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  1. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory...

  2. Peripheral treatment with enoxaparin exacerbates amyloid plaque pathology in Tg2576 mice.

    Science.gov (United States)

    Cui, Hao; King, Anna E; Jacobson, Glenn A; Small, David H

    2017-04-01

    Alzheimer's disease (AD) is a complex, progressive neurological disorder characterized by the formation of extracellular amyloid plaques composed of β-amyloid protein (Aβ), the key component in pathogenesis of AD. Peripheral administration of enoxaparin (ENO) reportedly reduces the level of Aβ and the amyloid plaques in the cortex of amyloid precursor protein (APP) transgenic mice. However, the exact mechanism of these effects is unclear. Our previous studies indicated that ENO can inhibit APP processing to Aβ in primary cortical cells from Tg2576 mice by downregulating BACE1 levels. This study examines whether ENO-induced reduction of amyloid load is due to the decreased APP processing to Aβ in Tg2576 mice. Surprisingly, our results indicated that ENO significantly increases the Aβ42/Aβ40 ratio in cortex and enhances the amyloid plaque load in both cortex and hippocampus, although overall APP processing was not influenced by ENO. Moreover, ENO stimulated the aggregation of both Aβ40 and Aβ42 in vitro. Although ENO has been reported to improve cognition in vivo and has potential as a therapeutic agent for AD, the results from our study suggest that ENO can exacerbate the amyloid pathology, and the strategy of using ENO for the treatment of AD may require further assessment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576 mice: greater stability of sAPP in the beta-amyloid depositing mice.

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    Jose Morales-Corraliza

    2009-09-01

    Full Text Available The metabolism of the amyloid precursor protein (APP and tau are central to the pathobiology of Alzheimer's disease (AD. We have examined the in vivo turnover of APP, secreted APP (sAPP, Abeta and tau in the wild-type and Tg2576 mouse brain using cycloheximide to block protein synthesis. In spite of overexpression of APP in the Tg2576 mouse, APP is rapidly degraded, similar to the rapid turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from the brain more slowly, particularly in the Tg2576 model where the half-life of both the endogenous murine and transgene-derived human sAPP is nearly doubled compared to wild-type mice. The important Abeta degrading enzymes neprilysin and IDE were found to be highly stable in the brain, and soluble Abeta40 and Abeta42 levels in both wild-type and Tg2576 mice rapidly declined following the depletion of APP. The cytoskeletal-associated protein tau was found to be highly stable in both wild-type and Tg2576 mice. Our findings unexpectedly show that of these various AD-relevant protein metabolites, sAPP turnover in the brain is the most different when comparing a wild-type mouse and a beta-amyloid depositing, APP overexpressing transgenic model. Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP in the beta-amyloid depositing Tg2576 mice may represent a neuroprotective response.

  4. Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury.

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    Conte, Valeria; Uryu, Kunihiro; Fujimoto, Scott; Yao, Yuemang; Rokach, Joshua; Longhi, Luca; Trojanowski, John Q; Lee, Virginia M-Y; McIntosh, Tracy K; Praticò, Domenico

    2004-08-01

    Traumatic brain injury is a well-recognized environmental risk factor for developing Alzheimer's disease. Repetitive concussive brain injury (RCBI) exacerbates brain lipid peroxidation, accelerates amyloid (Abeta) formation and deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated the effects of vitamin E on these four parameters in Tg2576 mice following RCBI. Eleven-month-old mice were randomized to receive either regular chow or chow-supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24 h apart) using a modified controlled cortical impact model of closed head injury. The same dietary regimens were maintained up to 8 weeks post-injury, when the animals were killed for biochemical and immunohistochemical analyses after behavioral evaluation. Vitamin E-treated animals showed a significant increase in brain vitamin E levels and a significant decrease in brain lipid peroxidation levels. After RBCI, compared with the group on regular chow, animals receiving vitamin E did not show the increase in Abeta peptides, and had a significant attenuation of learning deficits. This study suggests that the exacerbation of brain oxidative stress following RCBI plays a mechanistic role in accelerating Alphabeta accumulation and behavioral impairments in the Tg2576 mice.

  5. Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer's disease.

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    Bascoul-Colombo, Cécile; Guschina, Irina A; Maskrey, Benjamin H; Good, Mark; O'Donnell, Valerie B; Harwood, John L

    2016-06-01

    Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw mice

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    Karapetyan Adrine

    2008-09-01

    Full Text Available Abstract Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-Aβ28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP transgenic mice (Tg2576. Methods Mannan was purified, activated and chemically conjugated to Aβ28 peptide. Humoral immune responses induced by the immunization of mice with mannan-Aβ28 conjugate were analyzed using a standard ELISA. Aβ42 and Aβ40 amyloid burden, cerebral amyloid angiopathy (CAA, astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. Results Immunizations with low doses of mannan-Aβ28 induced potent and long-lasting anti-Aβ humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-Aβ antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-Aβ28 prevented Aβ plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant

  7. X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.

    LENUS (Irish Health Repository)

    Mitchell, Jacqueline C

    2009-12-01

    Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.

  8. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

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    Cribbs David H

    2008-04-01

    Full Text Available Abstract Background Inflammation is associated with Aβ pathology in Alzheimer's disease (AD and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months Tg2576 mice to a response that reduces Aβ pathology. Methods TG (n = 29 and WT (n = 27 mice were divided into sedentary (SED and exercised (RUN groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. Results IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED mice than in wildtype (WTSED (p = 0.04, p = 0.006. Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07. Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01 and soluble fibrillar Aβ (p = 0.01 were observed in the exercised transgenic animals. Conclusion Exercise shifts the immune response from innate to an adaptive or

  9. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

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    Jun-Peng Guo

    Full Text Available Patients of Alzheimer's disease (AD frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe, displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ, increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO, another iron chelator, selectively inhibited osteoclast (OC differentiation, without an obvious effect on osteoblast (OB differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  10. Neuritin attenuates cognitive function impairments in tg2576 mouse model of Alzheimer's disease.

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    Yoori Choi

    Full Text Available Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.

  11. Age-related synaptic dysfunction in Tg2576 mice starts as a failure in early long-term potentiation which develops into a full abolishment of late long-term potentiation.

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    Fernández-Fernández, Diego; Dorner-Ciossek, Cornelia; Kroker, Katja S; Rosenbrock, Holger

    2016-03-01

    Tg2576 mice are widely used to study amyloid-dependent synaptic dysfunction related to Alzheimer's disease. However, conflicting data have been reported for these mice with regard to basal transmission as well as the in vitro correlate of memory, long-term potentiation (LTP). Some studies show clear impairments, whereas others report no deficiency. The present study uses hippocampal slices from 3-, 10-, and 15-month-old wild-type (WT) and Tg2576 mice to evaluate synaptic function in each group, including experiments to investigate basal synaptic transmission, short- and long-term plasticity by inducing paired-pulse facilitation, and both early and late LTP. We show that synaptic function remains intact in hippocampal slices from Tg2576 mice at 3 months of age. However, both early and late LTP decline progressively during aging in these mice. This deterioration of synaptic plasticity starts affecting early LTP, ultimately leading to the abolishment of both forms of LTP in 15-month-old animals. In comparison, WT littermates display normal synaptic parameters during aging. Additional pharmacological investigation into the involvement of NMDA receptors and L-type voltage-gated calcium channels in LTP suggests a distinct mechanism of induction among age groups, demonstrating that both early and late LTP are differentially affected by these channels in Tg2576 mice during aging. © 2015 Wiley Periodicals, Inc.

  12. The early changes in behavior and the myelinated fibers of the white matter in the Tg2576 transgenic mouse model of Alzheimer's disease.

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    Zhang, Lei; Lu, Wei; Chen, Lin; Qiu, Xuan; Li, Chen; Huang, Chun-Xia; Gong, Xia; Min, Qi-Cheng; Lu, Fang; Wan, Jing-Yuan; Chao, Feng-Lei; Tang, Yong

    2013-10-25

    Recently, increasing evidences have indicated that abnormal behavior and white matter changes had appeared before senile plaques were formed in Alzheimer's disease (AD). However, the exact nature of these changes in behavior and white matter structure in early AD are unclear. This study used the Morris water maze, an ELISA assay, a transmission electron microscopic technique and new stereological methods to investigate the behavior, Aβ protein expression and white matter structure of Tg2576 transgenic mice at four ages. Only 10 months of age, the time latency in the Morris water maze tasks for Tg2576 transgenic mice were significantly longer than that of wild-type mice. The concentration of Aβ40 protein in the white matter of the Tg2576 transgenic mice was significantly increased in four ages mice, but the Aβ42 protein was significantly increased only in the 6-month-old mice. In 10-month-old mice, the axon volume in the white matter of the Tg2576 transgenic mice was significantly decreased when compared to the wild-type mice. These results suggest that the deposition of Aβ in the white matter of Tg2576 transgenic mice appeared before the spatial memory decline. The early detection of the Aβ content in the white matter of AD might help diagnose suspected AD. In addition, the axon changes in the white matter of AD might be one of the morphological causes of the behavioral deficits observed in 10-month-old transgenic mouse models of AD, and protecting the axons in the white matter might be an important method for delaying the progression of AD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer’s disease

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    Charlotte eBezzina

    2015-09-01

    Full Text Available The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment durably improves memory performances in the Tg2576 mouse model of Alzheimer’s disease. Recently, we evidenced a hypersynchronous brain network activity in young adult Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after environmental enrichment were associated with a reduction of neuronal network hypersynchrony. Thus, we exposed non-transgenic and Tg2576 mice to standard or enriched housing conditions for 10 weeks, starting at 3 months of age. Two weeks after environmental enrichment period, Tg2576 mice presented similar seizure susceptibility to a GABA receptor antagonist. Immediately after and two weeks after this enrichment period, standard and enriched-housed Tg2576 mice did not differ with regards to the frequency of interictal spikes on their electroencephalographic recordings. Thus, the long-lasting effect of this environmental enrichment protocol on memory capacities in Tg2576 mice is not mediated by a reduction of their cerebral aberrant neuronal activity at early ages.

