor tetrahydrolipstatin (THL), suggesting that cannabinoid synthesis results from the activation of Gq-coupled mAChRs present on Purkinje cells. The oxo-m–mediated suppression of LTP was also prevented in the presence of the M3 receptor antagonist DAU 5884, and was absent in M1/M3 receptor double-KO mice, identifying M3 receptors as primary oxo-m targets. Our findings allow for the possibility that cholinergic signaling in the cerebellum—which may result from long-term depression (LTD)-related disinhibition of cholinergic neurons in the vestibular nuclei—suppresses presynaptic LTP to prevent an up-regulation of transmitter release that opposes the reduction of postsynaptic responsiveness. This modulatory capacity of mAChR signaling could promote the functional penetrance of LTD. PMID:23776234

  20. Signal changes of bone marrow in MRI under long-term treatment with granulocyte colony-stimulating factors

    International Nuclear Information System (INIS)

    Scherer, A.; Engelbrecht, V.; May, P.; Moedder, U.; Neises, G.; Wendel, U.

    2001-01-01

    Purpose: Recurrent infections in patients with glycogen storage disease (GSD) type lb resulting from an associated neutropenia are frequently treated with granulocyte colony-stimulating factors (G-CSF). The aim of this study was to evaluate the changes occurring in bone marrow by magnetic resonance imaging (MRI) in these patients. Material and Methods: The distal femoral and tibial bones of six patients with GSD lb were evaluated by MRI. Four of these patients were treated with G-CSF for at least 3.9 to a maximum of 8.2 years (mean 5.8 years). The imaging sequences encompassed spin-echo as well as short-time inversion recovery sequences. 4 of the 6 patients had bone marrow aspirations. Results: The patients who had undergone therapy with G-CSF showed a marked increase in signal strength in STIR sequences which encompassed the entire medullar cavity. In T 1 -weighted images these areas were hypointense. Biopsies obtained from these patients showed a bone marrow hypercellularity. The patients without G-CSF therapy showed the same signal intensity changes but with a more discrete and localized pattern in the metaphyseal cavities. Conclusion: In subjects with GSD lb, an increased myelopoetic activity of the bone marrow which is intensified under long-term treatment with G-CSF can be demonstrated by MRI. (orig.) [de

  1. Enhanced treatment for depression in primary care : long-term outcomes of a psycho-educational prevention program alone and enriched with psychiatric consultation or cognitive behavioral therapy

    NARCIS (Netherlands)

    Conradi, H.J; De Jonge, P.; Kluiter, H; Smit, A.; Van Der Meer, K.; Jenner, J.A; van Os, T.W.D.P.; Emmelkamp, P.M G; Ormel, J.

    Background. The long-term outcome of major depression is often unfavorable, and because most cases of depression are managed by general practitioners (GPs), this places stress on the need to improve treatment in primary care. This study evaluated the long-term effects of enhancing the GP's usual

  2. Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

    Science.gov (United States)

    Murayama, Kou; Kitagami, Shinji

    2014-02-01

    Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

  3. Post-learning stress enhances long-term memory and differentially influences memory in females depending on menstrual stage.

    Science.gov (United States)

    Zoladz, Phillip R; Peters, David M; Cadle, Chelsea E; Kalchik, Andrea E; Aufdenkampe, Rachael L; Dailey, Alison M; Brown, Callie M; Scharf, Amanda R; Earley, McKenna B; Knippen, Courtney L; Rorabaugh, Boyd R

    2015-09-01

    Most work has shown that post-learning stress enhances long-term memory; however, there have been recent inconsistencies in this literature. The purpose of the present study was to examine further the effects of post-learning stress on long-term memory and to explore any sex differences that may exist. Male and female participants learned a list of 42 words that varied in emotional valence and arousal level. Following encoding, participants completed a free recall assessment and then submerged their hand into a bath of ice cold (stress) or lukewarm (no stress) water for 3 min. The next day, participants were given free recall and recognition tests. Stressed participants recalled more words than non-stressed participants 24h after learning. Stress also enhanced female participants' recall of arousing words when they were in the follicular, but not luteal, phase. These findings replicate previous work examining post-learning stress effects on memory and implicate the involvement of sex-related hormones in such effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

    Science.gov (United States)

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-02-23

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

  5. Enhancing long-term photostability of BiVO4 photoanodes for solar water splitting by tuning electrolyte composition

    Science.gov (United States)

    Lee, Dong Ki; Choi, Kyoung-Shin

    2018-01-01

    As the performance of photoelectrodes used for solar water splitting continues to improve, enhancing the long-term stability of the photoelectrodes becomes an increasingly crucial issue. In this study, we report that tuning the composition of the electrolyte can be used as a strategy to suppress photocorrosion during solar water splitting. Anodic photocorrosion of BiVO4 photoanodes involves the loss of V5+ from the BiVO4 lattice by dissolution. We demonstrate that the use of a V5+-saturated electrolyte, which inhibits the photooxidation-coupled dissolution of BiVO4, can serve as a simple yet effective method to suppress anodic photocorrosion of BiVO4. The V5+ species in the solution can also incorporate into the FeOOH/NiOOH oxygen-evolution catalyst layer present on the BiVO4 surface during water oxidation, further enhancing water-oxidation kinetics. The effect of the V5+ species in the electrolyte on both the long-term photostability of BiVO4 and the performance of the FeOOH/NiOOH oxygen-evolution catalyst layer is systematically elucidated.

  6. Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex

    Science.gov (United States)

    Chestek, Cynthia A.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Fan, Joline M.; Kaufman, Matthew T.; Churchland, Mark M.; Rivera-Alvidrez, Zuley; Cunningham, John P.; Ryu, Stephen I.; Shenoy, Krishna V.

    2011-08-01

    Cortically-controlled prosthetic systems aim to help disabled patients by translating neural signals from the brain into control signals for guiding prosthetic devices. Recent reports have demonstrated reasonably high levels of performance and control of computer cursors and prosthetic limbs, but to achieve true clinical viability, the long-term operation of these systems must be better understood. In particular, the quality and stability of the electrically-recorded neural signals require further characterization. Here, we quantify action potential changes and offline neural decoder performance over 382 days of recording from four intracortical arrays in three animals. Action potential amplitude decreased by 2.4% per month on average over the course of 9.4, 10.4, and 31.7 months in three animals. During most time periods, decoder performance was not well correlated with action potential amplitude (p > 0.05 for three of four arrays). In two arrays from one animal, action potential amplitude declined by an average of 37% over the first 2 months after implant. However, when using simple threshold-crossing events rather than well-isolated action potentials, no corresponding performance loss was observed during this time using an offline decoder. One of these arrays was effectively used for online prosthetic experiments over the following year. Substantial short-term variations in waveforms were quantified using a wireless system for contiguous recording in one animal, and compared within and between days for all three animals. Overall, this study suggests that action potential amplitude declines more slowly than previously supposed, and performance can be maintained over the course of multiple years when decoding from threshold-crossing events rather than isolated action potentials. This suggests that neural prosthetic systems may provide high performance over multiple years in human clinical trials.

  7. Microencapsulation of Ascorbic Acid for Enhanced Long-term Retention during Storage

    Science.gov (United States)

    2011-01-01

    of encapsulating agents—F30 + Instant 449, F30 + Instant MAPS, Hi Cap 100, F30 + GA + Hi Maize , F17 + Instant 449 and F30 + GA (combinations 5, 8...11, 6, 2 and 4 respectively)—warrant further evaluation. 8. Hi Maize appears to enhance the protective effect in the combinations studied. 9. The...foods is restricted or in cases of increased requirements for nutrients. AA has been used for fortification of food aid commodities (Food and

  8. Modelling and forecasting long-term dynamics of Western Baltic macrobenthic fauna in relation to climate signals and environmental change

    Science.gov (United States)

    Gröger, Joachim; Rumohr, Heye

    2006-05-01

    Long-term macrobenthos data from Kiel Bight in the Western Baltic collected between 1968 and 2000 have been correlated with the winter NAO index (North Atlantic Oscillation Index) and other environmental data such as temperature, salinity and oxygen content in the bottom water in order to detect systematic patterns related to so far unexplained abiotic signals in the dynamics of zoobenthic species assemblages. The benthos data come from a cluster of five stations (Süderfahrt/ Millionenviertel) in Kiel Bay. Our investigations concentrated on the macrobenthic dynamics with a focus on the number of species m - 2 (species richness). Using logarithms and the time series analysis approach of Box/Jenkins (ARIMA modelling, transfer function modelling) it was shown that species richness was strongly influenced by the winter NAO (adjusted for a linear time trend within the 1968-2000 period) and salinity (with a shift/lag of four years). Bootstrapping experiments (i.e. sampling from the error process) and analysis of prediction power (by means of the one- or more-years leaving-out method) showed that the parameter estimates behaved in a stable way, leading to a relatively robust model.

  9. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-08-01

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events. © 2017 Wiley Periodicals, Inc.

  10. Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism.

    Science.gov (United States)

    Silva, Guilherme Testa; Le Bé, Jean-Vincent; Riachi, Imad; Rinaldi, Tania; Markram, Kamila; Markram, Henry

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (brain slices (PN 12-15), mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100 μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.

  11. Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models

    Science.gov (United States)

    Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Joseph; Rosenfelt, Cory; Gertner, Michael J.; Campbell, Sean R.; Emerson, Danielle; Hinchey, Paul; Kollaros, Maria; Ferrick, Neal J.; Chambers, Daniel B.; Langer, Steven; Sust, Steven; Malik, Aatika; Terlizzi, Allison M.; Liebelt, David A.; Ferreiro, David; Sharma, Ali; Koenigsberg, Eric; Choi, Richard J.; Louneva, Natalia; Arnold, Steven E.; Featherstone, Robert E.; Siegel, Steven J.; Zukin, R. Suzanne; McDonald, Thomas V.; Bolduc, Francois V.; Jongens, Thomas A.; McBride, Sean M. J.

    2016-01-01

    Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model. PMID:27445731

  12. Sustained photosynthetic performance of Coffea spp. under long-term enhanced [CO2].

    Science.gov (United States)

    Ramalho, José C; Rodrigues, Ana P; Semedo, José N; Pais, Isabel P; Martins, Lima D; Simões-Costa, Maria C; Leitão, António E; Fortunato, Ana S; Batista-Santos, Paula; Palos, Isabel M; Tomaz, Marcelo A; Scotti-Campos, Paula; Lidon, Fernando C; DaMatta, Fábio M

    2013-01-01

    Coffee is one of the world's most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m(-2) s(-1)), RH (75%) and 380 or 700 μL CO2 L(-1) for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49%) when measured at 700 than at 380 μL CO2 L(-1). This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory) components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down-regulation was found, our

  13. Sustained photosynthetic performance of Coffea spp. under long-term enhanced [CO2].

    Directory of Open Access Journals (Sweden)

    José C Ramalho

    Full Text Available Coffee is one of the world's most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m(-2 s(-1, RH (75% and 380 or 700 μL CO2 L(-1 for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49% when measured at 700 than at 380 μL CO2 L(-1. This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down

  14. Sustained Photosynthetic Performance of Coffea spp. under Long-Term Enhanced [CO2

    Science.gov (United States)

    Ramalho, José C.; Rodrigues, Ana P.; Semedo, José N.; Pais, Isabel P.; Martins, Lima D.; Simões-Costa, Maria C.; Leitão, António E.; Fortunato, Ana S.; Batista-Santos, Paula; Palos, Isabel M.; Tomaz, Marcelo A.; Scotti-Campos, Paula; Lidon, Fernando C.; DaMatta, Fábio M.

    2013-01-01

    Coffee is one of the world’s most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m-2 s-1), RH (75%) and 380 or 700 μL CO2 L-1 for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49%) when measured at 700 than at 380 μL CO2 L-1. This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory) components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down-regulation was found, our data

  15. Startup and long term operation of enhanced biological phosphorus removal in continuous-flow reactor with granules.

    Science.gov (United States)

    Li, Dong; Lv, Yufeng; Zeng, Huiping; Zhang, Jie

    2016-07-01

    The startup and long term operation of enhanced biological phosphorus removal (EBPR) in a continuous-flow reactor (CFR) with granules were investigated in this study. Through reducing the settling time from 9min to 3min gradually, the startup of EBPR in a CFR with granules was successfully realized in 16days. Under continuous-flow operation, the granules with good phosphorus and COD removal performance were stably operated for more than 6months. And the granules were characterized with particle size of around 960μm, loose structure and good settling ability. During the startup phase, polysaccharides (PS) was secreted excessively by microorganisms to resist the influence from the variation of operational mode. Results of relative quantitative PCR indicated that granules dominated by polyphosphate-accumulating organisms (PAOs) were easier accumulated in the CFR because more excellent settling ability was needed in the system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. High signal in the adenohypophysis on T1-weighted images presumably due to manganese deposits in patients on long-term parenteral nutrition

    International Nuclear Information System (INIS)

    Dietemann, J.L.; Diniz, R.L.F.C.; Reis, M. Jr.; Neugroschl, C.; Soehsten, S. von; Reimund, J.M.; Baumann, R.; Warter, J.M.

    1998-01-01

    Hypermanganesaemia is reported in patients on long-term parenteral nutrition. Deposition of manganese, giving high signal on T1-weighted images, may involve the basal ganglia. MRI in nine patients (mean age 51 years, range 31-75 years) on long-term parenteral nutrition (mean duration 30 months, range 6-126 months), demonstrated high signal in the anterior pituitary gland on T1-weighted sagittal and coronal images. The gland appeared normal on T2-weighted images. Signal intensity in the basal ganglia on T1-weighted images was increased in all patients. Endocrine assessment showed no significant abnormality. Neurological examination showed a mild parkinsonian movement disorder in one patient. Hypermanganaesemia was present in all nine (1.3-2.8 μmol/l, mean 1.87 μmol/l). The high signal in the anterior pituitary gland was probably related to deposition of paramagnetic substances, especially manganese. (orig.)

  17. Intermediate and Long-term Outcomes of Mitomycin C-enhanced Trabeculectomy as a First Glaucoma Procedure in Uveitic Glaucoma.

    Science.gov (United States)

    Almobarak, Faisal A; Alharbi, Ali H; Morales, Jose; Aljadaan, Ibrahim

    2017-05-01

    To evaluate the intermediate and long-term outcomes of mitomycin C-enhanced trabeculectomy as a first glaucoma procedure in uveitic glaucoma. Retrospective cohort study included 70 eyes of 50 patients with uveitic glaucoma who underwent mitomycin C-enhanced trabeculectomy as a first glaucoma procedure at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between 1996 and 2014. The main outcome measures were: the intraocular pressure (IOP), the number of antiglaucoma medications, the presence of visually threatening complications, and the need for further surgeries to control the IOP. Surgical outcome of each eye was classified as an absolute success, qualified success, or failure, based on the main outcome measures. The mean follow-up period was 77.0 months (±40.9). The IOP and number of antiglaucoma medications decreased significantly from a mean of 39.5 mm Hg (±8.9) and 3.7 (±0.8) to 14.4 mm Hg (±6.9) and 1 (±1.3) at the last follow-up, respectively (Pglaucoma, a significant number of patients needed further procedures to control the pressure. Thus, continuous monitoring of the pressure and inflammation are crucial.

  18. Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala.

    Science.gov (United States)

    Suvrathan, Aparna; Bennur, Sharath; Ghosh, Supriya; Tomar, Anupratap; Anilkumar, Shobha; Chattarji, Sumantra

    2014-01-05

    Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of 'silent synapses', containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

  19. Long-term motor improvement after stroke is enhanced by short-term treatment with the alpha-2 antagonist, atipamezole.

    Science.gov (United States)

    Beltran, Erik J; Papadopoulos, Catherine M; Tsai, Shih-Yen; Kartje, Gwendolyn L; Wolf, William A

    2010-07-30

    Drugs that increase central noradrenergic activity have been shown to enhance the rate of recovery of motor function in pre-clinical models of brain damage. Less is known about whether noradrenergic agents can improve the extent of motor recovery and whether such improvement can be sustained over time. This study was designed to determine if increasing central noradrenergic tone using atipamezole, an alpha-2 adrenoceptor antagonist, could induce a long-term improvement in motor performance in rats subjected to ischemic brain damage caused by permanent middle cerebral artery occlusion. The importance of pairing physical "rehabilitation" with enhanced noradrenergic activity was also investigated. Atipamezole (1 mg/kg, s.c.) or vehicle (sterile saline) was administered once daily on Days 2-8 post-operatively. Half of each drug group was housed under enriched environment conditions supplemented with daily focused activity sessions while the other half received standard housing with no focused activity. Skilled motor performance in forelimb reaching and ladder rung walking was assessed for 8 weeks post-operatively. Animals receiving atipamezole plus rehabilitation exhibited significantly greater motor improvement in both behavioral tests as compared to vehicle-treated animals receiving rehabilitation. Interestingly, animals receiving atipamezole without rehabilitation exhibited a significant motor improvement in the ladder rung walk test but not the forelimb reaching test. These results suggest that a short-term increase in noradrenergic activity can lead to sustained motor improvement following stroke, especially when paired with rehabilitation. Published by Elsevier B.V.

  20. PKA-CREB-BDNF signaling pathway mediates propofol-induced long-term learning and memory impairment in hippocampus of rats.

    Science.gov (United States)

    Zhong, Yu; Chen, Jing; Li, Li; Qin, Yi; Wei, Yi; Pan, Shining; Jiang, Yage; Chen, Jialin; Xie, Yubo

    2018-04-20

    Studies have found that propofol can induce widespread neuroapoptosis in developing brains, which leads to cause long-term learning and memory abnormalities. However, the specific cellular and molecular mechanisms underlying propofol-induced neuroapoptosis remain elusive. The aim of the present study was to explore the role of PKA-CREB-BDNF signaling pathway in propofol-induced long-term learning and memory impairment during brain development. Seven-day-old rats were randomly assigned to control, intralipid and three treatment groups (n = 5). Rats in control group received no treatment. Intralipid (10%, 10 mL/kg) for vehicle control and different dosage of propofol for three treatment groups (50, 100 and 200 mg/kg) were administered intraperitoneally. FJB staining, immunohistochemistry analysis for neuronal nuclei antigen and transmission electron microscopy were used to detect neuronal apoptosis and structure changes. MWM test examines the long-term spatial learning and memory impairment. The expression of PKA, pCREB and BDNF was quantified using western blots. Propofol induced significant increase of FJB-positive cells and decrease of PKA, pCREB and BDNF protein levels in the immature brain of P7 rats. Using the MWM test, propofol-treated rats demonstrated long-term spatial learning and memory impairment. Moreover, hippocampal NeuN-positive cell loss, long-lasting ultrastructural abnormalities of the neurons and synapses, and long-term down-regulation of PKA, pCREB and BDNF protein expression in adult hippocampus were also found. Our results indicated that neonatal propofol exposure can significantly result in long-term learning and memory impairment in adulthood. The possible mechanism involved in the propofol-induced neuroapoptosis was related to down-regulation of PKA-CREB-BDNF signaling pathway. Copyright © 2018. Published by Elsevier B.V.

  1. Parametrisation of the orographic enhancement of precipitation and deposition in a long-term, long-range transport model

    Directory of Open Access Journals (Sweden)

    D. S. Lee

    Full Text Available Orographic enhancement of wet deposition arising from the 'seeder-feeder' effect is, by necessity, highly parametrised in long-range transport models of acid deposition that are long-term (i.e. annual average and spatially resolved at tens of kilometres. Here, we describe a mechanistic approach to the incorporation of these mechanisms into such a model. The model formulation required the following: precipitation rate by direction and quantification of the fractions that are orographic and non-orographic; treatment of the fast oxidation of sulfur dioxide in clouds; the directionality of the seeder-feeder process; and a quantitative basis for increasing wet deposition factors to account for the seeder-feeder process. The directionality of non-orographic precipitation was determined from meteorological data at 47 sites across the UK. Orographic precipitation varies on a much finer scale than can be interpolated from measurements, and thus a modelling approach was adopted. The directionality of the seeder-feeder effect was taken from measurements. The enhancement factor of the orographic component of precipitation, assumed to represent feeder-rain, was determined from a review of measurements. Fast oxidation of sulfur dioxide is an observed phenomenon in cap-cloud, but limited in duration. An adjustment was made to the sulfur dioxide oxidation rate in the model in locations where cap-cloud was assumed to be present. The results from the model were compared with UK deposition budgets and enhanced wet deposition maps. The revised parametrisation underestimated the UK wet deposition budgets of oxidised N and S, but spatial patterns of deposition were improved for much of the UK. It was concluded that this was a satisfactory outcome given the constraints of the statistical approach of weighting of deposition at receptors utilising straight line trajectories. The sensitivity of the model to directional constraints of seeder-feeder enhancement

  2. Parametrisation of the orographic enhancement of precipitation and deposition in a long-term, long-range transport model

    Directory of Open Access Journals (Sweden)

    D. S. Lee

    2000-11-01

    Full Text Available Orographic enhancement of wet deposition arising from the 'seeder-feeder' effect is, by necessity, highly parametrised in long-range transport models of acid deposition that are long-term (i.e. annual average and spatially resolved at tens of kilometres. Here, we describe a mechanistic approach to the incorporation of these mechanisms into such a model. The model formulation required the following: precipitation rate by direction and quantification of the fractions that are orographic and non-orographic; treatment of the fast oxidation of sulfur dioxide in clouds; the directionality of the seeder-feeder process; and a quantitative basis for increasing wet deposition factors to account for the seeder-feeder process. The directionality of non-orographic precipitation was determined from meteorological data at 47 sites across the UK. Orographic precipitation varies on a much finer scale than can be interpolated from measurements, and thus a modelling approach was adopted. The directionality of the seeder-feeder effect was taken from measurements. The enhancement factor of the orographic component of precipitation, assumed to represent feeder-rain, was determined from a review of measurements. Fast oxidation of sulfur dioxide is an observed phenomenon in cap-cloud, but limited in duration. An adjustment was made to the sulfur dioxide oxidation rate in the model in locations where cap-cloud was assumed to be present. The results from the model were compared with UK deposition budgets and enhanced wet deposition maps. The revised parametrisation underestimated the UK wet deposition budgets of oxidised N and S, but spatial patterns of deposition were improved for much of the UK. It was concluded that this was a satisfactory outcome given the constraints of the statistical approach of weighting of deposition at receptors utilising straight line trajectories. The sensitivity of the model to directional constraints of seeder-feeder enhancement was tested

  3. Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats.

    Science.gov (United States)

    Rashidy-Pour, Ali; Vafaei, Abbas Ali; Taherian, Abbas Ali; Miladi-Gorji, Hossein; Sadeghi, Hassan; Fathollahi, Yaghoub; Bandegi, Ahmad Reza

    2009-10-12

    This study was designed to investigate an interaction between acute restraint stress and corticosterone with verapamil, a blocker of L-type voltage-dependent calcium (VDC) channels on retrieval of long-term memory. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On retention test given 48 h after training, the latency to re-enter dark compartment of the apparatus was recorded. In Experiment 1, verapamil pretreatment (5, 10, or 20 mg/kg) enhanced the impairing effects of acute stress (which was applied for 10 min in a Plexiglass tube 30 min before the retention test) on memory retrieval. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress-induced impairment of memory retrieval is mediated, in part, by increased plasma levels of glucocorticoids. Verapamil did not change this response. In Experiment 2, pretreatment of an intermediate dose of verapamil also enhanced corticosterone-induced impairment of memory retrieval. In Experiments 3 and 4, acute stress or corticosterone did not change motor activity with or without prior treatment of verapamil, suggesting that stress or glucocorticoid-induced impairment of memory retrieval is not due to any gross disturbances in motor performance of animals. These findings indicate that blockade of L-type VDC channels enhances stress or glucocorticoid-induced impairment of memory retrieval, and provide evidence for the existence of an interaction between glucocorticoids and L-type VDC channels on memory retrieval.

  4. Long Term Care

    Science.gov (United States)

    ... us! Living with HD Long-Term Care Long Term Care Click here to download Long-Term Care for HD, (part of HDSA’s Family Guide ... on patient and family issues related to long-term HD care. For many caregivers of people with ...

  5. Wellbeing-enhancing occupation and organizational and environmental contributors in long-term dementia care facilities: an explorative study

    NARCIS (Netherlands)

    Smit, D.; Willemse, B.M.; de Lange, J.; Pot, A.M.

    2014-01-01

    ABSTRACT Background: Occupation remains an unmet need in long-term dementia care. To increase residents' occupation, knowledge of types of occupation related to wellbeing, and organizational and environmental characteristics encouraging involvement in these types of occupation, is indispensable.

  6. 76 FR 71560 - Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate...

    Science.gov (United States)

    2011-11-18

    ...The Environmental Protection Agency (EPA) is hosting a public meeting on December 7, 2011, to discuss the analytical methods for Cryptosporidium and the source water monitoring data from the Long Term 2 Enhanced Surface Water Treatment Rule (LT2 rule). This is the first of at least two meetings on the LT2 rule that EPA will host. At the December meeting, EPA will present its evaluation of the LT2 rule Cryptosporidium source water monitoring data, new information on the performance of Method 1623, as well as the latest information on Method 1623 improvements. A public meeting on the LT2 rule uncovered finished water reservoir requirement will occur in Spring 2012. Matters related to the uncovered finished water reservoir requirement will not be discussed at the December 7, 2011, meeting. The information discussed in these meetings is part of the review of the LT2 rule under the Six Year Review process announced as part of EPA's Retrospective Review Plan under Executive Order (E.O.) 13563 in August 2011. The LT2 rule requires a second round of Cryptosporidium monitoring, which is scheduled to start in 2015. The Stage 2 Microbial and Disinfection Byproducts (M/DBP) Federal Advisory Committee (FAC) recommended that EPA hold a public meeting on these issues prior to the second round of monitoring. Date and Location: The public meeting will be held on Wednesday, December 7, 2011, (8:30 a.m. to 5 p.m., Eastern Time), at the EPA East Building, Room 1153, 1201 Constitution Avenue NW., Washington, DC 20460. A separate Federal Register notice will be published to provide information on the date and location of the 2012 public meeting focused on the LT2 uncovered finished water reservoir requirement.

  7. Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus.

    Science.gov (United States)

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alkadhi, Karim A

    2010-04-01

    We have previously reported that caffeine prevented sleep deprivation-induced impairment of long-term potentiation (LTP) of area CA1 as well as hippocampus-dependent learning and memory performance in the radial arm water maze. In this report we examined the impact of long-term (4-week) caffeine consumption (0.3 g/L in drinking water) on synaptic plasticity (Alhaider et al., 2010) deficit in the dentate gyrus (DG) area of acutely sleep-deprived rats. The sleep deprivation and caffeine/sleep deprivation groups were sleep-deprived for 24 h by using the columns-in-water technique. We tested the effect of caffeine and/or sleep deprivation on LTP and measured the basal levels as well as stimulated levels of LTP-related molecules in the DG. The results showed that chronic caffeine administration prevented the impairment of early-phase LTP (E-LTP) in the DG of sleep-deprived rats. Additionally, chronic caffeine treatment prevented the sleep deprivation-associated decreases in the basal levels of the phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) and brain derived neurotrophic factor (BDNF) as well as in the stimulated levels of P-CaMKII in the DG area. The results suggest that chronic use of caffeine prevented anomalous changes in the basal levels of P-CaMKII and BDNF associated with sleep deprivation and as a result contributes to the revival of LTP in the DG region.

  8. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Cheng-Chia [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China); School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chang, Yu-Chao, E-mail: cyc@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2013-02-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  9. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    International Nuclear Information System (INIS)

    Yu, Cheng-Chia; Chang, Yu-Chao

    2013-01-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  10. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chang

    Full Text Available Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2 on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estrogen, and using these cells the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased sensitivities of doxorubicin and cisplatin in estrogen-exposed MCF-7 and T47D cells as compared to their respective control cells. Gene expression analysis of cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-aza-2-deoxycytidine and Trichostatin A prior to doxorubicin and cisplatin treatments. The 5-aza-2 deoxycytidine pre-treatment significantly decreased the estrogen-induced efficacy of doxorubicin and cisplatin, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In summary, the results of this study revealed that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the chemotherapy strategies for

  11. Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex.

    Science.gov (United States)

    Chavez, Candice M; McGaugh, James L; Weinberger, Norman M

    2013-03-01

    The basolateral amygdala (BLA) modulates memory, particularly for arousing or emotional events, during post-training periods of consolidation. It strengthens memories whose substrates in part or whole are stored remotely, in structures such as the hippocampus, striatum and cerebral cortex. However, the mechanisms by which the BLA influences distant memory traces are unknown, largely because of the need for identifiable target mnemonic representations. Associative tuning plasticity in the primary auditory cortex (A1) constitutes a well-characterized candidate specific memory substrate that is ubiquitous across species, tasks and motivational states. When tone predicts reinforcement, the tuning of cells in A1 shifts toward or to the signal frequency within its tonotopic map, producing an over-representation of behaviorally important sounds. Tuning shifts have the cardinal attributes of forms of memory, including associativity, specificity, rapid induction, consolidation and long-term retention and are therefore likely memory representations. We hypothesized that the BLA strengthens memories by increasing their cortical representations. We recorded multiple unit activity from A1 of rats that received a single discrimination training session in which two tones (2.0 s) separated by 1.25 octaves were either paired with brief electrical stimulation (400 ms) of the BLA (CS+) or not (CS-). Frequency response areas generated by presenting a matrix of test tones (0.5-53.82 kHz, 0-70 dB) were obtained before training and daily for 3 weeks post-training. Tuning both at threshold and above threshold shifted predominantly toward the CS+ beginning on day 1. Tuning shifts were maintained for the entire 3 weeks. Absolute threshold and bandwidth decreased, producing less enduring increases in sensitivity and selectivity. BLA-induced tuning shifts were associative, highly specific and long-lasting. We propose that the BLA strengthens memory for important experiences by increasing the

  12. Therapist-Assisted, Self-Administered Bibliotherapy to Enhance Parental Competence: Short- and Long-Term Effects

    Science.gov (United States)

    Hahlweg, Kurt; Heinrichs, Nina; Kuschel, Annett; Feldmann, Marit

    2008-01-01

    The efficacy of bibliotherapy has primarily been investigated in anxiety disorders, depression, or substance dependence. The efficacy of self-help books to increase parenting competence was only investigated in a few studies despite their broad dissemination in public. The aims of the study were to investigate the short- and long-term efficacy of…

  13. Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach.

    Science.gov (United States)

    Zeanandin, Gilbert; Balage, Michèle; Schneider, Stéphane M; Dupont, Joëlle; Hébuterne, Xavier; Mothe-Satney, Isabelle; Dardevet, Dominique

    2012-04-01

    Leucine acts as a signal nutrient in promoting protein synthesis in skeletal muscle and adipose tissue via mTOR pathway activation, and may be of interest in age-related sarcopenia. However, hyper-activation of mTOR/S6K1 has been suggested to inhibit the first steps of insulin signaling and finally promote insulin resistance. The impact of long-term dietary leucine supplementation on insulin signaling and sensitivity was investigated in old rats (18 months old) fed a 15% protein diet supplemented (LEU group) or not (C group) with 4.5% leucine for 6 months. The resulting effects on muscle and fat were examined. mTOR/S6K1 signaling pathway was not significantly altered in muscle from old rats subjected to long-term dietary leucine excess, whereas it was increased in adipose tissue. Overall glucose tolerance was not changed but insulin-stimulated glucose transport was improved in muscles from leucine-supplemented rats related to improvement in Akt expression and phosphorylation in response to food intake. No change in skeletal muscle mass was observed, whereas perirenal adipose tissue mass accumulated (+45%) in leucine-supplemented rats. A prolonged leucine supplementation in old rats differently modulates mTOR/S6K pathways in muscle and adipose tissue. It does not increase muscle mass but seems to promote hypertrophy and hyperplasia of adipose tissue that did not result in insulin resistance.

  14. Semantic congruency but not temporal synchrony enhances long-term memory performance for audio-visual scenes.

    Science.gov (United States)

    Meyerhoff, Hauke S; Huff, Markus

    2016-04-01

    Human long-term memory for visual objects and scenes is tremendous. Here, we test how auditory information contributes to long-term memory performance for realistic scenes. In a total of six experiments, we manipulated the presentation modality (auditory, visual, audio-visual) as well as semantic congruency and temporal synchrony between auditory and visual information of brief filmic clips. Our results show that audio-visual clips generally elicit more accurate memory performance than unimodal clips. This advantage even increases with congruent visual and auditory information. However, violations of audio-visual synchrony hardly have any influence on memory performance. Memory performance remained intact even with a sequential presentation of auditory and visual information, but finally declined when the matching tracks of one scene were presented separately with intervening tracks during learning. With respect to memory performance, our results therefore show that audio-visual integration is sensitive to semantic congruency but remarkably robust against asymmetries between different modalities.

  15. Using corporate governance to enhance 'long-term situation awareness' and assist in the avoidance of organisation-induced disasters.

    Science.gov (United States)

    Siemieniuch, C E; Sinclair, M A

    2008-03-01

    This paper considers the issue of how corporate governance can and should deal with the long-term understanding of systems health-what we may call 'long-term situation awareness' (i.e. which evolves and is coherent over time) for organisational systems (and their component sub systems) in the engineering domain. Many characteristics affect long-term situation awareness-the rate of change to processes, pressures for greater efficiency from existing resources, changes in personnel, cultural changes and changes to the operational environment of the organisational systems. Many disasters (e.g. Chernobyl, Flixborough, Piper Alpha) have a causal path that indicates a loss of group situation awareness, over a long period of time. The problem of the gradual, slow drift over many years towards unsafe conduct of company operations is discussed and examples of possible consequences provided. A 'parable' from the world of manufacturing is used to exemplify the problem. The paper goes on to discuss some ways by which this problem could be addressed and longer-term system situational awareness increased; essentially by good corporate governance, knowledge management and ownership of processes. Links are made to the literature on these topics, and a route map to help organisations to gain the benefits is offered.

  16. Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training.

    Science.gov (United States)

    Roberts, Llion A; Raastad, Truls; Markworth, James F; Figueiredo, Vandre C; Egner, Ingrid M; Shield, Anthony; Cameron-Smith, David; Coombes, Jeff S; Peake, Jonathan M

    2015-09-15

    We investigated functional, morphological and molecular adaptations to strength training exercise and cold water immersion (CWI) through two separate studies. In one study, 21 physically active men strength trained for 12 weeks (2 days per week), with either 10 min of CWI or active recovery (ACT) after each training session. Strength and muscle mass increased more in the ACT group than in the CWI group (P work (19%), type II muscle fibre cross-sectional area (17%) and the number of myonuclei per fibre (26%) increased in the ACT group (all P < 0.05), but not the CWI group. In another study, nine active men performed a bout of single-leg strength exercises on separate days, followed by CWI or ACT. Muscle biopsies were collected before and 2, 24 and 48 h after exercise. The number of satellite cells expressing neural cell adhesion molecule (NCAM) (10-30%) and paired box protein (Pax7) (20-50%) increased 24-48 h after exercise with ACT. The number of NCAM(+) satellite cells increased 48 h after exercise with CWI. NCAM(+) - and Pax7(+) -positive satellite cell numbers were greater after ACT than after CWI (P < 0.05). Phosphorylation of p70S6 kinase(Thr421/Ser424) increased after exercise in both conditions but was greater after ACT (P < 0.05). These data suggest that CWI attenuates the acute changes in satellite cell numbers and activity of kinases that regulate muscle hypertrophy, which may translate to smaller long-term training gains in muscle strength and hypertrophy. The use of CWI as a regular post-exercise recovery strategy should be reconsidered. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  17. Are changes in the mean or variability of climate signals more important for long-term stochastic growth rate?