  14. Severe In Vivo Hyper-Homocysteinemia is not Associated with Elevation of Amyloid-β Peptides in the Tg2576 Mice

    OpenAIRE

    Zhuo, Jia-Min; Praticò, Domenico

    2010-01-01

    Since hyper-homocysteinemia (HHcy) was recognized as a risk factor for Alzheimer’s disease (AD), many studies tried to induce HHcy in animal models to investigate its effect on amyloid-β protein precursor (AβPP) metabolism. Previous reports found that HHcy induced in AD transgenic mouse models, by either feeding a methionine-enriched diet or vitamin Bs deficient diet, is associated with elevation of amyloid-β (Aβ) levels. However, there is no data available on the effect of dietary interventi...

  15. Age-related changes of protein SUMOylation balance in the AβPP Tg2576 mouse model of Alzheimer's disease

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    Robert eNisticò

    2014-04-01

    Full Text Available Alzheimer's disease (AD is a complex disorder that affects the central nervous system causing a severe neurodegeneration. This pathology affects an increasing number of people worldwide due to the overall aging of the human population. In recent years SUMO protein modification has emerged as a possible cellular mechanism involved in AD. Some of the proteins engaged in the physiopathological process of AD, like BACE1, GSK3-β tau, AβPP and JNK, are in fact subject to protein SUMO modifications or interactions. Here, we have investigated the SUMO/deSUMOylation balance and SUMO-related proteins during the onset and progression of the pathology in the Tg2576 mouse model of AD. We examined four age-stages (1.5; 3; 6; 17 months old and observed shows an increase in SUMO-1 protein conjugation at 3 and 6 months in transgenic mice with respect to WT in both cortex and hippocampus. Interestingly this is paralleled by increased expression levels of Ubc9 and SENP1 in both brain regions. At 6 months of age also the SUMO-1 mRNA resulted augmented. SUMO-2-ylation was surprisingly decreased in old transgenic mice and was unaltered in the other time windows. The fact that alterations in SUMO/deSUMOylation equilibrium occur from the early phases of AD suggests that global posttranslational modifications may play an important role in the mechanisms underlying disease pathogenesis, thus providing potential targets for pharmacological interventions.

  16. Aluminum exposure through the diet: metal levels in AbetaPP transgenic mice, a model for Alzheimer's disease.

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    Gómez, Mercedes; Esparza, José L; Cabré, María; García, Tania; Domingo, José L

    2008-07-30

    Aluminum (Al), iron (Fe), copper (Cu), and zinc (Zn) cause have been implicated in the etiology of certain neurodegenerative disorders. Moreover, these elements cause the conformational changes of Alzheimer's amyloid beta protein. In this study, we determined the concentrations of Al, Cu, Zn, Fe, and Mn in various tissues of Tg 2576 (AbetaPP transgenic) Al-treated mice. Female Tg 2576 mice and wild-type littermates were exposed through the diet to 1mg Al/g for 6 months. At 11 months of age, metal concentrations were measured in various tissues. In brain, Al levels were higher in hippocampus than in cortex and cerebellum. In hippocampus, Cu concentrations decreased in non-treated Tg 2576 mice, while Zn levels were higher in Al-treated mice. Copper, Zn, Mn and Fe concentrations in liver, kidney and bone were not affected by Al exposure. The current results show that Al exposure of Tg 2576 and wild-type mice did not produce important metal changes related with the genotype, responding similarly both groups of animals. As Tg 2576 mice have been considered as a potential model for Alzheimer's disease (AD), the present results would not support the hypothetical role of Al in the etiology of AD.

  17. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

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    Koo Edward H

    2007-07-01

    Full Text Available Abstract Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs is associated with a reduced incidence of Alzheimer's disease (AD. We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition

  18. Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's Disease

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    Massaad, Cynthia A.; Amin, Samir K.; Hu, Lingyun; Mei, Yuan

    2010-01-01

    Background Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid β (Aβ) into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD. Methodology/Principal Findings In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer. Conclusions/Significance These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology. PMID:20479943

  19. Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer's disease.

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    Cynthia A Massaad

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid beta (Abeta into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer. CONCLUSIONS/SIGNIFICANCE: These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology.

  20. Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease.

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    Braidy, Nady; Essa, Musthafa Mohamed; Poljak, Anne; Selvaraju, Subash; Al-Adawi, Samir; Manivasagm, Thamilarasan; Thenmozhi, Arokiasamy Justin; Ooi, Lezanne; Sachdev, Perminder; Guillemin, Gilles J

    2016-10-04

    Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by extracellular plaques containing abnormal Amyloid Beta (Aβ) aggregates, intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, microglia-dominated neuroinflammation, and impairments in synaptic plasticity underlying cognitive deficits. Therapeutic strategies for the treatment of AD are currently limited. In this study, we investigated the effects of dietary supplementation of 4% pomegranate extract to a standard chow diet on neuroinflammation, and synaptic plasticity in APPsw/Tg2576 mice brain. Treatment with a custom mixed diet (pellets) containing 4% pomegranate for 15 months ameliorated the loss of synaptic structure proteins, namely PSD-95, Munc18-1, and SNAP25, synaptophysin, phosphorylation of Calcium/Calmodulin Dependent Protein Kinase IIα (p-CaMKIIα/ CaMKIIα), and phosphorylation of Cyclic AMP-Response Element Binding Protein (pCREB/CREB), inhibited neuroinflammatory activity, and enhanced autophagy, and activation of the phophoinositide-3-kinase-Akt-mammalian target of rapamycin signaling pathway. These neuroprotective effects were associated with reduced β-site cleavage of Amyloid Precursor Protein in APPsw/Tg2576 mice. Therefore, long-term supplementation with pomegranates can attenuate AD pathology by reducing inflammation, and altering APP-dependent processes.

  1. The effects of enhanced zinc on spatial memory and plaque formation in transgenic mice

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    Linkous, D.H.; Adlard, P.A.; Wanschura, P.B.; Conko, K.M.; Flinn, J.M.

    2009-01-01

    There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals. To further investigate this in the current study, two separate transgenic models of AD (Tg2576 and TgCRND8), together with wild type littermates were administered 10 ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both pre- and postnatally until 11 months of age, while TgCRND8 animals were treated for five months following weaning. Behavioral testing, consisting of "Atlantis" and "moving" platform versions of the Morris water maze, were conducted at the end of the study, and tissues were collected for immunohistochemical analysis of amyloid-β burden. Our data demonstrate that the provision of a zinc-enriched diet potentiated Alzheimer-like spatial memory impairments in the transgenic animals and was associated with reduced hippocampal amyloid-β plaque deposits. Zinc-related behavioral deficits were also demonstrated in wild type mice, which were sometimes as great as those present in the transgenic animals. However, zinc-related cognitive impairments in transgenic mice were greater than the summation of zinc effects in the wild type mice and the transgene effects.

  2. Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-β Precursor Protein Transgenic Mice

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    Liu, Peng; Reichl, John H.; Rao, Eshaan R.; McNellis, Brittany M.; Huang, Eric S.; Hemmy, Laura S.; Forster, Colleen L.; Kuskowski, Michael A.; Borchelt, David R.; Vassar, Robert; Ashe, Karen H.; Zahs, Kathleen R.

    2016-01-01

    There exist several dozen lines of transgenic mice that express human amyloid-β precursor protein (AβPP) with Alzheimer’s disease (AD)-linked mutations. AβPP transgenic mouse lines differ in the types and amounts of Aβ that they generate and in their spatiotemporal patterns of expression of Aβ assemblies, providing a toolkit to study Aβ amyloidosis and the influence of Aβ aggregation on brain function. More complete quantitative descriptions of the types of Aβ assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aβ toxicity in mice relates to the pathogenesis of AD. Here, we provide a direct quantitative comparison of amyloid plaque burdens and plaque sizes in four lines of AβPP transgenic mice. We measured the fraction of cortex and hippocampus occupied by dense-core plaques, visualized by staining with Thioflavin S, in mice from young adulthood through advanced age. We found that the plaque burdens among the transgenic lines varied by an order of magnitude: at 15 months of age, the oldest age studied, the median cortical plaque burden in 5XFAD mice was already ~4.5 times that of 21-month Tg2576 mice and ~15 times that of 21–24-month rTg9191 mice. Plaque-size distributions changed across the lifespan in a line- and region-dependent manner. We also compared the dense-core plaque burdens in the mice to those measured in a set of pathologically-confirmed AD cases from the Nun Study. Cortical plaque burdens in Tg2576, APPSwePS1ΔE9, and 5XFAD mice eventually far exceeded those measured in the human cohort. PMID:28059792

  3. Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer's disease.

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    Subash, Selvaraju; Essa, Musthafa Mohamed; Braidy, Nady; Al-Jabri, Ahood; Vaishnav, Ragini; Al-Adawi, Samir; Al-Asmi, Abdullah; Guillemin, Gilles J

    2016-12-01

    Alzheimer disease (AD) is one of the most common forms of dementia in the elderly. Several reports have suggested neurotoxic effects of amyloid beta protein (Aβ) and role of oxidative stress in AD. Figs are rich in fiber, copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good source of proanthocyanidins and quercetin which demonstrate potent antioxidant properties. We studied the effect of dietary supplementation with 4% figs grown in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice) mice model for AD. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 months and after 15 months using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. Tg mice that were fed a control diet without figs showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial, position discrimination learning ability, and motor coordination compared to the wild-type control mice on the same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our results suggest that dietary supplementation of figs may be useful for the improvement of cognitive and behavioral deficits in AD.

  4. Paternal spatial training enhances offspring's cognitive performance and synaptic plasticity in wild-type but not improve memory deficit in Alzheimer's mice.

    Science.gov (United States)

    Zhang, Shujuan; Li, Xiaoguang; Wang, Zhouyi; Liu, Yanchao; Gao, Yuan; Tan, Lu; Liu, Enjie; Zhou, Qiuzhi; Xu, Cheng; Wang, Xin; Liu, Gongping; Chen, Haote; Wang, Jian-Zhi

    2017-05-08

    Recent studies suggest that spatial training can maintain associative memory capacity in Tg2576 mice, but it is not known whether the beneficial effects can be inherited from the trained fathers to their offspring. Here, we exposed male wild-type and male 3XTg Alzheimer disease (AD) mice (3-m old) respectively to spatial training for one week and assessed the transgenerational effects in the F1 offspring when they were grown to 7-m old. We found that the paternal spatial training significantly enhanced progeny's spatial cognitive performance and synaptic transmission in wild-type mice. Among several synapse- or memory-associated proteins, we observed that the expression level of synaptotagmin 1 (SYT1) was significantly increased in the hippocampus of the paternally trained-offspring. Paternal training increased histone acetylation at the promoter of SYT1 in both fathers' and the offspring's hippocampus, and as well as in the fathers' sperm. Finally, paternal spatial training for one week did not improve memory and synaptic plasticity in 3XTg AD F1 offspring. Our findings suggest paternal spatial training for one week benefits the offspring's cognitive performance in wild-type mice with the mechanisms involving an enhanced transgenerational histone acetylation at SYT1 promoter.

  5. Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer's disease mice using magnetic resonance imaging (MRI).

    Science.gov (United States)

    Cheng, Kwok Kin; Chan, Pui Shan; Fan, Shujuan; Kwan, Siu Ming; Yeung, King Lun; Wáng, Yì-Xiáng J; Chow, Albert Hee Lum; Wu, Ed X; Baum, Larry

    2015-03-01

    Diagnosis of Alzheimer's disease (AD) can be performed with the assistance of amyloid imaging. The current method relies on positron emission tomography (PET), which is expensive and exposes people to radiation, undesirable features for a population screening method. Magnetic resonance imaging (MRI) is cheaper and is not radioactive. Our approach uses magnetic nanoparticles (MNPs) made of superparamagnetic iron oxide (SPIO) conjugated with curcumin, a natural compound that specifically binds to amyloid plaques. Coating of curcumin-conjugated MNPs with polyethylene glycol-polylactic acid block copolymer and polyvinylpyrrolidone by antisolvent precipitation in a multi-inlet vortex mixer produces stable and biocompatible curcumin magnetic nanoparticles (Cur-MNPs) with mean diameter MRI) of Tg2576 mouse brains after injection of Cur-MNPs, and no plaques could be found in non-transgenic mice. Immunohistochemical examination of the mouse brains revealed that Cur-MNPs were co-localized with amyloid plaques. Thus, Cur-MNPs have the potential for non-invasive diagnosis of AD using MRI. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Preserved Fronto-Striatal Plasticity and Enhanced Procedural Learning in a Transgenic Mouse Model of Alzheimer's Disease Overexpressing Mutant "hAPPswe"

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    Middei, Silvia; Geracitano, Raffaella; Caprioli, Antonio; Mercuri, Nicola; Ammassari-Teule, Martine

    2004-01-01

    Mutations in the amyloid precursor protein (APP) gene inducing abnormal processing and deposition of [beta]-amyloid protein in the brain have been implicated in the pathogenesis of Alzheimer's disease (AD). Although Tg2576 mice with the Swedish mutation ("hAPPswe") exhibit age-related [Alpha][beta]-plaque formation in brain regions like the…

  7. Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer's disease model; Effets transcriptomiques de l'uranium appauvri sur les metabolismes de l'acetylcholine et du cholesterol chez un modele de maladie d'Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Lestaevel, Ph.; Bensoussan, H.; Racine, R.; Airault, F.; Gourmelon, P.; Souidi, M. [Direction de la radioprotection de l' Homme, service de radiobiologie et d' epidemiologie, laboratoire de radiotoxicologie experimentale, institut de radioprotection et de surete nucleaire, BP no 17, 92262 Fontenay-aux-Roses cedex (France)

    2011-02-15

    Some heavy metals, or aluminium, could participate in the development of Alzheimer disease (AD). Depleted uranium (DU), another heavy metal, modulates the cholinergic system and the cholesterol metabolism in the brain of rats, but without neurological disorders. The aim of this study was to determine what happens in organisms exposed to DU that will/are developing the AD. This study was thus performed on a transgenic mouse model for human amyloid precursor protein (APP), the Tg2576 strain. The possible effects of DU through drinking water (20 mg/L) over an 8-month period were analyzed on acetylcholine and cholesterol metabolisms at gene level in the cerebral cortex. The mRNA levels of choline acetyl transferase (ChAT) vesicular acetylcholine transporter (VAChT) and ATP-binding cassette transporter A1 (ABC A1) decreased in control Tg2576 mice in comparison with wild-type mice (respectively -89%, -86% and -44%, p < 0.05). Chronic exposure of Tg2576 mice to DU increased mRNA levels of ChAT (+189%, p < 0.05), VAChT (+120%, p < 0.05) and ABC A1 (+52%, p < 0.05) compared to control Tg2576 mice. Overall, these modifications of acetylcholine and cholesterol metabolisms did not lead to increased disturbances that are specific of AD, suggesting that chronic DU exposure did not worsen the pathology in this experimental model. (authors)

  8. Innate Immunity Stimulation via Toll-Like Receptor 9 Ameliorates Vascular Amyloid Pathology in Tg-SwDI Mice with Associated Cognitive Benefits.

    Science.gov (United States)

    Scholtzova, Henrieta; Do, Eileen; Dhakal, Shleshma; Sun, Yanjie; Liu, Shan; Mehta, Pankaj D; Wisniewski, Thomas

    2017-01-25

    Alzheimer's disease (AD) is characterized by the presence of parenchymal amyloid-β (Aβ) plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles. Currently there are no effective treatments for AD. Immunotherapeutic approaches under development are hampered by complications related to ineffectual clearance of CAA. Genome-wide association studies have demonstrated the importance of microglia in AD pathogenesis. Microglia are the primary innate immune cells of the brain. Depending on their activation state and environment, microglia can be beneficial or detrimental. In our prior work, we showed that stimulation of innate immunity with Toll-like receptor 9 agonist, class B CpG (cytosine-phosphate-guanine) oligodeoxynucleotides (ODNs), can reduce amyloid and tau pathologies without causing toxicity in Tg2576 and 3xTg-AD mouse models. However, these transgenic mice have relatively little CAA. In the current study, we evaluated the therapeutic profile of CpG ODN in a triple transgenic mouse model, Tg-SwDI, with abundant vascular amyloid, in association with low levels of parenchymal amyloid deposits. Peripheral administration of CpG ODN, both before and after the development of CAA, negated short-term memory deficits, as assessed by object-recognition tests, and was effective at improving spatial and working memory evaluated using a radial arm maze. These findings were associated with significant reductions of CAA pathology lacking adverse effects. Together, our extensive evidence suggests that this innovative immunomodulation may be a safe approach to ameliorate all hallmarks of AD pathology, supporting the potential clinical applicability of CpG ODN. Recent genetic studies have underscored the emerging role of microglia in Alzheimer's disease (AD) pathogenesis. Microglia lose their amyloid-β-clearing capabilities with age and as AD progresses. Therefore, the ability to modulate microglia profiles offers a promising therapeutic avenue for reducing AD

  9. Effects of exercise on capillaries in the white matter of transgenic AD mice.

    Science.gov (United States)

    Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

    2017-09-12

    Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD.

  10. Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice

    Directory of Open Access Journals (Sweden)

    Janine Prange-Kiel

    2016-01-01

    Full Text Available Numerous studies show that 17β-estradiol (E2 protects against Alzheimer’s disease (AD induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice. In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases.

  11. Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice.

    Science.gov (United States)

    Sarkar, Sumit; Raymick, James; Ray, Balmiki; Lahiri, Debomoy K; Paule, Merle G; Schmued, Larry

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40 mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain.

  12. Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice

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    Yanxing eChen

    2014-05-01

    Full Text Available Background: It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD. Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD. Methods: We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD, with daily intranasal administration of insulin (1.75U/day for one week. The insulin- and control-treated mice were then anesthetized with single intraperitoneal injection of propofol (250 mg/kg body weight. Tau phosphorylation and tau protein kinases and phosphatases in the brains of mice 30 min and two hours after propofol injection were then investigated by using Western blots and immunohistochemistry.Results: Propofol strongly promoted hyperphosphorylation of tau at several AD-related phosphorylation sites. Intranasal administration of insulin attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling, and led to up-regulation of protein phosphatase 2A, a major tau phosphatase in the brain. Intranasal insulin also resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-Jun N-terminal kinase. Conclusion: Our results demonstrate that pretreatment with intranasal insulin prevents AD-like tau hyperphosphorylation. These findings provide the first evidence supporting that intranasal insulin administration might be used for the prevention of anesthesia-induced cognitive decline and increased risk for AD and dementia.