    Directory of Open Access Journals (Sweden)

    Bernardo García-Carreras

    Full Text Available Population dynamics are affected by changes in both the mean and standard deviation of climate, e.g., changes in average temperature are likely to affect populations, but so are changes in the strength of year-to-year temperature variability. The impacts of increases in average temperature are extensively researched, while the impacts of changes in climate variability are less studied. Is the greater attention given to changes in mean environment justified? To help answer this question we developed a simple population model, explicitly linked to an environmental process. We used the model to compare the sensitivities of a population's long-term stochastic growth rate, a measure of fitness, to changes in the mean and standard deviation of the environment. Results are interpreted in light of a comparative analysis of the relative magnitudes of change in means and standard deviations of biologically relevant climate variables in the United States. Results show that changes in the variability of the environment can be more important for many populations. Changes in mean conditions are likely to have a greater impact than changes in variability on populations far from their ideal environment, for example, populations near species range boundaries and potentially of conservation concern. Populations near range centres and close to their ideal environment are more likely to be affected by changes in variability. Among pest and insect disease vectors, as well as species of commercial value, populations likely to be of greatest economic and public health significance are those near species range centers, living in a near-ideal environment for the species. Observed changes in the variability of climate variables may benefit these populations.

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

    Directory of Open Access Journals (Sweden)

    Thomas Simon

    2012-01-01

    Full Text Available 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.

  19. 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.

  20. Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Lian-Feng Zhang

    2013-03-01

    Full Text Available The Amyloid-β (Aβ-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer's disease (AD in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day groups, or an Aricept (2 mg/kg body weight/day group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.

  1. Long-Term In Vitro Expansion of Salivary Gland Stem Cells Driven by Wnt Signals

    DEFF Research Database (Denmark)

    Maimets, Martti; Rocchi, Cecilia; Bron, Reinier

    2016-01-01

    Adult stem cells are the ultimate source for replenishment of salivary gland (SG) tissue. Self-renewal ability of stem cells is dependent on extrinsic niche signals that have not been unraveled for the SG. The ductal compartment in SG has been identified as the location harboring stem cells. Here...

  2. Long-term efficacy of methylphenidate in enhancing attention regulation, social skills, and academic abilities of childhood cancer survivors.

    Science.gov (United States)

    Conklin, Heather M; Reddick, Wilburn E; Ashford, Jason; Ogg, Susan; Howard, Scott C; Morris, E Brannon; Brown, Ronald; Bonner, Melanie; Christensen, Robbin; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

    2010-10-10

    Methylphenidate (MPH) ameliorates attention problems experienced by some cancer survivors in the short term, but its long-term efficacy is unproven. This study investigates the long-term effectiveness of maintenance doses of MPH in survivors of childhood brain tumors (n = 35) and acute lymphoblastic leukemia (n = 33) participating in a 12-month MPH trial. Measures of attention (Conners' Continuous Performance Test [CPT], Conners' Rating Scales [CRS]), academic abilities (Wechsler Individual Achievement Test [WIAT]), social skills (Social Skills Rating System [SSRS]), and behavioral problems (Child Behavior Checklist [CBCL]) were administered at premedication baseline and at the end of the MPH trial while on medication. A cancer control group composed of patients who were not administered MPH (brain tumor = 31 and acute lymphoblastic leukemia = 23) was assessed on the same measures 12 [corrected] months apart. For the MPH group, repeated measures analysis of variance revealed significant improvement in performance on a measure of sustained attention (CPT indices, P attention (CRS indices, P attention (Conners' Parent Rating Scale indices; P academic measure (WIAT) in either group. Attention and behavioral benefits of MPH for childhood cancer survivors are maintained across settings over the course of a year. Although academic gains were not identified, MPH may offer benefits in academic areas not assessed.

  3. Separating long-term deformation cycles and atmospheric signals at Mount St. Helens using PS-InSAR

    Science.gov (United States)

    Welch, M.

    2015-12-01

    Since its eruption in 1980, Mount St. Helens has experienced multiple inflation-deflation cycles associated with dome building eruptions. During the most recent dome-building episode, which spanned 2004 to 2008, GPS recorded the transition from pre-eruptive inflation to co-eruptive deflation and a final transition back to inflation. Such observations provide important constraints on the timing and mechanics of cyclic magma recharge and extrusion. Currently, the subtle surface deformation signal at St Helens is monitored primarily by ground based geodetic techniques like GPS. Satellite-based InSAR has the potential to substantially augment these techniques by providing spatially continuous, precise measurements of surface displacements, and may also reveal other volcanic or surficial processes too localized to be detected by ground based methods. Traditional interferometry is challenging to apply to volcanoes in the Cascades. Widespread phase decorrelation caused by persistent snow cover and dense vegetation, combined with large, elevation dependent atmospheric phase delays, mask or make deformation signals difficult to detect. By applying StaMPS, a Persistent Scatterers (PS) technique, phase decorrelation is mitigated by utilizing only the pixels with the highest, statistically derived, signal to noise ratio. However, atmospheric water vapor, which delays the radar signal, remains problematic, particularly on the volcano edifice. To assess the bias imposed by the atmosphere, we perform a series of sensitivity tests using a suite of methods including several that rely on the linear or power-law correlation of phase delay to topography and knowledge of the spatial scale of the signal. We also apply methods that calculate wet and dry phase delay from atmospheric reanalysis datasets such as ERA-Interim provided by the ECMWF. SAR data from the ERS, Envisat, and ALOS satellites, along with newer datasets, are processed with these tools to create a time series spanning

  4. Long-term outcome after cardioversion of atrial fibrillation: prediction of recurrence with P wave signal averaged ECG and chemoreflexsensitivity.

    Science.gov (United States)

    Budeus, Marco; Wieneke, Heinrich; Sack, Stefan; Erbel, Raimund; Perings, Christian

    2006-10-10

    The recurrence of atrial fibrillation after cardioversion was a general problem in medical practice. We wanted to test the hypothesis that the recurrence of atrial fibrillation could be predicted by measurements of P wave triggered P wave signal averaged ECG and chemoreflexsensitivity (CHRS) in 118 consecutive patients one day after successful electrical cardioversion. We measured the filtered P wave duration (FPD) and the root mean square voltage of the last 20 ms of the P wave (RMS 20) with P wave triggered P wave signal averaged ECG. The CHRS was calculated of a ratio between the difference of RR intervals in ECG and venous pO2 before and after 5-min oxygen inhalation. The pathologic CHRS was predefined as a CHRS below 3.0 ms/mm Hg. A recurrence of atrial fibrillation was observed in 57 patients (48%) during a 9.3-month follow-up. The left atrial size (41.9+/-4.0 vs. 39.3+/-3.1 mm, P or =126 ms and RMS 20 predict atrial fibrillation with a specificity of 77%, a sensitivity of 72%, a positive value of 75%, a negative predictive value of 75% and an accuracy of 75%. Patients with FPD > or =126 ms and RMS 20 wave signal averaged ECG and an analysis of CHRS. These methods seem to be appropriate to show a delayed atrial conduction and a neurovegetative imbalance which might be possible trigger mechanisms of reinitiating of atrial fibrillation.

  5. A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

    Science.gov (United States)

    Wijdenes, Pierre; Ali, Hasan; Armstrong, Ryden; Zaidi, Wali; Dalton, Colin; Syed, Naweed I.

    2016-10-01

    Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices.

  6. Effects of enhanced foster care on the long-term physical and mental health of foster care alumni.

    Science.gov (United States)

    Kessler, Ronald C; Pecora, Peter J; Williams, Jason; Hiripi, Eva; O'Brien, Kirk; English, Diana; White, James; Zerbe, Richard; Downs, A Chris; Plotnick, Robert; Hwang, Irving; Sampson, Nancy A

    2008-06-01

    Child maltreatment is a significant risk factor for adult mental disorders and physical illnesses. Although the child welfare system routinely places severely abused and/or neglected children in foster care, no controlled studies exist to determine the effectiveness of this intervention in improving the long-term health of maltreated youth. To present results of the first quasi-experimental study, to our knowledge, to evaluate the effects of expanded foster care treatment on the mental and physical health of adult foster care alumni. We used a quasi-experimental design to compare adult outcomes of alumni of a model private foster care program and 2 public programs. The latter alumni were eligible for but not selected by the private program because of limited openings. Propensity score weights based on intake records were adjusted for preplacement between-sample differences. Personal interviews administered 1 to 13 years after leaving foster care assessed the mental and physical health of alumni. A representative sample of 479 adult foster care alumni who were placed in foster care as adolescents (14-18 years of age) between January 1, 1989, and September 30, 1998, in private (n = 111) or public (n = 368) foster care programs in Oregon and Washington. More than 80% of alumni were traced, and 92.2% of those traced were interviewed. Caseworkers in the model program had higher levels of education and salaries, lower caseloads, and access to a wider range of ancillary services (eg, mental health counseling, tutoring, and summer camps) than caseworkers in the public programs. Youth in the model program were in foster care more than 2 years longer than those in the public programs. Private program alumni had significantly fewer mental disorders (major depression, anxiety disorders, and substance use disorders), ulcers, and cardiometabolic disorders, but more respiratory disorders, than did public program alumni. Public sector investment in higher-quality foster care

  7. Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus.

    Directory of Open Access Journals (Sweden)

    Koshiro Inoue

    Full Text Available Our six-week treadmill running training (forced exercise model has revealed that mild exercise (ME with an intensity below the lactate threshold (LT is sufficient to enhance spatial memory, while intense exercise (IE above the LT negates such benefits. To help understand the unrevealed neuronal and signaling/molecular mechanisms of the intensity-dependent cognitive change, in this rat model, we here investigated plasma corticosterone concentration as a marker of stress, adult hippocampal neurogenesis (AHN as a potential contributor to this ME-induced spatial memory, and comprehensively delineated the hippocampal transcriptomic profile using a whole-genome DNA microarray analysis approach through comparison with IE. Results showed that only IE had the higher corticosterone concentration than control, and that the less intense exercise (ME is better suited to improve AHN, especially in regards to the survival and maturation of newborn neurons. DNA microarray analysis using a 4 × 44 K Agilent chip revealed that ME regulated more genes than did IE (ME: 604 genes, IE: 415 genes, and only 41 genes were modified with both exercise intensities. The identified molecular components did not comprise well-known factors related to exercise-induced AHN, such as brain-derived neurotrophic factor. Rather, network analysis of the data using Ingenuity Pathway Analysis algorithms revealed that the ME-influenced genes were principally related to lipid metabolism, protein synthesis and inflammatory response, which are recognized as associated with AHN. In contrast, IE-influenced genes linked to excessive inflammatory immune response, which is a negative regulator of hippocampal neuroadaptation, were identified. Collectively, these results in a treadmill running model demonstrate that long-term ME, but not of IE, with minimizing running stress, has beneficial effects on increasing AHN, and provides an ME-specific gene inventory containing some potential regulators

  8. Altered regulation of Akt signaling with murine cerebral malaria, effects on long-term neuro-cognitive function, restoration with lithium treatment.

    Directory of Open Access Journals (Sweden)

    Minxian Dai

    /GSK3β signaling likely underlies long-term neurological sequelae observed in ECM and may yield adjunctive therapeutic targets for the management of CM.

  9. Long-Term Effects of TCM Yangqing Kangxian Formula on Bleomycin-Induced Pulmonary Fibrosis in Rats via Regulating Nuclear Factor-κB Signaling

    Directory of Open Access Journals (Sweden)

    Meng Li

    2017-01-01

    Full Text Available Objective. We aimed to evaluate the therapeutic effects and long-term effects of YKF and dissect the potential mechanisms. Materials and Methods. IPF rats were given YKF, prednisone, or pirfenidone, respectively, from day 1 to day 42, followed by a 28-day nonintervention interval through day 70. Forced vital capacity (FVC, histopathology, hydroxyproline (HYP contents, lung coefficient, blood inflammatory cell populations, inflammatory cytokine levels of the lung tissues, and the expression of proteins involved in nuclear factor- (NF- κB signaling pathway were evaluated on days 7, 14, 28, 42, and 70. Results. HYP contents, Ashcroft scores, lung coefficient, and pulmonary fibrosis blood cell populations increased significantly in IPF rats, while FVC declined. All the above-mentioned parameters were improved in treatment groups from day 7 up to day 70, especially in YKF group. The mRNA and protein expressions of tumor necrosis factor- (TNF- α significantly decreased, while interferon- (IFN- γ significantly increased, and phosphorylations of cytoplasm inhibitor of nuclear factor kappa-B kinase β (IKKβ, inhibitor of nuclear factor kappa-B α (IκBα, and NF-κB were obviously downregulated in YKF group from day 7 to day 70. Conclusion. YKF has beneficial protective and long-term effects on pulmonary fibrosis by anti-inflammatory response and alleviating fibrosis.

  10. 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.

  11. p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

    Science.gov (United States)

    Kim, Hyun-Bum; Lee, Seok; Hwang, Eun-Sang; Maeng, Sungho; Park, Ji-Ho

    2017-10-21

    Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Enhanced deficits in long-term potentiation in the adult dentate gyrus with 2nd trimester ethanol consumption.

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    Jennifer L Helfer

    Full Text Available Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1(st or 3(rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2(nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.

  13. Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation.

    Science.gov (United States)

    Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Álvaro; Garro-Martínez, Emilio; Linge, Raquel; Castro, Elena; Haberzettl, Robert; Fink, Heidrun; Bert, Bettina; Brosda, Jan; Romero, Beatriz; Crespo-Facorro, Benedicto; Pazos, Ángel

    2017-11-15

    Postsynaptic 5-HT 1A receptors (5-HT 1A R) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HT 1A Rs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HT 1A Rs in anxiety response after pre-exposure to an acute stressor. Under basal conditions, 5-HT 1A R overexpressing animals presented high corticosterone levels and a lower mineralocorticoid/glucocorticoid receptor ratio. After pre-exposure to a single stressor, they showed a high anxiety-like response, associated with a blunted increase in corticosterone levels and higher c-Fos activation in the prefrontal cortex. Moreover, these mice also presented a lack of downregulation of hippocampal long-term potentiation after stress exposure. Therefore, higher postsynaptic 5-HT 1A R activation might predispose to a high anxious phenotype and an impaired stress coping behavior.

  14. Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocamus of Wistar rats

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    Han D

    2011-07-01

    Full Text Available Dadong Han1, Yutao Tian2, Tao Zhang2, Guogang Ren3, Zhuo Yang11School of Medicine, The Key Laboratory of Bioactive Materials, Ministry of Education, 2College of Life Science, Nankai University, Tianjin, China; 3Science and Technology Research Institute, University of Hertfordshire, Hatfield, Hertfordshire, UKAbstract: This study focused on the effects of zinc oxide nanoparticles (nano-ZnO on spatial learning and memory and synaptic plasticity in the hippocampus of young rats, and tried to interpret the underlying mechanism. Rats were randomly divided into four groups. Nano-ZnO and phosphate-buffered saline were administered in 4-week-old rats for 8 weeks. Subsequently, performance in Morris water maze (MWM was determined, and then long-term potentiation (LTP and depotentiation were measured in the perforant pathway to dentate gyrus (DG in anesthetized rats. The data showed that, (1 in MWM, the escape latency was prolonged in the nano-ZnO group and, (2 LTP was significantly enhanced in the nano-ZnO group, while depotentiation was barely influenced in the DG region of the nano-ZnO group. This bidirectional effect on long-term synaptic plasticity broke the balance between stability and flexibility of cognition. The spatial learning and memory ability was attenuated by the alteration of synaptic plasticity in nano-ZnO-treated rats.Keywords: zinc oxide nanoparticles, synaptic plasticity, long-term potentiation, depotentiation, spatial learning, memory

  15. Enhanced long-term strength and durability of shotcrete with high-strength C{sub 12}A{sub 7} mineral-based accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Won, Jong-Pil, E-mail: jpwon@konkuk.ac.kr; Hwang, Un-Jong; Lee, Su-Jin

    2015-10-15

    This study evaluated the performance of shotcrete using high strength C{sub 12}A{sub 7} mineral-based accelerator that has been developed to improve the durability and long-term strength. Rebound, compressive strength and flexural strength were tested in the field. Test result showed that existing C{sub 12}A{sub 7} mineral-based accelerator exhibits better early strength than the high-strength C{sub 12}A{sub 7} mineral-based accelerator until the early age, but high-strength C{sub 12}A{sub 7} mineral-based accelerator shows about 29% higher at the long-term age of 28 days. Microstructural analysis such as scanning electron microscope (SEM), X-ray diffraction (XRD) and nitrogen adsorption method was evaluated to analyze long-term strength development mechanism of high strength C{sub 12}A{sub 7} mineral-based accelerator. As analysis result, it had more dense structure due to the reaction product by adding material that used to enhanced strength. It had better resistance performance in chloride ion penetration, freezing–thawing and carbonation than shotcrete that used existing C{sub 12}A{sub 7} mineral-based accelerator.

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

    Science.gov (United States)

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

    2007-03-01

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

  17. Activation of the Akt/mTOR signaling pathway: A potential response to long-term neuronal loss in the hippocampus after sepsis

    Directory of Open Access Journals (Sweden)

    Jia-nan Guo

    2017-01-01

    Full Text Available Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a “self-rescuing” feedback response to neuronal loss after sepsis.

  18. Docosahexaenoic acid signaling modulates cell survival in experimental ischemic stroke penumbra and initiates long-term repair in young and aged rats.

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    Tiffany N Eady

    Full Text Available Docosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats.Rats underwent 2 h of middle cerebral artery occlusion (MCAo. DHA, neuroprotectin D1 (NPD1 or vehicle (saline was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle.We suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.

  19. Ganzfeld stimulation or sleep enhance long term motor memory consolidation compared to normal viewing in saccadic adaptation paradigm.

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    Caroline Voges

    Full Text Available Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation ("Ganzfeld"-stimulation or sleep can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials - interspersed by an extinction block - which were followed by a two-hour break with or without visual deprivation (VD. Using additional adaptation and extinction blocks short and long (4 weeks term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep, might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation.

  20. Ganzfeld stimulation or sleep enhance long term motor memory consolidation compared to normal viewing in saccadic adaptation paradigm.

    Science.gov (United States)

    Voges, Caroline; Helmchen, Christoph; Heide, Wolfgang; Sprenger, Andreas

    2015-01-01

    Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation ("Ganzfeld"-stimulation or sleep) can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials - interspersed by an extinction block - which were followed by a two-hour break with or without visual deprivation (VD). Using additional adaptation and extinction blocks short and long (4 weeks) term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error) in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep), might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation.

  1. Visual Input Enhancement via Essay Coding Results in Deaf Learners' Long-Term Retention of Improved English Grammatical Knowledge

    Science.gov (United States)

    Berent, Gerald P.; Kelly, Ronald R.; Schmitz, Kathryn L.; Kenney, Patricia

    2009-01-01

    This study explored the efficacy of visual input enhancement, specifically "essay enhancement", for facilitating deaf college students' improvement in English grammatical knowledge. Results documented students' significant improvement immediately after a 10-week instructional intervention, a replication of recent research. Additionally, the…

  2. Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

    Directory of Open Access Journals (Sweden)

    Huang Z

    2015-03-01

    Full Text Available Zheyong Huang,1,* Chenguang Li,1,* Shan Yang,2 Jianfeng Xu,1 Yunli Shen,3 Xinxing Xie,4 Yuxiang Dai,1 Hao Lu,1 Hui Gong,5 Aijun Sun,1 Juying Qian,1 Junbo Ge1 1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, People’s Republic of China; 4Department of Cardiology, Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China; 5Institute of Biomedical Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: The long-lasting hypointensities in cardiac magnetic resonance (CMR were believed to originate from superparamagnetic iron oxide (SPIO-engulfed macrophages during long-term stem cell tracking. However, the iron clearance capacity of the ischemic heart was limited. Therefore, we speculated that the extracellular SPIO particles may also be involved in the generation of false-positive signals.Methods and results: Male swine mesenchymal stem cells (MSCs were incubated with SPIO for 24 hours, and SPIO labeling had no significant effects on either cell viability or differentiation. In vitro studies showed that magnetic resonance failed to distinguish SPIO from living SPIO-MSCs or dead SPIO-MSCs. Two hours after the establishment of the female swine acute myocardial infarction model, 2×107 male SPIO-labeled MSCs (n=5 or unlabeled MSCs (n=5 were transextracardially injected into the infarcted myocardium at ten distinct sites. In vivo CMR with T2 star weighted imaging-flash-2D sequence revealed a signal void corresponding to the initial SPIO-MSC injection sites. At 6 months after transplantation, CMR identified 32 (64% of the 50 injection sites, where massive Prussian blue-positive iron

  3. Context-specific activation of hippocampus and SN/VTA by reward is related to enhanced long-term memory for embedded objects.

    Science.gov (United States)

    Loh, Eleanor; Kumaran, Dharshan; Koster, Raphael; Berron, David; Dolan, Ray; Duzel, Emrah

    2016-10-01

    Animal studies indicate that hippocampal representations of environmental context modulate reward-related processing in the substantia nigra and ventral tegmental area (SN/VTA), a major origin of dopamine in the brain. Using functional magnetic resonance imaging (fMRI) in humans, we investigated the neural specificity of context-reward associations under conditions where the presence of perceptually similar neutral contexts imposed high demands on a putative hippocampal function, pattern separation. The design also allowed us to investigate how contextual reward enhances long-term memory for embedded neutral objects. SN/VTA activity underpinned specific context-reward associations in the face of perceptual similarity. A reward-related enhancement of long-term memory was restricted to the condition where the rewarding and the neutral contexts were perceptually similar, and in turn was linked to co-activation of the hippocampus (subfield DG/CA3) and SN/VTA. Thus, an ability of contextual reward to enhance memory for focal objects is closely linked to context-related engagement of hippocampal-SN/VTA circuitry. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Long-term neurocognitive dysfunction in offspring via NGF/ ERK/CREB signaling pathway caused by ketamine exposure during the second trimester of pregnancy in rats.

    Science.gov (United States)

    Li, Yanan; Li, Xinran; Guo, Cen; Li, Lina; Wang, Yuxin; Zhang, Yiming; Chen, Yu; Liu, Wenhan; Gao, Li

    2017-05-09

    Early life exposure to ketamine caused neurohistopathologic changes and persistent cognitive dysfunction. For this study, a pregnant rat model was developed to investigate neurocognitive effects in the offspring, following ketamine exposure during the second trimester. Pregnant rats on gestational day 14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition test, and fear conditioning) at postnatal days (P25-30). Furthermore, hippocampal morphology of the offspring (P30) was examined via Nissl staining and hippocampal dendritic spine density was determined via Golgi staining. The hippocampal protein levels of nerve growth factor (NGF), extracellular signal-regulated kinase (ERK), phosphorylated-ERK (p-ERK), cyclic adenosine monophosphate response element-binding (CREB), p-CREB, synaptophysin (SYP), synapsin (SYN), and postsynaptic density-95 (PSD95) were measured via western blot. Additionally, SCH772984 (an ERK inhibitor) was used to evaluate both role and underlying mechanism of the ERK pathway in PC12 cells. We found that ketamine caused long-term neurocognitive dysfunction, reduced the density of the dendritic spin, caused neuronal loss, and down-regulated the expression of NGF, ERK, p-ERK, mitogen, and stress-activated protein kinase (MSK), CREB, p-CREB, SYP, SYN, and PSD95 in the hippocampus. These results suggest that ketamine induced maternal anesthesia during period of the fetal brain development can cause long-term neurocognitive dysfunction in the offspring, which likely happens via inhibition of the NGF-ERK-CREB pathway in the hippocampus. Our results highlight the central role of ERK in neurocognition.

  5. ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

    Directory of Open Access Journals (Sweden)

    Nicola J Darling

    Full Text Available Disruption of protein folding in the endoplasmic reticulum (ER causes ER stress. Activation of the unfolded protein response (UPR acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2 signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

  6. Dual-Function Au@Y2O3:Eu3+ Smart Film for Enhanced Power Conversion Efficiency and Long-Term Stability of Perovskite Solar Cells.

    Science.gov (United States)

    Kim, Chang Woo; Eom, Tae Young; Yang, In Seok; Kim, Byung Su; Lee, Wan In; Kang, Yong Soo; Kang, Young Soo

    2017-07-28

    In the present study, a dual-functional smart film combining the effects of wavelength conversion and amplification of the converted wave by the localized surface plasmon resonance has been investigated for a perovskite solar cell. This dual-functional film, composed of Au nanoparticles coated on the surface of Y 2 O 3 :Eu 3+ phosphor (Au@Y 2 O 3 :Eu 3+ ) nanoparticle monolayer, enhances the solar energy conversion efficiency to electrical energy and long-term stability of photovoltaic cells. Coupling between the Y 2 O 3 :Eu 3+ phosphor monolayer and ultraviolet solar light induces the latter to be converted into visible light with a quantum yield above 80%. Concurrently, the Au nanoparticle monolayer on the phosphor nanoparticle monolayer amplifies the converted visible light by up to 170%. This synergy leads to an increased solar light energy conversion efficiency of perovskite solar cells. Simultaneously, the dual-function film suppresses the photodegradation of perovskite by UV light, resulting in long-term stability. Introducing the hybrid smart Au@Y 2 O 3 :Eu 3+ film in perovskite solar cells increases their overall solar-to-electrical energy conversion efficiency to 16.1% and enhances long-term stability, as compared to the value of 15.2% for standard perovskite solar cells. The synergism between the wavelength conversion effect of the phosphor nanoparticle monolayer and the wave amplification by the localized surface plasmon resonance of the Au nanoparticle monolayer in a perovskite solar cell is comparatively investigated, providing a viable strategy of broadening the solar spectrum utilization.

  7. ESR dosimetry of fossil enamel: Some comments about measurement precision, long-term signal fading and dose-response curve fitting

    International Nuclear Information System (INIS)

    Duval, M.; Moreno, V. G.; Gruen, R.

    2013-01-01

    This work deals with the specific studies of three main sources of uncertainty in electron spin resonance (ESR) dosimetry/dating of fossil tooth enamel: (1) the precision of the ESR measurements, (2) the long-term signal fading the selection of the fitting function. They show a different influence on the equivalent dose (DE) estimates. Repeated ESR measurements were performed on 17 different samples: results show a mean coefficient of variation of the ESR intensities of 1.20±0.23 %, inducing a mean relative variability of 3.05±2.29 % in the DE values. ESR signal fading over 5 y was also observed: its magnitude seems to be quite sample dependant but is nevertheless especially important for the most irradiated aliquots. This fading has an apparent random effect on the DE estimates. Finally, the authors provide new insights and recommendations about the fitting of ESR dose-response curves of fossil enamel with a double saturating exponential (DSE) function. The potential of a new variation of the DSE was also explored. Results of this study also show that the choice of the fitting function is of major importance, maybe more than the other sources previously mentioned, in order to get accurate final DE values. (authors)

  8. Criterion 6: Maintenance and enhancement of long-term multiple socioeconomic benefits to meet the needs of societies

    Science.gov (United States)

    Stephen R. Shifley; Francisco X. Aguilar; Nianfu Song; Susan I. Stewart; David J. Nowak; Dale D. Gormanson; W. Keith Moser; Sherri Wormstead; Eric J. Greenfield

    2012-01-01

    Forests provide an array of products and services that maintain and enhance benefits to our society and economy. Benefits derived from forests may be categorized into wood products, nontimber products and services, and ecosystem services. The value and volume of these products and services indicate the importance of forests for a wide variety of uses.Tracking values,...

  9. Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

    Science.gov (United States)

    Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

  10. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    International Nuclear Information System (INIS)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-01-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  11. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  12. 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.

  13. Kootenai River Wildlife Habitat Enhancement Project : Long-term Bighorn Sheep/Mule Deer Winter and Spring Habitat Improvement Project : Wildlife Mitigation Project, Libby Dam, Montana : Management Plan.

    Energy Technology Data Exchange (ETDEWEB)

    Yde, Chis

    1990-06-01

    The Libby hydroelectric project, located on the Kootenai River in northwestern Montana, resulted in several impacts to the wildlife communities which occupied the habitats inundated by Lake Koocanusa. Montana Department of Fish, Wildlife and Parks, in cooperation with the other management agencies, developed an impact assessment and a wildlife and wildlife habitat mitigation plan for the Libby hydroelectric facility. In response to the mitigation plan, Bonneville Power Administration funded a cooperative project between the Kootenai National Forest and Montana Department of Fish, Wildlife and Parks to develop a long-term habitat enhancement plan for the bighorn sheep and mule deer winter and spring ranges adjacent to Lake Koocanusa. The project goal is to rehabilitate 3372 acres of bighorn sheep and 16,321 acres of mule deer winter and spring ranges on Kootenai National Forest lands adjacent to Lake Koocanusa and to monitor and evaluate the effects of implementing this habitat enhancement work. 2 refs.

  14. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway.

    Science.gov (United States)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway - a pathway closely associated with synaptic plasticity and learning and memory - was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  15. Suppression of cytochrome p450 reductase enhances long-term hematopoietic stem cell repopulation efficiency in mice.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Bone marrow microenvironment (niche plays essential roles in the fate of hematopoietic stem cells (HSCs. Intracellular and extracellular redox metabolic microenvironment is one of the critical factors for the maintenance of the niche. Cytochrome P450 reductase (CPR is an obligate electron donor to all microsomal cytochrome P450 enzymes (P450 or CYP, and contributes to the redox metabolic process. However, its role in maintaining HSCs is unknown. OBJECTIVE: To examine the effects of low CPR expression on HSCs function using a mouse model of globally suppressed Cpr gene expression (Cpr Low, CL mice. METHODS: Hematopoietic cell subpopulations in bone marrow (BM and peripheral blood (PB from WT and CL mice were examined for their repopulation and differentiation ability upon BM competitive transplantation and enriched HSC (LKS(+ transplantation. Effects of low CPR expression on hematopoiesis were examined by transplanting normal BM cells into CL recipients. Reactive oxygen species (ROS, cell cycle, and apoptosis in CL mice were analyzed by flow cytometry for DCF-DA fluorescence intensity, Ki67 protein, and Annexin-V, respectively. RESULTS: The levels of ROS in BM cells, HPCs and HSCs were comparable between CL and WT mice. In comparison to WT mice, the number of LT-HSCs or ST-HSCs was lower in CL mice while CMPs, GMPs and MEPs in CL mice were higher than that in WT control. Competitive transplantation assay revealed enhanced repopulation capacity of HSCs with low CPR expression, but no difference in differentiation potential upon in vitro experiments. Furthermore, lymphoid differentiation of donor cells decreased while their myeloid differentiation increased under CL microenvironment although the overall level of donor hematopoietic repopulation was not significantly altered. CONCLUSIONS: Our studies demonstrate that suppressing CPR expression enhances the repopulation efficiency of HSCs and a low CPR expression microenvironment favors

  16. Using single-walled carbon nanotubes nonwoven films as scaffolds to enhance long-term cell proliferation in vitro.

    Science.gov (United States)

    Meng, Jie; Song, Li; Meng, Jie; Kong, Hua; Zhu, Guangjin; Wang, Chaoying; Xu, Lianghua; Xie, Sishen; Xu, Haiyan

    2006-11-01

    Carbon nanotubes have attracted intensive interests in biomedical research in recent years. In this study, a novel type of carbon nanotubes material so called nonwoven single-walled carbon nanotubes (SWNTs) with nanotopographic structure and macroscopic volume was used as cell growing scaffold. The morphology and surface chemistry of nonwoven SWNTs were observed and characterized through scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. The cells were cultivated in nonwoven SWNTs and in other types of substrate as control. The cells growth behaviors including adhesion, proliferation, and cytoskeletal development was investigated by using cell viability assay and confocal observation. The experimental results indicated that nonwoven SWNTs exhibited significant enhancement to the cells adhesion and proliferation in at least 3 weeks. Numerous and highly organized cytoskeletal structures were observed when the cells were cultured in nonwoven SWNTs. Furthermore, an obvious promotional influence of the cells cultivated in nonwoven SWNTs scaffold upon the proliferation of those growing in the other kind of substrate through cell-cell communication had been found. The results obtained in this work are of significance to in vitro cell amplification in large scale, tissue regeneration, or guided repair, as well as biomedical device application.

  17. Polyvinylidene fluoride/siloxane nanofibrous membranes for long-term continuous CO2 -capture with large absorption-flux enhancement.

    Science.gov (United States)

    Lin, Yi-Feng; Wang, Chi-Sen; Ko, Chia-Chieh; Chen, Chien-Hua; Chang, Kai-Shiun; Tung, Kuo-Lun; Lee, Kueir-Rarn

    2014-02-01

    In a CO2 membrane contactor system, CO2 passes through a hydrophobic porous membrane in the gas phase to contact the amine absorbent in the liquid phase. Consequently, additional CO2 gas is absorbed by amine absorbents. This study examines highly porous polyvinylidene fluoride (PVDF)/siloxane nanofibrous layers that are modified with hydrophobic fluoroalkylsilane (FAS) functional groups and successfully coated onto a macroporous Al2 O3 membrane. The performance of these materials in a membrane contactor system for CO2 absorption is also investigated. Compared with pristine PVDF nanofibrous membranes, the PVDF/siloxane nanofibrous membranes exhibit greater solvent resistance and mechanical strength, making them more suitable for use in CO2 capture by the membrane contactor. The PVDF/siloxane nanofibrous layer in highly porous FAS-modified membranes can prevent the wetting of the membrane by the amine absorbent; this extends the periods of continuous CO2 absorption and results in a high CO2 absorption flux with a minimum of 500 % enhancement over that of the uncoated membranes. This study suggests the potential use of an FAS-modified PVDF/siloxane nanofibrous membrane in a membrane contactor system for CO2 absorption. The resulting hydrophobic membrane contactor also demonstrates the potential for large-scale CO2 absorption during post-combustion processes in power plants. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

    Directory of Open Access Journals (Sweden)

    Tomoko Inagaki

    Full Text Available Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia.The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats.The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.

  19. Training Lymnaea in the presence of a predator scent results in a long-lasting ability to form enhanced long-term memory.

    Science.gov (United States)

    Forest, Jeremy; Sunada, Hiroshi; Dodd, Shawn; Lukowiak, Ken

    2016-06-01

    Lymnaea exposed to crayfish effluent (CE) gain an enhanced ability to form long-term memory (LTM). We test the hypothesis that a single CE exposure and operant conditioning training leads to long lasting changes in the capability of snails to form LTM when tested in pond water four weeks later. We trained both juvenile and adult snails with a single 0.5 h training session in CE and show that LTM was present 24 h later. Snails trained in a similar manner in just pond water show no LTM. We then asked if such training in CE conferred enhanced memory forming capabilities on these snails four weeks later. That is, would LTM be formed in these snails four weeks later following a single 0.5 h training session in pond water? We found that both adult and juvenile snails previously trained in CE one month previously had enhanced LTM formation abilities. The injection of a DNA methylation blocker, 5-AZA, prior to training in adult snails blocked enhanced LTM formation four weeks later. Finally, this enhanced LTM forming ability was not passed on to the next generation of snails.

  20. Activation of nicotinic α(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1ΔE9 mice

    DEFF Research Database (Denmark)

    Söderman, Andreas; Mikkelsen, Jens D; West, Mark J

    2011-01-01

    Amyloid β (Aβ) plays a central role in Alzheimer's disease (AD) and binds to the nicotinic α(7) receptor (α(7) nAChR). Little is known about the degree to which the binding of Aβ to the α(7) nAChR influences the role of this receptor in long-term potentiation (LTP), however. We have studied...... enhancement of LTP expressed in area CA1. However, in the Tg mice the application of SSR180711 did not result in an increase in LTP beyond control levels. The amount of binding of the α(7) nAChR ligand 125-I-α-bungarotoxin was not different between in Tg and Wt mice. These findings indicate that the α(7) n...