  13. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models

    Science.gov (United States)

    Gong, Bing; Pan, Yong; Vempati, Prashant; Zhao, Wei; Knable, Lindsay; Ho, Lap; Wang, Jun; Sastre, Magdalena; Ono, Kenjiro; Sauve, Anthony A.; Pasinetti, Giulio M.

    2013-01-01

    Nicotinamide adenine dinucleotide (NAD)+, a coenzyme involved in redox activities in the mitochondrial electron transport chain, has been identified as a key regulator of the lifespan-extending effects, and the activation of NAD+ expression has been linked with a decrease in beta-amyloid (Aβ) toxicity in Alzheimer’s disease (AD). Nicotinamide riboside (NR) is a NAD+ precursor, it promotes peroxisome proliferator-activated receptor-γ coactivator 1 (PGC)-1α expression in the brain. Evidence has shown that PGC-1α is a crucial regulator of Aβ generation because it affects β-secretase (BACE1) degradation. In this study we tested the hypothesis that NR treatment in an AD mouse model could attenuate Aβ toxicity through the activation of PGC-1α-mediated BACE1 degradation. Using the Tg2576 AD mouse model, using in vivo behavioral analyses, biochemistry assays, small hairpin RNA (shRNA) gene silencing and electrophysiological recording, we found (1) dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD+ in the cerebral cortex; (2) application of NR to hippocampal slices (10 µM) for 4 hours abolishes the deficits in long-term potentiation recorded in the CA1 region of Tg2576 mice; (3) NR treatment promotes PGC-1α expression in the brain coinciding with enhanced degradation of BACE1 and the reduction of Aβ production in Tg2576 mice. Further in vitro studies confirmed that BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos, in which BACE1 degradation was prevented by PGC-1α-shRNA gene silencing; and (4) NR treatment and PGC-1α overexpression enhance BACE1 ubiquitination and proteasomal degradation. Our studies suggest that dietary treatment with NR might benefit AD cognitive function and synaptic plasticity, inpart by promoting PGC-1α-mediated BACE1

  14. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models.

    Science.gov (United States)

    Gong, Bing; Pan, Yong; Vempati, Prashant; Zhao, Wei; Knable, Lindsay; Ho, Lap; Wang, Jun; Sastre, Magdalena; Ono, Kenjiro; Sauve, Anthony A; Pasinetti, Giulio M

    2013-06-01

    Nicotinamide adenine dinucleotide (NAD)(+), a coenzyme involved in redox activities in the mitochondrial electron transport chain, has been identified as a key regulator of the lifespan-extending effects, and the activation of NAD(+) expression has been linked with a decrease in beta-amyloid (Aβ) toxicity in Alzheimer's disease (AD). Nicotinamide riboside (NR) is a NAD(+) precursor, it promotes peroxisome proliferator-activated receptor-γ coactivator 1 (PGC)-1α expression in the brain. Evidence has shown that PGC-1α is a crucial regulator of Aβ generation because it affects β-secretase (BACE1) degradation. In this study we tested the hypothesis that NR treatment in an AD mouse model could attenuate Aβ toxicity through the activation of PGC-1α-mediated BACE1 degradation. Using the Tg2576 AD mouse model, using in vivo behavioral analyses, biochemistry assays, small hairpin RNA (shRNA) gene silencing and electrophysiological recording, we found (1) dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD(+) in the cerebral cortex; (2) application of NR to hippocampal slices (10 μM) for 4 hours abolishes the deficits in long-term potentiation recorded in the CA1 region of Tg2576 mice; (3) NR treatment promotes PGC-1α expression in the brain coinciding with enhanced degradation of BACE1 and the reduction of Aβ production in Tg2576 mice. Further in vitro studies confirmed that BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos, in which BACE1 degradation was prevented by PGC-1α-shRNA gene silencing; and (4) NR treatment and PGC-1α overexpression enhance BACE1 ubiquitination and proteasomal degradation. Our studies suggest that dietary treatment with NR might benefit AD cognitive function and synaptic plasticity, in part by promoting PGC-1α-mediated BACE1

  15. Citalopram Ameliorates Impairments in Spatial Memory and Synaptic Plasticity in Female 3xTgAD Mice

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is the primary cause of dementia. There is no effective treatment. Amyloid-β peptide (Aβ plays an important role in the pathogenesis and thus strategies suppressing Aβ production and accumulation seem promising. Citalopram is an antidepressant drug and can decrease Aβ production and amyloid plaques in transgenic mice of AD and humans. Whether citalopram can ameliorate memory deficit was not known yet. We tested the effects of citalopram on behavioral performance and synaptic plasticity in female 3xTgAD mice, a well-characterized model of AD. Mice were treated with citalopram or water from 5 months of age for 3 months. Citalopram treatment at approximately 10 mg/kg/day significantly improved spatial memory in the Morris water maze (MWM test, while not affecting anxiety-like and depression-like behavior in 3xTgAD mice. Further, hippocampal long-term potentiation (LTP impairment in 3xTgAD mice was reversed by citalopram treatment. Citalopram treatment also significantly decreased the levels of insoluble Aβ40 in hippocampal and cortical tissues in 3xTgAD mice, accompanied with a reduced amyloid precursor protein (APP. Together, citalopram treatment may be a promising strategy for AD and further clinical trials should be conducted to verify the effect of citalopram on cognition in patients with AD or mild cognitive impairment.

  16. Combined Gene Therapy Using AdsVEGFR2 and AdsTie2 With Chemotherapy Reduces the Growth of Human Ovarian Cancer and Formation of Ascites in Mice.

    Science.gov (United States)

    Tuppurainen, Laura; Sallinen, Hanna; Karvonen, Anni; Valkonen, Elina; Laakso, Hanne; Liimatainen, Timo; Hytönen, Elisa; Hämäläinen, Kirsi; Kosma, Veli-Matti; Anttila, Maarit; Ylä-Herttuala, Seppo

    2017-06-01

    Ovarian cancer is highly dependent on tumor microvessels and angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2 combined with paclitaxel and carboplatin for the treatment of ovarian cancer. An intraperitoneal human ovarian cancer xenograft model in nude mice (n = 44) was used in this study. Gene therapy was given intravenously when the presence of sizable tumors was confirmed in magnetic resonance imaging. The study groups were as follows: AdCMV as a control (group I), AdCMV with chemotherapy (group II), AdsVEGFR2 and AdsTie2 (group III), and AdsVEGFR2 and AdsTie2 with chemotherapy (group IV). Antitumor effectiveness was assessed by overall tumor growth, ascites, immunohistochemistry, microvessel density, and sequential magnetic resonance imaging analyses. AdsVEGFR2 and AdsTie2 gene therapy (group III) significantly reduced tumor weights as compared with group II (P = 0.007). Accumulation of ascites was significantly reduced when the mice were treated with AdsVEGFR2 and AdsTie2 gene therapy or with combined gene therapy and chemotherapy as compared with controls (P = 0.029 and P = 0.010, respectively). Vascular endothelial growth factor and Ang2 levels in ascites fluid were elevated after the gene therapy. Combined inhibition of VEGF/VEGFR2 and Ang/Tie2 pathways provided efficient therapy for ovarian cancer in mice. In addition, antiangiogenic gene therapy has potential as a treatment for the accumulation of ascites.

  17. Impaired spatial learning and unaltered neurogenesis in a transgenic model of Alzheimer's disease after oral aluminum exposure.

    Science.gov (United States)

    Ribes, D; Colomina, M T; Vicens, P; Domingo, J L

    2010-08-01

    Although it is well established that aluminum (Al) is neurotoxic, the potential role of this element in the etiology of Alzheimer's disease (AD) is not well established. In this study, we evaluated the effects of oral Al exposure on spatial learning, memory and neurogenesis in Tg2576 mice, an animal model of AD in which Abeta plaques start to be deposited at 9 months of age. Aluminum was given as Al lactate (11 mg/g of food) for 6 months. At 11 months of age a water maze test was carried out to evaluate learning and memory. Subsequently, mice were injected with bromo-deoxyuridine (BrdU) and sacrificed 24 hours or 28 days after the last injection in order to assess proliferation, survival and differentiation of neurons. We observed impaired acquisition in the water maze task in Al-treated Tg2576 mice, as well as worse memory in the Al-exposed groups. In terms of neurogenesis, no effects of aluminum were observed in proliferation, survival and differentiation. The results of this investigation suggest that Tg2576 mice fed for 210 days with rodent chow supplemented with Al lactate at 11 mg/g of food have impaired spatial learning although their neurogenesis remains unmodified.

  18. Alleviating Effects of Baechu Kimchi Added Ecklonia cava on Postprandial Hyperglycemia in Diabetic Mice.

    Science.gov (United States)

    Lee, Hyun-Ah; Song, Yeong-Ok; Jang, Mi-Soon; Han, Ji-Sook

    2013-09-01

    In this study, we investigated the inhibitory effects of Baechu kimchi added Ecklonia cava on the activities of α-glucosidase and α-amylase and its alleviating effect on the postprandial hyperglycemia in STZ-induced diabetic mice. Baechu kimchi added Ecklonia cava (BKE, 15%) was fermented at 5°C for 28 days. Optimum ripened BKE was used in this study as it showed the strongest inhibitory activities on α-glucosidase and α-amylase by fermentation time among the BKEs in our previous study. The BKE was extracted with 80% methanol and the extract solution was concentrated, and then used in this study. The BKE extract showed higher inhibitory activities than Baechu kimchi extract against α-glucosidase and α-amylase. The IC50 values of the BKE extract against α-glucosidase and α-amylase were 0.58 and 0.35 mg/mL, respectively; BKE exhibited a lower α-glucosidase inhibitory activity but a higher α-amylase inhibitory activity than those of acarbose. The BKE extract alleviated postprandial hyperglycemia caused by starch loading in normal and streptozotocin-induced diabetic mice. Furthermore, the BKE extract significantly lowered the incremental area under the curve in both normal and diabetic mice (P<0.05). These results indicated that the BKE extract may delay carbohydrate digestion and thus glucose absorption.

  19. Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like neuropathology in 3×Tg-AD mice.

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    Xiao-Xin Yan

    Full Text Available The comorbidity between epilepsy and Alzheimer's disease (AD is a topic of growing interest. Senile plaques and tauopathy are found in epileptic human temporal lobe structures, and individuals with AD have an increased incidence of spontaneous seizures. However, why and how epilepsy is associated with enhanced AD-like pathology remains unknown. We have recently shown β-secretase-1 (BACE1 elevation associated with aberrant limbic axonal sprouting in epileptic CD1 mice. Here we sought to explore whether BACE1 upregulation affected the development of Alzheimer-type neuropathology in mice expressing mutant human APP, presenilin and tau proteins, the triple transgenic model of AD (3×Tg-AD. 3×Tg-AD mice were treated with pilocarpine or saline (i.p. at 6-8 months of age. Immunoreactivity (IR for BACE1, β-amyloid (Aβ and phosphorylated tau (p-tau was subsequently examined at 9, 11 or 14 months of age. Recurrent convulsive seizures, as well as mossy fiber sprouting and neuronal death in the hippocampus and limbic cortex, were observed in all epileptic mice. Neuritic plaques composed of BACE1-labeled swollen/sprouting axons and extracellular AβIR were seen in the hippocampal formation, amygdala and piriform cortices of 9 month-old epileptic, but not control, 3×Tg-AD mice. Densities of plaque-associated BACE1 and AβIR were elevated in epileptic versus control mice at 11 and 14 months of age. p-Tau IR was increased in dentate granule cells and mossy fibers in epileptic mice relative to controls at all time points examined. Thus, pilocarpine-induced chronic epilepsy was associated with accelerated and enhanced neuritic plaque formation and altered intraneuronal p-tau expression in temporal lobe structures in 3×Tg-AD mice, with these pathologies occurring in regions showing neuronal death and axonal dystrophy.

  20. Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice

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    Lydia Giménez-Llort

    2010-01-01

    Full Text Available The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD- like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid 42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies.

  1. Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice.

    Science.gov (United States)

    Giménez-Llort, Lydia; García, Yoelvis; Buccieri, Karla; Revilla, Susana; Suñol, Cristina; Cristofol, Rosa; Sanfeliu, Coral

    2010-10-12

    The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD-) like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid β 42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies.

  2. Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT.

    Science.gov (United States)

    Fuchigami, Takeshi; Yamashita, Yuki; Haratake, Mamoru; Ono, Masahiro; Yoshida, Sakura; Nakayama, Morio

    2014-05-01

    We report radioiodinated chalcone derivatives as new SPECT imaging probes for amyloid β (Aβ) plaques. The monoethyleneoxy derivative 2 and allyloxy derivative 8 showed a high affinity for Aβ(1-42) aggregates with Ki values of 24 and 4.5 nM, respectively. Fluorescent imaging demonstrated that 2 and 8 clearly stained thioflavin-S positive Aβ plaques in the brain sections of Tg2576 transgenic mice. In vitro autoradiography revealed that [(125)I]2 displayed no clear accumulation toward Aβ plaques in the brain sections of Tg2576 mice, whereas the accumulation pattern of [(125)I]8 matched with the presence of Aβ plaques both in the brain sections of Tg2576 mice and an AD patient. In biodistribution studies using normal mice, [(125)I]2 showed preferable in vivo pharmacokinetics (4.82%ID/g at 2 min and 0.45%ID/g at 60 min), while [(125)I]8 showed only a modest brain uptake (1.62%ID/g at 2 min) with slow clearance (0.56%ID/g at 60 min). [(125)I]8 showed prospective binding properties for Aβ plaques, although further structural modifications are needed to improve the blood brain barrier permeability and washout from brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Early temporal short-term memory deficits in double transgenic APP/PS1 mice.

    Science.gov (United States)

    Lagadec, Saioa; Rotureau, Lolita; Hémar, Agnès; Macrez, Nathalie; Delcasso, Sebastien; Jeantet, Yannick; Cho, Yoon H

    2012-01-01

    We tested single APP (Tg2576) transgenic, PS1 (PS1dE9) transgenic, and double APP/PS1 transgenic mice at 3 and 6 months of age on the acquisition of a hippocampal-dependent operant "differential reinforcement of low rate schedule" (DRL) paradigm. In this task mice are required to wait for at least 10 seconds (DRL-10s) between 2 consecutive nose poke responses. Our data showed that while single APP and PS1 transgene expression did not affect DRL learning and performance, mice expressing double APP/PS1 transgenes were impaired in the acquisition of DRL-10s at 6 months, but not at 3 months of age. The same impaired double transgenic mice, however, were perfectly capable of normal acquisition of signaled DRL-10s (SDRL-10s) task, a hippocampal-independent task, wherein mice were required to emit responses when the end of the 10-second delay was signaled by a lighting of the chamber. The age-dependent and early deficits of APP/PS1 mice suggest that the appetitive DRL paradigm is sensitive to the amyloid pathology present in double APP/PS1 mice, and that this mouse line represents a good model with which to study the efficacy of therapeutic strategies against Alzheimer's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. The problem of genotype and sex differences in life expectancy in transgenic AD mice.

    Science.gov (United States)

    Rae, Eric A; Brown, Richard E

    2015-10-01

    The lifespan of mice shows genotype, sex and laboratory effects, but little is known about genotype or sex differences in life expectancy of mouse models of Alzheimer's disease (AD). This paper examines the lifespan of males and females of different mouse models of AD and their wildtype strains. Genotype and sex dependent differences in longevity have important implications for designing experiments with Alzheimer's mouse models, comparing genotype and sex differences in aging mouse models, designing drug treatment regimes and the translation of mouse data to human clinical studies. We conclude that the concept of aging and age-related disorders in mice must be reconsidered based on genotype and sex differences in mouse life expectancy data. Use of concepts such as relative age, prospective lifespan and proportion of lifespan remaining should be included in studies of age-related changes in mouse brains and behavior. Finally, measures such as the Frailty Index, which is independent of chronological age might be used to determine a common scale of aging for all mouse strains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. AAV-HGFK1 and Ad-p53 cocktail therapy prolongs survival of mice with colon cancer.

    Science.gov (United States)

    Nie, Biao; Shen, Zan; Wen, Jun-Bao; Wong, Oscar Gee-Wan; Hsueh, Wayne D; Huo, Long-Fei; Kung, Hsiang-Fu; Jiang, Bo; Lin, Marie C M

    2008-09-01

    This study tried to evaluate the application of a novel cancer gene therapy using recombinant adeno-associated virus (AAV) carrying the kringle 1 domain of human hepatocyte growth factor (AAV-HGFK1) in combination with recombinant adenovirus carrying p53 gene (Ad-p53). BALB/c and nude mice models of colon cancer were established and the mice were treated with AAV-HGFK1 alone or in combination with Ad-p53. Combination of AAV-HGFK1 and Ad-p53 significantly prolonged the survival of the mice and also significantly inhibited primary and secondary tumor growth. Histochemical examination of the tumors revealed that AAV-HGFK1+Ad-p53 combinatorial treatment not only induced necrosis and apoptosis in the tumors but also suppressed tumor angiogenesis. The antiangiogenesis effect could likely be attributed to the ability of AAV-HGFK1+Ad-p53 viral cocktail to inhibit endothelial cell migration and proliferation. AAV-HGFK1+Ad-p53 also inhibited tumor cell growth in vitro by inhibiting epidermal growth factor receptor phosphorylation. Therefore, AAV-HGFK1+Ad-p53 cocktail therapy has a significantly higher therapeutic effect than AAV-HGFK1 or Ad-p53 alone and is a novel promising gene therapy for colon cancer.

  6. Metallothionein family: the multipurpose protein. Influence of Mt1 in the Tg2576 mouse model of ALzheimer's disease

    OpenAIRE

    Comes Orpinell, Gemma

    2017-01-01

    La malaltia d’Alzheimer és la demència més comuna que afecta el 40% de la població de més de 80 anys d’edat. Amb l’envelliment de la població i la falta de teràpies efectives, s’ha estimat que la prevalença de la malaltia d’aquí 30 anys serà el doble, convertint-se així en una important càrrega sanitària i econòmica. Clínicament, la malaltia d’Alzheimer es defineix per una pèrdua progressiva de funcions cognitives que condueixen a la demència i la mort. Neuropatològicament, destaquen sign...