  1. Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

    DEFF Research Database (Denmark)

    Christiansen, Lasse; Larsen, Malte Nejst; Grey, Michael James

    2017-01-01

    demands for timing and accuracy to individual proficiency promotes motor skill learning and drives the iM1-CSE resulting in enhanced performance of the non-trained hand. The results underline the importance of increasing task difficulty progressively and individually in skill learning and rehabilitation......It is well established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor...... excitability of the left non-trained hand. Subjects practiced a visuomotor tracking task engaging right digit V for 6 weeks with either progressively increasing task difficulty (PT) or no progression (NPT). Corticospinal excitability (CSE) was evaluated from the resting motor threshold (rMT) and recruitment...

  2. Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved long-term survival.

    Science.gov (United States)

    Ali, Ayyaz; Patel, Amit; Ali, Ziad; Abu-Omar, Yasir; Saeed, Amber; Athanasiou, Thanos; Pepper, John

    2011-08-01

    Aortic valve replacement in patients with aortic stenosis is usually followed by regression of left ventricular hypertrophy. More complete resolution of left ventricular hypertrophy is suggested to be associated with superior clinical outcomes; however, its translational impact on long-term survival after aortic valve replacement has not been investigated. Demographic, operative, and clinical data were obtained retrospectively through case note review. Transthoracic echocardiography was used to measure left ventricular mass preoperatively and at annual follow-up visits. Patients were classified according to their reduction in left ventricular mass at 1 year after the operation: group 1, less than 25 g; group 2, 25 to 150 g; and group 3, more than 150 g. Kaplan-Meier and multivariable Cox regression were used. A total of 147 patients were discharged from the hospital after aortic valve replacement for aortic stenosis between 1991 and 2001. Preoperative left ventricular mass was 279 ± 98 g in group 1 (n = 47), 347 ± 104 g in group 2 (n = 62), and 491 ± 183 g in group 3 (n = 38) (P regression such as ischemic heart disease or hypertension, valve type, or valve size used. Ten-year actuarial survival was not statistically different in patients with enhanced left ventricular mass regression when compared with the log-rank test (group 1, 51% ± 9%; group 2, 54% ± 8%; and group 3, 72% ± 10%) (P = .26). After adjustment, left ventricular mass reduction of more than 150 g was demonstrated as an independent predictor of improved long-term survival on multivariate analysis (P = .02). Our study is the first to suggest that enhanced postoperative left ventricular mass regression, specifically in patients undergoing aortic valve replacement for aortic stenosis, may be associated with improved long-term survival. In view of these findings, strategies purported to be associated with superior left ventricular mass regression should be considered when undertaking

  3. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

    Energy Technology Data Exchange (ETDEWEB)

    Suman, Shubhankar [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States); Johnson, Michael D. [Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States); Fornace, Albert J. [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States); Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States)

    2012-10-01

    Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.

  4. 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...

  5. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

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

  6. 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...

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

    Science.gov (United States)

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

    2011-10-01

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

  8. Web-Enhanced Instruction and Learning: Findings of a Short- and Long-Term Impact Study and Teacher Use of NASA Web Resources

    Science.gov (United States)

    McCarthy, Marianne C.; Grabowski, Barbara L.; Koszalka, Tiffany

    2003-01-01

    Over a three-year period, researchers and educators from the Pennsylvania State University (PSU), University Park, Pennsylvania, and the NASA Dryden Flight Research Center (DFRC), Edwards, California, worked together to analyze, develop, implement and evaluate materials and tools that enable teachers to use NASA Web resources effectively for teaching science, mathematics, technology and geography. Two conference publications and one technical paper have already been published as part of this educational research series on Web-based instruction and learning. This technical paper, Web-Enhanced Instruction and Learning: Findings of a Short- and Long-Term Impact Study, is the culminating report in this educational research series and is based on the final report submitted to NASA. This report describes the broad spectrum of data gathered from teachers about their experiences using NASA Web resources in the classroom. It also describes participating teachers responses and feedback about the use of the NASA Web-Enhanced Learning Environment Strategies reflection tool on their teaching practices. The reflection tool was designed to help teachers merge the vast array of NASA resources with the best teaching methods, taking into consideration grade levels, subject areas and teaching preferences. The teachers described their attitudes toward technology and innovation in the classroom and their experiences and perceptions as they attempted to integrate Web resources into science, mathematics, technology and geography instruction.

  9. Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

    Science.gov (United States)

    Chen, Nihong; Bi, Taiyong; Zhou, Tiangang; Li, Sheng; Liu, Zili; Fang, Fang

    2015-07-15

    Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Beranger, G.

    2003-01-01

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

  11. 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...

  12. Dose-dependent effect of donepezil administration on long-term enhancement of visually evoked potentials and cholinergic receptor overexpression in rat visual cortex.

    Science.gov (United States)

    Chamoun, Mira; Groleau, Marianne; Bhat, Menakshi; Vaucher, Elvire

    2016-09-01

    Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0.5 and 1mg/kg) during a 2-week visual training to examine the effect on visually evoked potentials and to profile the expression of cholinergic receptor subtypes. The visual training was performed daily, 10min a day, for 2weeks. One week after the last training session, visual evoked potentials were recorded, or the mRNA expression level of muscarinic (M1-5) and nicotinic (α/β) receptors subunits was determined by quantitative RT-PCR. The visual stimulation coupled with any of the two doses of donepezil produced significant amplitude enhancement of cortical evoked potentials compared to pre-training values. The enhancement induced by the 1mg/kg dose of donepezil was spread to neighboring spatial frequencies, suggesting a better sensitivity near the visual detection threshold. The M3, M4, M5 and α7 receptors mRNA were upregulated in the visual cortex for the higher dose of donepezil but not the lower one, and the receptors expression was stable in the somatosensory (non-visual control) cortex. Therefore, higher levels of acetylcholine within the cortex sustain the increased intensity of the cortical response and trigger the upregulation of cholinergic receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Long-term exposure to enhanced ultraviolet-B radiation in the sub-arctic does not cause oxidative stress in Vaccinium myrtillus

    International Nuclear Information System (INIS)

    Taulavuori, E.; Bäckman, M.; Taulavuori, K.; Gwynn-Jones, D.; Johanson, U.; Laine, K.; Callaghan, T.; Sonesson, M.; Björn, L.O.

    1998-01-01

    The aim of this work was to assess whether or not oxidative stress had developed in a dwarf shrub bilberry (Vaccinium myrtillus L.) under long-term exposure to enhanced levels of ultraviolet-B (u.v.-B) radiation. The bilberry plants were exposed to increased u.v.-B representing a 15 stratospheric ozone depletion for seven full growing seasons (19911997) at Abisko, Swedish Lapland (68N). The oxidative stress was assessed on leaves and stems by analysing ascorbate and glutathione concentrations, and activities of the closely related enzymes ascorbate peroxidase (EC 1.11.1.11) and glutathione reductase (EC 1.6.4.2). The affects of autumnal leaf senescence and stem cold hardening on these variables were also considered. The results showed that the treatment caused scarcely any response in the studied variables, indicating that u.v.-B flux representing a 15 ozone depletion under clear sky conditions is not sufficient to cause oxidative stress in the bilberry. It is suggested that no strain was evoked since adaptation was possible under such u.v.-B increases. The studied variables did, however, respond significantly to leaf senescence and especially to stem cold hardening. (author)

  14. Dietary 2'-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents.

    Directory of Open Access Journals (Sweden)

    Enrique Vazquez

    Full Text Available 2´-fucosyllactose (2´-FL is an abundant human milk oligosaccharide (HMO in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS function, such as hippocampal long term potentiation (LTP and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA, specifically the vagus nerve, and L-fucose (Fuc may play a role. This study had two aims: (1 determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2 confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

  15. Circular siRNAs for Reducing Off-Target Effects and Enhancing Long-Term Gene Silencing in Cells and Mice.

    Science.gov (United States)

    Zhang, Liangliang; Liang, Duanwei; Chen, Changmai; Wang, Yuan; Amu, Gubu; Yang, Jiali; Yu, Lijia; Dmochowski, Ivan J; Tang, Xinjing

    2018-03-02

    Circular non-coding RNAs are found to play important roles in biology but are still relatively unexplored as a structural motif for chemically regulating gene function. Here, we investigated whether small interfering RNA (siRNA) with a circular structure can circumvent off-target gene silencing, a problem often observed with standard linear duplex siRNA. In the present work, we, for the first time, synthesized a series of circular siRNAs by cyclizing two ends of a single-stranded RNA (sense or antisense strand) to construct circular siRNAs that were more resistant to enzymatic degradation. Gene silencing of GFP and luciferase was successfully achieved using these circular siRNAs with circular sense strand RNAs and their complementary linear antisense strand RNAs. The off-target effect of sense strand RNAs was evaluated and no cross off-target effects were observed. In addition, we successfully achieved longer gene-silencing efficiency in mice with circular siRNAs than with linear siRNAs. These results indicate the promise of circular siRNAs for overcoming off-target effects of siRNAs and enhancing the possible long-term effect of siRNA gene silencing in basic research and drug development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

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

  17. Modulation of long-term endothelial-barrier integrity is conditional to the cross-talk between Akt and Src signaling.

    Science.gov (United States)

    Gao, Fei; Sabbineni, Harika; Artham, Sandeep; Somanath, Payaningal R

    2017-10-01

    Although numerous studies have implicated Akt and Src kinases in vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1)-induced endothelial-barrier regulation, a link between these two pathways has never been demonstrated. We determined the long-term effects of Akt inhibition on Src activity and vice versa, and in turn, on the human microvascular endothelial cell (HMEC) barrier integrity at the basal level, and in response to growth factors. Our data showed that Akt1 gene knockdown increases gap formation in HMEC monolayer at the basal level. Pharmacological inhibition of Akt, but not Src resulted in exacerbated VEGF-induced vascular leakage and impaired Ang-1-induced HMEC-barrier protection in vitro at 24 hr. Whereas inhibition of Akt had no effect on VEGF-induced HMEC gap formation in the short term, inhibition of Src blunted this process. In contrast, inhibition of Akt disrupted the VEGF and Ang-1 stabilized barrier integrity in the long-term while inhibition of Src did not. Interestingly, both long-term Akt inhibition and Akt1 gene knockdown in HMECs resulted in increased Tyr416 phosphorylation of Src. Treatment of HMECs with transforming growth factor-β1 (TGFβ1) that inhibited Akt Ser473 phosphorylation in the long-term, activated Src through increased Tyr416 phosphorylation and decreased HMEC-barrier resistance. The effect of TGFβ1 on endothelial-barrier breakdown was blunted in Akt1 deficient HMEC monolayers, where endothelial-barrier resistance was already impaired compared to the control. To our knowledge, this is the first report demonstrating a direct cross-talk between Akt and Src in endothelial-barrier regulation. © 2017 Wiley Periodicals, Inc.

  18. Long-term treatment with the pure anti-estrogen fulvestrant durably remodels estrogen signaling in BG-1 ovarian cancer cells.

    OpenAIRE

    Badia, Eric; Docquier, Aurélie; Busson, Muriel; Lapierre, Marion; Pujol, Pascal; Balaguer, Patrick; Cavailles, Vincent

    2012-01-01

    International audience; Most ovarian cancers are estrogen-positive and hormonal treatments using anti-estrogens or aromatase inhibitors are under investigation for treating the tumors that are resistant to conventional therapies. In this study, the long-term effects of two anti-estrogens, namely 4-hydroxytamoxifen and fulvestrant (or ICI182,780), were investigated in ERα-positive BG1 epithelial ovarian cancer cells. To this aim, cells were grown in the presence of anti-estrogen concentrations...

  19. [BETA-ADRENERGIC REGULATION OF THE ADENYLYL CYCLASE SIGNALING SYSTEM IN MYOCARDIUM AND BRAIN OF RATS WITH OBESITY AND TYPES 2 DIABETES MELLITUS AND THE EFFECT OF LONG-TERM INTRANASAL INSULIN TREATMENT].

    Science.gov (United States)

    Kuznetsova, L A; Sharova, T S; Pertseva, M N; Shpakov, A O

    2015-01-01

    The stimulating effect of norepinephrine, isoproterenol and selective β-adrenoceptor (β3-AR) agonists BRL 37344 and CL 316.243 on the adenylyl cyclase signaling system (ACSS) in the brain and myocardium of young and mature rats (disease induction at 2 and 4 months, respectively) with experimental obesity and type 2 diabetes mellitus (DM2), and the influence of long-term treatment of animals with intranasal insulin (I-I) were studied. The AC stimulatory effects of β-agonist isoproterenol in animals with obesity and DM2 was shown to be practically unchanged. The respective effects of norepinephrine on the AC activity were attenuated in the brain of young and mature rats and in the myocardium if mature rats, and the I-I treatment led to their partial recovery. In the brain and myocardium of mature rats with obesity and DM2, the enhancement of the AC stimulatory effects of β3-AR agonists was observed, white in young rats the influence of the same pathological conditions was lacking. The I-I treatment decreased the AC stimulatory effects of β3-agonists to their levels in the control. Since functional disruption of the adrenergic agonist-sensitive ACSS can lead to metabolic syndrome and DM2, the recovery of this system by the I-I treatment offers one of the ways to correct these diseases and their complications in the nervous and cardiovascular systems.

  20. Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

    Directory of Open Access Journals (Sweden)

    Mariangela Scarduzio

    Full Text Available Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs and androgens (ARs. We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN. Long-term depression (LTD and long-term potentiation (LTP caused by different patterns of high frequency stimulation (HFS of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase and E2 (P450-aromatase from testosterone (T. We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

  1. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer.

    Directory of Open Access Journals (Sweden)

    Laxmidhar Das

    Full Text Available Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

  2. Leaf saponins of Quillaja brasiliensis enhance long-term specific immune responses and promote dose-sparing effect in BVDV experimental vaccines.

    Science.gov (United States)

    Cibulski, Samuel; Rivera-Patron, Mariana; Suárez, Norma; Pirez, Macarena; Rossi, Silvina; Yendo, Anna Carolina; de Costa, Fernanda; Gosmann, Grace; Fett-Neto, Arthur; Roehe, Paulo Michel; Silveira, Fernando

    2018-01-02

    Saponin-based adjuvants are promising adjuvants that enhance both humoral and T-cell-mediated immunity. One of the most used natural products as vaccine adjuvants are Quillaja saponaria bark saponins and its fraction named Quil A®. Despite that, its use has been restricted for human use due to safety issues. As an alternative, our group has been studying the congener species Quillaja brasiliensis saponins and its performance as vaccine adjuvants, which have shown to trigger humoral and cellular immune responses comparable to Quil A® but with milder side effects. Here, we studied a semi purified aqueous extract (AE) and a previously little characterized saponin-enriched fraction (QB-80) from Q. brasiliensis as vaccine adjuvants and an inactivated virus (bovine viral diarrhea virus, BVDV) antigen co-formulated in experimental vaccines in mice model. For the first time, we show the spectra pattern of the Q. brasiliensis saponins by MALDI-TOF, a novel and cost-effective method that could be used to characterize different batches during saponins production. Both AE and QB-80 exhibited noteworthy chemical similarities to Quil A®. In addition, the haemolytic activity and toxicity were assessed, showing that both AE and QB-80 were less toxic than Quil A®. When subcutaneously inoculated in mice, both fractions promoted long-term strong antibody responses encompassing specific IgG1 and IgG2a, enhanced the avidity of IgG antibodies, induced a robust DTH reaction and significantly increased IFN-ɣ production in T CD4 + and T CD8 + cells. Furthermore, we have proven herein that AE has the potential to promote dose-sparing, substantially reducing the dose of antigen required for the BVDV vaccines and still eliciting a mixed Th1/Th2 strong immune response. Based on these results, and considering that AE is a raw extract, easier and cheaper to produce than commercially available saponins, this product can be considered as candidate to be escalated from experimental to

  3. Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

    DEFF Research Database (Denmark)

    Christiansen, Lasse; Larsen, Malte Nejst; Grey, Michael James

    2017-01-01

    It is well-established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor e...

  4. Short-Term Success versus Long-Term Failure: A Simulation-Based Approach for Understanding the Potential of Zambia’s Fertilizer Subsidy Program in Enhancing Maize Availability

    Directory of Open Access Journals (Sweden)

    Andreas Gerber

    2016-10-01

    Full Text Available In Sub-Saharan Africa, food-related policies such as fertilizer subsidy programs (FSPs have undergone a revival and triggered a controversy about their impact. In this article I applied a simulation-based approach to examine the FSPs’ short- and long-term potential for increasing maize availability in Zambia. The study revealed that FSPs are an effective policy measure to enhance maize availability in the short-term. However, in the long-term, the food system becomes dependent on the government’s annual expenses. The dependency occurs because FSPs fail to build up adequate stock levels of soil organic matter (SOM, which is an important source of resilience and productivity, and thus represents a long-term leverage point in Zambia’s maize production system. For this reason, alternative policies that combine increasing productivity and building up SOM stock levels were analyzed. They were found to be a viable means for enhancing long-term maize availability. The study concludes that gradually reducing investments in FSPs while simultaneously promoting farming practices that build up SOM stock levels is a promising strategy to enhance maize availability sustainably.

  5. Few-layer antimonene decorated microfiber: ultra-short pulse generation and all-optical thresholding with enhanced long term stability

    Science.gov (United States)

    Song, Yufeng; Liang, Zhiming; Jiang, Xiantao; Chen, Yunxiang; Li, Zhongjun; Lu, Lu; Ge, Yanqi; Wang, Ke; Zheng, Jilin; Lu, Shunbin; Ji, Jianhua; Zhang, Han

    2017-12-01

    Antimonene, a new type of mono/few-layer two-dimensional (2D) mono-elemental material purely consisting of antimony similar as graphene and phosphorene, has been theoretically predicted with excellent optical response and enhanced stability. Herein, we experimentally investigated the broadband nonlinear optical response of highly stable few-layer antimonene (FLA) by performing an open-aperture Z-scan laser measurement. Thanks to the direct bandgap and resonant absorption at the telecommunication band, we demonstrated the feasibility of FLA-decorated microfiber not only as an optical saturable absorber for ultrafast photonics operation, but also as a stable all-optical pulse thresholder that can effectively suppress the transmission noise, boost the signal-to-noise ratio (SNR), and reshape the deteriorated input signal. Our findings, as the first prototypic device of absorption of antimonene, might facilitate the development of antimonene-based optical communication technologies towards high stability and practical applications in the future.

  6. Downregulation of eca-mir-128 in seminal exosomes and enhanced expression of CXCL16 in the stallion reproductive tract are associated with long-term persistence of equine arteritis virus.

    Science.gov (United States)

    Carossino, Mariano; Dini, Pouya; Kalbfleisch, Theodore S; Loynachan, Alan T; Canisso, Igor F; Shuck, Kathleen M; Timoney, Peter J; Cook, R Frank; Balasuriya, Udeni B R

    2018-02-14

    Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene ( CXCL16S ) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. Here, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of miRNAs. Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented herein suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion. IMPORTANCE Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the CXCL16 gene ( CXCL16S ) and is maintained despite induction of local inflammatory, humoral and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first

  7. Impacts of long-term enhanced UV-B radiation on bryophytes in two sub-Arctic heathland sites of contrasting water availability.

    Science.gov (United States)

    Arróniz-Crespo, M; Gwynn-Jones, D; Callaghan, T V; Núñez-Olivera, E; Martínez-Abaigar, J; Horton, P; Phoenix, G K

    2011-09-01

    Anthropogenic depletion of stratospheric ozone in Arctic latitudes has resulted in an increase of ultraviolet-B radiation (UV-B) reaching the biosphere. UV-B exposure is known to reduce above-ground biomass and plant height, to increase DNA damage and cause accumulation of UV-absorbing compounds in polar plants. However, many studies on Arctic mosses tended to be inconclusive. The importance of different water availability in influencing UV-B impacts on lower plants in the Arctic has been poorly explored and might partially explain the observed wide variation of responses, given the importance of water in controlling bryophyte physiology. This study aimed to assess the long-term responses of three common sub-Arctic bryophytes to enhanced UV-B radiation (+UV-B) and to elucidate the influence of water supply on those responses. Responses of three sub-Arctic bryophytes (the mosses Hylocomium splendens and Polytrichum commune and the liverwort Barbilophozia lycopodioides) to +UV-B for 15 and 13 years were studied in two field experiments using lamps for UV-B enhancement with identical design and located in neighbouring areas with contrasting water availability (naturally mesic and drier sites). Responses evaluated included bryophyte abundance, growth, sporophyte production and sclerophylly; cellular protection by accumulation of UV-absorbing compounds, β-carotene, xanthophylls and development of non-photochemical quenching (NPQ); and impacts on photosynthesis performance by maximum quantum yield (F(v) /F(m)) and electron transport rate (ETR) through photosystem II (PSII) and chlorophyll concentrations. Responses were species specific: H. splendens responded most to +UV-B, with reduction in both annual growth (-22 %) and sporophyte production (-44 %), together with increased β-carotene, violaxanthin, total chlorophyll and NPQ, and decreased zeaxanthin and de-epoxidation of the xanthophyll cycle pool (DES). Barbilophozia lycopodioides responded less to +UV-B, showing

  8. Labeling of adipose-derived stem cells with quantum dots provides stable and long-term fluorescent signal for ex vivo cell tracking.

    Science.gov (United States)

    Costa, Clautina R M; Feitosa, Matheus L T; Bezerra, Dayseanny O; Carvalho, Yulla K P; Olivindo, Rodrigo F G; Fernando, Pablo B; Silva, Gustavo C; Silva, Mirna L G; Ambrósio, Carlos E; Conde Júnior, Airton M; Argolo Neto, Napoleão M; Costa Silva, Laís M; Carvalho, Maria A M

    2017-04-01

    Stem cells derived from adipose tissue (ADSC) have been used in cell therapy as an alternative to treat chronic and degenerative diseases. Using biomedical and image trials to track the cells when infused in the target tissue is essential to control cell migration and adhesion. The objective of the present study was to label and assess the adhesion of goat adipose tissue-derived stem cells (g-ADSC) after cell infusion in animal models by tracking luminescent intracytoplasmatic nanocrystals. The cells were labeled by using Qdots. The g-ADSCs infused with nanocrystal were prepared either fresh or fixed and further visualized under a fluorescence microscope. The labeled cells were infused in the goat mammary glands and mouse testicles and kidneys via tail vein injection. Thirty days after cell infusion, biopsy was carried out for analyses. The g-ADSC cultures were presented with high cellularity and fibroblast morphology, even after infusion of the nanocrystals. It was possible, by processing in paraffin and under fluorescence microscopy, demonstrating the success of the labeling in the long term. Freezing mammary gland biopsies in liquid NO 2 did not alter the quality of labeling with Qdots. Therefore, g-ADSCs can be labeled with intracytoplasmatic nanocrystals (Qdots) enabling their in vitro and ex vivo tracking.

  9. Long-term depression-associated signaling is required for an in vitro model of NMDA receptor-dependent synapse pruning.

    Science.gov (United States)

    Henson, Maile A; Tucker, Charles J; Zhao, Meilan; Dudek, Serena M

    2017-02-01

    Activity-dependent pruning of synaptic contacts plays a critical role in shaping neuronal circuitry in response to the environment during postnatal brain development. Although there is compelling evidence that shrinkage of dendritic spines coincides with synaptic long-term depression (LTD), and that LTD is accompanied by synapse loss, whether NMDA receptor (NMDAR)-dependent LTD is a required step in the progression toward synapse pruning is still unknown. Using repeated applications of NMDA to induce LTD in dissociated rat neuronal cultures, we found that synapse density, as measured by colocalization of fluorescent markers for pre- and postsynaptic structures, was decreased irrespective of the presynaptic marker used, post-treatment recovery time, and the dendritic location of synapses. Consistent with previous studies, we found that synapse loss could occur without apparent net spine loss or cell death. Furthermore, synapse loss was unlikely to require direct contact with microglia, as the number of these cells was minimal in our culture preparations. Supporting a model by which NMDAR-LTD is required for synapse loss, the effect of NMDA on fluorescence colocalization was prevented by phosphatase and caspase inhibitors. In addition, gene transcription and protein translation also appeared to be required for loss of putative synapses. These data support the idea that NMDAR-dependent LTD is a required step in synapse pruning and contribute to our understanding of the basic mechanisms of this developmental process. Published by Elsevier Inc.

  10. Long term study of mechanical

    Directory of Open Access Journals (Sweden)

    Ahmed M. Diab

    2016-06-01

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

  11. a long-term study

    OpenAIRE

    Petereit, Frank

    2016-01-01

    The hospital mortality rate of renal transplant patients admitted to intensive care units (ICU) is considered to be significantly higher compared to general ICU patients. Data concerning the long term outcomes of these patients is lacking. Furthermore, little data exists to guide the management of immunosuppression (IS) in critically ill patients on ICU. The author hypothesizes that a reduced IS on ICU will not lead to significantly increased long-term mortality, rejections and transplant fai...

  12. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.

    2009-01-01

    to represent large-diameter axons that have failed to myelinate. Conditional neuregulin-1 ablation resulted in a reduced sensitivity to noxious mechanical stimuli. These findings emphasize the importance of neuregulin-1 in mediating the signaling between axons and both myelinating and nonmyelinating Schwann...... cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood Udgivelsesdato: 2009/6/17...

  13. A relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior.

    Directory of Open Access Journals (Sweden)

    Jacki M Rorabaugh

    Full Text Available Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM display signatures of hedonic feeding including bingeing and altered DA receptor (R numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day exposure to the IAM, rats given 8-12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR. This activation was negatively correlated with orexin (Orx neuron activation in the lateral hypothalamus/perifornical area (LH/PeF, a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p. equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  14. Signal-transducing adaptor protein-2 promotes generation of functional long-term memory CD8+ T cells by preventing terminal effector differentiation.

    Science.gov (United States)

    Muraoka, Daisuke; Seo, Naohiro; Hayashi, Tae; Hyuga-Amaike, Chisaki; Okamori, Kana; Tawara, Isao; Harada, Naozumi; Shiku, Hiroshi

    2017-05-09

    Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade. Following T cell activation, STAP2 expression was transiently reduced but was subsequently recovered and augmented. Analysis using small-interfering RNA (siRNA) demonstrated that restored STAP2 expression was associated with the activation of STAT3/SOCS3 signals and maintenance of cytotoxic T lymphocytes (CTLs) secondary responses by preventing their differentiation into terminal effector cells. Notably, this STAP2-dependent memory differentiation was observed in the spleen, but not in the lymph nodes (LNs). These findings indicate an essential role for STAP2 in the generation of a high-quality memory CD8+ CTLs periphery, and suggest the therapeutic potential of STAP2 in cancer patients.

  15. [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; Phospitalization (OR=1.7; CI95%: 1.4-2.1; Plong-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 significantly less risk of long-term hospitalization than those of large cities. We found no influence of material and social deprivation in the long-term hospitalizations. Long-term hospitalization in psychiatry only concerns a minority of patients but represents the fifth of the total number of days of

  16. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.

    2009-01-01

    Neuregulin-1 has a key role in mediating signaling between axons and Schwann cells during development. A limitation to studying its role in adulthood is the embryonic lethality of global Nrg1 gene deletion. We used the Cre-loxP system to generate transgenic mice in which neuregulin-1 is condition......Neuregulin-1 has a key role in mediating signaling between axons and Schwann cells during development. A limitation to studying its role in adulthood is the embryonic lethality of global Nrg1 gene deletion. We used the Cre-loxP system to generate transgenic mice in which neuregulin-1...... is conditionally ablated in the majority of small-diameter and a proportion of large-diameter sensory neurons that have axons conducting in the C- and Adelta-fiber range, respectively. Sensory neuron-specific neuregulin-1 ablation resulted in abnormally large Remak bundles with axons clustered in "polyaxonal...... cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood Udgivelsesdato: 2009/6/17...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein....../day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P......) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet....

  18. Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens.

    Science.gov (United States)

    Renteria, Rafael; Buske, Tavanna R; Morrisett, Richard A

    2018-03-01

    The nucleus accumbens (NAc) is a critical component of the mesocorticolimbic system and is involved in mediating the motivational and reinforcing aspects of ethanol consumption. Chronic intermittent ethanol (CIE) exposure is a reliable model to induce ethanol dependence and increase volitional ethanol consumption in mice. Following a CIE-induced escalation of ethanol consumption, NMDAR (N-methyl-D-aspartate receptor)-dependent long-term depression in D1 dopamine receptor expressing medium spiny neurons of the NAc shell was markedly altered with no changes in plasticity in D1 dopamine receptor medium spiny neurons from the NAc core. This disruption of plasticity persisted for up to 2 weeks after cessation of ethanol access. To determine if changes in AMPA receptor (AMPAR) composition contribute to this ethanol-induced neuroadaptation, we monitored the rectification of AMPAR excitatory postsynaptic currents (EPSCs). We observed a marked decrease in the rectification index in the NAc shell, suggesting the presence of GluA2-lacking AMPARs. There was no change in the amplitude of spontaneous EPSCs (sEPSCs), but there was a transient increase in sEPSC frequency in the NAc shell. Using the paired pulse ratio, we detected a similar transient increase in the probability of neurotransmitter release. With no change in sEPSC amplitude, the change in the rectification index suggests that GluA2-containing AMPARs are removed and replaced with GluA2-lacking AMPARs in the NAc shell. This CIE-induced alteration in AMPAR subunit composition may contribute to the loss of NMDAR-dependent long-term depression in the NAc shell and therefore may constitute a critical neuroadaptive response underlying the escalation of ethanol intake in the CIE model. © 2017 Society for the Study of Addiction.

  19. Enhancing thermal stability of a highly concentrated insulin formulation with Pluronic F-127 for long-term use in microfabricated implantable devices.

    Science.gov (United States)

    Li, Jason; Chu, Michael K; Lu, Brian; Mirzaie, Sako; Chen, Kuan; Gordijo, Claudia R; Plettenburg, Oliver; Giacca, Adria; Wu, Xiao Yu

    2017-08-01

    Development of highly concentrated formulations of protein and peptide drugs is a major challenge due to increased susceptibility to aggregation and precipitation. Numerous drug delivery systems including implantable and wearable controlled-release devices require thermally stable formulations with high concentrations due to limited device sizes and long-term use. Herein we report a highly concentrated insulin gel formulation (up to 80 mg/mL, corresponding to 2200 IU/mL), stabilized with a non-ionic amphiphilic triblock copolymer (i.e., Pluronic F-127 (PF-127)). Chemical and physical stability of insulin was found to be improved with increasing polymer concentration, as evidenced by reduced insulin fibrillation, formation of degradation products, and preserved secondary structure as measured by HPLC and circular dichroism spectroscopy, respectively. This formulation exhibits excellent insulin stability for up to 30 days in vitro under conditions of continuous shear at 37 °C, attributable to the amphiphilic properties of the copolymer and increased formulation viscosity. The mechanism of stabilizing insulin structure by PF-127 was investigated by coarse-grained molecular dynamics (CG-MD), all-atom MD, and molecular docking simulations. The computation results revealed that PF-127 could reduce fibrillation of insulin by stabilizing the secondary structure of unfolded insulin and forming hydrophobic interaction with native insulin. The gel formulations contained in microfabricated membrane-reservoir devices released insulin at a constant rate dependent on both membrane porosity and copolymer concentration. Subcutaneous implantation of the gel formulation-containing devices into diabetic rats resulted in normal blood glucose levels for the duration of drug release. These findings suggest that the thermally stable gel formulations are suitable for long-term and implantable drug delivery applications.

  20. `Snacking' causes long term attenuation of HPA axis stress responses and enhancement of brain FosB/delta FosB expression in rats

    Science.gov (United States)

    Christiansen, A.M.; DeKloet, A.D; Ulrich-Lai, Y.M.; Herman, J.P.

    2011-01-01

    A history of limited, intermittent intake of palatable food (sucrose drink) attenuates hypothalamic-pituitary-adrenal (HPA) axis stress responses and induces markers of neuronal plasticity in stress- and reward-regulatory brain regions. Synaptic plasticity could provide a mechanism for long-term changes in neuronal function, implying that sucrose stress-dampening may endure over long periods of time. The present study tests the persistence of HPA axis dampening and plasticity after cessation of palatable drinking. Adult, male Long-Evans rats (n = 10–13) with free access to water and chow were given additional twice-daily access to 4 ml sucrose (30%) or water for 14 days. Rats were subsequently tested for HPA responsiveness to an acute (20-minute) restraint stress at 1, 6 and 21 days after the cessation of sucrose. Brains were collected for immunohistochemical analysis of FosB/deltaFosB, a marker of long-term neuronal plasticity, in the basolateral amygdala and nucleus accumbens. Prior sucrose consumption significantly decreased the plasma corticosterone response to restraint at one day after the last palatable drink presentation, and also increased FosB/deltaFosB-positive cells in the basolateral amygdala and in the nucleus accumbens core. This HPA-dampening persisted through 21 days after the termination of the palatable drink, as did the increased FosB/deltaFosB immunoreactivity in both the BLA and the NuAc core. These data suggest that chronic palatable food intake causes lasting changes in stress/reward-modulatory circuitry and that the suppressed hormonal response to stress that can persist well beyond periods of palatable drink exposure. PMID:21262247

  1. Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2017-04-01

    Full Text Available Summary: Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC function. Latexin (Lxn is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1 was a potential downstream target with a dramatic downregulation in Lxn-null HSCs. Enforced expression of Thbs1 restored the Lxn inactivation-mediated HSC phenotypes. This study reveals that Lxn plays an important role in the maintenance of homeostatic hematopoiesis, and it may lead to development of safe and effective approaches to manipulate HSCs for clinical benefit. : In this article, Liang and colleagues show that loss of latexin in vivo expands the HSC population and increases their survival and engraftment. Latexin regulates HSC function and hematopoiesis via the Thbs1 signaling pathway. Keywords: latexin, hematopoietic stem cell, repopulating advantage, expansion, survival, thrombospondin 1

  2. Heterogeneous hCG and hMG commercial preparations result in different intracellular signalling but induce a similar long-term progesterone response in vitro.

    Science.gov (United States)

    Riccetti, Laura; Klett, Danièle; Ayoub, Mohammed Akli; Boulo, Thomas; Pignatti, Elisa; Tagliavini, Simonetta; Varani, Manuela; Trenti, Tommaso; Nicoli, Alessia; Capodanno, Francesco; La Sala, Giovanni Battista; Reiter, Eric; Simoni, Manuela; Casarini, Livio

    2017-10-01

    Are four urinary hCG/menotropin (hMG) and one recombinant preparation characterized by different molecular features and do they mediate specific intracellular signaling and steroidogenesis? hCG and hMG preparations have heterogeneous compositions and mediate preparation-specific cell signaling and early steroidogenesis, although similar progesterone plateau levels are achieved in 24 h-treated human primary granulosa cells in vitro. hCG is the pregnancy hormone marketed as a drug for ARTs to induce final oocyte maturation and ovulation, and to support FSH action. Several hCG formulations are commercially available, differing in source, purification methods and biochemical composition. Commercial hCG preparations for ART or research purposes were compared in vitro. The different preparations were quantified by immunoassay with calibration against the hCG standard (Fifth IS; NIBSC 07/364). Immunoreactivity patterns, isoelectric points and oligosaccharide contents of hCGs were evaluated using reducing and non-reducing Western blotting, capillary isoelectric-focusing immunoassay and lectin-ELISA, respectively. Functional studies were performed in order to evaluate intracellular and total cAMP, progesterone production and β-arrestin 2 recruitment by ELISA and BRET, in both human primary granulosa lutein cells (hGLC) and luteinizing hormone (LH)/hCG receptor (LHCGR)-transfected HEK293 cells, stimulated by increasing hormone concentrations. Statistical analysis was performed using two-way ANOVA and Bonferroni post-test or Mann-Whitney's U-test as appropriate. Heterogeneous profiles were found among preparations, revealing specific molecular weight patterns (20-75 KDa range), isoelectric points (4.0-9.0 pI range) and lectin binding (P hCG/hMG preparations is provided in International Units (IU) by in-vivo bioassay and calibration against an International Standard, although it is an unsuitable unit of measure for in-vitro studies. The re-calibration against recombinant h

  3. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling.