  7. DHA Improves Cognition and Prevents Dysfunction of Entorhinal Cortex Neurons in 3xTg-AD Mice

    Science.gov (United States)

    Arsenault, Dany; Julien, Carl; Tremblay, Cyntia; Calon, Frédéric

    2011-01-01

    Defects in neuronal activity of the entorhinal cortex (EC) are suspected to underlie the symptoms of Alzheimer's disease (AD). Whereas neuroprotective effects of docosahexaenoic acid (DHA) have been described, the effects of DHA on the physiology of EC neurons remain unexplored in animal models of AD. Here, we show that DHA consumption improved object recognition (↑12%), preventing deficits observed in old 3xTg-AD mice (↓12%). Moreover, 3xTg-AD mice displayed seizure-like akinetic episodes, not detected in NonTg littermates and partly prevented by DHA (↓50%). Patch-clamp recording revealed that 3xTg-AD EC neurons displayed (i) loss of cell capacitance (CC), suggesting reduced membrane surface area; (ii) increase of firing rate versus injected current (F-I) curve associated with modified action potentials, and (iii) overactivation of glutamatergic synapses, without changes in synaptophysin levels. DHA consumption increased CC (↑12%) and decreased F-I slopes (↓21%), thereby preventing the opposite alterations observed in 3xTg-AD mice. Our results indicate that cognitive performance and basic physiology of EC neurons depend on DHA intake in a mouse model of AD. PMID:21383850

  8. DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice.

    Directory of Open Access Journals (Sweden)

    Dany Arsenault

    2011-02-01

    Full Text Available Defects in neuronal activity of the entorhinal cortex (EC are suspected to underlie the symptoms of Alzheimer's disease (AD. Whereas neuroprotective effects of docosahexaenoic acid (DHA have been described, the effects of DHA on the physiology of EC neurons remain unexplored in animal models of AD. Here, we show that DHA consumption improved object recognition (↑12%, preventing deficits observed in old 3xTg-AD mice (↓12%. Moreover, 3xTg-AD mice displayed seizure-like akinetic episodes, not detected in NonTg littermates and partly prevented by DHA (↓50%. Patch-clamp recording revealed that 3xTg-AD EC neurons displayed (i loss of cell capacitance (CC, suggesting reduced membrane surface area; (ii increase of firing rate versus injected current (F-I curve associated with modified action potentials, and (iii overactivation of glutamatergic synapses, without changes in synaptophysin levels. DHA consumption increased CC (↑12% and decreased F-I slopes (↓21%, thereby preventing the opposite alterations observed in 3xTg-AD mice. Our results indicate that cognitive performance and basic physiology of EC neurons depend on DHA intake in a mouse model of AD.

  9. Diffusion tensor magnetic resonance imaging of the brain in APP transgenic mice: a cohort study.

    Directory of Open Access Journals (Sweden)

    Hans-Peter Müller

    Full Text Available INTRODUCTION: Fast in-vivo high resolution diffusion tensor imaging (DTI of the mouse brain has recently been shown to enable cohort studies by the combination of appropriate pulse sequences and cryogenically cooled resonators (CCR. The objective of this study was to apply this DTI approach at the group level to β-amyloid precursor protein (APP transgenic mice. METHODS: Twelve mice (5 wild type, 7 APP transgenic tg2576 underwent DTI examination at 156(2 × 250 µm(3 spatial resolution with a CCR at ultrahigh field (11.7 T. Diffusion images were acquired along 30 gradient directions plus 5 references without diffusion encoding with a total acquisition time of 35 minutes. Fractional anisotropy (FA maps were statistically compared by whole brain-based spatial statistics (WBSS at the group level vs. wild type controls. RESULTS: FA-map comparison showed characteristic regional patterns of differences between the groups with localizations associated with Alzheimer's disease in humans, such as the hippocampus, the entorhinal cortex, and the caudoputamen. CONCLUSION: In this proof-of-principle study, regions associated with amyloid-β deposition could be identified by WBSS of FA maps in APP transgenic mice vs. wild type mice. Thus, DTI in the mouse brain acquired at 11.7 T by use of a CCR was demonstrated to be feasible for cohort studies.

  10. Amyloid-β42 Alters Apolipoprotein E Solubility in Brains of Mice with Five Familial AD Mutations

    Science.gov (United States)

    Youmans, Katherine Lynn; Leung, Steffi; Zhang, Juan; Maus, Erika; Baysac, Kathleen; Bu, Guojun; Vassar, Robert; Yu, Chunjiang; LaDu, Mary Jo

    2011-01-01

    Amyloid plaques composed of the 42 amino acid form of amyloid-beta peptide (Aβ42) are a pathological hallmark of Alzheimer’s disease (AD), but soluble and intraneuronal Aβ42 are the more proximal causes of synaptic dysfunction and neurotoxicity. Apolipoprotein E (apoE) modulates this disease process, as inheritance of the ε4 allele of the apoE gene is the primary genetic risk factor for AD. To address the solubility of Aβ42 and apoE, a protein extraction protocol in the presence of minimal to extensive Aβ42 pathology was optimized. Sequential extractions with TBS, TBS+Triton X-100 (TBSX), and guanidine-HCl (GuHCl) or formic acid (FA) were used with tissue from young and old wild type or mice expressing 5 familial AD mutations (5xFAD), in disease-susceptible or –resistant brain regions. In older 5xFAD mice, the extraction of insoluble Aβ42 and m-apoE protein was increased with FA compared to GuHCl. The 5 FAD mutations significantly increase production of Aβ42, recapitulating AD-like pathology at a greatly accelerated rate. Consistent protein extraction and the specificity of extractions for soluble or membrane-associated proteins were demonstrated. Age-dependent increases in Aβ42 were observed in all extraction fractions, particularly in the cortex and hippocampus. In both young and old 5xFAD mice, Aβ42 is TBS- or GuHCl-soluble. While in WT mice m-apoE is TBSX-soluble, in 5xFAD mice m-apoE is TBS- or GuHCl-soluble. Thus, the extraction profile of Aβ42 paralleled that of m-apoE in 5xFAD mice. As now characterized, this method identifies the extraction profile for disease-relevant brain proteins, both normal or modified due to neuropathological processes. PMID:21219931

  11. DHA diet reduces AD pathology in young APPswe/PS1ΔE9 transgenic mice: Possible Gender Effects

    OpenAIRE

    Perez, Sylvia E.; Berg, Brian M.; Moore, Kenneth A.; He, Bin; Counts, Scott E.; Fritz, Jason J.; Hu, Yuan-Shih; Lazarov, Orly; Lah, James J.; Mufson, Elliott J.

    2010-01-01

    Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA) lowers the risk of Alzhemier’s disease (AD). We examined the effects of short-term (3 months) DHA enriched diet on plaque deposition and synaptic deficts in forebrain of young APPswe/PS1ΔE9 transgenic (tg) and non-transgenic (ntg) mice. Gas chromatography revealed a significant increase in DHA concomitant with a decrease of arachidonic acid in both brain and liver in mice fed with DHA. Female tg...

  12. The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

    OpenAIRE

    Solon-Biet, Samantha M.; McMahon, Aisling C.; Ballard, J. William O.; Ruohonen, Kari; Wu, Lindsay E.; Cogger, Victoria C.; Warren, Alessandra; Huang, Xin; Pichaud, Nicolas; Melvin, Richard G.; Gokarn, Rahul; Khalil, Mamdouh; Turner, Nigel; Cooney, Gregory J.; Sinclair, David A.

    2014-01-01

    The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health...

  13. Human-relevant Levels of Added Sugar Consumption Increase Female Mortality and Lower Male Fitness in Mice

    Science.gov (United States)

    Ruff, James S.; Suchy, Amanda K.; Hugentobler, Sara A.; Sosa, Mirtha M.; Schwartz, Bradley L.; Morrison, Linda C.; Gieng, Sin H.; Shigenaga, Mark K.; Potts, Wayne K.

    2013-01-01

    Consumption of added sugar has increased over recent decades and is correlated with numerous diseases. Rodent models have elucidated mechanisms of toxicity, but only at concentrations beyond typical human exposure. Here we show that comparatively low levels of added sugar consumption have substantial negative effects on mouse survival, competitive ability, and reproduction. Using Organismal Performance Assays (OPAs) – in which mice fed human-relevant concentrations of added sugar (25% Kcal from a mixture of fructose and glucose [F/G]) and control mice compete in seminatural enclosures for territories, resources and mates – we demonstrate that F/G-fed females experience a two-fold increase in mortality while F/G-fed males control 26% fewer territories and produce 25% less offspring. These findings represent the lowest level of sugar consumption shown to adversely affect mammalian health. Clinical defects of F/G-fed mice were decreased glucose clearance and increased fasting cholesterol. Our data highlight that physiological adversity can exist when clinical disruptions are minor, and suggest that OPAs represent a promising technique for unmasking negative effects of toxicants. PMID:23941916

  14. Impaired Attention in the 3xTgAD Model of Alzheimer’s Disease Assessed Using a Translational Touchscreen Method for Mice: Rescue by Donepezil (Aricept)

    Science.gov (United States)

    Romberg, Carola; Mattson, Mark P.; Mughal, Mohamed R.; Bussey, Timothy J.; Saksida, Lisa M.

    2011-01-01

    Several mouse models of Alzheimer’s Disease (AD) with abundant β-amyloid and/or aberrantly phosphorylated tau develop memory impairments. However, multiple non-mnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals. Currently, it is unclear whether mutations in the β-amyloid precursor protein (APP) and tau are sufficient to cause similar, AD-like attention deficits in mouse models of the disease. To address this question, we tested 3xTgAD mice (which express APPswe, PS1M146V and tauP301L mutations) and wild type control mice on a newly-developed touchscreen-based 5-choice serial reaction time test of attention and response control. The 3xTgAD mice attended less accurately to short, spatially unpredictable stimuli when the attentional demand of the task was high, and also showed a general tendency to make more perseverative responses than wild type mice. The attentional impairment of 3xTgAD mice was comparable to that of AD patients in two aspects; first, although 3xTgAD mice initially responded as accurately as wild type mice, they subsequently failed to sustain their attention over the duration of the task; second, the ability to sustain attention was enhanced by the cholinesterase inhibitor donepezil (Aricept). These findings demonstrate that familial AD mutations not only affect memory, but also cause significant impairments in attention, a cognitive domain supported by the prefrontal cortex and its afferents. Because attention deficits are likely to affect memory encoding and other cognitive abilities, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD. PMID:21368062

  15. Chronic exposure to aluminum and melatonin through the diet: neurobehavioral effects in a transgenic mouse model of Alzheimer disease.