    Science.gov (United States)

    Xiong, Yuyan; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-05-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells.

  4. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

    Science.gov (United States)

    Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-01-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells. PMID:24860943

  5. Re-imagining long-term services and supports: towards livable environments, service capacity, and enhanced community integration, choice, and quality of life for seniors.

    Science.gov (United States)

    Kane, Rosalie A; Cutler, Lois J

    2015-04-01

    In the half century since enactment of the 1965 Great Society programs, accomplishments were gradually made to improve access to and quality of long-term services and supports (LTSS), including: mitigation of financial and care abuses in nursing facilities (NFs); substantial rebalancing of LTSS towards consumer-preferred home-and-community-based services (HCBS); increasing flexible consumer-centered HCBS including payment to family caregivers; and more assisted-living and housing options for seniors with heavy care needs. A unified planning and advocacy agenda across age and disability type and greater consumer transparency fueled progress. Nonetheless, LTSS is a broken system; persistent problems interfere with substantial and necessary change. These include; over-emphasis on safety for LTSS consumers; inattention to physical environments in all settings; regulatory and professional rigidity; and poor communication and information. Our recommendations are aimed at builders and designers, LTSS professionals, regulators, and educators/trainers; the last may be crucial in forging new consensus and over-coming entrenched beliefs. Policy recommendations include relatively narrow steps-for example, requiring single occupancy in all NFs and assisted living settings financed with public dollars-to broad reworking of the prerequisites for livable age-friendly (and dementia-friendly) communities and for a capable, flexible LTSS workforce. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Three-dimensional graphene sheets with NiO nanobelt outgrowths for enhanced capacity and long term high rate cycling Li-ion battery anode material

    Science.gov (United States)

    Shi, Waipeng; Zhang, Yingmeng; Key, Julian; Shen, Pei Kang

    2018-03-01

    An efficient synthesis method to grow well attached NiO nanobelts from 3D graphene sheets (3DGS) is reported herein. Ni-ion exchanged resin provides the initial Ni reactant portion, which serves both as a catalyst to form 3DGS and then as a seeding agent to grow the NiO nanobelts. The macroporous structure of 3DGS provides NiO containment to achieve a high cycling stability of up to 445 mAh g-1 after 360 cycles (and >112% capacity retention after 515 cycles) at a high current density of 2 A g-1. With a 26.8 wt.% content of NiO on 3DGS, increases in specific and volumetric capacity were 41.6 and 75.7% respectively over that of 3DGS at matching current densities. Therefore, the seeded growth of NiO nanobelts from 3DGS significantly boosts volumetric capacity, while 3DGS enables high rate long term cycling of the NiO. The high rate cycling stability of NiO on 3DGS can be attributed to (i) good attachment and contact to the large surface of 3DGS, (ii) high electron conductivity and rapid Li-ion transfer (via the interconnected, highly conductive graphitized walls of 3DGS) and (iii) buffering void space in 3DGS to contain volume expansion of NiO during charge/discharge.

  7. 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

  8. Long-term data archiving

    Energy Technology Data Exchange (ETDEWEB)

    Moore, David Steven [Los Alamos National Laboratory

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  10. Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.

    Science.gov (United States)

    Ahmed, Faruk; Khan, Moududur R; Akhtaruzzaman, Mohammad; Karim, Rezaul; Williams, Gail; Torlesse, Harriet; Darnton-Hill, Ian; Dalmiya, Nita; Banu, Cadi P; Nahar, Badrun

    2010-10-01

    Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.

  11. Intermittent hypoxia-induced respiratory long-term facilitation is dominated by enhanced burst frequency, not amplitude, in spontaneously breathing urethane-anesthetized neonatal rats.

    Science.gov (United States)

    Reid, Inefta M; Solomon, Irene C

    2014-01-01

    Acute intermittent hypoxia (AIH) triggers a form of respiratory plasticity known as long-term facilitation (LTF), which is manifested as a progressive increase in respiratory motor activity that lasts for minutes to hours after the hypoxic stimulus is removed. Respiratory LTF has been reported in numerous animal models, but it appears to be influenced by a variety of factors (e.g., species, age, and gender). While most studies focusing on respiratory LTF have been conducted in adult (including young adult) rat preparations, little is known about the influence of postnatal maturation on AIH-induced respiratory LTF. To begin to address this issue, we examined diaphragm EMG activity in response to and at 5-min intervals for 60 min following three 5-min episodes of hypoxia (8% O2) in urethane-anesthetized spontaneously breathing P14-P15 neonatal rats (n=15). For these experiments, the hypoxic episodes were separated by hyperoxia (40% O2), and all rats were continuously supplied with ~4% CO2. During the AIH trials, burst frequency was increased by ~20-90% above baseline in each of the rats examined while changes in burst amplitude were highly variable. Following the AIH episodes, respiratory LTF was characterized by predominantly an increase in burst frequency (fLTF) ranging from ~10% to 55%, with most rats exhibiting a 20-40% increase. In seven rats, however, an increase in amplitude (ampLTF) (~10%, n=3; ~20%, n=3; ~30%, n=1) was also noted. These data suggest that in contrast to observations in anesthetized ventilated adult rats, in anesthetized spontaneously breathing P14-P15 neonatal rats, respiratory LTF is dominated by fLTF, not ampLTF. © 2014 Elsevier B.V. All rights reserved.

  12. Long-term manure amendments and chemical fertilizers enhanced soil organic carbon sequestration in a wheat (Triticum aestivum L.)-maize (Zea mays L.) rotation system.

    Science.gov (United States)

    Zhang, Shuiqing; Huang, Shaomin; Li, Jianwei; Guo, Doudou; Lin, Shan; Lu, Guoan

    2017-06-01

    The carbon sequestration potential is affected by cropping system and management practices, but soil organic carbon (SOC) sequestration potential under fertilizations remains unclear in north China. This study examined SOC change, total C input to soil and, via integration of these estimates over years, carbon sequestration efficiency (CSE, the ratio of SOC change over C input) under no fertilization (control), chemical nitrogen fertilizer alone (N) or combined with phosphorus and potassium fertilizers (NP, NK, PK and NPK), or chemical fertilizers combined with low or high (1.5×) manure input (NPKM and 1.5NPKM). Results showed that, as compared with the initial condition, SOC content increased by 0.03, 0.06, 0.05, 0.09, 0.16, 0.26, 0.47 and 0.68 Mg C ha -1 year -1 under control, N, NK, PK, NP, NPK, NPKM and 1.5NPKM treatments respectively. Correspondingly, the C inputs of wheat and maize were 1.24, 1.34, 1.55, 1.33, 2.72, 2.96, 2.97 and 3.15 Mg ha -1 year -1 respectively. The long-term fertilization-induced CSE showed that about 11% of the gross C input was transformed into SOC pool. Overall, this study demonstrated that decade-long manure input combined with chemical fertilizers can maintain high crop yield and lead to SOC sequestration in north China. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  13. Long-term working memory.

    Science.gov (United States)

    Ericsson, K A; Kintsch, W

    1995-04-01

    To account for the large demands on working memory during text comprehension and expert performance, the traditional models of working memory involving temporary storage must be extended to include working memory based on storage in long-term memory. In the proposed theoretical framework cognitive processes are viewed as a sequence of stable states representing end products of processing. In skilled activities, acquired memory skills allow these end products to be stored in long-term memory and kept directly accessible by means of retrieval cues in short-term memory, as proposed by skilled memory theory. These theoretical claims are supported by a review of evidence on memory in text comprehension and expert performance in such domains as mental calculation, medical diagnosis, and chess.

  14. Analysing long term discursive processes

    DEFF Research Database (Denmark)

    Horsbøl, Anders

    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...... 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...

  15. Murine model of long term obstructive jaundice

    Science.gov (United States)

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

    2016-01-01

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

  16. Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long-term outcomes and risk factors for hypervascular transformation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Seek [Chonbuk National University Medical School and Hospital, Department of Radiology, Jeonju-si, Chonbuk (Korea, Republic of); Song, Ji Soo; Lee, Hyun Kyung; Han, Young Min [Chonbuk National University Medical School and Hospital, Department of Radiology, Jeonju-si, Chonbuk (Korea, Republic of); Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Research Institute of Clinical Medicine, Chonbuk (Korea, Republic of)

    2016-10-15

    To evaluate the long-term outcomes and imaging features associated with hypervascularization of hypovascular nodules that show T2 iso-/hypointensity and hypointensity on hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) images in patients with chronic liver disease. Sixty patients and 114 nodules, which were hypovascular and iso-/hypointense on T2-weighted images and hypointense on HBP of gadoxetic acid-enhanced MRI, were included. We evaluated the effect of baseline clinical features, baseline MR features and growth rate on subsequent hypervascularization. Twenty-seven nodules in 21 patients transformed to hypervascular hepatocellular carcinoma (HCC). Using multivariate Cox analysis, T1 hyperintensity (hazard ratio [HR] = 2.69, P = 0.021), previous history of HCC (HR = 2.64, P = 0.021), and initial nodule size (HR = 1.09, P = 0.046) were identified to be associated with hypervascularization. The growth rate of nodules was a more powerful determinant of subsequent hypervascularization than baseline clinical and MR features. At long-term follow-up after >3 years, only one nodule with T1 isointensity showed hypervascularization. Careful follow-up or diagnostic procedures, such as biopsy, should be considered for up to 3 years after detection of hypointense nodules on HBP with T1 hyperintensity or a higher growth rate. (orig.)

  17. 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.

  18. Magnetic Beads Enhance Adhesion of NIH 3T3 Fibroblasts: A Proof-of-Principle In Vitro Study for Implant-Mediated Long-Term Drug Delivery to the Inner Ear.

    Science.gov (United States)

    Aliuos, Pooyan; Schulze, Jennifer; Schomaker, Markus; Reuter, Günter; Stolle, Stefan R O; Werner, Darja; Ripken, Tammo; Lenarz, Thomas; Warnecke, Athanasia

    2016-01-01

    Long-term drug delivery to the inner ear may be achieved by functionalizing cochlear implant (CI) electrodes with cells providing neuroprotective factors. However, effective strategies in order to coat implant surfaces with cells need to be developed. Our vision is to make benefit of electromagnetic field attracting forces generated by CI electrodes to bind BDNF-secreting cells that are labelled with magnetic beads (MB) onto the electrode surfaces. Thus, the effect of MB-labelling on cell viability and BDNF production were investigated. Murine NIH 3T3 fibroblasts-genetically modified to produce BDNF-were labelled with MB. Atomic force and bright field microscopy illustrated the internalization of MB by fibroblasts after 24 h of cultivation. Labelling cells with MB did not expose cytotoxic effects on fibroblasts and allowed adhesion on magnetic surfaces with sufficient BDNF release. Our data demonstrate a novel approach for mediating enhanced long-term adhesion of BDNF-secreting fibroblasts on model electrode surfaces for cell-based drug delivery applications in vitro and in vivo. This therapeutic strategy, once transferred to cells suitable for clinical application, may allow the biological modifications of CI surfaces with cells releasing neurotrophic or other factors of interest.

  19. Magnetic Beads Enhance Adhesion of NIH 3T3 Fibroblasts: A Proof-of-Principle In Vitro Study for Implant-Mediated Long-Term Drug Delivery to the Inner Ear.

    Directory of Open Access Journals (Sweden)

    Pooyan Aliuos

    Full Text Available Long-term drug delivery to the inner ear may be achieved by functionalizing cochlear implant (CI electrodes with cells providing neuroprotective factors. However, effective strategies in order to coat implant surfaces with cells need to be developed. Our vision is to make benefit of electromagnetic field attracting forces generated by CI electrodes to bind BDNF-secreting cells that are labelled with magnetic beads (MB onto the electrode surfaces. Thus, the effect of MB-labelling on cell viability and BDNF production were investigated.Murine NIH 3T3 fibroblasts-genetically modified to produce BDNF-were labelled with MB.Atomic force and bright field microscopy illustrated the internalization of MB by fibroblasts after 24 h of cultivation. Labelling cells with MB did not expose cytotoxic effects on fibroblasts and allowed adhesion on magnetic surfaces with sufficient BDNF release.Our data demonstrate a novel approach for mediating enhanced long-term adhesion of BDNF-secreting fibroblasts on model electrode surfaces for cell-based drug delivery applications in vitro and in vivo. This therapeutic strategy, once transferred to cells suitable for clinical application, may allow the biological modifications of CI surfaces with cells releasing neurotrophic or other factors of interest.

  20. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and morphologic MRI of cartilage in the long-term follow-up after Legg–Calvé–Perthes disease (LCPD)

    International Nuclear Information System (INIS)

    Holstein, Arne; Zilkens, Christoph; Bittersohl, Bernd

    2011-01-01

    The purpose of the present study was to evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the detection of cartilage changes versus morphologic imaging in the long-term course of Legg–Calvé–Perthes disease (LCPD). A total of 31 hips in 26 patients (mean age, 30.0 years; range, 18–54 years) who were diagnosed with LCPD in childhood were included. Twenty-one radiographically normal contralateral hips served as controls. dGEMRIC indices of femoral and acetabular cartilage in the weight-bearing zone. Cartilage morphology was classified on radial PD-weighted images according to the modified Outerbridge classification. Mean dGEMRIC values of cartilage were significantly lower in hips after LCPD than in the radiographically normal contralateral hips (513 ± 100 ms vs. 579 ± 103 ms; P = 0.026). In 24 out of 31 LCPD hips and in 4 out of 21 radiographically normal contralateral hips, morphological cartilage changes were noted. Analysis of variance analysis revealed a significant influence of Outerbridge grading on decreased T1-values (P = 0.031). Our results suggest that dGEMRIC at 1.5 T is suitable to assess cartilage quality changes in the long-term follow-up after LCPD. The evaluation of biochemical cartilage quality with dGEMRIC may provide additional information about early cartilage changes occurring without visible alterations of cartilage morphology.

  1. Navigating Long-Term Care

    Directory of Open Access Journals (Sweden)

    James D. Holt MD

    2017-03-01

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

  2. Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice.

    Science.gov (United States)

    Liu, Yi; Zhang, Cuiping; Li, Zhenyu; Wang, Chi; Jia, Jianhang; Gao, Tianyan; Hildebrandt, Gerhard; Zhou, Daohong; Bondada, Subbarao; Ji, Peng; St Clair, Daret; Liu, Jinze; Zhan, Changguo; Geiger, Hartmut; Wang, Shuxia; Liang, Ying

    2017-04-11

    Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1) was a potential downstream target with a dramatic downregulation in Lxn-null HSCs. Enforced expression of Thbs1 restored the Lxn inactivation-mediated HSC phenotypes. This study reveals that Lxn plays an important role in the maintenance of homeostatic hematopoiesis, and it may lead to development of safe and effective approaches to manipulate HSCs for clinical benefit. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Long-term feeding of hydroalcoholic extract powder of Lepidium meyenii (maca) enhances the steroidogenic ability of Leydig cells to alleviate its decline with ageing in male rats.

    Science.gov (United States)

    Yoshida, K; Ohta, Y; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Tamada, H

    2018-02-01

    This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats. © 2017 Blackwell Verlag GmbH.

  4. Positive assortative mating with selection restrictions on group coancestry enhances gain while conserving genetic diversity in long-term forest tree breeding.

    Science.gov (United States)

    Rosvall, O; Mullin, T J

    2003-08-01

    Selection and mating principles in a closed breeding population (BP) were studied by computer simulation. The BP was advanced, either by random assortment of mates (RAM), or by positive assortative mating (PAM). Selection was done with high precision using clonal testing. Selection considered both genetic gain and gene diversity by "group-merit selection", i.e. selection for breeding value weighted by group coancestry of the selected individuals. A range of weights on group coancestry was applied during selection to vary parent contributions and thereby adjust the balance between gain and diversity. This resulted in a series of scenarios with low to high effective population sizes measured by status effective number. Production populations (PP) were selected only for gain, as a subset of the BP. PAM improved gain in the PP substantially, by increasing the additive variance (i.e. the gain potential) of the BP. This effect was more pronounced under restricted selection when parent contributions to the next generation were more balanced with within-family selection as the extreme, i.e. when a higher status effective number was maintained in the BP. In that case, the additional gain over the BP mean for the clone PP and seed PPs was 32 and 84% higher, respectively, for PAM than for RAM in generation 5. PAM did not reduce gene diversity of the BP but increased inbreeding, and in that way caused a departure from Hardy-Weinberg equilibrium. The effect of inbreeding was eliminated by recombination during the production of seed orchard progeny. Also, for a given level of inbreeding in the seed orchard progeny or in a mixture of genotypes selected for clonal deployment, gain was higher for PAM than for RAM. After including inbreeding depression in the simulation, inbreeding was counteracted by selection, and the enhancement of PAM on production population gain was slightly reduced. In the presence of inbreeding depression the greatest PP gain was achieved at still higher

  5. The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA receptor responses via a CaMKII pathway.

    Science.gov (United States)

    Nishizaki, Tomoyuki; Matsumura, Takuro

    2002-01-31

    The present study was conducted to assess the effect of aniracetam and its metabolites, such as 2-pyrrolidinone, p-anisic acid, and anisamide butyrate, on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, heteromerically formed of GluR1,2 (GluR1 and GluR2), GluR1,3 (GluR1 and GluR3), and GluR1,2,3 (GluR1, GluR2, and GluR3), expressed in Xenopus oocytes. 2-Pyrrolidinone potentiated kainate-evoked currents through GluR1,2,3 channels in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 300 microM, with a maximal effect at 100 microM. The potentiation was long-lasting, reaching approximately 180% of basal levels 60 min after 5-min treatment with 2-pyrrolidinone at 100 microM. 2-Pyrrolidinone (100 microM) potentiated GluR1,3 channel currents as observed in GluR1,2,3, but instead it depressed GluR1,2 currents. Aniracetam and p-anisic acid potentiated GluR1,2,3 channel currents, but to a lesser extent, each about 130 and 103% of basal levels 60 min after treatment at 100 microM. In contrast, anisamide butyrate had no potentiating effect on the currents. Potentiation of GluR1,2,3 channel currents obtained with 2-pyrrolidinone was inhibited by KN-93, a selective inhibitor of calcium/calmodulin-dependent protein kinase (CaMKII), while it was not affected by GF109203X, a selective inhibitor of protein kinase C or H-89, a selective inhibitor of cAMP-dependent protein kinase. The results of the present study suggest that 2-pyrrolidinone persistently enhances activity of the Ca2+-permeable AMPA receptors, GluR1,3 and GluR1,2,3, by interacting with CaMKII.

  6. Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder.

    Directory of Open Access Journals (Sweden)

    Hidehiro Umehara

    Full Text Available Selective serotonin reuptake inhibitors (SSRI are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD, while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics.We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS to examine the combined effects of genetic variants on the clinical response in OCD.While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses.Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.

  7. Induction of synaptic long-term potentiation after opioid withdrawal.

    Science.gov (United States)

    Drdla, Ruth; Gassner, Matthias; Gingl, Ewald; Sandkühler, Jürgen

    2009-07-10

    mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate receptors and a rise of postsynaptic calcium concentrations. In contrast, the acute depression by opioids is induced presynaptically at these synapses. Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and signal transduction pathways with OIH. These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia.

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

    Science.gov (United States)

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

    2001-01-01

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

  9. Long-term exposure to enhanced UV-B radiation has no significant effects on growth or secondary compounds of outdoor-grown Scots pine and Norway spruce seedlings

    International Nuclear Information System (INIS)

    Turtola, Satu; Sallas, Leena; Holopainen, Jarmo K.; Julkunen-Tiitto, Riitta; Kainulainen, Pirjo

    2006-01-01

    The effects of long-term enhanced UV-B radiation on growth and secondary compounds of two conifer species were studied in an outdoor experiment. Scots pine (Pinus sylvestris) seedlings were exposed for two growing seasons and Norway spruce (Picea abies) seedlings for three growing seasons to supplemental UV-B radiation, corresponding to a 30% increase in ambient UV-B radiation. The experiment also included appropriate controls for ambient and increased UV-A radiation. Enhanced UV-B did not affect the growth of the conifer seedlings. In addition, neither the concentrations of terpenes and phenolics in the needles nor the concentrations of terpenes in the wood were affected. However, in the UV-A control treatment the concentrations of diterpenes in the wood of Scots pine decreased significantly compared to the ambient control. Apparently, a small increase in UV-B radiation has no significant effects on the secondary compounds and growth of Scots pine and Norway spruce seedlings. - Enhanced UV-B does not affect the growth and secondary compounds of boreal conifer seedlings

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  12. Long-term multipactor discharge in multicarrier systems

    International Nuclear Information System (INIS)

    Anza, S.; Vicente, C.; Gimeno, B.; Boria, V. E.; Armendariz, J.

    2007-01-01

    A new mechanism of long-term multipactor in multicarrier systems is studied employing both analytical and numerical methods. In particular, the investigation is focused on the impact that a realistic secondary emission yield at low energies produces on the development of long term multipactor. A novel analytical model for this interperiod charge accumulation is presented using the traditional multipactor theory for parallel plates, and approximating the multicarrier signal as a single-carrier signal modulated by a pulsed signal envelope. The analytical predictions are verified by numerical simulations for a typical rectangular waveguide. The analytical and numerical results demonstrate that the susceptibility of the system to develop a long-term multipactor discharge increases with higher values of low-energy secondary emission yield

  13. Signal changes of bone marrow in MRI under long-term treatment with granulocyte colony-stimulating factors; Veraenderungen des Knochenmarksignals in der MRT unter Langzeittherapie mit Granulozytenkolonie stimulierenden Faktoren

    Energy Technology Data Exchange (ETDEWEB)

    Scherer, A.; Engelbrecht, V.; May, P.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Neises, G. [Duesseldorf Univ. (Germany). Klinik fuer Stoffwechselstoerungen und Ernaehrung; Wendel, U. [Duesseldorf Univ. (Germany). Klinik fuer Allgemeine Paediatrie

    2001-02-01

    Purpose: Recurrent infections in patients with glycogen storage disease (GSD) type lb resulting from an associated neutropenia are frequently treated with granulocyte colony-stimulating factors (G-CSF). The aim of this study was to evaluate the changes occurring in bone marrow by magnetic resonance imaging (MRI) in these patients. Material and Methods: The distal femoral and tibial bones of six patients with GSD lb were evaluated by MRI. Four of these patients were treated with G-CSF for at least 3.9 to a maximum of 8.2 years (mean 5.8 years). The imaging sequences encompassed spin-echo as well as short-time inversion recovery sequences. 4 of the 6 patients had bone marrow aspirations. Results: The patients who had undergone therapy with G-CSF showed a marked increase in signal strength in STIR sequences which encompassed the entire medullar cavity. In T{sub 1}-weighted images these areas were hypointense. Biopsies obtained from these patients showed a bone marrow hypercellularity. The patients without G-CSF therapy showed the same signal intensity changes but with a more discrete and localized pattern in the metaphyseal cavities. Conclusion: In subjects with GSD lb, an increased myelopoetic activity of the bone marrow which is intensified under long-term treatment with G-CSF can be demonstrated by MRI. (orig.) [German] Ziel: Patienten mit Glykogenspeichererkrankung (GSD) Typ lb werden aufgrund einer erhoehten Infektionsneigung bei Leukozytenfunktionsstoerung haeufig mit Granulozytenkolonie stimulierenden Faktoren (G-CSF) behandelt. Unser Ziel war es, bei diesen Patienten Veranderungen des Knochenmarksignals in der MRT zu evaluieren. Material und Methode: Die distalen Ober- und Unterschenkelknochen von 6 Patienten mit GSD lb wurden in der MRT untersucht. Vier dieser Patienten wurden durchschnittlich seit 5,8 Jahren mit G-CSF behandelt, zwei Patienten erhielten keine G-CSF-Therapie. Die Bildgebung umfasste Spin-Echo- sowie Short-time-inversion-recovery (STIR

  14. Long-term mortality after poliomyelitis

    DEFF Research Database (Denmark)

    Nielsen, Nete Munk; Rostgaard, Klaus; Juel, Knud

    2003-01-01

    .18-3.37). Apart from polio patients with respiratory failure, long-term mortality did not appear to increase until 20 years after discharge. Contracting severe paralytic poliomyelitis at a young age seemed to increase long-term mortality. The most common causes of death were polio sequelae (standardized mortality...... patients. CONCLUSIONS: Survivors of poliomyelitis, especially severely paralyzed polio patients, have an increased long-term mortality....

  15. HOME LONG-TERM CARE IN POLAND

    Directory of Open Access Journals (Sweden)

    Ewa Kułagowska

    2011-06-01

    Full Text Available The considerable proportion of the elderly, the chronically ill and the disabled in community is an economic and organizational challenge for the state social policy. It requires a large, steadily increasing financing from the public funds and creating an optional care model to fulfill the needs of citizens and guarantee high quality services. Development of the long-term care is one of the problems to be solved. This paper presents: – a long-term care forms, organization and tasks; – a role of long-term care but particularly home longterm care to protect health in Poland; – problems related with home long-term care functioning.

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

    Science.gov (United States)

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

    2016-01-01

    Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4 months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. PMID:26341144

  17. Financing long term liabilities (Germany)

    International Nuclear Information System (INIS)

    2003-01-01

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

  18. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    Science.gov (United States)

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  19. Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

    2016-05-01

    We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  20. PI3K signalling in GnRH actions on dispersed goldfish pituitary cells: relationship with PKC-mediated LH and GH release and regulation of long-term effects on secretion and total cellular hormone availability.

    Science.gov (United States)

    Pemberton, Joshua G; Orr, Michael E; Stafford, James L; Chang, John P

    2014-09-01

    Goldfish pituitary cells are exposed to two GnRHs, salmon (s)GnRH and chicken (c)GnRH-II. Phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) both participate in acute sGnRH- and cGnRH-II-stimulated LH and GH release. Using goldfish pituitary cells, we examined the relationship between PI3K and PKC in acute LH and GH secretion, and PI3K involvement in chronic hormone release and total LH and GH availability. The PI3K inhibitor LY294002 did not affect PKC agonists-induced LH or GH release, and PKC agonists did not alter PI3K p85 phosphorylation, suggesting PKC activation is not upstream of PI3K in acute hormone release. In 2, 6, 12 and 24h treatments, LY294002 did not affect LH release but stimulated total LH availability at 6h. sGnRH stimulatory actions on LH release and total availability at 12 and 24h, and cGnRH-II effects on these parameters at 6h were inhibited by LY294002. LY294002 enhanced basal GH release at 2 and 6h, but reduced total GH at 12 and 24h. Increased GH release was seen following 6, 12 and 24h of sGnRH, and 2, 6 and 24h of cGnRH-II treatment but total GH availability was only elevated by 24h cGnRH-II treatment. Whereas LY294002 inhibited GH release responses to sGnRH at 12h and cGnRH-II at 6h, it attenuated cGnRH-II-elicited, but not sGnRH-induced, effects on total GH. These results indicate that PI3K differentially modulates long-term basal and GnRH-stimulated hormone release, and total hormone availability, in a time-, cell-type-, and GnRH isoform-selective manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Long-term outcomes of young people who attempted suicide

    NARCIS (Netherlands)

    Grisham, Jessica R; Williams, Alishia D

    2014-01-01

    IMPORTANCE Suicidal behavior has increased since the onset of the global recession, a trend that may have long-term health and social implications. OBJECTIVE To test whether suicide attempts among young people signal increased risk for later poor health and social functioning above and beyond a

  2. Long-term survival after perforated diverticulitis

    NARCIS (Netherlands)

    J. Vermeulen (Jan); M.P. Gosselink (Martijn Pieter); W.C.J. Hop (Wim); E. van der Harst (Erwin); B.E. Hansen (Bettina); G.H.H. Mannaerts (Guido); P-P. Coene (Peter Paul); W.F. Weidema (Wibo); J.F. Lange (Johan)

    2011-01-01

    textabstractAim: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. Method: All patients

  3. The Long-Term Swap Rate and a General Analysis of Long-Term Interest Rates

    OpenAIRE

    Francesca Biagini; Alessandro Gnoatto; Maximilian H\\"artel

    2015-01-01

    We introduce here for the first time the long-term swap rate, characterised as the fair rate of an overnight indexed swap with infinitely many exchanges. Furthermore we analyse the relationship between the long-term swap rate, the long-term yield, see [4], [5], and [25], and the long-term simple rate, considered in [8] as long-term discounting rate. We finally investigate the existence of these long-term rates in two term structure methodologies, the Flesaker-Hughston model and the linear-rat...

  4. The Implementation of Long-Term Care

    Directory of Open Access Journals (Sweden)

    Andreja Rafaelič

    2012-12-01

    Full Text Available Long-term care is a new area of social protection that is based on the users needs and their understanding of the quality of life. In other countries direct payments are an important part of the long-term care systems. Discussed in the article are the development of direct payments in Slovenia and other countries. Different systems of long term care and direct payment schemes are presented. The slovene long term care system is provided through different laws and social secruity pillars and has yet to be established. Experiences of the pilot project in direct funding with the resettlements to the community are presented in the last part of the article. Direct payments are very effective in terms of resettlement of people from institutions into the community. New solutions for the new long term care law that will promote deinstitutionalisation and the development of community services are suggested.

  5. Industrial Foundations as Long-Term Owners

    DEFF Research Database (Denmark)

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

    Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... and particularly that industrial foundations possess characteristics that promote long-termism. Policymakers, business owners and managers interested in promoting long-term governance models should therefore reconsider the role of ownership structure....

  6. Acquirement and enhancement of remote speech signals

    Science.gov (United States)

    Lü, Tao; Guo, Jin; Zhang, He-yong; Yan, Chun-hui; Wang, Can-jin

    2017-07-01

    To address the challenges of non-cooperative and remote acoustic detection, an all-fiber laser Doppler vibrometer (LDV) is established. The all-fiber LDV system can offer the advantages of smaller size, lightweight design and robust structure, hence it is a better fit for remote speech detection. In order to improve the performance and the efficiency of LDV for long-range hearing, the speech enhancement technology based on optimally modified log-spectral amplitude (OM-LSA) algorithm is used. The experimental results show that the comprehensible speech signals within the range of 150 m can be obtained by the proposed LDV. The signal-to-noise ratio ( SNR) and mean opinion score ( MOS) of the LDV speech signal can be increased by 100% and 27%, respectively, by using the speech enhancement technology. This all-fiber LDV, which combines the speech enhancement technology, can meet the practical demand in engineering.

  7. An optimized lead system for long-term esophageal electrocardiography.

    Science.gov (United States)

    Niederhauser, T; Haeberlin, A; Marisa, T; Mattle, D; Abächerli, R; Goette, J; Jacomet, M; Vogel, R

    2014-04-01

    Long-term electrocardiography (ECG) featuring adequate atrial and ventricular signal quality is highly desirable. Routinely used surface leads are limited in atrial signal sensitivity and recording capability impeding complete ECG delineation, i.e. in the presence of supraventricular arrhythmias. Long-term esophageal ECG might overcome these limitations but requires a dedicated lead system and recorder design. To this end, we analysed multiple-lead esophageal ECGs with respect to signal quality by describing the ECG waves as a function of the insertion level, interelectrode distance, electrode shape and amplifier's input range. The results derived from clinical data show that two bipolar esophageal leads, an atrial lead with short (15 mm) interelectrode distance and a ventricular lead with long (80 mm) interelectrode distance provide non-inferior ventricular signal strength and superior atrial signal strength compared to standard surface lead II. High atrial signal slope in particular is observed with the atrial esophageal lead. The proposed esophageal lead system in combination with an increased recorder input range of ±20 mV minimizes signal loss due to excessive electrode motion typically observed in esophageal ECGs. The design proposal might help to standardize long-term esophageal ECG registrations and facilitate novel ECG classification systems based on the independent detection of ventricular and atrial electrical activity.

  8. Computational Theory Underlying Acute Vestibulo-ocular Reflex Motor Learning with Cerebellar Long-Term Depression and Long-Term Potentiation.

    Science.gov (United States)

    Inagaki, Keiichiro; Hirata, Yutaka

    2017-08-01

    The vestibulo-ocular reflex (VOR) can be viewed as an adaptive control system that maintains compensatory eye movements during head motion. As the cerebellar flocculus is intimately involved in this adaptive motor control of the VOR, the VOR has been a popular model system for investigating cerebellar motor learning. Long-term depression (LTD) and long-term potentiation (LTP) at the parallel fiber-Purkinje cell synapses are considered to play major roles in cerebellar motor learning. A recent study using mutant mice demonstrated cerebellar motor learning with hampered LTD; the study concluded that the parallel fiber-Purkinje cell LTD is not essential. More recently, multiple forms of plasticity have been found in the cerebellum, and they are believed to contribute to cerebellar motor learning. However, it is still unclear how synaptic plasticity modifies the signal processing that underlies motor learning in the flocculus. A computational simulation suggested that the plasticity present in mossy fiber-granule cell synapses improves VOR-related sensory-motor information transferred into granule cells, whereas the plasticity in the molecular layer stores this information as a memory under guidance from climbing fiber teaching signals. Thus, motor learning and memory are thought to be induced mainly by LTD and LTP at parallel fiber-Purkinje cell synapses and by rebound potentiation at molecular interneuron-Purkinje cell synapses among the multiple forms of plasticity in the cerebellum. In this study, we focused on the LTD and LTP at parallel fiber-Purkinje cell synapses. Based on our simulation, we propose that acute VOR motor learning accomplishes by simultaneous enhancement of eye movement signals via LTP and suppression of vestibular signals via LTD to increase VOR gain (gain-up learning). To decrease VOR gain (gain-down learning), these two signals are modified in the opposite directions; namely, LTD suppresses eye movement signals, whereas LTP enhances vestibular

  9. Signal enhancement with variable span linear filters

    CERN Document Server

    Benesty, Jacob; Jensen, Jesper R

    2016-01-01

    This book introduces readers to the novel concept of variable span speech enhancement filters, and demonstrates how it can be used for effective noise reduction in various ways. Further, the book provides the accompanying Matlab code, allowing readers to easily implement the main ideas discussed. Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal-to-noise ratio, Wiener, and tradeoff filters (including their new generalizations) can be obtained using the variable span filter framework. It then illustrates how the variable span filters can be applied in various contexts, namely in single-channel STFT-based enhancement, in multichannel enhancement in both the time and STFT domains, and, lastly, in time-domain binaural enhancement. In these contexts, the properties of ...

  10. Signal Enhancement with Variable Span Linear Filters

    DEFF Research Database (Denmark)

    Benesty, Jacob; Christensen, Mads Græsbøll; Jensen, Jesper Rindom

    . Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal...... the time and STFT domains, and, lastly, in time-domain binaural enhancement. In these contexts, the properties of these filters are analyzed in terms of their noise reduction capabilities and desired signal distortion, and the analyses are validated and further explored in simulations....