    Science.gov (United States)

    Di Paolo, Celeste; Reverte, Ingrid; Colomina, Maria Teresa; Domingo, José L; Gómez, Mercedes

    2014-07-01

    Aluminum (Al) is a known neurotoxic element involved in the etiology of some serious neurodegenerative disorders such as Alzheimer disease (AD). Antioxidants like melatonin might protect neurons against the damage produced in AD. The APPSWE (Tg2576) transgenic mouse is one of the most used animal models developed to mimic AD damage. In the present study, wild type and Tg2576 mice were orally exposed during 14 months to Al, melatonin, and citric acid, as well as to all possible combinations between them. At 17 months of age, mice were evaluated for behavior using the open-field test and the Morris water maze. Transgenic animals exposed to melatonin only and to Al plus citric acid plus melatonin showed a good acquisition. No effects on acquisition in the Morris water maze were observed in wild type mice. With respect to the retention of the task, only melatonin wild type animals, and Al plus citric acid plus melatonin transgenic mice showed retention during the acquisition. Control wild type animals and Al plus citric acid plus melatonin transgenic mice showed good long term retention. Melatonin improved learning and spatial memory in Al-exposed transgenic mice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Sex-specific effects of high fat diet on indices of metabolic syndrome in 3xTg-AD mice: implications for Alzheimer's disease.

    Science.gov (United States)

    Barron, Anna M; Rosario, Emily R; Elteriefi, Reem; Pike, Christian J

    2013-01-01

    Multiple factors of metabolic syndrome have been implicated in the pathogenesis of Alzheimer's disease (AD), including abdominal obesity, insulin resistance, endocrine dysfunction and dyslipidemia. High fat diet, a common experimental model of obesity and metabolic syndrome, has been shown to accelerate cognitive decline and AD-related neuropathology in animal models. However, sex interacts with the metabolic outcomes of high fat diet and, therefore, may alter neuropathological consequences of dietary manipulations. This study examines the effects of sex and high fat diet on metabolic and AD-related neuropathological outcomes in 3xTg-AD mice. Three month-old male and female 3xTg-AD mice were fed either standard or high fat diets for 4 months. Obesity was observed in all high fat fed mice; however, ectopic fat accumulation, hyperglycemia and hyperinsulinemia were observed only in males. Interestingly, despite the different metabolic outcomes of high fat diet, the neuropathological consequences were similar: both male and female mice maintained under high fat diet exhibited significant worsening in behavioral performance and hippocampal accumulation of β-amyloid protein. Because high fat diet resulted in obesity and increased AD-like pathology in both sexes, these data support a role of obesity-related factors in promoting AD pathogenesis.

  17. Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial.

    Science.gov (United States)

    Davtyan, Hayk; Ghochikyan, Anahit; Petrushina, Irina; Hovakimyan, Armine; Davtyan, Arpine; Poghosyan, Anna; Marleau, Annette M; Movsesyan, Nina; Kiyatkin, Anatoly; Rasool, Suhail; Larsen, Anna Kirstine; Madsen, Peter Juul; Wegener, Karen Malene; Ditlevsen, Dorte Kornerup; Cribbs, David H; Pedersen, Lars Ostergaard; Agadjanyan, Michael G

    2013-03-13

    The Alzheimer's disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in the brain. However, attempts at targeting the main culprits, neurotoxic Aβ peptides, have thus far proven unsuccessful for improving cognitive function. Recent clinical trials with passively administrated anti-Aβ antibodies failed to slow cognitive decline in mild to moderate AD patients, but suggest that an immunotherapeutic approach could be effective in patients with mild AD. Using an AD mouse model (Tg2576), we tested the immunogenicity (cellular and humoral immune responses) and efficacy (AD-like pathology) of clinical grade Lu AF20513 vaccine. We found that Lu AF20513 induces robust "non-self" T-cell responses and the production of anti-Aβ antibodies that reduce AD-like pathology in the brains of Tg2576 mice without inducing microglial activation and enhancing astrocytosis or cerebral amyloid angiopathy. A single immunization with Lu AF20513 induced strong humoral immunity in mice with preexisting memory T-helper cells. In addition, Lu AF20513 induced strong humoral responses in guinea pigs and monkeys. These data support the translation of Lu AF20513 to the clinical setting with the aims of: (1) inducing therapeutically potent anti-Aβ antibody responses in patients with mild AD, particularly if they have memory T-helper cells generated after immunizations with conventional tetanus toxoid vaccine, and (2) preventing pathological autoreactive T-cell responses.

  18. [Effect of Qingxin Kaiqiao fang on learning and memory ability and morphology of hippocampal nerve cells in AD mice].

    Science.gov (United States)

    Hu, Hai-Yan; Meng, Qiong; Jiang, Zhe; Zhu, Wei-Ming; Eang, Wen-Hua; Zhang, Xiao-Yan

    2008-05-01

    To study the effect of the Qingxin Kaiqiao fang on learning and memory ability and shape hippocampal nerve cells in Alzheimer disease (AD). One handred and fifty mice were divid into five groups: blank group, model group, two groups of treatment by Qingxin Kaiqiao fang (14.82, 7.41 g x kg(-1)), piracetan comparison group (0.42 g x kg(-1)). The model group was orally given AlCl3 (200 mg x kg(-1)) every day. For Qingxin Kaiqiaofang and piracetan groups, AlCl3 treatment was given for 6 days at the beginning, followed by giving orally AlCl3 in the morning and drug in the afternoon for 8 weeks. Then, learning and memory aility, the contents of nitric oxide (NO), NO synthase (NOS) and acetylcholinesterase (AchE) in brain, and morphology of hippocampal nerve cells were investigated. Learning and memory ability of Qingxin Kaiqiaofang groups was improved, compared with comparison group; the difference was significant (P nerve cells from damaged obviously. The contents of NO, NOS and AchE in mice of treatment groups were lower than those of comparison group; the difference was significant (P nerve cells, and treat Alzheimer disease.

  19. Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet.

    Directory of Open Access Journals (Sweden)

    Rupinder K Sodhi

    Full Text Available The present study investigates the potential of lansoprazole (a proton pump inhibitor and agonist of liver x receptors in experimental dementia of AD type. Streptozotocin [STZ, 3 mg/kg, injected intracerebroventricular (i.c.v, and high fat diet (HFD, administered for 90 days] were used to induce dementia in separate groups of Swiss mice. Morris water maze (MWM test was performed to assess learning and memory of the animals. A battery of biochemical and histopathological studies were also performed. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH and thiobarbituric acid reactive species (TBARS. Brain acetylcholinestrase (AChE activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO was measured as a marker of inflammation. STZ and HFD produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ/HFD treated mice exhibited a marked accentuation of AChE activity, TBARS and MPO levels along with a fall in GSH levels. Further, the stained micrographs of STZ/HFD treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. Lansoprazole treatment significantly attenuated STZ and HFD -induced memory deficits, biochemical and histopathological alterations. It also prevented HFD-induced rise in the cholesterol level. Therefore, the findings demonstrate potential of lansoprazole in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory effects. Moreover, both cholesterol-dependent as well as cholesterol-independent effects of lansoprazole appear to play a role. In addition study indicates the role of liver x receptors in dementia.

  20. Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature.

    Science.gov (United States)

    Caccamo, Antonella; De Pinto, Vito; Messina, Angela; Branca, Caterina; Oddo, Salvatore

    2014-06-04

    Elevated mammalian target of rapamycin (mTOR) signaling has been found in Alzheimer's disease (AD) patients and is linked to diabetes and aging, two known risk factors for AD. However, whether hyperactive mTOR plays a role in the cognitive deficits associated with AD remains elusive. Here, we genetically reduced mTOR signaling in the brains of Tg2576 mice, a widely used animal model of AD. We found that suppression of mTOR signaling reduced amyloid-β deposits and rescued memory deficits. Mechanistically, the reduction in mTOR signaling led to an increase in autophagy induction and restored the hippocampal gene expression signature of the Tg2576 mice to wild-type levels. Our results implicate hyperactive mTOR signaling as a previous unidentified signaling pathway underlying gene-expression dysregulation and cognitive deficits in AD. Furthermore, hyperactive mTOR signaling may represent a molecular pathway by which aging contributes to the development of AD. Copyright © 2014 the authors 0270-6474/14/347988-11$15.00/0.

  1. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice.

    Science.gov (United States)

    Solon-Biet, Samantha M; McMahon, Aisling C; Ballard, J William O; Ruohonen, Kari; Wu, Lindsay E; Cogger, Victoria C; Warren, Alessandra; Huang, Xin; Pichaud, Nicolas; Melvin, Richard G; Gokarn, Rahul; Khalil, Mamdouh; Turner, Nigel; Cooney, Gregory J; Sinclair, David A; Raubenheimer, David; Le Couteur, David G; Simpson, Stephen J

    2014-03-04

    The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Streptozotocin-induced diabetes increases amyloid plaque deposition in AD transgenic mice through modulating AGEs/RAGE/NF-κB pathway.