  11. Long-Term Retardation of Uranium in the KURT Environment

    International Nuclear Information System (INIS)

    Baik, Min Hoon; Shin, Joo Do; Park, Tae Jin

    2016-01-01

    One of possibilities resolving this issue is to study the migration and retardation processes of radionuclides in the subsurface environments by using naturally occurring radionuclides as analogues of radioactive waste. To date, however, the long-term behavior of radionuclides in a granitic groundwater system is not yet fully understood. The ubiquitous presence of uranium (U) in rocks makes it an ideal natural analogue for studying the behaviors of radionuclides in a deep geological repository for the final disposal of HLW. In this study, long-term retardation behavior of natural uranium was investigated using granite rock samples taken from the KURT (KAERI Underground Research Tunnel), located in Daejeon city. The distribution of uranium and its binding mechanism in granite samples were investigated using the sequential chemical extraction (SCE) technique combined with X-ray diffraction (XRD) and ICP-MS methods. In this study, the long-term retardation of uranium in the KURT environment was investigated using SCE and EPMA techniques combined with ICP-MS and XRD. Results showed that long-term interaction of rock with groundwater can change U species and mineralize dissolved U, which can consequently contribute to the retardation of U in the fractured granitic rock environment. This study will help us to understand the long-term behavior of radionuclides migrating through the fractured granite rock and then enhance the reliability of the safety assessment for a HLW repository

  12. Signal Enhancement with Variable Span Linear Filters

    DEFF Research Database (Denmark)

    Benesty, Jacob; Christensen, Mads Græsbøll; Jensen, Jesper Rindom

    This book introduces readers to the novel concept of variable span speech enhancement filters, and demonstrates how it can be used for effective noise reduction in various ways. Further, the book provides the accompanying Matlab code, allowing readers to easily implement the main ideas discussed....... Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal......-to-noise ratio, Wiener, and tradeoff filters (including their new generalizations) can be obtained using the variable span filter framework. It then illustrates how the variable span filters can be applied in various contexts, namely in single-channel STFT-based enhancement, in multichannel enhancement in both...

  13. Environmental and genetic preconditioning for long-term anoxia responses requires AMPK in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Bobby L LaRue

    2011-02-01

    Full Text Available Preconditioning environments or therapeutics, to suppress the cellular damage associated with severe oxygen deprivation, is of interest to our understanding of diseases associated with oxygen deprivation. Wildtype C. elegans exposed to anoxia enter into a state of suspended animation in which energy-requiring processes reversibly arrest. C. elegans at all developmental stages survive 24-hours of anoxia exposure however, the ability of adult hermaphrodites to survive three days of anoxia significantly decreases. Mutations in the insulin-like signaling receptor (daf-2 and LIN-12/Notch (glp-1 lead to an enhanced long-term anoxia survival phenotype.In this study we show that the combined growth environment of 25°C and a diet of HT115 E. coli will precondition adult hermaphrodites to survive long-term anoxia; many of these survivors have normal movement after anoxia treatment. Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia. Mutations in genes encoding components of AMPK (aak-2, aakb-1, aakb-2, aakg-2 suppress the environmentally and genetically induced long-term anoxia survival phenotype. We further determine that there is a correlation between the animals that survive long-term anoxia and increased levels of carminic acid staining, which is a fluorescent dye that incorporates in with carbohydrates such as glycogen.We conclude that small changes in growth conditions such as increased temperature and food source can influence the physiology of the animal thus affecting the responses to stress such as anoxia. Furthermore, this supports the idea that metformin should be further investigated as a therapeutic tool for treatment of oxygen-deprived tissues. Finally, the capacity for an animal to survive long bouts of severe oxygen deprivation is likely dependent on specific subunits of the heterotrimeric

  14. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

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

  15. 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

  16. Reforming long-term care in Europe

    National Research Council Canada - National Science Library

    Costa-i-Font, Joan

    2011-01-01

    .... Offers the very latest analysis of long-term care reform agendas in Europe. Compares countries comparatively less studied with the experiences of reform in Germany, the UK, Netherlands and Sweden...

  17. 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...

  18. Long-term outcomes after severe shock.

    Science.gov (United States)

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations.

  19. Manganese in long term paediatric parenteral nutrition.

    OpenAIRE

    Reynolds, A P; Kiely, E; Meadows, N

    1994-01-01

    The current practice of providing manganese supplementation to neonates on long term parenteral nutrition is leading to a high incidence of hypermanganesaemia. Magnetic resonance imaging (MRI) studies in adults on long term manganese parenteral nutrition have shown changes in TI weighted MRI images and similar findings in a neonate receiving trace element supplementation are reported here. Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times upper reference limit). ...

  20. Nutritional deficit and Long Term Potentiation alterations

    Directory of Open Access Journals (Sweden)

    M. Petrosino

    2009-01-01

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

  1. A new long-term care manifesto.

    Science.gov (United States)

    Kane, Robert L

    2015-04-01

    This article argues for a fresh look at how we provide long-term care (LTC) for older persons. Essentially, LTC offers a compensatory service that responds to frailty. Policy debate around LTC centers on costs, but we are paying for something we really don't want. Building societal enthusiasm (or even support) for LTC will require re-inventing and re-branding. LTC has three basic components: personal care, housing, and health care (primarily chronic disease management). They can be delivered in a variety of settings. It is rare to find all three done well simultaneously. Personal care (PC) needs to be both competent and compassionate. Housing must provide at least minimal amenities and foster autonomy; when travel time for PC raises costs dramatically, some form of clustered housing may be needed. Health care must be proactive, aimed at preventing exacerbations of chronic disease and resultant hospitalizations. Enhancing preferences means allowing taking informed risks. Payment incentives should reward both quality of care and quality of life, but positive outcomes must be defined as slowing decline. Paying for services but not for housing under Medicaid would automatically level the playing field between nursing homes (NH) and community-based services. Regulations should achieve greater parity between NH and community care and include both positive and negative feedback. Providing post-acute care should be separate from LTC. Using the tripartite LTC framework, we can create innovative flexible approaches to providing needed services for frail older persons in formats that are both desirable and affordable. Such care will be more socially desirable and hence worth paying for. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. 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.

  3. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H.; Ekholm, O.; Sjøgren, P.

    2017-01-01

    Background: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid therapy does not seem to provide pain relief, improvement in HRQOL and physical capacity in CNCP patients in a general population.......,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...

  4. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid therapy does not seem to provide pain relief, improvement in HRQOL and physical capacity in CNCP patients in a general population.......,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...

  5. 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...

  6. Long-term characteristics of nuclear emulsion

    International Nuclear Information System (INIS)

    Naganawa, N; Kuwabara, K

    2010-01-01

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

  7. Valuing a long-term care facility.

    Science.gov (United States)

    Mellen, C M

    1992-10-01

    The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

  8. 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...... Morten Bennedsen, INSEAD and Professor Joseph Fan, Chinese University of Hong Kong. It consists of 40 questions regarding assets in the family and roadblocks facing the family firm. The Family Business Map determines that the level of family assets in KALK is high, while the level of roadblocks is severe...

  9. PSA modeling of long-term accident sequences

    International Nuclear Information System (INIS)

    Georgescu, Gabriel; Corenwinder, Francois; Lanore, Jeanne-Marie

    2014-01-01

    In the context of the extension of PSA scope to include external hazards, in France, both operator (EDF) and IRSN work for the improvement of methods to better take into account in the PSA the accident sequences induced by initiators which affect a whole site containing several nuclear units (reactors, fuel pools,...). These methodological improvements represent an essential prerequisite for the development of external hazards PSA. However, it has to be noted that in French PSA, even before Fukushima, long term accident sequences were taken into account: many insight were therefore used, as complementary information, to enhance the safety level of the plants. IRSN proposed an external events PSA development program. One of the first steps of the program is the development of methods to model in the PSA the long term accident sequences, based on the experience gained. At short term IRSN intends to enhance the modeling of the 'long term' accident sequences induced by the loss of the heat sink or/and the loss of external power supply. The experience gained by IRSN and EDF from the development of several probabilistic studies treating long term accident sequences shows that the simple extension of the mission time of the mitigation systems from 24 hours to longer times is not sufficient to realistically quantify the risk and to obtain a correct ranking of the risk contributions and that treatment of recoveries is also necessary. IRSN intends to develop a generic study which can be used as a general methodology for the assessment of the long term accident sequences, mainly generated by external hazards and their combinations. This first attempt to develop this generic study allowed identifying some aspects, which may be hazard (or combinations of hazards) or related to initial boundary conditions, which should be taken into account for further developments. (authors)

  10. Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

    Science.gov (United States)

    Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

    2017-10-13

    The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

  11. Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles

    Directory of Open Access Journals (Sweden)

    Kong Lingxin

    2008-04-01

    Full Text Available Abstract Background Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1 particles that contain chimeric glycoprotein C (gC – glial cell line-derived neurotrophic factor (GDNF or brain-derived neurotrophic factor (BDNF proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression. Results Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal

  12. The long term characteristics of greenschist

    Science.gov (United States)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  13. Long-Term Stability of Social Participation

    Science.gov (United States)

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  14. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...

  15. Professionalism in Long-Term Care Settings

    Science.gov (United States)

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  16. Pituitary diseases : long-term psychological consequences

    NARCIS (Netherlands)

    Tiemensma, Jitske

    2012-01-01

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

  17. Long-term effects of ionizing radiation

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  18. Asthma Medicines: Long-Term Control

    Science.gov (United States)

    ... or injected, are sometimes of value to get asthma quickly under control when a child is beginning long-term asthma therapy. Inhaled corticosteroids ... Updated 11/21/2015 Source Guide to Your Childs Allergies and Asthma (Copyright © 2011 American Academy of Pediatrics) The information ...

  19. Long-term effects of directed forgetting.

    Science.gov (United States)

    Hupbach, Almut

    2018-03-01

    The intention to forget reduces the accessibility of information in memory, which is commonly explained with temporary retrieval difficulties. Long-term effects have rarely been studied, and results are inconsistent. The present study re-assessed the long-term effects of directed forgetting (DF). Participants encoded a first list of items (L1), and were then instructed to forget or to remember this list. Immediately afterwards, all participants were presented with a second list to remember. In Experiment 1, memory for L1 and L2 was assessed after a 24-h delay. The forget cue reduced the number of items that were recalled from L1. Experiment 2 implemented a 12-h delay between encoding and test that was either filled with day-time wakefulness or night-time sleep. Replicating the findings of Exp. 1, recall of L1 was reduced in the forget in comparison to the remember condition. Sleep in comparison to wakefulness significantly strengthened L1 memory in the remember group only. Taken together, the present study shows that the intention to forget can have long-lasting consequences. This suggests that different mechanisms underlie the short- and long-term effects of DF, with long-term effects potentially reflecting the preferential consolidation of information that has been identified as important during encoding.

  20. Long-term music training modulates the recalibration of audiovisual simultaneity.

    Science.gov (United States)

    Jicol, Crescent; Proulx, Michael J; Pollick, Frank E; Petrini, Karin

    2018-04-23

    To overcome differences in physical transmission time and neural processing, the brain adaptively recalibrates the point of simultaneity between auditory and visual signals by adapting to audiovisual asynchronies. Here, we examine whether the prolonged recalibration process of passively sensed visual and auditory signals is affected by naturally occurring multisensory training known to enhance audiovisual perceptual accuracy. Hence, we asked a group of drummers, of non-drummer musicians and of non-musicians to judge the audiovisual simultaneity of musical and non-musical audiovisual events, before and after adaptation with two fixed audiovisual asynchronies. We found that the recalibration for the musicians and drummers was in the opposite direction (sound leading vision) to that of non-musicians (vision leading sound), and change together with both increased music training and increased perceptual accuracy (i.e. ability to detect asynchrony). Our findings demonstrate that long-term musical training reshapes the way humans adaptively recalibrate simultaneity between auditory and visual signals.

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

    Energy Technology Data Exchange (ETDEWEB)

    Calin-Jageman, Robert J

    2009-09-12

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

  2. Long-Term Control Medications for Lung Diseases

    Science.gov (United States)

    ... Medications Asthma Medications Long-Term Control Medications Long-Term Control Medications Make an Appointment Ask a Question Refer Patient Long-term control medications are taken daily to control and ...

  3. Science and society: the role of long-term studies in environmental stewardship

    Science.gov (United States)

    Charles T. Driscoll; Kathleen F. Lambert; F. Stuart Chapin; David J. Nowak; Thomas A. Spies; Frederick J. Swanson; David B. Kittredge; Clarisse M. Hart

    2012-01-01

    Long-term research should play a crucial role in addressing grand challenges in environmental stewardship. We examine the efforts of five Long Term Ecological Research Network sites to enhance policy, management, and conservation decisions for forest ecosystems. In these case studies, we explore the approaches used to inform policy on atmospheric deposition, public...

  4. 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 Fascia thickness decreased significantly in both the asymptomatic and symptomatic groups (P Fascia thickness (P =.49) and presence of a heel...... spur (P =.88) at baseline had no impact on prognosis. At follow-up, fascia thickness and echogenicity had normalized in only 24% of the asymptomatic group. The mean fat pad thickness was 9.0 mm in patients who had received a US-guided corticosteroid injection and 9.4 mm in those who had not been given...

  5. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  6. French Approach for Long Term Storage Safety

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  7. Experiences of long-term tranquillizer use

    DEFF Research Database (Denmark)

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

    2001-01-01

    The aim of the article is to analyse narrative descriptions and experiences of long-term tranquillizer use. The analysis is based on a Danish in-depth study of 50 informants with a self-diagnosed dependency on tranquillizers. The theoretical analysis is dependent on psychodynamic reasoning. Furth...... use. Important themes frequently mentioned in the clients' descriptions are traumatic childhood experiences, identity problems, life crises in adulthood and difficulties in stopping taking psychotropic drugs....

  8. Long term evolution 4G and beyond

    CERN Document Server

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania

    2016-01-01

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

  9. Long-Term Contracting with Markovian Consumers

    OpenAIRE

    Marco Battaglini

    2005-01-01

    To study how a firm can capitalize on a long-term customer relationship, we characterize the optimal contract between a monopolist and a consumer whose preferences follow a Markov process. The optimal contract is nonstationary and has infinite memory, but is described by a simple state variable. Under general conditions, supply converges to the efficient level for any degree of persistence of the types and along any history, though convergence is history-dependent. In contrast, as with consta...

  10. The 2013 Long-Term Budget Outlook

    Science.gov (United States)

    2013-09-01

    and Social Security. Population projections depend on projections of fertility , immigration, and mortality. For fertility rates, CBO adopted the...projections, which differ from those of the Social Security trustees. Together, CBO’s long-term assump- tions about fertility , mortality, and...such as obesity and future medical technology, CBO has based its mortality projec- tions on a simple extrapolation of past trends. Conse- quently

  11. Long-Term Hearing Results After Ossiculoplasty.

    Science.gov (United States)

    Cox, Matthew D; Trinidade, Aaron; Russell, James Shep; Dornhoffer, John L

    2017-04-01

    To determine if the OOPS index is predictive of long-term hearing results after ossiculoplasty. Case series with retrospective chart review. Tertiary care otology practice. Adult and pediatric patients (3-88 years of age). Ossiculoplasty with cartilage tympanoplasty, with or without mastoidectomy. Primary outcome measures included short-term hearing results (pure-tone average air-bone gap [PTA-ABG] measured between 60 days and 1 year after surgery), long-term hearing results (PTA-ABG measured ≥5 years after surgery), and the rate of successful ABG closure to ≤20 dB. Secondary measures included the need for revision surgery, delayed tympanic membrane graft failure, worsening conductive hearing loss (after an initially satisfactory hearing result), and recurrence of cholesteatoma. There was no significant difference between adults and children for short-term hearing results (average post-op PTA-ABG was 18.9 dB vs. 19.8 dB, respectively; p = 0.544), long-term hearing results (average final PTA-ABG was 19.3 dB vs. 19.4 dB, respectively; p = 0.922), or rate of ABG closure to less than 20 dB (63.1% vs. 58.0%, p = 0.282). Spearman's rank-order correlation (ρ) identified a strong positive correlation between OOPS index score and average post-operative PTA-ABG (ρ = 0.983; p hearing outcomes in adult and pediatric patients undergoing ossiculoplasty in both the short term and the long term.

  12. Long-term effects of acoustic reafference training (ART).

    Science.gov (United States)

    Pizzera, Alexandra; Hohmann, Tanja; Streese, Lukas; Habbig, Anja; Raab, Markus

    2017-11-01

    In sport visual feedback is often used to enhance performance, mostly neglecting the auditory modality. However, athletes produce natural sounds when they move (acoustic reafferences) which they perceive and use to control their movements. We examined the short- and long-term effects of a training intervention on a complex movement by using acoustic reafferences. Natural step sounds produced during hurdling were recorded and played back to the participants immediately before each trial, with an increase (fast group), decrease (slow group), or no manipulation (control group) in the tempo. All groups increased their hurdling performance regarding overall running time, with the slow group showing the best performance development. After a 10-week retention, the fast and slow group further increased performance, whereas the control group declined. The repeated experience with acoustic information associated with the rhythmic pattern of hurdling may have helped developing a cognitive representation of that movement, especially regarding long-term effects.

  13. Long-Term Environmental Research Programs - Evolving Capacity for Discovery

    Science.gov (United States)

    Swanson, F. J.

    2008-12-01

    Long-term forestry, watershed, and ecological research sites have become critical, productive nodes for environmental science research and in some cases for work in the social sciences and humanities. The Forest Service's century-old Experimental Forests and Ranges and the National Science Foundation's 28- year-old Long-Term Ecological Research program have been remarkably productive in both basic and applied sciences, including characterization of acid rain and old-growth ecosystems and development of forest, watershed, and range management systems for commercial and other land use objectives. A review of recent developments suggests steps to enhance the function of collections of long-term research sites as interactive science networks. The programs at these sites have evolved greatly, especially over the past few decades, as the questions addressed, disciplines engaged, and degree of science integration have grown. This is well displayed by small, experimental watershed studies, which first were used for applied hydrology studies then more fundamental biogeochemical studies and now examination of complex ecosystem processes; all capitalizing on the legacy of intensive studies and environmental monitoring spanning decades. In very modest ways these collections of initially independent sites have functioned increasingly as integrated research networks addressing inter-site questions by using common experimental designs, being part of a single experiment, and examining long-term data in a common analytical framework. The network aspects include data sharing via publicly-accessible data-harvester systems for climate and streamflow data. The layering of one research or environmental monitoring network upon another facilitates synergies. Changing climate and atmospheric chemistry highlight a need to use these networks as continental-scale observatory systems for assessing the impacts of environmental change on ecological services. To better capitalize on long-term

  14. Murine model of long-term obstructive jaundice.

    Science.gov (United States)

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

    2016-11-01

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

  15. Long-term EARLINET dust observations

    Science.gov (United States)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be

  16. LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA.

    Science.gov (United States)

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

    2015-10-01

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

  17. Long-term governance for sustainability

    International Nuclear Information System (INIS)

    Martell, M.

    2007-01-01

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

  18. Long-term outcomes of infantile spasms

    Directory of Open Access Journals (Sweden)

    Seak Hee Oh

    2010-01-01

    Full Text Available Purpose : The aims of this study were to investigate the long-term outcomes in children with infantile spasms (IS and to identify the prognostic factors influencing their neurodevelopment. Methods : We retrospectively evaluated seventy two children over five years old who were treated for IS at Asan Medical Center, Seoul, Korea, between 1994 and 2007. Forty-three children were contacted by telephone or medical follow-up to assess their current neurodevelopmental status. Multiple logistic regression was used to calculate odds ratios (ORs and 95% confidence interval (95% CIs of risk factors for unfavorable outcomes. Results : The mean follow-up duration for these 43 children was 7.2¡?#?.5 ;years (range, 4.5 to 13.0 years. Of these, 13 (30.2% had cryptogenic and 30 (69.8% had symptomatic IS. Eleven (25.6% children were initially treated with adrenocorticotrophic hormone (ACTH therapy, with a mean treatment lag of 1.3¡?#?.9 ;months (range; 0.1 to 7.0 months. Eighteen (41.8% children clinically responded to initial treatment, as shown by EEG response. Overall, 22 (51.2% children had at least moderate neurodevelopmental disorders and 2 (4.8% died. In univariate analysis, etiology (symptomatic and poor electroclinical response to initial treatment were related to long-term unfavorable outcomes. In multivariate analysis, response to primary treatment was the sole significant independent risk factor with a high OR. Conclusion : Overall prognosis of children with IS was poor. Electroclinical non-responsiveness to initial treatment was related to unfavorable long-term outcomes, indicating that initial control of seizures may be important in reducing the likelihood of poor neurodevelopment.

  19. Transcriptional regulation of long-term potentiation.

    Science.gov (United States)

    Bliim, Nicola; Leshchyns'ka, Iryna; Sytnyk, Vladimir; Janitz, Michael

    2016-10-01

    Long-term potentiation (LTP), the persistent strengthening of synapses following high levels of stimulation, is a form of synaptic plasticity that has been studied extensively as a possible mechanism for learning and memory formation. The strengthening of the synapse that occurs during LTP requires cascades of complex molecular processes and the coordinated remodeling of pre-synaptic and post-synaptic neurons. Despite over four decades of research, our understanding of the transcriptional mechanisms and molecular processes underlying LTP remains incomplete. Identification of all the proteins and non-coding RNA transcripts expressed during LTP may provide greater insight into the molecular mechanisms involved in learning and memory formation.

  20. Human Behaviour in Long-Term Missions

    Science.gov (United States)

    1997-01-01

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

  1. Long Term Planning at IQ Metal

    DEFF Research Database (Denmark)

    2017-01-01

    This is a Danish version. This case about long term planning at the owner-managed manufacturing firm IQ Metal shows how the future management and ownership may be organized to utilize owner assets and minimize roadblocks. Initially, the owner-manager Bo Fischer Larsen explains how he acquired...... in The Owner Strategy Map into the questionnaire available on www.ejerstrategi-kortet.dk. Lastly, the Owner Strategy Map's recommendation of how to organize the future management and ownership of IQ Metal is explained....

  2. Rising Long-term Interest Rates

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    Rather than chronicle recent developments in European long-term interest rates as such, this paper assesses the impact of increases in those interest rates on economic performance and inflation. That puts us in a position to evaluate the economic pressures for further rises in those rates...... spending, debt service costs and shrinking fiscal space. There are also countervailing positive effects, which render the net negative effects on spending and the real costs of borrowing relatively small. The illustrative projections, based on techniques derived from an analysis of how financial markets...

  3. Long-term fasting and re-feeding in penguins.

    Science.gov (United States)

    Groscolas, R; Robin, J P

    2001-03-01

    Spontaneous fasting during reproduction (sometimes with a full stomach) and moult is a major characteristic of the annual cycle of penguins. Long-term fasting (up to four months in male emperor penguins) is anticipated by the accumulation of fat (incubation fast) and of fat and protein (moult fast). During most of the incubation fast, birds rely almost entirely on lipids as an energy source, body proteins being spared. However, below a critical (but non-total) fat store depletion, marked behavioural, metabolic, and endocrine changes occur. Spontaneous locomotor activity increases and the egg is transitorily left unincubated for increasingly long periods, until its definitive abandon and the bird departs to re-feed at sea. These changes are thought to be activated by an endogenous re-feeding signal triggered before lethal energy depletion. An increase in body protein catabolism in the face of a reduction in lipid availability and utilisation, and an increase in circulating corticosterone vs. a decrease in plasma prolactin, are likely to be major metabolic and hormonal components of this signal. The survival and rapid restoration of energy stores in birds having departed to re-feed at a stage of near total lipid depletion demonstrates the effectiveness of the re-feeding signal. Penguins, and possibly other seabirds, are therefore appropriate animal models for understanding the long-term interactions between body energy reserves and fasting, breeding and feeding physiology and behaviour.

  4. Toward a comprehensive long term nicotine policy.

    Science.gov (United States)

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

    2005-06-01

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

  5. Long-term environmental behaviour of radionuclides

    International Nuclear Information System (INIS)

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

    2000-04-01

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

  6. Sleep facilitates long-term face adaptation.

    Science.gov (United States)

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

    2013-10-22

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

  7. Andra long term memory project - 59277

    International Nuclear Information System (INIS)

    Charton, Patrick; Boissier, Fabrice; Martin, Guillaume

    2012-01-01

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

  8. Institutionalization and Organizational Long-term Success

    Directory of Open Access Journals (Sweden)

    Denise L. Fleck

    2007-05-01

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

  9. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-08-01

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

  10. Long-term environmental behaviour of radionuclides

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-04-01

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

  11. Neo bladder long term follow-up

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  12. Amyloid osteoarthropathy in long term hemodialysis patients

    International Nuclear Information System (INIS)

    Orzincolo, C.; Cardona, P.; Vita, G.; Bedani, P.L.; Farinelli, A.; Scutellari, P.N.

    1988-01-01

    The accumulation of amyloid in the bone and joint system has recently been recognized as a peculiar disease in patients undergoing long-term hemodialysis (5 years at least), especially in those who use cuprophan membranes. The pathology of amyloidosis is characterized by deposits of amyloid (β microglobulin mainly) in the bone, in the synovia, and in pericapsular soft tissues. The skeleton of 46 long-term hemodialysis patients (19 males and 27 females) was studied by X-ray; bone and joint abnormalities due to amyloid deposition were observed in 45% of cases. The shoulder, hip, and wrist were the most frequently involved joints. Destructive spondyloarthorapathy was present in 15% of cases. The radiographic patterns of AOD are generally divided into axial and peripheral lesions. In the appendicular skeleton abnormalities include: well-defined lytic areas (geodes), pathologic fractures, marginal erosions, and particular soft tissue swelling. Destructive spondyloarthropathy is frequently present in the cervical spine (85% of our cases) and is characterized by narrowing of the invertebral space, marginal erosion, and subchondral bone sclerosis of the vertebral body

  13. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    International Nuclear Information System (INIS)

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas

    2007-01-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

  14. Chronic sodium salicylate administration enhances population spike long-term potentiation following a combination of theta frequency primed-burst stimulation and the transient application of pentylenetetrazol in rat CA1 hippocampal neurons.

    Science.gov (United States)

    Gholami, Masoumeh; Moradpour, Farshad; Semnanian, Saeed; Naghdi, Nasser; Fathollahi, Yaghoub

    2015-11-15

    The effect of chronic administration of sodium salicylate (NaSal) on the excitability and synaptic plasticity of the rodent hippocampus was investigated. Repeated systemic treatment with NaSal reliably induced tolerance to the anti-nociceptive effect of NaSal (one i.p. injection per day for 6 consecutive days). Following chronic NaSal or vehicle treatment, a series of electrophysiological experiments on acute hippocampal slices (focusing on the CA1 circuitry) were tested whether tolerance to NaSal would augment pentylenetetrazol (PTZ)-induced long-term potentiation (LTP) and /or epileptic activity, and whether the augmentation was the same after priming activity with a natural stimulus pattern prior to PTZ. We noted an altered synaptic input-to-spike transformation, such that neuronal firing increased after a given synaptic drive. Population spike-LTP (PS-LTP) was increased in the NaSal-tolerant animals, but only when it was induced via a combination of electrical stimulation (theta pattern primed-burst stimulation) and the transient application of PTZ. Identifying and understanding these changes in neuronal excitability and synaptic plasticity following chronic salicylate treatment could prove useful in the clinical diagnosis or treatment of chronic aspirin-induced, or even idiopathic, seizure activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Long-term effects of synthetic fibers on concrete pipes

    Science.gov (United States)

    Farrokhi Gozarchi, Sasan

    The studies undertaken by this research were to evaluate the long-term performance and durability of synthetic fiber-reinforced concrete pipes. The target long-term performance is for 9000 hours. Two sets of pipes 8 ft. (2400 mm) long with inside diameters of 24 in. (600 mm) and 36 in. (1200 mm) were manufactured, with a wall thickness of 3 and 4 in., respectively. The pipes were produced based on ASTM C76, for a Class III type with a Wall B. The two set of pipes included RCP's (as control) and SYN-FRCP's. The SYN-FRCP's had several fiber dosages ranging from 6 lb/yd3 (3.5 kg/m 3) to 12 lb/yd3 (7.0 kg/m3) in order to evaluate the long-term performance of synthetic fiber-reinforced concrete pipes. The pipes were pre-cracked until the first visible crack was observed in the three-edge bearing test. As a result, the sustained load simulated, was calculated from the Peak D-load observed; and also the appropriate fiber dosages required for the 24. in (600 mm) and 36 in. (900 mm) pipes were obtained. Three of the 24 in. and three of the 36 in. pipes were installed in 7 ft. (2100 mm) and 8 ft. (2400 mm) wide trenches with 16 ft. (4800 mm) and 18 ft. (5500 mm) of cover respectively. The pipe was initially backfilled with native soil up to 2 ft. (600 mm) and 4 ft. (1200 mm) over the top of the pipe then backfilled again with pea-gravel weighing 100 lb/ft3, to a height of 14ft. to simulate the sustained loading. A type two installation was used during the development of the test setup. Once the long-term test set up was complete, the data was immediately recorded, and vertical deflections were observed from the time-dependent behavior of the pipes. It was observed from results obtained from the three-edge bearing test, that synthetic fibers improve the mechanical properties of concrete pipes, in dry-cast manufacturing. Also, it was observed from the time-dependent deformation, that there was no significant deformation of SYN-FRCP, while the shear capacity was enhanced. Based

  16. 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

  17. A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

    Science.gov (United States)

    Munjal, Sagar; Brand-Schieber, Elimor; Allenby, Kent; Spierings, Egilius L H; Cady, Roger K; Rapoport, Alan M

    2017-12-01

    DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms. This was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months. A total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all

  18. The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Kira V. Derkach

    2015-01-01

    Full Text Available In the last years the treatment of type 2 diabetes mellitus (DM2 was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC activity in the hypothalamus and normalized AC stimulation by β-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

  19. Autobiographical reasoning in long-term fandom

    Directory of Open Access Journals (Sweden)

    C. Lee Harrington

    2010-09-01

    Full Text Available We explore the social psychological processes through which fan-based experiences become situated in fans' larger life narratives. Drawing on original survey data with long-term U.S. soap opera fans, we examine how the psychological mechanism of autobiographical reasoning functions in fans' construction of self-narratives over time. The case study presented here is a subset of a larger investigation into the age-related structure of fans' activities, identities, and interpretive capacities. Situated at the intersections of gerontological (life span/life course theory and contemporary fan studies, our project mines relatively uninvestigated theoretical terrain. We conclude with a brief discussion of implications for future fan studies.

  20. Technology for long-term care.

    Science.gov (United States)

    Tak, Sunghee H; Benefield, Lazelle E; Mahoney, Diane Feeney

    2010-01-01

    Severe staff shortages in long-term care (LTC) make it difficult to meet the demands of the growing aging population. Further, technology-savvy Baby Boomers are expected to reshape the current institutional environments toward gaining more freedom and control in their care and lives. Voices from business, academia, research, advocacy organizations, and government bodies suggest that innovative technological approaches are the linchpin that may prepare society to cope with these projected demands. In this article, we review the current state of aging-related technology, identify potential areas for efficacy testing on improving the quality of life of LTC residents in future research, and discuss barriers to implementation of LTC technology. Finally, we present a vision of future technology use that could transform current care practices. Copyright 2010, SLACK Incorporated.

  1. Long term performance of radon mitigation systems

    International Nuclear Information System (INIS)

    Prill, R.; Fisk, W.J.

    2002-01-01

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

  2. Long term radioactive waste management policy

    International Nuclear Information System (INIS)

    Andrei, V.; Glodeanu, F.; Dina, D.

    2001-01-01

    Radioactive waste management is a key issue of the environmental policy of any company. According to the Romanian Nuclear Act (Law 111/1996) and the Environmental Protection Act (Law 137/1996) the owner is responsible for the management of all radioactive waste effluents at the nuclear installations, including the technical and cost components. The developed policy incorporates the practice in the EU Member States and in the country of the plant supplier (Canada). On short term, the priorities of our radioactive waste management policy are to extend the spent fuel storage capacity using the dry storage technology. On long term the policy includes a facilities for L/ILW packaging for disposal in a new surface repository to be built on the Cernavoda NPP site. For HLW the interim storage for about 50 years will provide the necessary time to select and implement the geological disposal, in accordance with the best international practice. (authors)

  3. Long-term Consequences of Early Parenthood

    DEFF Research Database (Denmark)

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

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

  4. Long-term stability of salivary cortisol

    DEFF Research Database (Denmark)

    Garde, A H; Hansen, Åse Marie

    2005-01-01

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

  5. Long term radiological impact of thorium extraction

    International Nuclear Information System (INIS)

    Menard, S.; Schapira, J.P.

    1995-01-01

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

  6. Dynamics of long-term genomic selection

    Directory of Open Access Journals (Sweden)

    Jannink Jean-Luc

    2010-08-01

    Full Text Available Abstract Background Simulation and empirical studies of genomic selection (GS show accuracies sufficient to generate rapid gains in early selection cycles. Beyond those cycles, allele frequency changes, recombination, and inbreeding make analytical prediction of gain impossible. The impacts of GS on long-term gain should be studied prior to its implementation. Methods A simulation case-study of this issue was done for barley, an inbred crop. On the basis of marker data on 192 breeding lines from an elite six-row spring barley program, stochastic simulation was used to explore the effects of large or small initial training populations with heritabilities of 0.2 or 0.5, applying GS before or after phenotyping, and applying additional weight on low-frequency favorable marker alleles. Genomic predictions were from ridge regression or a Bayesian analysis. Results Assuming that applying GS prior to phenotyping shortened breeding cycle time by 50%, this practice strongly increased early selection gains but also caused the loss of many favorable QTL alleles, leading to loss of genetic variance, loss of GS accuracy, and a low selection plateau. Placing additional weight on low-frequency favorable marker alleles, however, allowed GS to increase their frequency earlier on, causing an initial increase in genetic variance. This dynamic led to higher long-term gain while mitigating losses in short-term gain. Weighted GS also increased the maintenance of marker polymorphism, ensuring that QTL-marker linkage disequilibrium was higher than in unweighted GS. Conclusions Losing favorable alleles that are in weak linkage disequilibrium with markers is perhaps inevitable when using GS. Placing additional weight on low-frequency favorable alleles, however, may reduce the rate of loss of such alleles to below that of phenotypic selection. Applying such weights at the beginning of GS implementation is important.

  7. Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251

    International Nuclear Information System (INIS)

    Radaelli, Antonia; Nacsa, Janos; Tsai, W.-P.; Edghill-Smith, Yvette; Zanotto, Carlo; Elli, Veronica; Venzon, David; Tryniszewska, Elzbieta; Markham, Phil; Mazzara, Gail P.; Panicali, Dennis; Morghen, Carlo De Giuli; Franchini, Genoveffa

    2003-01-01

    A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-α. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals

  8. Effects of enhancing soil organic carbon sequestration in the topsoil by fertilization on crop productivity and stability: Evidence from long-term experiments with wheat-maize cropping systems in China.

    Science.gov (United States)

    Zhang, Xubo; Sun, Nan; Wu, Lianhai; Xu, Minggang; Bingham, Ian J; Li, Zhongfang

    2016-08-15

    Although organic carbon sequestration in agricultural soils has been recommended as a 'win-win strategy' for mitigating climate change and ensuring food security, great uncertainty still remains in identifying the relationships between soil organic carbon (SOC) sequestration and crop productivity. Using data from 17 long-term experiments in China we determined the effects of fertilization strategies on SOC stocks at 0-20cm depth in the North, North East, North West and South. The impacts of changes in topsoil SOC stocks on the yield and yield stability of winter wheat (Triticum aestivum L.) and maize (Zea mays L.) were determined. Results showed that application of inorganic fertilizers (NPK) plus animal manure over 20-30years significantly increased SOC stocks to 20-cm depth by 32-87% whilst NPK plus wheat/maize straw application increased it by 26-38% compared to controls. The efficiency of SOC sequestration differed between regions with 7.4-13.1% of annual C input into the topsoil being retained as SOC over the study periods. In the northern regions, application of manure had little additional effect on yield compared to NPK over a wide range of topsoil SOC stocks (18->50MgCha(-1)). In the South, average yield from manure applied treatments was 2.5 times greater than that from NPK treatments. Moreover, the yield with NPK plus manure increased until SOC stocks (20-cm depth) increased to ~35MgCha(-1). In the northern regions, yield stability was not increased by application of NPK plus manure compared to NPK, whereas in the South there was a significant improvement. We conclude that manure application and straw incorporation could potentially lead to SOC sequestration in topsoil in China, but beneficial effects of this increase in SOC stocks to 20-cm depth on crop yield and yield stability may only be achieved in the South. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  11. CERN Services for Long Term Data Preservation

    CERN Document Server

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

    2016-01-01

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

  12. Long-term outcome of neuroparacoccidioidomycosis treatment

    Directory of Open Access Journals (Sweden)

    Fabio Francesconi

    2011-02-01

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

  13. Alpine Soils as long-term Bioindicators

    Science.gov (United States)

    Nestroy, O.

    2009-04-01

    Alpine soils as long-term bioindicators The introductory words concern the definitions and peculiarities of alpine soils and their position in the Austrian Soil Classification 2000 in comparison with the World Reference Base for Soil Resources 2006. The important parameters for genesis and threats for these soils in steep and high positions are discussed. It must be emphasized that the main threats are the very different kinds of erosion e.g. by water, wind and snow, and also by skiing (end of season) as well as and mountain-biking (mainly summer-sport). Due the very slow regeneration and - in this connection - due to the very slow changes of the soil entities, these soils give an utmost importance as a long-time bioindicator. With regard to the climate change one can assume an increase in the content of organic matter on site, but also an increase of erosion and mass movement on the other site, e. g. in kind of "plaiken" (soil slide) as result of an increasing intensity of rainfall. It lies partly in our hands to diminish the number and the intensity of the threats, we can influence the soil development, but the result to reach a new ecological equilibrium is very long - in case of alpine soil more than two generations.

  14. Long-term world energy supply

    International Nuclear Information System (INIS)

    Knizia, K.

    1979-01-01

    The problem of the extent to which new nuclear power plants are to be added, or the possibility of a complete ban on nuclear power in the Federal Republic of Germany, is now very much under discussion again. On the basis of the study published by the Conservation Commission of the World Energy Conference, 'World Energy - Looking Ahead to 2020,' whose findings are probably still on the conservative side, it is demonstrated that disastrous conditions will arise in most areas of the world unless the energy requirement can be met. There is still time to develop solutions by means of today's technologies and resources in order to ensure the long term continuity of energy supply. However, this will not be possible without the immediate and undisturbed expansion of nuclear energy, including the use of breeder reactors at the earliest possible date. In view of these perspectives there is no reason why the expansion of energy supply worldwide should not be assigned the same priority as the development of all-destructive weapons systems. (orig.) [de

  15. Long-term Variability of Beach Cusps

    Science.gov (United States)

    Pianca, C.; Holman, R. A.; Siegle, E.

    2016-02-01

    The most curious morphological features observed on beaches are the cusps. Due to their rhythmic spacing, beach cusps have attracted many observers and many, often contradictory, theories as to their form. Moreover, most of the research about beach cusps has focused on their formation. Few had available long time series to study such things as the variability of alongshore and cross-shore position and spacing on the cusp field, the presence, longevity and interactions between higher and lower sets of cusps, and the processes by which cusp fields extend, shrink or change length scale. The purpose of this work is to use long-term data sets of video images from two study sites, an intermediate (Duck, USA, 26 years) and a reflective beach (Massaguaçu, Brazil, 3 years), to investigate the temporal and spatial changes of cusps conditions. Time-evolving shoreline data were first extracted using an algorithm called ASLIM (Pianca et al 2015). Cusps were then identified based on the band-passed variability of time exposure image data about this shoreline as a function of elevation relative to MSL. The identified beaches cusps will be analyzed for cusp spacing, positions (upper or lower cusps), alongshore variability, merging events, percentage of cusp events, patterns of the events and time scales of variability. Finally, the relationship of these characteristics to environmental conditions (wave, tides, beach conditions) will be studied.

  16. Long term results of childhood dysphonia treatment.

    Science.gov (United States)

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

    2014-05-01

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

  17. Long-term plutonium storage: Design concepts

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  18. [Percutaneous transhepatic bilioplasty: long-term results].

    Science.gov (United States)

    Righi, D; Martina, M C; Tola, E; Fonio, P; Fronda, G R; Gandini, G

    1990-10-01

    We report the results of a long-term follow-up of 40/101 patients with benign biliary strictures treated with percutaneous balloon dilatation (PBD) at the Radiology Department of the University of Turin, from March 1983 to March 1990. We excluded all the patients who were not followed or treated after June 1988, being their follow-up shorter than 18 months. All patients underwent accurate clinical, biological (AST, ALT, gammaGT, alcaline phosphatase) and US controls. Mean follow-up was 33.5 months. Mean success rate was 75% in strictures of bilioenteric anastomosis, 86% in iatrogenic strictures of the common bile duct, 65% in sclerosing cholangitis, 80% in papillary strictures in which endoscopic treatment had not been possible for anatomical reasons. Our results, compared to the most important radiological and surgical series, show PBD to have lower morbidity than surgery and no mortality during the so-called peroperative period (30 days). Moreover, in case of recurrences, PBD can be repeated without further complications and does not affect eventual surgery.

  19. Long-Term Soft Denture Lining Materials

    Directory of Open Access Journals (Sweden)

    Grzegorz Chladek

    2014-08-01

    Full Text Available Long-term soft denture lining (LTSDL materials are used to alleviate the trauma associated with wearing complete dentures. Despite their established clinical efficacy, the use of LTSDLs has been limited due to the unfavorable effects of the oral environment on some of their mechanical and performance characteristics. The unresolved issue of LTSDL colonization by Candida albicans is particularly problematic. Silicone-based LTSDL (SLTSDL materials, which are characterized by more stable hardness, sorption and solubility than acrylic-based LTSDLs (ALTSDLs, are currently the most commonly used LTSDLs. However, SLTSDLs are more prone to debonding from the denture base. Moreover, due to their limitations, the available methods for determining bond strength do not fully reflect the actual stability of these materials under clinical conditions. SLTSDL materials exhibit favorable viscoelastic properties compared with ALTSDLs. Furthermore, all of the lining materials exhibit an aging solution-specific tendency toward discoloration, and the available cleansers are not fully effective and can alter the mechanical properties of LTSDLs. Future studies are needed to improve the microbiological resistance of LTSDLs, as well as some of their performance characteristics.

  20. Long term agreements energy efficiency. Progress 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-11-01

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

  1. Containment long-term operational integrity

    International Nuclear Information System (INIS)

    Sammataro, R.F.

    1990-01-01

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

  2. Long term results of mandibular distraction

    Directory of Open Access Journals (Sweden)

    Batra Puneet

    2006-03-01

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

  3. Long term results of compression sclerotherapy.

    Science.gov (United States)

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

    2003-01-01

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

  4. Long-term predictions using natural analogues

    International Nuclear Information System (INIS)

    Ewing, R.C.

    1995-01-01

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

  5. Long term prediction of flood occurrence

    Directory of Open Access Journals (Sweden)

    C. Aguilar

    2016-05-01

    Full Text Available How long a river remembers its past is still an open question. Perturbations occurring in large catchments may impact the flow regime for several weeks and months, therefore providing a physical explanation for the occasional tendency of floods to occur in clusters. The research question explored in this paper may be stated as follows: can higher than usual river discharges in the low flow season be associated to a higher probability of floods in the subsequent high flow season? The physical explanation for such association may be related to the presence of higher soil moisture storage at the beginning of the high flow season, which may induce lower infiltration rates and therefore higher river runoff. Another possible explanation is persistence of climate, due to presence of long-term properties in atmospheric circulation. We focus on the Po River at Pontelagoscuro, whose catchment area amounts to 71 000 km2. We look at the stochastic connection between average river flows in the pre-flood season and the peak flows in the flood season by using a bivariate probability distribution. We found that the shape of the flood frequency distribution is significantly impacted by the river flow regime in the low flow season. The proposed technique, which can be classified as a data assimilation approach, may allow one to reduce the uncertainty associated to the estimation of the flood probability.

  6. 26 CFR 1.460-1 - Long-term contracts.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Long-term contracts. 1.460-1 Section 1.460-1...) INCOME TAXES Taxable Year for Which Items of Gross Income Included § 1.460-1 Long-term contracts. (a..., building, installation, or construction of property is a long-term contract under section 460 and what...

  7. Orlistat for the long-term treatment of obesity.

    Science.gov (United States)

    Harp, J B

    1999-02-01

    Orlistat, a potent gastrointestinal lipase inhibitor, is a member of a new class of drugs designed for the long-term treatment of obesity. When given with a fat-containing meal, orlistat reduces dietary fat absorption by approximately 30%, which equates to a decrease in caloric absorption of approximately 200 kilocalories per day. A 2-year European study found a mean decrease in body weight of 10.2% (10.3 kg) in the orlistat group compared to 6.1% (6.1 kg) in the placebo group at 1 year. Additionally, 9.3% of the orlistat group versus 2.1% of the placebo group lost >20% of their initial weight. Serum lipids and diabetes control are also improved by orlistat. Related to orlistat's mechanism of action, side effects include oily spotting, flatulence and frequent loose stools, but not frank diarrhea or intestinal malabsorption. Vitamin D and beta-carotene levels decreased, but remained within the normal range. In summary, orlistat is the first example of a new class of antiobesity drugs that enhances weight loss and weight maintenance by interfering with dietary fat absorption. Orlistat has tolerable gastrointestinal side effects and no major drug toxicity. Orlistat is a viable adjunct to lifestyle interventions used in the long-term management of obesity. (c) 1999 Prous Science. All rights reserved.

  8. Binaural auditory beats affect long-term memory.

    Science.gov (United States)

    Garcia-Argibay, Miguel; Santed, Miguel A; Reales, José M

    2017-12-08

    The presentation of two pure tones to each ear separately with a slight difference in their frequency results in the perception of a single tone that fluctuates in amplitude at a frequency that equals the difference of interaural frequencies. This perceptual phenomenon is known as binaural auditory beats, and it is thought to entrain electrocortical activity and enhance cognition functions such as attention and memory. The aim of this study was to determine the effect of binaural auditory beats on long-term memory. Participants (n = 32) were kept blind to the goal of the study and performed both the free recall and recognition tasks after being exposed to binaural auditory beats, either in the beta (20 Hz) or theta (5 Hz) frequency bands and white noise as a control condition. Exposure to beta-frequency binaural beats yielded a greater proportion of correctly recalled words and a higher sensitivity index d' in recognition tasks, while theta-frequency binaural-beat presentation lessened the number of correctly remembered words and the sensitivity index. On the other hand, we could not find differences in the conditional probability for recall given recognition between beta and theta frequencies and white noise, suggesting that the observed changes in recognition were due to the recollection component. These findings indicate that the presentation of binaural auditory beats can affect long-term memory both positively and negatively, depending on the frequency used.

  9. 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.

  10. The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

    Directory of Open Access Journals (Sweden)

    Helen L Fitzsimons

    Full Text Available A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.

  11. The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

    Science.gov (United States)

    Fitzsimons, Helen L; Schwartz, Silvia; Given, Fiona M; Scott, Maxwell J

    2013-01-01

    A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs) correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.

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

    Science.gov (United States)

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

    2015-10-01

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

  13. Long-term monitoring of breath methane.

    Science.gov (United States)

    Polag, Daniela; Keppler, Frank

    2018-05-15

    In recent years, methane as a component of exhaled human breath has been considered as a potential bioindicator providing information on microbial activity in the intestinal tract. Several studies indicated a relationship between breath methane status and specific gastrointestinal disease. So far, almost no attention has been given to the temporal variability of breath methane production by individual persons. Thus here, for the first time, long-term monitoring was carried out measuring breath methane of three volunteers over periods between 196 and 1002days. Results were evaluated taking into consideration the health status and specific medical intervention events for each individual during the monitoring period, and included a gastroscopy procedure, a vaccination, a dietary change, and chelate therapy. As a major outcome, breath methane mixing ratios show considerable variability within a person-specific range of values. Interestingly, decreased breath methane production often coincided with gastrointestinal complaints whereas influenza infections were mostly accompanied by increased breath methane production. A gastroscopic examination as well as a change to a low-fructose diet led to a dramatic shift of methane mixing ratios from high to low methane production. In contrast, a typhus vaccination as well as single chelate injections resulted in significant short-term methane peaks. Thus, this study clearly shows that humans can change from high to low methane emitters and vice versa within relatively short time periods. In the case of low to medium methane emitters the increase observed in methane mixing ratios, likely resulting from immune reactions and inflammatory processes, might indicate non-microbial methane formation under aerobic conditions. Although detailed reaction pathways are not yet known, aerobic methane formation might be related to cellular oxidative-reductive stress reactions. However, a detailed understanding of the pathways involved in human

  14. Perinatal respiratory infections and long term consequences

    Directory of Open Access Journals (Sweden)

    Luciana Indinnimeo

    2015-10-01

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

  15. The long-term nuclear explosives predicament

    International Nuclear Information System (INIS)

    Swahn, J.

    1992-01-01

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

  16. Long term results of pyeloplasty in adults

    International Nuclear Information System (INIS)

    Tayib, Abdul Malik

    2004-01-01

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

  17. Long term stability of atomic time scales

    Science.gov (United States)

    Petit, Gérard; Arias, Elisa Felicitas

    2012-08-01

    International Atomic Time TAI gets its stability from some 400 atomic clocks worldwide that generate the free atomic scale EA L and its accuracy from a small number of primary frequency standards (PFS) which frequency measurements are used to steer the EAL frequency. Because TAI is computed in "real - time" (every month) and has operational constraints, it is not optimal and the BIPM computes in deferred time another time scale TT(BIPM), which is based on a weighted average of the evaluations of TAI frequency by the PFS. We show that a point has been reached where the stability of atomic time scales, the accuracy of primary frequency standards, and the capabilities of frequency transfer are approximately at a similar level, in the low 10 - 16 in relative frequency. The goal is now to reach and surpass 1x10 - 16 and the three fields are in various stages of advancement towards this aim. We review the stability and accuracy recently achieved by frequency standards, focusing on primary frequency standards on one hand, and on new secondary realizations e.g. based on optical transitions on the other hand. We study how these performances can translate to the performance of atomic time scales, and the possible implications of the availability of new high - accuracy frequency standards operating on a regular basis. Finally we show how time transfer is trying to keep up with the progresses of frequency standards. Time transfer is presently the limiting factor at short averaging time (e.g. 1 - 2 weeks) but it should not be limiting the long term stability of atomic time scales, which is the main need of many applications in astronomy.

  18. HLW Long-term Management Technology Development

    International Nuclear Information System (INIS)

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

    2010-02-01

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

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

    Science.gov (United States)

    Acorn, Jonathan R

    2010-01-01

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

  20. A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10?mg plus permeation enhancer DDM, for the acute treatment of episodic migraine

    OpenAIRE

    Munjal, Sagar; Brand-Schieber, Elimor; Allenby, Kent; Spierings, Egilius L.H.; Cady, Roger K.; Rapoport, Alan M.

    2017-01-01

    Background DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10?mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-?-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety...

  1. Bronchopulmonary Dysplasia Early Changes Leading To Long Term Consequences

    Directory of Open Access Journals (Sweden)

    Anne eHilgendorff

    2015-02-01

    Full Text Available Neonatal Chronic Lung Disease, i.e. Bronchopulmonary Dysplasia (BPD is characterized by impaired pulmonary development. Triggered by different risk factors including infections, hyperoxia and mechanical ventilation of the immature lung, remodeling of the extracellular matrix, apoptosis as well as altered growth factor signaling characterize the disease. The immediate consequences have been studied in different animal models supported by in vitro approaches leading to the successful application of these findings to the clinical setting in the past. Nonetheless, existing information about long-term consequences of the identified early and most likely sustained changes to the developing lung is limited. Interesting results point towards a tremendous impact on the pulmonary repair capacity as well as aging related processes in the adult lung.

  2. Luminance-dependent long-term chromatic adaptation.

    Science.gov (United States)

    Vincent, Joris; Kale, Alex M; Buck, Steven L

    2016-03-01

    There is theoretical and empirical support for long-term adaptation of human vision to chromatic regularities in the environment. The current study investigates whether relationships of luminance and chromaticity in the natural environment could drive chromatic adaptation independently and differently for bright and dark colors. This is motivated by psychophysical evidence of systematic difference shifts in red-green chromatic sensitivities between contextually bright- versus dark-colored stimuli. For some broad classes of scene content, consistent shifts in chromaticity are found between high and low light levels within images. Especially in those images in which sky and terrain are juxtaposed, this shift has direction and magnitude consistent with the observed psychophysical shifts in the red-green balance between bright and dark colors. Taken together, these findings suggest that relative weighting of M- and L-cone signals could be adapted, in a luminance-dependent fashion, to regularities in the natural environment.

  3. Northern European long term climate archives

    Energy Technology Data Exchange (ETDEWEB)

    Hohl, Veronica [Stockholm Univ. (Sweden)

    2005-01-01

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

  4. Northern European long term climate archives

    International Nuclear Information System (INIS)

    Hohl, Veronica

    2005-01-01

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

  5. Long-term stable water vapor permeation barrier properties of SiN/SiCN/SiN nanolaminated multilayers grown by plasma-enhanced chemical vapor deposition at extremely low pressures

    International Nuclear Information System (INIS)

    Choi, Bum Ho; Lee, Jong Ho

    2014-01-01

    We investigated the water vapor permeation barrier properties of 30-nm-thick SiN/SiCN/SiN nanolaminated multilayer structures grown by plasma enhanced chemical vapor deposition at 7 mTorr. The derived water vapor transmission rate was 1.12 × 10 −6 g/(m 2 day) at 85 °C and 85% relative humidity, and this value was maintained up to 15 000 h of aging time. The X-ray diffraction patterns revealed that the nanolaminated film was composed of an amorphous phase. A mixed phase was observed upon performing high resolution transmission electron microscope analysis, which indicated that a thermodynamically stable structure was formed. It was revealed amorphous SiN/SiCN/SiN multilayer structures that are free from intermixed interface defects effectively block water vapor permeation into active layer

  6. Signal-enhancement reflective pulse oximeter with Fresnel lens

    Science.gov (United States)

    Chung, Shuang-Chao; Sun, Ching-Cherng

    2016-09-01

    In this paper, a new reflective pulse oximeter is proposed and demonstrated with implanting a Fresnel lens, which enhances the reflected signal. An optical simulation model incorporated with human skin characteristics is presented to evaluate the capability of the Fresnel lens. In addition, the distance between the light emitting diode and the photodiode is optimized. Compared with the other reflective oximeters, the reflected signal light detected by the photodiode is enhanced to more than 140%.

  7. Manipulating insulin signaling to enhance mosquito reproduction

    Directory of Open Access Journals (Sweden)

    Rasgon Jason L

    2009-08-01

    Full Text Available Abstract Backgrond In the mosquito Aedes aegypti the insulin/insulin growth factor I signaling (IIS cascade is a key regulator of many physiological processes, including reproduction. Two important reproductive events, steroidogenesis in the ovary and yolk synthesis in the fat body, are regulated by the IIS cascade in mosquitoes. The signaling molecule phosphatase and tensin homolog (PTEN is a key inhibitor of the IIS cascade that helps modulate the activity of the IIS cascade. In Ae. aegypti, six unique splice variants of AaegPTEN were previously identified, but the role of these splice variants, particularly AaegPTEN3 and 6, were unknown. Results Knockdown of AaegPTEN or its specific splice variant AaegPTEN6 (the splice variant thought to regulate reproduction in the ovary and fat body using RNAi led to a 15–63% increase in egg production with no adverse effects on egg viability during the first reproductive cycle. Knockdown of AaegPTEN3, expressed predominantly in the head, had no effect on reproduction. We also characterized the protein expression patterns of these two splice variants during development and in various tissues during a reproductive cycle. Conclusion Previous studies in a range of organisms, including Drosophila melanogaster and Caenorhabditis elegans, have demonstrated that disruption of the IIS cascade leads to decreased reproduction or sterility. In this study we demonstrate that knockdown of the IIS inhibitor PTEN can actually increase reproduction in the mosquito, at least during the first reproductive cycle.

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

    Science.gov (United States)

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

    2016-08-01

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

  9. Satisfaction in Long-Term Marriages.

    Science.gov (United States)

    Fields, Nina S.

    1983-01-01

    Examines the impact of sexual satisfaction and the congruence of mates' perceptions on overall marital satisfaction in 290 people who had been married 18 to 32 years. Results showed respondents were, overall, satisfied with their marriages. The relationsihps were enhanced by empathy and congruence of perceptions. (Author/JAC)

  10. Long term behaviour of singularly perturbed parabolic degenerated equation

    OpenAIRE

    Faye, Ibrahima; Frenod, Emmanuel; Seck, Diaraf

    2011-01-01

    In this paper we consider models for short-term, mean-term and long-term morphodynamics of dunes and megariples. We give an existence and uniqueness result for long term dynamics of dunes. This result is based on a time-space periodic solution existence result for degenerated parabolic equation that we set out. Finally the mean-term and long-term models are homogenized.

  11. Assessment of Long-Term Mate Preferences in Iran

    OpenAIRE

    Mohammad Atari

    2017-01-01

    Previous research suggests that assessment of mate preferences has received relatively little psychometric attention from researchers, particularly in non-Western cultures. The current research was designed to (1) extend previous findings on long-term mate preferences by using a qualitative strategy, (2) develop a psychometrically sound scale for assessment of long-term mate preferences in men, and (3) develop a sex-neutral scale for assessment of long-term mate preferences. Six dimensions of...

  12. Helmholtz resonator enhancement of photoacoustic signals

    Science.gov (United States)

    McClenny, W. A.; Bennett, C. A., Jr.; Russwurm, G. M.; Richmond, R.

    1981-02-01

    A Helmholtz resonator attached to a nonresonant photoacoustic cell enhances the responsivity to trace gas absorption by as much as a factor of 15.3. A simple system model based on a lumped parameter approach predicts the experimentally determined resonance frequency f sub zero within 6% for all five resonator volumes tried and gives a pressure amplitude response at resonance proportional to f sub zero to the -5/2, which is the approximate experimental dependence. Optimization of response based on the model shows a pressure amplitude dependence on a to the 1/2, the square root of the radius of the cylindrical tube connecting the cell and the resonator.

  13. Digital payloads - Enhanced performance through signal processing

    Science.gov (United States)

    Bjornstrom, G.

    A transparent signal-processing payload architecture applicable to mobile communication satellites is introduced, and its features and implementation issues are discussed. In its basic form it is characterized by the formation of a large number of narrowband beams directed at the individual users on ground, and is demonstrated to offer improved transmit power efficiency, frequency-reuse capability and traffic-routing flexibility. The processor implementation is envisaged to make extensive use of digital processing functions and ASIC technology combined with advanced SAW techniques. In addition to its inherent attractive features, this architecture provides many of the benefits of full onboard regeneration and processing while preserving most of the flexibility of conventional analog transponders. Simplified derivatives of the basic configuration that offer reduced processing complexity while preserving the essential advantages gained are also presented. Although initially conceived for FDMA/SCPC-type traffic, the concept can also be adapted to other transmission formats.

  14. Audit of long-term and short-term liabilities

    OpenAIRE

    Korinko M.D.; Kushnir Y.O.

    2017-01-01

    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, th...

  15. Effects of pre-encoding stress on brain correlates associated with the long-term memory for emotional scenes.

    Directory of Open Access Journals (Sweden)

    Janine Wirkner

    Full Text Available Recent animal and human research indicates that stress around the time of encoding enhances long-term memory for emotionally arousing events but neural evidence remains unclear. In the present study we used the ERP old/new effect to investigate brain dynamics underlying the long-term effects of acute pre-encoding stress on memory for emotional and neutral scenes. Participants were exposed either to the Socially Evaluated Cold Pressure Test (SECPT or a warm water control procedure before viewing 30 unpleasant, 30 neutral and 30 pleasant pictures. Two weeks after encoding, recognition memory was tested using 90 old and 90 new pictures. Emotional pictures were better recognized than neutral pictures in both groups and related to an enhanced centro-parietal ERP old/new difference (400-800 ms during recognition, which suggests better recollection. Most interestingly, pre-encoding stress exposure specifically increased the ERP old/new-effect for emotional (unpleasant pictures, but not for neutral pictures. These enhanced ERP/old new differences for emotional (unpleasant scenes were particularly pronounced for those participants who reported high levels of stress during the SECPT. The results suggest that acute pre-encoding stress specifically strengthens brain signals of emotional memories, substantiating a facilitating role of stress on memory for emotional scenes.

  16. Foreign Ownership and Long-term Survival

    DEFF Research Database (Denmark)

    Kronborg, Dorte; Thomsen, Steen

    2006-01-01

    Does foreign ownership enhance or decrease a firm's chances of survival? Over the 100 year period 1895-2001 this paper compares the survival of foreign subsidiaries in Denmark to a control sample matched by industry and firm size. We find that foreign-owned companies have higher survival probabil......Does foreign ownership enhance or decrease a firm's chances of survival? Over the 100 year period 1895-2001 this paper compares the survival of foreign subsidiaries in Denmark to a control sample matched by industry and firm size. We find that foreign-owned companies have higher survival...... probability. On average exit risk for domestic companies is 2.3 times higher than for foreign companies. First movers like Siemens, Philips, Kodak, Ford, GM or Goodyear have been active in the country for almost a century. Relative foreign survival increases with company age. However, the foreign survival...... advantage appears to be eroded by globalization, it decreases over time and disappears at the end of the century....

  17. Data management to enhance long-term watershed research capacity

    Science.gov (United States)

    Water resources are under growing pressure globally, and in the face of projected climate change, uncertainty about precipitation frequency and intensity; evapotranspiration, runoff, and snowmelt poses severe societal challenges. Interdisciplinary environmental research across natural and social sc...

  18. Long-term oxytocin administration enhances the experience of attachment.

    Science.gov (United States)

    Bernaerts, Sylvie; Prinsen, Jellina; Berra, Emmely; Bosmans, Guy; Steyaert, Jean; Alaerts, Kaat

    2017-04-01

    The neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. Previous studies showed that a single-dose of exogenously administered OT can affect trust and feelings of attachment insecurity. With the present study, we explored the effects of two weeks of daily OT administration on measures of state and trait attachment using a double-blind between-subjects randomized placebo-controlled design. In 40 healthy young adult men state and trait attachment were assessed before and after two weeks of daily intranasal OT (24 IU) or placebo using the State Adult Attachment Scale and the Inventory of Parent and Peer Attachment. Mood, social responsiveness and quality of life were additionally assessed as secondary outcome measures. Reductions in attachment avoidance and increases in reports of attachment toward peers were reported after two weeks of OT treatment. Further, treatment-induced changes were most pronounced for participants with less secure attachment towards their peers. indicating that normal variance at baseline modulated treatment response. OT treatment was additionally associated with changes in mood, indicating decreases in feelings of tension and (tentatively) anger in the OT group, not in the placebo group. Further, at the end of the two-week trial, both treatment groups (OT, placebo) reported to experience an increase in social responsiveness and quality of life, but the effects were only specific to the OT-treatment in terms of reports on 'social motivation'. In summary, the observed improvements on state and trait dimensions of attachment after a multiple-dose treatment with OT provide further evidence in support of a pivotal role of OT in promoting the experience of attachment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Long-term depression of climbing fiber-evoked calcium transients in Purkinje cell dendrites.

    NARCIS (Netherlands)

    J.T. Weber (John); C.I. de Zeeuw (Chris); C.R.W. Hansel (Christian); D.J. Linden (David)

    2003-01-01

    textabstractIn recent years much has been learned about the molecular requirements for inducing long-term synaptic depression (LTD) in various brain regions. However, very little is known about the consequences of LTD induction for subsequent signaling events in postsynaptic neurons. We have

  20. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

    Science.gov (United States)

    Koshibu, K; Gräff, J; Mansuy, I M

    2011-01-26

    Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously. Our work recently demonstrated that epigenetic mechanisms in the adult brain are in part regulated by protein phosphatase 1 (PP1), a protein Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures involved in emotional processing like the amygdala, it may therefore be involved in the regulation of fear memory, a form of memory related to post-traumatic stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular suppressor of fear memory and synaptic plasticity in the amygdala that can control chromatin remodeling in neurons. We show that the selective inhibition of the nuclear pool of PP1 in amygdala neurons significantly alters posttranslational modifications (PTMs) of histones and the expression of several memory-associated genes. These alterations correlate with enhanced fear memory, and with an increase in long-term potentiation (LTP) that is transcription-dependent. Our results underscore the importance of nuclear PP1 in the amygdala as an epigenetic regulator of emotional memory, and the relevance of protein phosphatases as potential targets for therapeutic treatment of brain disorders like PTSD. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Immunostimulatory and Other Haematological Effects of Long Term ...

    African Journals Online (AJOL)

    Carica papaya Linn. (Caricaceae)is used traditionally to treat malaria, hypertension, sickle cell anemia and diabetes. Its long-term hypoglycaemic and anti-obesity effects in normal rabbits are documented. This study assessed the long term immunostimulatory and other haematological effects of aqueous C. papaya leaf ...

  2. Sacrococcygeal teratoma: Clinical characteristics and long-term ...

    African Journals Online (AJOL)

    2009-10-05

    Oct 5, 2009 ... Background/Purpose:The excision of sacrococcygeal teratoma (SCT) may be associated with significant long-term morbidity for the child. We reviewed our experience with SCT in a tertiary health care facility in a developing country with particular interest on the long-term sequelae. Methods: Between ...

  3. Sacrococcygeal teratoma: Clinical characteristics and long-term ...

    African Journals Online (AJOL)

    Background/Purpose : The excision of sacrococcygeal teratoma (SCT) may be associated with significant long-term morbidity for the child. We reviewed our experience with SCT in a tertiary health care facility in a developing country with particular interest on the long-term sequelae. Methods : Between January 1990 and ...

  4. Long-Term Gowth Opportunities in Ethiopia | Alemu | Ethiopian ...

    African Journals Online (AJOL)

    Ethiopian Journal of Economics ... The paper attempts to investigate the role of institutions in the long-term growth performance of Ethiopia. In this study, it is hypothesized that the long-term growth of the country, apart from traditional factors of production i.e. capital and labor is largely influenced by institutional factors.

  5. Long-term sealability of spent fuel casks

    International Nuclear Information System (INIS)

    Kato, O.; Kosaki, A.; Ito, C.; Ozaki, S.; Iitsuka, S.

    1993-01-01

    This report presents the results of long-term sealability test of full-scale model casks which have been in progress since 1990. (O.Kato and C.Ito 1992) The purpose is to confirm the long-term sealability of the casks. (J.P.N.)

  6. How Does Long-Term Finance Affect Economic Volatility?

    NARCIS (Netherlands)

    Demirgüç-Kunt, A.; Horváth, Bálint; Huizinga, Harry

    2016-01-01

    In an approach analogous to Rajan and Zingales (1998), we examine how the ability to access long-term debt affects firm-level growth volatility. We find that firms in industries with stronger preference to use long-term finance relative to short-term finance experience lower growth volatility in

  7. Long-Term Mortality of Emergency Medical Services Patients

    DEFF Research Database (Denmark)

    Bøtker, Morten Thingemann; Terkelsen, Christian J; Sørensen, Jan N.

    2017-01-01

    STUDY OBJECTIVE: Emergency medical services (EMS) provides out-of-hospital care to patients with life-threatening conditions, but the long-term outcomes of EMS patients are unknown. We seek to determine the long-term mortality of EMS patients in Denmark. METHODS: We analyzed linked EMS, hospital...

  8. Private Placements as Sources of Long Term Funds for publicly ...

    African Journals Online (AJOL)

    Private Placements as Sources of Long Term Funds for publicly quoted firms in the Nigerian Capital Market. ... AFRREV IJAH: An International Journal of Arts and Humanities ... Abstract. Private placements are gradually becoming means of raising long-term funds in the Nigerian capital market by publicly quoted companies.

  9. Long-term forest ecosystem research: a programmatic view

    Science.gov (United States)

    Wayne Swank; James Vose

    2010-01-01

    Long-term research provides the building blocks of knowledge needed to address natural resource and environmental issues. "Long-term" has frequently been considered to span decades with a time frame that usually encompasses at least one generation of scientists and frequently two or more generations. In the rich history of forest science, the origin of long-...

  10. Psychological symptoms as long-term consequences of war experiences

    NARCIS (Netherlands)

    Priebe, S.; Jankovic Gavrilovic, J.; Bremner, S.; Ajdukovic, D.; Franciskovic, T.; Galeazzi, G.M.; Kucukalic, A.; Lecic-Tosevski, D.; Morina, N.; Popovski, M.; Schützwohl, M.; Bogic, M.

    2013-01-01

    Background/Aims: War experiences can affect mental health, but large-scale studies on the long-term impact are rare. We aimed to assess long-term mental health consequences of war in both people who stayed in the conflict area and refugees. Method: On average 8 years after the war in former

  11. Factors associated with long-term mortality in acute pancreatitis

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Matzen, Peter; Bendtsen, Flemming

    2011-01-01

    Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes...

  12. Albumin: Creatinine Ratio during long term Diabetes Mellitus in the ...

    African Journals Online (AJOL)

    Albumin: Creatinine Ratio during long term Diabetes Mellitus in the Assessment of early Nephropathy in Sudanese Population. ... Further studies with 24 hour urine sample are recommended for assessment of Microalbuminuria in long term Diabetic patients, provided that the patients are on a normal diet with regular ...

  13. 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....

  14. Quantification of long term emission potential from landfills

    NARCIS (Netherlands)

    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate

  15. Long-term effects of a preoperative smoking cessation programme

    DEFF Research Database (Denmark)

    Villebro, Nete Munk; Pedersen, Tom; Møller, Ann M

    2008-01-01

    Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation.......Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation....

  16. Long-Term Follow Up of Superficial Bladder Tumors | Shelbaia ...

    African Journals Online (AJOL)

    Conclusion: The treatment of superficial TCC may be done by relatively minor endoscopic procedures, but the disease itself is a serious condition that merits close long-term follow-up. Key words: bladder tumors, transitional cell carcinoma (TCC), ND: YAG lasers, transurethral resection (TURT) Suivi à long terme des ...

  17. Long Term Incentives for Residential Customers Using Dynamic Tariff

    DEFF Research Database (Denmark)

    Huang, Shaojun; Wu, Qiuwei; Nielsen, Arne Hejde

    2015-01-01

    This paper reviews several grid tariff schemes, including flat tariff, time-of-use, time-varying tariff, demand charge and dynamic tariff (DT), from the perspective of the long term incentives. The long term incentives can motivate the owners of flexible demands to change their energy consumption...

  18. Inflammatory markers in relation to long-term air pollution

    NARCIS (Netherlands)

    Mostafavi Montazeri, Nahid|info:eu-repo/dai/nl/375290575; Vlaanderen, Jelle|info:eu-repo/dai/nl/31403160X; Chadeau-Hyam, Marc; Beelen, Rob|info:eu-repo/dai/nl/30483100X; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard|info:eu-repo/dai/nl/069553475; Kyrtopoulos, Soterios Α; Vermeulen, Roel|info:eu-repo/dai/nl/216532620

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term

  19. Long term physical and chemical stability of polyelectrolyte multilayer membranes

    NARCIS (Netherlands)

    de Grooth, Joris; Haakmeester, Brian; Wever, Carlos; Potreck, Jens; de Vos, Wiebe Matthijs; Nijmeijer, Dorothea C.

    2015-01-01

    This work presents a detailed investigation into the long term stability of polyelectrolyte multilayer (PEM) modified membranes, a key factor for the application of these membranes in water purification processes. Although PEM modified membranes have been frequently investigated, their long term

  20. Long-term effects of childbirth in MS

    NARCIS (Netherlands)

    D'hooghe, M.B.; Nagels, G.; Uitdehaag, B.M.J.

    2010-01-01

    Background: The uncertainty about long-term effects of childbirth presents MS patients with dilemmas. Methods: Based on clinical data of 330 female MS patients, the long-term effects of childbirth were analysed, using a cross-sectional study design. Four groups of patients were distinguished: (1)

  1. Long-term follow-up of obstetric studies

    NARCIS (Netherlands)

    Teune, M.J.

    2013-01-01

    This thesis focuses on long-term child follow-up after obstetric studies. Obstetric randomized controlled clinical trials (RCTs) are performed to evaluate the effectiveness of perinatal interventions. However, most often only short-term outcomes are reported, while long-term outcomes are just as

  2. Long-term neutrino flux integrations

    International Nuclear Information System (INIS)

    Haxton, W.C.

    1990-11-01

    The standard solar model predicts that the sun's luminosity has increased by 40% over the past 5 Gyrs of main-sequence burning, reflecting the evolving chemistry of the solar core. This increase is accompanied by an exponential growth in the 8 B neutrino flux, with a doubling time of 0.85 Gyr. I describe an unusual nuclear system that, in principle, could yield a quantitative terrestrial record of these past changes, and discuss some of the practical obstacles to reading this record. I also argue that there exists a ''twin'' of the 37 Cl solar neutrino experiment that could be mounted with modest effort. The experiment, in which neutrinos incident on an iodine-bearing liquid produce the noble gas 127 Xe, should enjoy a number of advantages over 37 Cl: a substantially larger counting rate, a potentially greater relative sensitivity to 7 Be neutrinos, lower cosmic ray backgrounds, and a cleaner signal for the 127 Xe decay. I discuss the physics that could be learned from such a detector, emphasizing in particular the virtues of a passive, high counting rate experiment that could be operated cheaply over the long times that might pass before the next galactic supernova. 16 refs., 2 figs

  3. EEPIC - Enhancing Employability through Positive Interventions for improving Career potential: the impact of a high support career guidance intervention on the wellbeing, hopefulness, self-efficacy and employability of the long-term unemployed - a study protocol for a randomised controlled trial.

    Science.gov (United States)

    Whelan, Nuala; McGilloway, Sinéad; Murphy, Mary P; McGuinness, Colm

    2018-02-26

    Labour market policy (LMP) and its implementation have undergone rapid change internationally in the last three decades with a continued trend towards active LMP. In Ireland however, this shift has been more recent with ongoing reforms since 2012 and a concomitant move toward active labour market 'work-first' policy design (i.e. whereby unemployed people are compulsorily required to work in return for their social welfare benefits). Labour market policies vary from those that require this compulsory approach to those which enable the unemployed to move towards sustainable quality work in the labour market through upskilling (human capital approach). Despite this, however, long-term unemployment-a major cause of poverty and social exclusion-remains high, while current employment support approaches aimed at sustainable re-employment are, arguably, unevaluated and under examined. This study examines the effectiveness of a new high support career guidance intervention in terms of its impact on aspects of wellbeing, perceived employability and enhancing career sustainability. The study involves a single-centre randomised, controlled, partially blinded trial. A total of 140 long-term unemployed job-seekers from a disadvantaged urban area will be randomly assigned to two groups: (1) an intervention group; and (2) a 'service as usual' group. Each group will be followed up immediately post intervention and six months later. The primary outcome is wellbeing at post intervention and at six-month follow-up. The secondary outcome is perceived employability, which includes a number of different facets including self-esteem, hopefulness, resilience and career self-efficacy. The study aims to assess the changes in, for example, psychological wellbeing, career efficacy and hopefulness, that occur as a result of participation in a high support intervention vs routinely available support. The results will help to inform policy and practice by indicating whether a therapeutic approach

  4. Environmental Management Long-Term Stewardship 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 the completion of facility cleanup. Long-term stewardship is administered and overseen by the U.S. Department of Energy Environmental Management Office of Science and Technology. This report describes the background of long-term stewardship and gives general guidance about considerations when ownership and/or responsibility of a site should be transferred to a long-term stewardship program. This guidance document will assist the U.S. Department of Energy in: (a) ensuring that the long-term stewardship program leads transition planning with respect to facility and site areas, and (b) describing 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.

  5. The Long Term Features of Tropical Cyclones Nearby Taiwan

    Science.gov (United States)

    Wu, Yueh-Shyuan; Lee, Cheng-Shang

    2017-04-01

    Tropical cyclone (TC) activity is affected by several factors. The variability of TC activity over the western North Pacific (WNP) has been examined in the past decade. Previous studies showed that TC activity (such as TC number, intensity and tracks) has multiscale variation or affected by natural oscillation of different scales. However, most of these studies focused mainly on the entire WNP. Very few studies examined the variability of annual TC track or the variability of TC number in the area nearby Taiwan, which caused severe economic loss and life damage to Taiwan in the typhoon season. The main purpose of this study is to analyze the variation of TC activity nearby Taiwan to address its long term features, and also the possible relationship with the associated flow patterns. Preliminary results of wavelet analysis showed that the TC number nearby Taiwan during 1970-2014 had multiscale variations. The following analysis focused on the scale about 4- and 11-year signals, in the targeted area of 118o-125oE, 20o-27oN. The positive phases of both scale 4 and scale 11 showed a tendency of TC tracks toward Taiwan area, while the negative phases showed a lower tendency toward Taiwan. An empirical orthogonal function (EOF) analysis was applied on the 4-yr and the 11-yr filtered 500-hPa wind fields and geopotential heights. Results showed that the 4-yr signal was mostly dominated by the 500-hPa U- and V-wind fields, suggesting that the TC track patterns were affected mainly by the midlevel steering flow. On the other hand, the 11-yr signal was mostly dominated by the 500-hPa U-wind field and geopotential anomalies, indicating that the main cause of the difference in TC occurrence nearby Taiwan was the location of TC formation.

  6. Adaptive optics for enhanced signal in CARS microscopy.

    Science.gov (United States)

    Wright, A J; Poland, S P; Girkin, J M; Freudiger, C W; Evans, C L; Xie, X S

    2007-12-24

    We report the use of adaptive optics with coherent anti-Stokes Raman scattering (CARS) microscopy for label-free deep tissue imaging based on molecular vibrational spectroscopy. The setup employs a deformable membrane mirror and a random search optimization algorithm to improve signal intensity and image quality at large sample depths. We demonstrate the ability to correct for both system and sample-induced aberrations in test samples as well as in muscle tissue in order to enhance the CARS signal. The combined system and sample-induced aberration correction increased the signal by an average factor of approximately 3x for the test samples at a depth of 700 microm and approximately 6x for muscle tissue at a depth of 260 microm. The enhanced signal and higher penetration depth offered by adaptive optics will augment CARS microscopy as an in vivo and in situ biomedical imaging modality.

  7. Long-term survival following radiofrequency ablation of colorectal liver metastases

    DEFF Research Database (Denmark)

    Babawale, Simeon Niyi; Jensen, Thomas Mandøe; Frøkjær, Jens Brøndum

    2015-01-01

    were evaluated, both before and after ablation therapies, with contrast enhanced computerised tomography and contrast enhanced ultrasonography. Histological evidence of malignant liver metastases was obtained in the few instances where contrast enhanced ultrasonography gave equivocal results. Accesses......AIM: To retrospectively evaluate the long-term survival of patients that received radiofrequency ablation (RFA) therapies of colorectal liver metastases. METHODS: In 2005 to 2008, RFA of 105 colorectal liver metastases (CRLM) were performed on 49 patients in our institution. The liver metastases...

  8. Abstracts 1987. New Horizons in Long Term Care: A Report on the Long Term Care Research and Demonstration Projects.

    Science.gov (United States)

    Illinois State Dept. of Public Aid, Springfield.

    This booklet provides a description of 14 projects which were awarded funds during fiscal year 1987 for collaborative research in long-term care to find new ways to treat long-term care patients in Illinois nursing homes. It includes the organization or institution receiving the award, an abstract of the research proposal, and the name of the…

  9. Dying and death within the culture of long-term care facilities in Canada.

    Science.gov (United States)

    Cable-Williams, Beryl; Wilson, Donna M

    2017-03-01

    To identify the influence of the culture in Canadian long-term care facilities on the awareness of impending death and initiation of a palliative approach to care for residents aged 85 years and older. Many long-term care residents die after long, dwindling dying trajectories, yet palliative care is often not provided until within a few hours or days of death. Focused ethnography. Data were collected in three long-term care facilities in south-central Ontario, Canada, through interviews with residents, family members and staff members, observation, artefact review and a focus group. Data were analysed using a constant comparative technique. Four cultural influences on the awareness of impending death and consequent initiation of a palliative approach to care were identified: (i) the care demands in long-term care facilities and the resources available to meet these demands; (ii) the belief that long-term care facilities are for living; (iii) the belief that no one should die in pain; and (iv) the belief that no one should die alone. Commonly held beliefs about the role of long-term care facilities and what is viewed as acceptable care in them mediated the acknowledgement of dying. Late initiation of palliative care was the consequence. In addition, the contextual factors of a low staff-to-resident ratio and reduced staff preparation for palliative care were also influential for a delayed response to dying. Because strongly held long-term care cultural beliefs underlie care, more timely palliative care for long-term care residents is likely to require the development of an understanding that living and dying are not dichotomous, but rather unfold together from admission until death. Enhanced staff-to-resident ratios and staff training on palliative care will also be necessary to permit long-term care facility staff to focus beyond the currently expected day-to-day care of living residents to provide high-quality end-of-life care throughout the often protracted

  10. Hypoxia-induced phrenic long-term facilitation: emergent properties.

    Science.gov (United States)

    Devinney, Michael J; Huxtable, Adrianne G; Nichols, Nicole L; Mitchell, Gordon S

    2013-03-01

    As in other neural systems, plasticity is a hallmark of the neural system controlling breathing. One spinal mechanism of respiratory plasticity is phrenic long-term facilitation (pLTF) following acute intermittent hypoxia. Although cellular mechanisms giving rise to pLTF occur within the phrenic motor nucleus, different signaling cascades elicit pLTF under different conditions. These cascades, referred to as Q and S pathways to phrenic motor facilitation (pMF), interact via cross-talk inhibition. Whereas the Q pathway dominates pLTF after mild to moderate hypoxic episodes, the S pathway dominates after severe hypoxic episodes. The biological significance of multiple pathways to pMF is unknown. This review will discuss the possibility that interactions between pathways confer emergent properties to pLTF, including pattern sensitivity and metaplasticity. Understanding these mechanisms and their interactions may enable us to optimize intermittent hypoxia-induced plasticity as a treatment for patients that suffer from ventilatory impairment or other motor deficits. © 2013 New York Academy of Sciences.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-05

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  13. Analysis of Enhanced Velocity Signals Observed during Solar Flares ...

    Indian Academy of Sciences (India)

    2003-10-28

    Oct 28, 2003 ... close to the vicinity of the hard X-ray source regions as observed with. RHESSI. The power maps of the active region show enhancement in the frequency regime 5–6.5mHz, while there is feeble or no enhancement of these signals in 2–4 mHz frequency band. High energy particles with sufficient momentum ...

  14. Modeling long-term dynamics of electricity markets

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  15. 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.

  16. Long-term biological performance of injectable and degradable calcium phosphate cement

    NARCIS (Netherlands)

    Grosfeld, E.C.; Hoekstra, J.W.M.; Herber, R.P.; Ulrich, D.J.O.; Jansen, J.A.; Beucken, J.J.J.P van den

    2016-01-01

    Enhancing degradation of poorly degrading injectable calcium phosphate (CaP) cements (CPCs) can be achieved by adding poly(lactic-co-glycolic acid) (PLGA) microparticles, generating porosity after polymer degradation. CPC-PLGA has proven to be biodegradable, although its long-term biological

  17. Long-term Care Nurses' Communication Difficulties with People Living with Dementia in Taiwan

    Directory of Open Access Journals (Sweden)

    Jing-Jy Wang, PhD

    2013-09-01

    Conclusion: The results can serve as reference for planning dementia communication education for school curriculum to enhance student nurses' communication abilities and for junior nurses working in long-term or acute care settings to increase nurses' patient-centered communication abilities with the ultimate goal of improving quality of care for patients with dementia.

  18. Tree ring imprints of long-term changes in climate in western ...

    Indian Academy of Sciences (India)

    Prakash

    2009-10-26

    Oct 26, 2009 ... Tree ring imprints of long-term changes in climate in western Himalaya, India. 699. J. Biosci. 34(5), November 2009. 1. Introduction. Earth's climate has been constantly changing in the geological past. However, change in atmospheric chemistry due to enhanced anthropogenic activity during the past.

  19. Short-term mudflat dynamics drive long-term cyclic salt marsh dynamics

    NARCIS (Netherlands)

    Bouma, T.; van Belzen, J; Balke, T; van Dalen, J.H.; Klaassen, P.; Hartog, A. M.; Callaghan, D.P.; Hu, Z.; Stive, M.J.F.; Temmerman, S.; Herman, P.M.J.

    2016-01-01

    Our study aims to enhance process understanding of the long-term (decadal and longer) cyclic marsh dynamics by identifying the mechanisms that translate large-scale physical forcing in the system into vegetation change, in particular (i) the initiation of lateral erosion on an expanding marsh,

  20. Short-term mudflat dynamics drive long-term cyclic salt marsh dynamics

    NARCIS (Netherlands)

    Bouma, T.J.; van Belzen, J.; Balke, T.; van Dalen, J.; KLaassen, P.; Hartog, A.M.; Callaghan, D.P.; Hu, Z.; Stive, M.J.F.; Temmerman, S.; Herman, P.M.J.

    2016-01-01

    Our study aims to enhance process understanding of the long-term (decadal and longer) cyclic marsh dynamics by identifying the mechanisms that translate large-scale physical forcing in the system into vegetation change, in particular (i) the initiation of lateral erosion on an expanding

  1. Long-Term Resource Adequacy, Long-Term Flexibility Requirements, and Revenue Sufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Milligan, Michael [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bloom, Aaron P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Townsend, Aaron [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ela, Erik [Electric Power Research Institute; Botterud, Audun [Argonne National Laboratory; Levin, Todd [Argonne National Laboratory

    2018-02-15

    Variable generation (VG) can reduce market prices over time and also the energy that other suppliers can sell in the market. The suppliers that are needed to provide capacity and flexibility to meet the long-term reliability requirements may, therefore, earn less revenue. This chapter discusses the topics of resource adequacy and revenue sufficiency - that is, determining and acquiring the quantity of capacity that will be needed at some future date and ensuring that those suppliers that offer the capacity receive sufficient revenue to recover their costs. The focus is on the investment time horizon and the installation of sufficient generation capability. First, the chapter discusses resource adequacy, including newer methods of determining adequacy metrics. The chapter then focuses on revenue sufficiency and how suppliers have sufficient opportunity to recover their total costs. The chapter closes with a description of the mechanisms traditionally adopted by electricity markets to mitigate the issues of resource adequacy and revenue sufficiency and discusses the most recent market design changes to address these issues.

  2. 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.

  3. Geographic variation in long-term oxygen therapy in Denmark : factors related to adherence to guidelines for long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbæk, Thomas Jørgen; Lange, Peter; Viskum, K

    2001-01-01

    STUDY OBJECTIVES: To evaluate regional differences in adherence to guidelines for long-term oxygen therapy (LTOT) in Denmark and to determine factors related to compliance with these guidelines. DESIGN: Cross-sectional study and analysis of a nationwide database (Danish Oxygen Register). SETTING:...... organizations responsible for treatment should play a more forceful role in implementing the guidelines. This could be done by enhanced educational efforts, by monitoring of adherence, or even by centralizing the prescription right to departments with pulmonary physicians....

  4. The long-term power purchase: Recovery of capacity costs

    International Nuclear Information System (INIS)

    Cross, P.S.

    1990-01-01

    As electric utilities increase their reliance on the long-term power purchase as an alternative to utility-owned generation, the appropriate rate treatment of the costs established in the purchase agreement assumes growing importance. In the November 9, 1989, issue, the authors examined the recent trend among state regulators to treat the long-term purchase in a manner similar to the addition by a utility of a new plant, including a full-scale prudence review. This installment will review recent rulings on the related issue of rate recovery of long-term capacity costs through the fuel cost adjustment clause

  5. Cyclic and Long-Term Variation of Sunspot Magnetic Fields

    Science.gov (United States)

    2014-10-15

    AFRL-RV-PS- TP-2014-0009 AFRL-RV-PS- TP-2014-0009 CYCLIC AND LONG-TERM VARIATION OF SUNSPOT MAGNETIC FIELDS Alexei A. Pevtsov, et al. 15...TITLE AND SUBTITLE Cyclic and Long-Term Variation of Sunspot Magnetic Fields 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62601F...from the Mount Wilson Observatory (MWO) were used to study the long-term variations of sunspot field strengths from 1920 to 1958. Following a modified

  6. Ecosystem responses to climate change at a Low Arctic and a High Arctic long-term research site

    Science.gov (United States)

    John E. Hobbie; Gaius R. Shaver; Edward B. Rastetter; Jessica E. Cherry; Scott J. Goetz; Kevin C. Guay; William A. Gould; George W. Kling

    2017-01-01

    Long-term measurements of ecological effects of warming are often not statistically significant because of annual variability or signal noise. These are reduced in indicators that filter or reduce the noise around the signal and allow effects of climate warming to emerge. In this way, certain indicators act as medium pass filters integrating the signal over years-to-...

  7. Long-term lunar stations: Some ecological considerations

    Science.gov (United States)

    Maguire, Bassett, Jr.; Scott, Kelly W.

    1992-01-01

    A major factor for long-term success of a lunar station is the ability to keep an agroecosystem functioning at a desirable, stable steady-state with ecological stability and reliability. Design for a long-lived extraterrestrial manned station must take into account interactions among its subsystems to insure that overall functionality is enhanced (or at least not compromised). Physical isolation of feed production, human living areas, recycling, and other systems may be straightforward, however, microbiological isolation will be very difficult. While it is possible to eliminate plant-associated microbiological communities by growing the plants asepticallly, it is not practical to keep plants germ-free on a large scale if humans are working with them. Ecological theory strongly suggests that some kinds of communities or organisms effectively increase the stability of ecosystems and will protect the plants from potential pathogens. A carefully designed and maintained (lunar-derived) soil can provide a variety of habitats for effective microbial buffers while adding structure to the agroecosystem. A soil can also increase ecosystem reliability through buffering otherwise large element and compound fluctuations (of nutrients, wastes, etc.) as well as buffering temperature level and atmosphere composition. We are doing experiments in ecological dynamics and attempting to extend the relevant theories.

  8. Multicenter evaluation of signal enhancement algorithms for hearing aids

    NARCIS (Netherlands)

    Luts, Heleen; Eneman, Koen; Wouters, Jan; Schulte, Michael; Vormann, Matthias; Buechler, Michael; Dillier, Norbert; Houben, Rolph; Dreschler, Wouter A.; Froehlich, Matthias; Puder, Henning; Grimm, Giso; Hohmann, Volker; Leijon, Arne; Lombard, Anthony; Mauler, Dirk; Spriet, Ann

    2010-01-01

    In the framework of the European HearCom project, promising signal enhancement algorithms were developed and evaluated for future use in hearing instruments. To assess the algorithms' performance, five of the algorithms were selected and implemented on a common real-time hardware/software platform.

  9. The influence of organizational characteristics on employee solidarity in the long-term care sector.

    Science.gov (United States)

    Cramm, Jane M; Strating, Mathilde M H; Nieboer, Anna P

    2013-03-01

    This article is a report of a study that identifies organizational characteristics explaining employee solidarity in the long-term care sector. Employee solidarity reportedly improves organizations' effectiveness and efficiency. Although general research on solidarity in organizations is available, the impact of the organizational context on solidarity in long-term care settings is lacking. Cross-sectional survey. The study was carried out in Dutch long-term care. A total of 313 nurses, managers and other care professionals in 23 organizations were involved. Organizational characteristics studied were centralization, hierarchical culture, formal and informal exchange of information and leadership style. The study was carried out in 2009. Findings.  All organizational characteristics significantly correlated with employee solidarity in the univariate analyses. In the multivariate analyses hierarchical culture, centralization, exchange of formal and informal information and transformational leadership appears to be important for solidarity among nurses, managers and other professionals in long-term care organizations, but not transactional and passive leadership styles. The study increased our knowledge of solidarity among nurses, managers and other professionals in the long-term care settings. Organizational characteristics that enhance solidarity are high levels of formal and informal information exchange, less hierarchical authority, decentralization and transformational leadership styles. © 2012 Blackwell Publishing Ltd.

  10. Beyond post-marketing research and MedWatch: Long-term studies of drug risks.

    Science.gov (United States)

    Resnik, David B

    2007-10-01

    Critics of the drug safety system have discussed many different potential reforms, ranging from mandatory registration of clinical trials to increasing the power of regulatory agencies, but few have discussed one of the most important ways of enhancing safety: increasing the number of long-term studies of medications. Long-term studies of the risks and benefits of drugs can provide useful information for regulators, healthcare professionals, and patients. Government funding agencies should lead the effort to conduct long-term studies of drugs, but private companies should also be required to lend financial support. Because cost-effectiveness is likely to be an important consideration in conducting this research, funding agencies should focus, at first, on drugs that are used to treat common, chronic conditions.

  11. Equity of access under Korean national long-term care insurance: implications for long-term care reform.

    Science.gov (United States)

    Park, Ju Moon

    2015-09-15

    The national long-term care insurance was implemented in July 2008. Few studies have been conducted with representative national survey data since the long-term care insurance was introduced. Therefore, this study examines the extent to which equity in the use of long-term care has been achieved in Korea. The Aday-Andersen model was used as a conceptual model, based on the Korean Health Panel Study which was conducted in 2011. Descriptive and logistic regression analysis was performed to examine the relationship between the dependent and independent variables and the relative importance of factors as predictors of utilization. The results of this study indicated that those who rated his or her health to be fair, good, and very good, had no limited activities, were disabled, and had insurance coverage were more likely to use long-term care services, respectively. Their decision to use long-term care was primarily affected by need (health status, limited activity, disability) and enabling (insurance coverage) factors. The findings also indicated that the introduction of a national long-term care insurance program did not yield a fully equitable distribution of services. Long-term care reforms in Korea should continue to concentrate on expanding insurance coverage and reducing the inequities reflected in disparities in consumer cost-sharing and associated patterns of utilization across plans. The subsequent impact on managed care and expenditures need to be more fully understood.

  12. Long-Term Visual Training Increases Visual Acuity and Long-Term Monocular Deprivation Promotes Ocular Dominance Plasticity in Adult Standard Cage-Raised Mice.

    Science.gov (United States)

    Hosang, Leon; Yusifov, Rashad; Löwel, Siegrid

    2018-01-01

    For routine behavioral tasks, mice predominantly rely on olfactory cues and tactile information. In contrast, their visual capabilities appear rather restricted, raising the question whether they can improve if vision gets more behaviorally relevant. We therefore performed long-term training using the visual water task (VWT): adult standard cage (SC)-raised mice were trained to swim toward a rewarded grating stimulus so that using visual information avoided excessive swimming toward nonrewarded stimuli. Indeed, and in contrast to old mice raised in a generally enriched environment (Greifzu et al., 2016), long-term VWT training increased visual acuity (VA) on average by more than 30% to 0.82 cycles per degree (cyc/deg). In an individual animal, VA even increased to 1.49 cyc/deg, i.e., beyond the rat range of VAs. Since visual experience enhances the spatial frequency threshold of the optomotor (OPT) reflex of the open eye after monocular deprivation (MD), we also quantified monocular vision after VWT training. Monocular VA did not increase reliably, and eye reopening did not initiate a decline to pre-MD values as observed by optomotry; VA values rather increased by continued VWT training. Thus, optomotry and VWT measure different parameters of mouse spatial vision. Finally, we tested whether long-term MD induced ocular dominance (OD) plasticity in the visual cortex of adult [postnatal day (P)162-P182] SC-raised mice. This was indeed the case: 40-50 days of MD induced OD shifts toward the open eye in both VWT-trained and, surprisingly, also in age-matched mice without VWT training. These data indicate that (1) long-term VWT training increases adult mouse VA, and (2) long-term MD induces OD shifts also in adult SC-raised mice.

  13. Considering extraction constraints in long-term oil price modelling

    International Nuclear Information System (INIS)

    Rehrl, Tobias; Friedrich, Rainer; Voss, Alfred

    2005-01-01

    Apart from divergence about the remaining global oil resources, the peak oil discussion can be reduced to a dispute about the time rate at which these resources can be supplied. On the one hand it is problematic to project oil supply trends without taking both - prices as well as supply costs - explicitly into account. On the other hand are supply cost estimates however itself heavily dependent on the underlying extraction rates and are actually only valid within a certain business-as-usual extraction rate scenario (which itself is the task to determine). In fact, even after having applied enhanced recovery technologies, the rate at which an oil field can be exploited is quite restricted. Above a certain level an additional extraction rate increase can only be costly achieved at risks of losses in the overall recoverable amounts of the oil reservoir and causes much higher marginal cost. This inflexibility in extraction can be overcome in principle by the access to new oil fields. This indicates why the discovery trend may roughly form the long-term oil production curve, at least for price-taking suppliers. The long term oil discovery trend itself can be described as a logistic process with the two opposed effects of learning and depletion. This leads to the well-known Hubbert curve. Several attempts have been made to incorporate economic variables econometrically into the Hubbert model. With this work we follow a somewhat inverse approach and integrate Hubbert curves in our Long-term Oil Price and EXtraction model LOPEX. In LOPEX we assume that non-OPEC oil production - as long as the oil can be profitably discovered and extracted - is restricted to follow self-regulative discovery trends described by Hubbert curves. Non-OPEC production in LOPEX therefore consists of those Hubbert cycles that are profitable, depending on supply cost and price. Endogenous and exogenous technical progress is extra integrated in different ways. LOPEX determines extraction and price

  14. In search of the elusive long-term price

    International Nuclear Information System (INIS)

    Connor, M.J.; Combs, J.

    1989-01-01

    The Uranium Institute, WNFM, and past USCEA sessions described and compared existing price reporting systems. The McGraw-Hill conference led to a rather heated discussion as to the propriety of spot prices having the influence they do on amounts paid in long-term contracts. The Ux representative proposed a future's market as a way that producers could hedge against some of the uncertainty of volatile spot market. In discussing the search for the elusive long-term price, there are two interrelated issues. The first is obvious-the search for a starting or initializing price that is representative of recently-signed or pending long-term contracts. The second is less obvious, but perhaps more important-the search for a successful mechanism for determining later delivery values in long-term contracts. This paper addresses the question of pricing mechanisms first

  15. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    International Nuclear Information System (INIS)

    T. Haney R. VanHorn

    2007-01-01

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used to determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality

  16. Radiation effects after low dose chronic long-term exposure

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Friesecke, I.

    1997-01-01

    This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

  17. 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.

  18. Strategies to meet the need for long-term data.

    Science.gov (United States)

    Chalmers, John; Woodward, Mark; Borghi, Claudio; Manolis, Athanasios; Mancia, Giuseppe

    2016-08-01

    Chronic diseases afflict patients for many years, often to the end of life, and there is increasing need for estimating lifelong risk and for evaluating the effects of treatment in the long term. Yet recommendations for lifelong treatment are most frequently based on findings from randomized clinical trials lasting only a few years. There is therefore a clear need for much longer term data, and here we present the advantages and disadvantages of many strategies, including the use of long-term posttrial follow-up, of long-term prospective cohort studies, registry databases, and of administrative databases. We also emphasize the need for long-term cost-effectiveness studies. One of the most promising strategies comes from linkage of data gathered through the ever-expanding pool of administrative databases worldwide with data from other sources, including randomized trials and the many forms of observational study.

  19. Long-term bridge performance high priority bridge performance issues.

    Science.gov (United States)

    2014-10-01

    Bridge performance is a multifaceted issue involving performance of materials and protective systems, : performance of individual components of the bridge, and performance of the structural system as a whole. The : Long-Term Bridge Performance (LTBP)...

  20. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    Energy Technology Data Exchange (ETDEWEB)

    T. Haney

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  1. Long-Term Quiescent Fibroblast Cells Transit into Senescence

    Science.gov (United States)

    Marthandan, Shiva; Priebe, Steffen; Hemmerich, Peter; Klement, Karolin; Diekmann, Stephan

    2014-01-01

    Cellular senescence is described to be a consequence of telomere erosion during the replicative life span of primary human cells. Quiescence should therefore not contribute to cellular aging but rather extend lifespan. Here we tested this hypothesis and demonstrate that cultured long-term quiescent human fibroblasts transit into senescence due to similar cellular mechanisms with similar dynamics and with a similar maximum life span as proliferating controls, even under physiological oxygen conditions. Both, long-term quiescent and senescent fibroblasts almost completely fail to undergo apoptosis. The transition of long-term quiescent fibroblasts into senescence is also independent of HES1 which protects short-term quiescent cells from becoming senescent. Most significantly, DNA damage accumulates during senescence as well as during long-term quiescence at physiological oxygen levels. We suggest that telomere-independent, potentially maintenance driven gradual induction of cellular senescence during quiescence is a counterbalance to tumor development. PMID:25531649

  2. Ethical Dimensions of Autonomy in Long-Term Care.

    Science.gov (United States)

    Collopy, Bart J.

    1990-01-01

    Long-term care of the elderly raises conflicts between personal autonomy and well-being. Assessments of decision-making capacity and definitions of negative and positive autonomy pose value-laden dilemmas for caregivers. (SK)

  3. Long-term Outcomes of Childhood Onset Nephrotic Syndrome.

    Science.gov (United States)

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated.

  4. Modelled long term trends of surface ozone over South Africa

    CSIR Research Space (South Africa)

    Naidoo, M

    2011-10-01

    Full Text Available timescale seeks to provide a spatially comprehensive view of trends while also creating a baseline for comparisons with future projections of air quality through the forcing of air quality models with modelled predicted long term meteorology. Previous...

  5. Silaffin peptides as a novel signal enhancer for gravimetric biosensors.

    Science.gov (United States)

    Nam, Dong Hyun; Lee, Jeong-O; Sang, Byoung-In; Won, Keehoon; Kim, Yong Hwan

    2013-05-01

    Application of biomimetic silica formation to gravimetric biosensors has been conducted for the first time. As a model system, silaffin peptides fused with green fluorescent protein (GFP) were immobilized on a gold quartz crystal resonator for quartz crystal microbalances using a self-assembled monolayer. When a solution of silicic acid was supplied, silica particles were successfully deposited on the Au surface, resulting in a significant change in resonance frequency (i.e., signal enhancement) with the silaffin-GFP. However, frequency was not altered when bare GFP was used as a control. The novel peptide enhancer is advantageous because it can be readily and quantitatively conjugated with sensing proteins using recombinant DNA technology. As a proof of concept, this study shows that the silaffin domains can be employed as a novel and efficient biomolecular signal enhancer for gravimetric biosensors.

  6. Long-Term Care Insurance and Life Insurance Demand

    OpenAIRE

    Volker Meier

    1998-01-01

    This article investigates the interaction between life insurance and long-term care insurance markets on the demand side. In the model utility depends on both consumption and bequest, and utility from consumption is contingent on the state of health. While the demand for life insurance increases both with decreasing income and with a rising degree of altruism, the influences of these two parameters on the demand for long-term care insurance are ambiguous. If the utility shock arising from dis...

  7. Long-Term Prognosis of Ischemic Stroke in Young Adults

    OpenAIRE

    Varona, Jose F.

    2010-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

  8. Long-term patient survival in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten

    2011-01-01

    Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain.......Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain....

  9. Long term acroecosystem research in the Southern Plains

    Science.gov (United States)

    Jean L. Steiner; Patrick J. Starks; Jurgen Garbrecht; Daniel Moriasi; Paul Bartholomew; Jim Neel; Kenneth E. Turner; Brian Northup

    2016-01-01

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at the USDA-ARS Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita River Experimental Watershed (LWREW) in 1961 and in the Fort Cobb...

  10. 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

  11. Subjective social status predicts long-term smoking abstinence.

    Science.gov (United States)

    Reitzel, Lorraine R; Businelle, Michael S; Kendzor, Darla E; Li, Yisheng; Cao, Yumei; Castro, Yessenia; Mazas, Carlos A; Cofta-Woerpel, Ludmila; Cinciripini, Paul M; Wetter, David W

    2011-02-25

    The relationship between subjective social status (SSS), a person's perception of his/her relative position in the social hierarchy, and the ability to achieve long-term smoking abstinence during a specific quit attempt is unknown. The purpose of this study was to examine the relationship between SSS and long-term smoking abstinence among 421 racially/ethnically diverse smokers undergoing a specific quit attempt, as well as the interactive effects of race/ethnicity and sex. The main effects and moderated relationships of SSS on biochemically-confirmed, continuous smoking abstinence through 26 weeks post-quit were examined using continuation ratio logit models adjusted for sociodemographics and smoking characteristics. Even after adjusting for the influence of socioeconomic status and other covariates, smokers endorsing lower SSS were significantly less likely to maintain long-term smoking abstinence during a specific quit attempt than those with higher SSS (OR = 1.14, 95% CI: 1.00 - 1.28; p = 0.044). The statistical significance of this relationship, however, did not vary by race/ethnicity or sex. SSS independently predicts long-term smoking abstinence during a specific quit attempt. SSS may be a useful screener to identify smokers at elevated risk of relapse who may require additional attention to facilitate long-term abstinence. More research is needed to understand the mechanisms underlying the relationship between SSS and long-term smoking abstinence in order to appropriately tailor treatment to facilitate abstinence among lower SSS smokers.

  12. Enhancement of signal sensitivity in a heterogeneous neural network refined from synaptic plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiumin; Small, Michael, E-mail: ensmall@polyu.edu.h, E-mail: 07901216r@eie.polyu.edu.h [Department of Electronic and Information Engineering, Hong Kong Polytechnic University, Hung Hom, Kowloon (Hong Kong)

    2010-08-15

    Long-term synaptic plasticity induced by neural activity is of great importance in informing the formation of neural connectivity and the development of the nervous system. It is reasonable to consider self-organized neural networks instead of prior imposition of a specific topology. In this paper, we propose a novel network evolved from two stages of the learning process, which are respectively guided by two experimentally observed synaptic plasticity rules, i.e. the spike-timing-dependent plasticity (STDP) mechanism and the burst-timing-dependent plasticity (BTDP) mechanism. Due to the existence of heterogeneity in neurons that exhibit different degrees of excitability, a two-level hierarchical structure is obtained after the synaptic refinement. This self-organized network shows higher sensitivity to afferent current injection compared with alternative archetypal networks with different neural connectivity. Statistical analysis also demonstrates that it has the small-world properties of small shortest path length and high clustering coefficients. Thus the selectively refined connectivity enhances the ability of neuronal communications and improves the efficiency of signal transmission in the network.

  13. T cell resistance to activation by dendritic cells requires long-term culture in simulated microgravity

    Science.gov (United States)

    Bradley, Jillian H.; Stein, Rachel; Randolph, Brad; Molina, Emily; Arnold, Jennifer P.; Gregg, Randal K.

    2017-11-01

    Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines. Finally, the effector T cells acquire the weaponry needed to destroy microbial invaders and tumors. Studies conducted on T cells during spaceflight, or using Earth-based culture systems, have shown reduced production of cytokines, proliferation and effector functions as compared to controls. This may account for the cases of viral reactivation events and opportunistic infections associated with astronauts of numerous missions. This work has largely been based upon the outcome of T cell activation by stimulatory factors that target select T cell signaling pathways rather than the complex, signaling events related to the natural process of antigen presentation by DC. This study tested the response of an ovalbumin peptide-specific T cell line, OT-II TCH, to activation by DC when the T cells were cultured 24-120 h in a simulated microgravity (SMG) environment generated by a rotary cell culture system. Following 72 h culture of T cells in SMG (SMG-T) or control static (Static-T) conditions, IL-2 production by the T cells was reduced in SMG-T cells compared to Static-T cells upon stimulation by phorbol 12-myristate 13-acetate (PMA) and ionomycin. However, when the SMG-T cells were stimulated with DC and peptide, IL-2 was significantly increased compared to Static-T cells. Such enhanced IL-2 production by SMG-T cells peaked at 72 h SMG culture time and decreased thereafter. When

  14. T cell resistance to activation by dendritic cells requires long-term culture in simulated microgravity.

    Science.gov (United States)

    Bradley, Jillian H; Stein, Rachel; Randolph, Brad; Molina, Emily; Arnold, Jennifer P; Gregg, Randal K

    2017-11-01

    Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines. Finally, the effector T cells acquire the weaponry needed to destroy microbial invaders and tumors. Studies conducted on T cells during spaceflight, or using Earth-based culture systems, have shown reduced production of cytokines, proliferation and effector functions as compared to controls. This may account for the cases of viral reactivation events and opportunistic infections associated with astronauts of numerous missions. This work has largely been based upon the outcome of T cell activation by stimulatory factors that target select T cell signaling pathways rather than the complex, signaling events related to the natural process of antigen presentation by DC. This study tested the response of an ovalbumin peptide-specific T cell line, OT-II TCH, to activation by DC when the T cells were cultured 24-120 h in a simulated microgravity (SMG) environment generated by a rotary cell culture system. Following 72 h culture of T cells in SMG (SMG-T) or control static (Static-T) conditions, IL-2 production by the T cells was reduced in SMG-T cells compared to Static-T cells upon stimulation by phorbol 12-myristate 13-acetate (PMA) and ionomycin. However, when the SMG-T cells were stimulated with DC and peptide, IL-2 was significantly increased compared to Static-T cells. Such enhanced IL-2 production by SMG-T cells peaked at 72 h SMG culture time and decreased thereafter

  15. A Search for Long-term Slow Slip Along the Cascadia Subduction Zone

    Science.gov (United States)

    Nuyen, C.; Schmidt, D. A.

    2016-12-01

    Japan's Nankai Trough and the Cascadia Subduction Zone are often compared as analogous systems due to their striking similarities, which include relatively high thermal gradients, young incoming plates, and the occurrence of short-term slow slip episodes (SSEs). However, a lack of long-term SSEs in Cascadia sets it apart from Nankai, which experiences both short- and long-term SSEs. This disparity between Cascadia and Nankai begs the question of whether long-term SSEs are in fact absent in Cascadia. We examine GPS data from the PBO and PANGA networks to determine whether or not Cascadia has hosted a long-term SSE in the past 20 years. A preliminary review of the time series does not reveal any large-scale multi-year transients, such as has been documented in Japan and Alaska where over 5 cm of surface displacement is seen over multiple years. In order to more clearly recognize possible small amplitude long-term SSEs in Cascadia, the GPS data are reduced as follows: time series are cleaned by removing (1) continental water loading terms, (2) transient displacements of known short-term SSEs, and (3) common mode signals that span the network. After cleaning, the GPS data are manually inspected for coherent trends between stations. To further identify small amplitude slip events that persist for months-to-years, we invert the cleaned time series in Cascadia for fault slip using a principle component analysis-based inversion method. We also perform a suite of synthetic forward models to better understand how a long-term slow slip event might appear in the time series. Results from this research have direct implications for Cascadia in terms of moment release, stress redistributions, and seismic cycles. In a broader sense, these results also influence the global knowledge of SSEs by giving a better understanding of the full range of slip modes in Cascadia.

  16. 12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

    Science.gov (United States)

    DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

    2010-01-01

    Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

  17. Enhancing Raman signals with an interferometrically controlled AFM tip

    International Nuclear Information System (INIS)

    Oron-Carl, Matti; Krupke, Ralph

    2013-01-01

    We demonstrate the upgrade of a commercial confocal Raman microscope into a tip-enhanced Raman microscope/spectroscopy system (TERS) by integrating an interferometrically controlled atomic force microscope into the base of an existing upright microscope to provide near-field detection and thus signal enhancement. The feasibility of the system is demonstrated by measuring the Raman near-field enhancement on thin PEDOT:PSS films and on carbon nanotubes within a device geometry. An enhancement factor of 2–3 and of 5–6 is observed, respectively. Moreover, on a nanotube device we show local conductivity measurement and its correlation to Raman and topography recordings. Upgrading an existing upright confocal Raman microscope in the demonstrated way is significantly cheaper than purchasing a complete commercial TERS system. (paper)

  18. Fingerprinting the Impacts of Aerosols on Long-Term Trends of the Indian Summer Monsoon Regional Rainfall

    Science.gov (United States)

    Laul, K. M.; Kim, K. M.

    2010-01-01

    In this paper, we present corroborative observational evidences from satellites, in-situ observations, and re-analysis data showing possible impacts of absorbing aerosols (black carbon and dust) on subseasonal and regional summer monsoon rainfall over India. We find that increased absorbing aerosols in the Indo-Gangetic Plain in recent decades may have lead to long-term warming of the upper troposphere over northern India and the Tibetan Plateau, enhanced rainfall in northern India and the Himalayas foothill regions in the early part (may-June) of the monsoon season, followed by diminished rainfall over central and southern India in the latter part (July-August) of the monsoon season. These signals which are consistent with current theories of atmospheric heating and solar dimming by aerosol and induced cloudiness in modulating the Indian monsoon, would have been masked by conventional method of using al-India rainfall averaged over the entire monsoon season.

  19. Synaptic long-term potentiation realized in Pavlov's dog model based on a NiOx-based memristor

    Science.gov (United States)

    Hu, S. G.; Liu, Y.; Liu, Z.; Chen, T. P.; Yu, Q.; Deng, L. J.; Yin, Y.; Hosaka, Sumio

    2014-12-01

    Synaptic Long-Term Potentiation (LTP), which is a long-lasting enhancement in signal transmission between neurons, is widely considered as the major cellular mechanism during learning and memorization. In this work, a NiOx-based memristor is found to be able to emulate the synaptic LTP. Electrical conductance of the memristor is increased by electrical pulse stimulation and then spontaneously decays towards its initial state, which resembles the synaptic LTP. The lasting time of the LTP in the memristor can be estimated with the relaxation equation, which well describes the conductance decay behavior. The LTP effect of the memristor has a dependence on the stimulation parameters, including pulse height, width, interval, and number of pulses. An artificial network consisting of three neurons and two synapses is constructed to demonstrate the associative learning and LTP behavior in extinction of association in Pavlov's dog experiment.

  20. Long-term costs of colorectal cancer treatment in Spain.

    Science.gov (United States)

    Corral, Julieta; Castells, Xavier; Molins, Eduard; Chiarello, Pietro; Borras, Josep Maria; Cots, Francesc

    2016-02-16

    Assessing the long-term cost of colorectal cancer (CRC) increases our understanding of the disease burden. The aim of this paper is to estimate the long-term costs of CRC care by stage at diagnosis and phase of care in the Spanish National Health Service. Retrospective study on resource use and direct medical cost of a cohort of 699 patients diagnosed and treated for CRC in 2000-2006, with follow-up until 30 June 2011, at Hospital del Mar (Barcelona). The Kaplan-Meier sample average estimator was used to calculate observed 11-year costs, which were then extrapolated to 16 years. Bootstrap percentile confidence intervals were calculated for the mean long-term cost per patient by stage. Phase-specific, long-term costs for the entire CRC cohort were also estimated. With regard to stage at diagnosis, the mean long-term cost per patient ranged from €20,708 (in situ) to €47,681 (stage III). The estimated costs increased at more advanced stages up to stage III and then substantially decreased in stage IV. In terms of treatment phase, the mean cost of the initial period represented 24.8 % of the total mean long-term cost, whereas the cost of continuing and advanced care phases represented 16.9 and 58.3 %, respectively. This study is the first to provide long-term cost estimates for CRC treatment, by stage at diagnosis and phase of care, based on data from clinical practice in Spain, and it will contribute useful information for future studies on cost-effectiveness and budget impact of different therapeutic innovations in Spain.

  1. Volunteer provision of long-term care for older people in Thailand and Costa Rica.

    Science.gov (United States)

    Lloyd-Sherlock, Peter; Pot, Anne Margriet; Sasat, Siriphan; Morales-Martinez, Fernando

    2017-11-01

    Demand for long-term care services for older people is increasing rapidly in low- and middle-income countries. Countries need to establish national long-term care systems that are sustainable and equitable. The Governments of Costa Rica and Thailand have implemented broadly comparable interventions to deploy volunteers in long-term home care. Both countries trained older volunteers from local communities to make home visits to impoverished and vulnerable older people and to facilitate access to health services and other social services. Costa Rica and Thailand are upper-middle-income countries with strong traditions of community-based health services that they are now extending into long-term care for older people. Between 2003 and 2013 Thailand's programme trained over 51 000 volunteers, reaching almost 800 000 older people. Between 2010 and 2016 Costa Rica established 50 community care networks, serving around 10 000 people and involving over 5000 volunteers. Despite some evidence of benefits to the physical and mental health of older people and greater uptake of other services, a large burden of unmet care needs and signs of a growth of unregulated private services still exist. There is scope for low- and middle-income countries to develop large-scale networks of community-based long-term care volunteers. The capacity of volunteers to enhance the quality of life of clients is affected by the local availability of care services. Volunteer care networks should be complemented by other initiatives, including training about health in later life for volunteers, and investment in community long-term care services.

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

    Directory of Open Access Journals (Sweden)

    Lee Yong-Seok

    2008-06-01

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

  3. Innovative culture in long-term care settings: the influence of organizational characteristics.

    Science.gov (United States)

    Nieboer, Anna P; Strating, Mathilde M H

    2012-01-01

    Innovative cultures have been reported to enhance the creation and implementation of new ideas and working methods in organizations. Although there is considerable research on the impact of organizational context on the innovativeness of organizations, the same is not the case for research on the organizational characteristics responsible for an innovative culture in (long-term) care settings. The aim of this study was to identify organizational characteristics that explain innovative culture in the (long-term) care sector. A large cross-sectional study in Dutch long-term care-nursing homes and/or elderly homes, care organizations for the handicapped, and long-term mental health care organizations-was conducted. A total of 432 managers and care professionals in 37 organizations participated. The Group Innovation Inventory was used to measure innovative culture in long-term care organizations. Structural characteristics of the organization were centralization and formalization, environmental dynamism and competitiveness, internal and external exchange of information, leadership style, commitment to quality improvement, and the organization's innovative strategy. The determinants of an innovative culture were estimated with a two-level random-intercepts and fixed-slopes model. Multilevel regression models were used to account for the organizational clustering of individuals within the 37 care organizations. Environmental dynamism, job codification, formal external exchange of information, transformational leadership, commitment to quality, and an exploratory and exploitative innovation strategy were all significantly correlated with an innovative culture in the multivariate multilevel analysis; the other characteristics were not. The explained organizational- and individual-level variance was 52.5% and 49.2%, respectively. The results point to substantial differences in innovative cultures between and within care organizations that can, in part, be explained by

  4. Men's Sheds: enabling environments for Australian men living with and without long-term disabilities.

    Science.gov (United States)

    Hansji, Neeraj L; Wilson, Nathan J; Cordier, Reinie

    2015-05-01

    The health of Australian men has recently received greater attention. Men's Sheds are named in national policy as an exemplar community-based organisation for the betterment of men's psychosocial health; yet, the evidence base to support this is limited. This study investigates the comparative experience of men with long-term disabilities and men without long-term disabilities who go to a Men's Shed and to what extent this provides these men with an enabling, as opposed to disabling, environment. Data were collected from 12 individual interviews with men with long-term disabilities (5) and men without long-term disabilities (6), including 1 interview with the male Men's Shed Coordinator (MSC); participant observation within the shed; and a document received from the female MSC regarding the funding the Shed receives. Interviews explored the men's experiences at the Shed and their sense of belonging and social inclusion. Participants had any type of long-term disability and had been attending the shed for a minimum of 1 month. Data were collected between May and September 2013 and were analysed using the constant comparative method of grounded theory. The core theme that emerged was an enabling community space. The four sub-themes were: a community and social hub; an equalising space; a safe and supportive male environment; and meaningful male activities. The current literature exemplifies Men's Sheds to be important community-based organisations beneficial to men's health and well-being. For men living with long-term disabilities, this study illuminates that Men's Sheds offer an environment of equality, facilitating a collegial and egalitarian culture. Men can partake in enabling activities and enjoy the company of other men enhancing their sense of belonging and social inclusion as well as interact with other community groups that occupy the same space as the Men's Shed. © 2014 John Wiley & Sons Ltd.

  5. Deleting HDAC3 Rescues Long-Term Memory Impairments Induced by Disruption of the Neuron-Specific Chromatin Remodeling Subunit BAF53b

    Science.gov (United States)

    Shu, Guanhua; Kramár, Enikö A.; López, Alberto J.; Huynh, Grace; Wood, Marcelo A.; Kwapis, Janine L.

    2018-01-01

    Multiple epigenetic mechanisms, including histone acetylation and nucleosome remodeling, are known to be involved in long-term memory formation. Enhancing histone acetylation by deleting histone deacetylases, like HDAC3, typically enhances long-term memory formation. In contrast, disrupting nucleosome remodeling by blocking the neuron-specific…

  6. Effects of Long-Term Protein Restriction on Meat Quality, Muscle Amino Acids, and Amino Acid Transporters in Pigs.

    Science.gov (United States)

    Yin, Jie; Li, Yuying; Zhu, Xiaotong; Han, Hui; Ren, Wenkai; Chen, Shuai; Bin, Peng; Liu, Gang; Huang, Xingguo; Fang, Rejun; Wang, Bin; Wang, Kai; Sun, Liping; Li, Tiejun; Yin, Yulong

    2017-10-25

    This study aimed to investigate the long-term effects of protein restriction from piglets to finishing pigs for 16 weeks on meat quality, muscle amino acids, and amino acid transporters. Thirty-nine piglets were randomly divided into three groups: a control (20-18-16% crude protein, CP) and two protein restricted groups (17-15-13% CP and 14-12-10% CP). The results showed that severe protein restriction (14-12-10% CP) inhibited feed intake and body weight, while moderate protein restriction (17-15-13% CP) had little effect on growth performance in pigs. Meat quality (i.e., pH, color traits, marbling, water-holding capacity, and shearing force) were tested, and the results exhibited that 14-12-10% CP treatment markedly improved muscle marbling score and increased yellowness (b*). pH value (45 min) was significantly higher in 17-15-13% CP group than that in other groups. In addition, protein restriction reduced muscle histone, arginine, valine, and isoleucine abundances and enhanced glycine and lysine concentrations compared with the control group, while the RT-PCR results showed that protein restriction downregulated amino acids transporters. Mechanistic target of rapamycin (mTOR) signaling pathway was inactivated in the moderate protein restricted group (17-15-13% CP), while severe protein restriction with dietary 14-12-10% CP markedly enhanced mTOR phosphorylation. In conclusion, long-term protein restriction affected meat quality and muscle amino acid metabolism in pigs, which might be associated with mTOR signaling pathway.

  7. Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD).

    Science.gov (United States)

    He, Yao; Kulasiri, Don; Samarasinghe, Sandhya

    2016-08-21

    Synaptic plasticity induces bidirectional modulations of the postsynaptic response following a synaptic transmission. The long term forms of synaptic plasticity, named long term potentiation (LTP) and long term depression (LTD), are critical for the antithetic functions of the memory system, memory formation and removal, respectively. A common Ca(2+) signalling upstream triggers both LTP and LTD, and the critical proteins and factors coordinating the LTP/LTD inductions are not well understood. We develop an integrated model based on the sub-models of the indispensable synaptic proteins in the emergence of synaptic plasticity to validate and understand their potential roles in the expression of synaptic plasticity. The model explains Ca(2+)/calmodulin (CaM) complex dependent coordination of LTP/LTD expressions by the interactions among the indispensable proteins using the experimentally estimated kinetic parameters. Analysis of the integrated model provides us with insights into the effective timescales of the key proteins and we conclude that the CaM pool size is critical for the coordination between LTP/LTD expressions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. REGULAR REHEARSAL HELPS IN CONSOLIDATION OF LONG TERM MEMORY

    Directory of Open Access Journals (Sweden)

    Milind Parle

    2006-03-01

    Full Text Available Memory, one of the most complex functions of the brain comprises of multiple components such as perception, registration, consolidation, storage, retrieval and decay. The present study was undertaken to evaluate the impact of different training sessions on the retention capacity of rats. The capacity of retention of learnt task was measured using exteroceptive behavioral models such as Hexagonal swimming pool apparatus, Hebb-Williams maze and Elevated plus-maze. A total of 150 rats divided into fifteen groups were employed in the present study. The animals were subjected to different training sessions during first three days. The ability to retain the learned task was tested after single, sub-acute, acute, sub-chronic and chronic exposure to above exteroceptive memory models in separate groups of animals. The memory score of all animals was recorded after 72 h, 192 h and 432 h of their last training trial. Rats of single exposure group did not show any effect on memory. Sub-acute training group animals showed improved memory up to 72 h only, where as in acute and sub-chronic training groups this memory improvement was extended up to 192 h. The rats, which were subjected to chronic exposures showed a significant improvement in retention capacity that lasted up to a period of eighteen days. These observations suggest that repeated rehearsals at regular intervals are probably necessary for consolidation of long-term memory. It was observed that sub-acute, acute and sub-chronic exposures, improved the retrieval ability of rats but this memory improving effect was short lived. Thus, rehearsal or training plays a crucial role in enhancing one's capacity of retaining the learnt information

  9. 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.

  10. 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)

  11. Mesozoic long-term eustatic cycles and their uncertain hierarchy

    Directory of Open Access Journals (Sweden)

    Dmitry A. Ruban

    2015-07-01

    Full Text Available Global sea-level has changed in a cyclic manner through geologic history, but the regularities of these changes are yet to be fully understood. Despite certain (and sometimes significant differences, the available Mesozoic eustatic curves permit the outlining of long-term eustatic cycles, which are provisionally defined as cycles recognizable at the stage level and higher. Interpretation of the Triassic eustatic curves indicates two orders of long-term cycles and a 1st-order sea-level rise throughout the entire period. The Jurassic eustatic curves imply cyclicity of one or two orders, and a 1st-order eustatic rise during the entire period is also evident. Most challenges are interpretations for the Cretaceous; two to four orders of long-term eustatic cycles can be established for this period. Generally, the hierarchy of the long-term eustatic cycles might have changed through the Mesozoic. If so, and if one considers differences of cycles of the same order between the periods of this era, it is difficult to apply “standard” hierarchical classifications to the documented cycles. The hypothetical uncertainty of the hierarchy of the Mesozoic long-term eustatic cycles is an important challenge for modern researchers.

  12. Common Calibration Source for Monitoring Long-term Ozone Trends

    Science.gov (United States)

    Kowalewski, Matthew

    2004-01-01

    Accurate long-term satellite measurements are crucial for monitoring the recovery of the ozone layer. The slow pace of the recovery and limited lifetimes of satellite monitoring instruments demands that datasets from multiple observation systems be combined to provide the long-term accuracy needed. A fundamental component of accurately monitoring long-term trends is the calibration of these various instruments. NASA s Radiometric Calibration and Development Facility at the Goddard Space Flight Center has provided resources to minimize calibration biases between multiple instruments through the use of a common calibration source and standardized procedures traceable to national standards. The Facility s 50 cm barium sulfate integrating sphere has been used as a common calibration source for both US and international satellite instruments, including the Total Ozone Mapping Spectrometer (TOMS), Solar Backscatter Ultraviolet 2 (SBUV/2) instruments, Shuttle SBUV (SSBUV), Ozone Mapping Instrument (OMI), Global Ozone Monitoring Experiment (GOME) (ESA), Scanning Imaging SpectroMeter for Atmospheric ChartographY (SCIAMACHY) (ESA), and others. We will discuss the advantages of using a common calibration source and its effects on long-term ozone data sets. In addition, sphere calibration results from various instruments will be presented to demonstrate the accuracy of the long-term characterization of the source itself.

  13. Long-term psychosocial consequences of surgical congenital malformations.

    Science.gov (United States)

    Diseth, Trond H; Emblem, Ragnhild

    2017-10-01

    Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

  14. 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

  15. Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.

    Science.gov (United States)

    Bell, Genevieve A; Fadool, Debra Ann

    2017-05-15

    Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to

  16. 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

  17. Influence of Whipping on Long term Vertical Bending Moment

    DEFF Research Database (Denmark)

    Baarholm, G. S.; Jensen, Jørgen Juncher

    2004-01-01

    approach. Effect of whipping is included by assuming that the whipping and wave induced response are independent, but the effect of correlation of the long term extreme value is also studied. Numerical calculations are performed using a nonlinear, hydroelastic strip theory as suggested by (Xia et al 1998...... to introduce ways to improve the efficiency in the calculation. A method to determine the long term extremes by considering only a few short term sea state is applied. Long term extreme values are estimated using a set of sea states which have a certain probability of occurrence, known as the contour line......This paper is concerned with estimating the response value corresponding to a long return period, say a twenty years. Time domain simulation is required to obtain the nonlinear response, and long time series are required to limit the statistical uncertainty in the simulations. It is crucial...

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

    Science.gov (United States)

    Lichtenberg, Peter A

    2014-01-01

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

  19. Sexuality and Physical Intimacy in Long Term Care

    Science.gov (United States)

    Lichtenberg, Peter A.

    2015-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long term care and presents two case examples. A semi-structured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing needs for protection with needs for autonomy. PMID:24354331

  20. Long-term visual associations affect attentional guidance.

    Science.gov (United States)

    Olivers, Christian N L

    2011-06-01

    When observers perform a visual search task, they are assumed to adopt an attentional set for what they are looking for. The present experiment investigates the influence of long-term visual memory associations on this attentional set. On each trial, observers were asked to search a display for a grayscale version of a known traffic sign. On each trial, a distractor sign was drawn in full color. This color could either be related or unrelated to the target sign. Distractors interfered more with search when their color was related (e.g. red when the target was a stop sign), implying that long-term color associations resulted in inadvertent attentional guidance, even though color was irrelevant to the task. The results add to the growing body of evidence that long-term memory representations automatically affect attentional orienting. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Ethics and Intimate Sexual Activity in Long-Term Care.

    Science.gov (United States)

    Metzger, Eran

    2017-07-01

    A case is presented in which the staff of a long-term care facility discovers that the husband of a resident with dementia is engaged in sexual activity with her. The case illustrates a dilemma for long-term care facilities that create a home-like environment with a goal of maximizing residents' autonomy while ensuring their safety. An approach to assessing capacity to consent to intimate sexual activity is described, followed by guidelines that nursing homes can implement to support residents who wish to engage in sexual activity. Recommendations are also offered for supporting long-term care staff and family members of residents who are interested in intimate sexual activity. © 2017 American Medical Association. All Rights Reserved.

  2. Long-term impact of sales promotion on brand image

    Directory of Open Access Journals (Sweden)

    Danijela Mandić

    2009-12-01

    Full Text Available Sales promotion (SP is an inevitable tool in the marketing communications mix, especially in the FMCG markets, due to pressures such as retailers’ growing demands and increasing competition. This has proven to be an issue for many companies, especially those with a premium brand positioning and those concerned about the impact that SP might have on the long-term image of the company. Despite the fact that literature is replete with research on SP, it seems to be vastly generalized and mostly focused on price reductions. Thus, this paper aims to analyze and discuss the issue of the long-term impact that SP has on companies, especially on premium brands in the FMCG markets. It concludes that, when used properly and strategically, SP may have a positive long-term impact on brands.

  3. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are ralated to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product. (author)

  4. Acute and long-term psychiatric side effects of mefloquine

    DEFF Research Database (Denmark)

    Ringqvist, Åsa; Bech, Per; Glenthøj, Birte

    2015-01-01

    psychiatric side effects were retrospectively assessed using the SCL-90-R and questions based on Present State Examination (PSE). Subjects reporting suspected psychotic states were contacted for a personal PSE interview. Electronic records of psychiatric hospitalizations and diagnoses were cross-checked. Long-term......BACKGROUND: The aim of the study was to explore the profile of acute and long-term psychiatric side effects associated with mefloquine. METHODS: Subjects (n = 73) reported to a Danish national register during five consecutive years for mefloquine associated side effects were included. Acute...... symptoms were found in 15% and were time-limited. Illusions/hallucinations were more frequently observed among women. Cases of hypomania/mania in the acute phase were 5.5%. Significant long-term mental health effects were demonstrated for the SF-36 subscales mental health (MH), role emotional (RE...

  5. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for the long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are related to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product

  6. Winning market positioning strategies for long term care facilities.

    Science.gov (United States)

    Higgins, L F; Weinstein, K; Arndt, K

    1997-01-01

    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application.

  7. How to improve long-term outcome after liver transplantation?

    Science.gov (United States)

    Durand, François

    2018-02-01

    The outcome of liver transplantation has markedly improved in the last 3 decades. Although early post-transplantation outcomes have improved over time, this is not true of the long-term outcome. The majority of late deaths are not related to graft dysfunction, and with the advent of new antiviral agents, recurrence of hepatitis B and hepatitis C after transplantation may no longer represent a source of graft loss and patient's death in the long term. The complications of metabolic syndrome may represent an increasing source of morbidity and mortality after transplantation. This study discusses these modifiable factors associated with late mortality to improve the long-term results of transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Subjective social status predicts long-term smoking abstinence

    Directory of Open Access Journals (Sweden)

    Cofta-Woerpel Ludmila

    2011-02-01

    Full Text Available Abstract Background The relationship between subjective social status (SSS, a person's perception of his/her relative position in the social hierarchy, and the ability to achieve long-term smoking abstinence during a specific quit attempt is unknown. The purpose of this study was to examine the relationship between SSS and long-term smoking abstinence among 421 racially/ethnically diverse smokers undergoing a specific quit attempt, as well as the interactive effects of race/ethnicity and sex. Methods The main effects and moderated relationships of SSS on biochemically-confirmed, continuous smoking abstinence through 26 weeks post-quit were examined using continuation ratio logit models adjusted for sociodemographics and smoking characteristics. Results Even after adjusting for the influence of socioeconomic status and other covariates, smokers endorsing lower SSS were significantly less likely to maintain long-term smoking abstinence during a specific quit attempt than those with higher SSS (OR = 1.14, 95% CI: 1.00 - 1.28; p = 0.044. The statistical significance of this relationship, however, did not vary by race/ethnicity or sex. Conclusions SSS independently predicts long-term smoking abstinence during a specific quit attempt. SSS may be a useful screener to identify smokers at elevated risk of relapse who may require additional attention to facilitate long-term abstinence. More research is needed to understand the mechanisms underlying the relationship between SSS and long-term smoking abstinence in order to appropriately tailor treatment to facilitate abstinence among lower SSS smokers.

  9. Long-term surface EMG monitoring using K-means clustering and compressive sensing

    Science.gov (United States)

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2015-05-01

    In this work, we present an advanced K-means clustering algorithm based on Compressed Sensing theory (CS) in combination with the K-Singular Value Decomposition (K-SVD) method for Clustering of long-term recording of surface Electromyography (sEMG) signals. The long-term monitoring of sEMG signals aims at recording of the electrical activity produced by muscles which are very useful procedure for treatment and diagnostic purposes as well as for detection of various pathologies. The proposed algorithm is examined for three scenarios of sEMG signals including healthy person (sEMG-Healthy), a patient with myopathy (sEMG-Myopathy), and a patient with neuropathy (sEMG-Neuropathr), respectively. The proposed algorithm can easily scan large sEMG datasets of long-term sEMG recording. We test the proposed algorithm with Principal Component Analysis (PCA) and Linear Correlation Coefficient (LCC) dimensionality reduction methods. Then, the output of the proposed algorithm is fed to K-Nearest Neighbours (K-NN) and Probabilistic Neural Network (PNN) classifiers in order to calclute the clustering performance. The proposed algorithm achieves a classification accuracy of 99.22%. This ability allows reducing 17% of Average Classification Error (ACE), 9% of Training Error (TE), and 18% of Root Mean Square Error (RMSE). The proposed algorithm also reduces 14% clustering energy consumption compared to the existing K-Means clustering algorithm.

  10. Long-term stability scintillation tiles for LHCb detector

    CERN Document Server

    Grinyov, B V; Khlapova, N P; Lebedev, V N; Melnychuk, S V; Senchyshyn, V G

    2004-01-01

    Accelerated thermal aging tests of materials-UPS-923A, UPS-96G, UPS-96GM and their analogues, SCSN-81 (Kuraray) and BC-408 (Bicron)- were made. A forecast of tile lifetime was made for normal conditions of usage (20% reduction of light output and 50% reduction of the bulk attenuation length (BAL) and technical attenuation length (TAL). Scintillator UPS-96GM has the most long-term stability of parameters- more than 11 yr. BC-408 samples have the minimum lifetime ~7 yr. The long-term stability, calculated by light yield reduction, of UPS-96G, UPS-923A and SCSN-81 is 10, 9 and 8 yr, respectively.

  11. Long-term stability scintillation tiles for LHCb detector

    International Nuclear Information System (INIS)

    Grinyov, B.V.; Khlapova, N.P.; Senchyshyn, V.G.; Lebedev, V.N.; Adadurov, A.F.; Melnychuk, S.V.

    2004-01-01

    Accelerated thermal aging tests of materials - UPS-923A, UPS-96G, UPS-96GM and their analogues, SCSN-81 (Kuraray) and BC-408 (Bicron) - were made. A forecast of tile lifetime was made for normal conditions of usage (20% reduction of light output and 50% reduction of the bulk attenuation length (BAL) and technical attenuation length (TAL). Scintillator UPS-96GM has the most long-term stability of parameters--more than 11 yr. BC-408 samples have the minimum lifetime ∼7 yr. The long-term stability, calculated by light yield reduction, of UPS-96G, UPS-923A and SCSN-81 is 10, 9 and 8 yr, respectively

  12. Long-term recurrence and death rates after acute pancreatitis

    DEFF Research Database (Denmark)

    Lund, Helle; Tønnesen, Hanne; Tønnesen, Maja Hanne

    2006-01-01

    The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death.......The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death....

  13. [Analysis of long-term survivors in anaplastic thyroid carcinoma].

    Science.gov (United States)

    Yoshida, Akira; Matuzu, Kenichi

    2012-07-01

    We analyzed the clinicopathologic and therapeutic factors associated with long-term survival in 449 patients with anaplastic carcinoma registered with the Anaplastic Thyroid Carcinoma Consortium of Japan. Univariate analysis showed a significant relationship between long-term survival of more than 1 year and the following factors: the appearance of acute symptom; WBC thyroid gland after surgery; no distant metastasis at initial diagnosi; complete resection of gross tumor; and administration of external irradiation (40 Gy) and chemotherapy. In multivariate analysis, only tumor diameter (disease.

  14. On the long-term analysis with finite elements

    International Nuclear Information System (INIS)

    Argyris, J.H.; Szimmat, J.; Willam, K.J.

    1975-01-01

    Following a presentation of concrete creep, a brief summary of the direct and incremental calculation methods on long-term behaviour is given. This is followed by a survey of the method of the inner state variables, which on the one hand gives a uniform framework for the various formulations of concrete creep, and on the other hand leads to a computer-ready calculation process. Two examples on long-term behaviour illustrate the regions of application of the computer methods. (orig./LH) [de

  15. Long-term creep test with finite elements

    International Nuclear Information System (INIS)

    Argyris, J.H.; Szimmat, J.; Willam, K.J.

    1975-01-01

    Following a presentation of concrete creep, a brief summary of the direct and incremental calculation methods for long-term creep behaviour is given. In addition, a survey on the methods of the inner state variables is given which, on the one hand, gives a uniform framework for the various formulations of concrete creep, and on the other hand leads to a computable calculation method. Two examples on long-term creep behaviour illustrate the application field of the calculation method. (orig./LH) [de

  16. 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...... to the confounding effect related to a family history of renal disease. DESCARTES board members emphasize the importance of optimal risk–benefit assessment and proper information to the prospective donor, which should also include recommendations on health-promoting behaviour post-donation....

  17. General practitioners and long-term neurological conditions.

    Science.gov (United States)

    Gibson, Jeremy

    2008-01-01

    General practitioners (GPs) can have a significant role to play in the management of individuals with long-term neurological conditions (LTNC). This paper looks at various roles and responsibilities of GPs in the management of these patients. This paper is based on a Medline literature search using the key words 'general practitioner;''rehabilitation;''long-term;' and 'neurological'. The findings are broadly divided into diagnostic, supportive and palliative roles. GPs have a lot to offer individuals with LTNC, but recent changes in the way they work, especially in the UK, may hamper their role.

  18. The Challenge of Long-Term Climate Change

    Science.gov (United States)

    Hasselmann, K.; Latif, M.; Hooss, G.; Azar, C.; Edenhofer, O.; Jaeger, C. C.; Johannessen, O. M.; Kemfert, C.; Welp, M.; Wokaun, A.

    2003-12-01

    Climate policy needs to address the multidecadal to centennial time scale of climate change. Although the realization of short-term targets is an important first step, to be effective climate policies need to be conceived as long-term programs that will achieve a gradual transition to an essentially emission-free economy on the time scale of a century. This requires a considerably broader spectrum of policy measures than the primarily market-based instruments invoked for shorter term mitigation policies. A successful climate policy must consist of a dual approach focusing on both short-term targets and long-term goals.

  19. Mapping long-term wetland response to climate

    Science.gov (United States)

    Zhou, Q.; Gallant, A.; Rover, J.

    2016-12-01

    Wetlands provide unique feeding and breeding habitat for numerous waterfowl species. The distribution of wetlands has been considerably changed due to agricultural land conversion and hydrologic modification. Climate change may further impact wetlands through altered moisture regimes. This study characterized long-term variation in wetland conditions by using dense time series from all available Landsat data from 1985 to 2014. We extracted harmonic frequencies from 30 years to two years to delineate the long-term variation in all seven Landsat bands. A cluster analysis and unsupervised classification then enabled us to map different classes of wetland response. We demonstrated the method in the Prairie Pothole Region in North Dakota.

  20. A NOVEL APPROACH FOR LONG TERM SOLAR RADIATION PREDICTION

    Directory of Open Access Journals (Sweden)

    Manju Khanna

    2018-10-01

    Full Text Available With present stress, being laid on green energy worldwide, harnessing solar energy for commercial use has importance in sizing and long-term prediction of solar radiation. However, with continuous changing environment parameters, it is quite difficult for long-term prediction of solar radiation. In the past research scholars, have carried out solar prediction only for a few days, which is insufficient to exploit the radiation for sizing and harnessing the solar energy for commercial use. To overcome this gap, present work utilizes application of lifting wavelet transform along with ANFIS to predict the radiation for long duration.