    Science.gov (United States)

    Wang, Xu; Yu, Song; Hu, Jiang-Ping; Wang, Chun-Yan; Wang, Yue; Liu, Hai-Xing; Liu, Yu-Li

    2014-08-01

    An increasing number of studies have demonstrated of that diabetes mellitus (DM) is associated with an increased prevalence of Alzheimer disease (AD), the underlying mechanisms are still obscure. We developed a streptozotocin (STZ)-induced diabetic AD transgenic mouse model and evaluated the effect of hyperglycemia on senile plaque formation. Our data showed that administration of STZ increased the level of blood glucose and increased the advanced glycation end products (AGEs) in brain tissue, and further enhanced the expression levels of the receptor for AGEs (RAGE) and the nuclear factor-kappa B (NF-κB) in the brain, and accelerated the senile plaque formation in the transgenic mice. Our results showed that STZ-induced insulin-deficient hyperglycemia caused the pathophysiology of AD in APP/PS1 transgenic mice by modulating the AGEs/RAGE/NF-κB pathway. Our study suggests that there is a close linkage of DM and cerebral amyloidosis in the pathogenesis of AD.

  3. Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Pham Serena

    2011-08-01

    Full Text Available Abstract Background Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates. Results Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis. Conclusions Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.

  4. Age-dependent modifications of AMPA receptor subunit expression levels and related cognitive effects in 3xTg-AD mice

    Directory of Open Access Journals (Sweden)

    Pamela eCantanelli

    2014-08-01

    Full Text Available GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of AMPA receptors (AMPARs, the major mediators of fast excitatory transmission in the mammalian central nervous system. Most AMPARs are Ca2+-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA undergoes an editing process that results in a Q to R substitution, a key factor in the regulation of AMPAR Ca2+-permeability. AMPARs lacking GluA2 or containing the unedited subunit are permeable to Ca2+ and Zn2+. The phenomenon physiologically modulates synaptic plasticity while, in pathologic conditions, leads to increased vulnerability to excitotoxic neuronal death. Given the importance of these subunits, we have therefore evaluated possible associations between changes in expression levels of AMPAR subunits and development of cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model of Alzheimer’s disease. With qRT-PCR, we assayed hippocampal mRNA expression levels of GluA1-4 subunits occurring in young [3 months of age (m.o.a.] and old (12 m.o.a Tg-AD mice and made comparisons with levels found in age-matched wild type (WT mice. Efficiency of GluA2 RNA editing was also analyzed. All animals were cognitively tested for short- and long-term spatial memory with the Morris Water Maze (MWM navigation task. 3xTg-AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits, with the exception of GluA2. Editing remained fully efficient with aging in 3xTg-AD and WT mice. A one-to-one correlation analysis between MWM performances and GluA1-4 mRNA expression profiles showed negative correlations between GluA2 levels and MWM performances in young 3xTg-AD mice. On the contrary, positive correlations between GluA2 mRNA and MWM performances were found in young WT mice. Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4 subunits may help in maintaining cognition in pre-symptomatic 3xTg-AD mice.

  5. Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Musthafa Mohamed Essa

    Full Text Available Alzheimer's disease (AD is a devastating age-related neurodegenerative disease with no specific treatment at present. The APPsw/Tg2576 mice exhibit age-related deterioration in memory and learning as well as amyloid-beta (Aβ accumulation, and this mouse strain is considered an effective model for studying the mechanism of accelerated brain aging and senescence. The present study was aimed to investigate the beneficial effects of dietary supplements pomegranate, figs, or the dates on suppressing inflammatory cytokines in APPsw/Tg2576 mice. Changes in the plasma cytokines and Aβ, ATP, and inflammatory cytokines were investigated in the brain of transgenic mice. Significantly enhanced levels of inflammatory cytokines IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, TNF-α and Eotaxin activity were decreased by administration of the diet supplements containing pomegranates, figs, or dates. In addition, putative delays in the formation of senile plaques, as indicated by a decreasing tendency of brain Aβ1-40 and Aβ1-42 contents, were observed. Thus, novel results mediated by reducing inflammatory cytokines during aging may represent one mechanism by which these supplements exert their beneficial effects against neurodegenerative diseases such as AD.

  6. Cognitive and emotional alterations in young Alzheimer's disease (3xTgAD) mice: effects of neonatal handling stimulation and sexual dimorphism.

    Science.gov (United States)

    Cañete, T; Blázquez, G; Tobeña, A; Giménez-Llort, L; Fernández-Teruel, A

    2015-03-15

    Alzheimer disease is the most common neurodegenerative disorder and cause of senile dementia. It is characterized by an accelerated memory loss, and alterations of mood, reason, judgment and language. The main neuropathological hallmarks of the disorder are β-amyloid (βA) plaques and neurofibrillary Tau tangles. The triple transgenic 3xTgAD mouse model develops βA and Tau pathologies in a progressive manner which mimicks the pattern that takes place in the human brain with AD, and showing cognitive alterations characteristic of the disease. The present study intended to examine whether 3xTgAD mice of both sexes present cognitive, emotional and other behavioral alterations at the early age of 4 months, an age in which only some intraneuronal amyloid accumulation is found. Neonatal handling (H) is an early-life treatment known to produce profound and long-lasting behavioral and neurobiological effects in rodents, as well as improvements in cognitive functions. Therefore, we also aimed at evaluating the effects of H on the behavioral/cognitive profile of 4-month-old male and female 3xTgAD mice. The results indicate that, (1) 3xTgAD mice present spatial learning/memory deficits and emotional alterations already at the early age of 4 months, (2) there exists sexual dimorphism effects on several behavioral variables at this age, (3) neonatal handling exerts a preventive effect on some cognitive (spatial learning) and emotional alterations appearing in 3xTgAD mice already at early ages, and 4) H treatment appears to produce stronger positive effects in females than in males in several spatial learning measures and in the open field test. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The protective effect of intrasplenic transplantation of Ad-IL-18BP/IL-4 gene-modified fetal hepatocytes on ConA-induced hepatitis in mice.

    Science.gov (United States)

    Shao, Xueting; Qian, Yun; Xu, Chenhuai; Hong, Bo; Xu, Wanhong; Shen, Ling; Jin, Changzhong; Wu, Zhigang; Tong, Xiangmin; Yao, Hangping

    2013-01-01

    Concanavalin A (ConA)-induced hepatitis is an experimental murine model mirroring the pathology of human autoimmune hepatitis. To investigate the effects of intrasplenically transplanted fetal hepatocytes (BNL.CL2) transfected with recombinant adenovirus vector expressing the IL-18 binding protein (IL-18BP) and IL-4 fusion protein on ConA-induced hepatitis in mice. Ad-IL-18BP/IL-4 was used to infect BNL.CL2 cells. IL-4 and IL-18BP fusion protein expression were detected by ELISA and Western blotting. BNL.CL2 cells infected with Ad-IL-18BP/IL-4 were intrasplenically transplanted into mice. After 10 days, mice were injected with ConA (15 mg/kg), and sacrificed 18 hours later. Liver injury was assessed by serum transaminase and liver histology. TNF-α, IL-18, IL-4, IL-10, IL-12p70 and monocyte-chemoattracting protein (MCP)-1 levels in serum and liver homogenates were detected by ELISA. Signaling molecules in liver homogenates were analyzed by Western blotting. Ad-IL-18BP/IL-4 effectively expressed the IL-18BP/IL-4 fusion protein for more than 14 days in BNL.CL12 cells. Treatment of mice with Ad-IL-18BP/IL-4-BNL.CL2 before ConA injection significantly reduced the elevated plasma levels of transaminases compared with ConA control groups. TNF-α, IL-18, IL-12p70 and MCP-1 levels in serum and liver homogenates from mice transplanted with Ad-IL-18BP/IL-4-BNL.CL2 were lower and IL-4 and IL-10 levels were higher than control groups. Phosphorylation levels of NF-κB p65, AKT, p38 and JNK1/2 in liver homogenates were markedly suppressed by Ad-IL-18BP/IL-4. Ad-IL-18BP/IL-4 was effectively transfected into mouse BNL.CL2 cells. Intrasplenic transplantation of Ad-IL-18BP/IL-4-BNL.CL12 cells alleviated the severity of inflammation in ConA-induced experimental hepatitis and provides a useful basis for the targeted gene therapy of liver disease.

  8. The protective effect of intrasplenic transplantation of Ad-IL-18BP/IL-4 gene-modified fetal hepatocytes on ConA-induced hepatitis in mice.

    Directory of Open Access Journals (Sweden)

    Xueting Shao

    Full Text Available Concanavalin A (ConA-induced hepatitis is an experimental murine model mirroring the pathology of human autoimmune hepatitis.To investigate the effects of intrasplenically transplanted fetal hepatocytes (BNL.CL2 transfected with recombinant adenovirus vector expressing the IL-18 binding protein (IL-18BP and IL-4 fusion protein on ConA-induced hepatitis in mice.Ad-IL-18BP/IL-4 was used to infect BNL.CL2 cells. IL-4 and IL-18BP fusion protein expression were detected by ELISA and Western blotting. BNL.CL2 cells infected with Ad-IL-18BP/IL-4 were intrasplenically transplanted into mice. After 10 days, mice were injected with ConA (15 mg/kg, and sacrificed 18 hours later. Liver injury was assessed by serum transaminase and liver histology. TNF-α, IL-18, IL-4, IL-10, IL-12p70 and monocyte-chemoattracting protein (MCP-1 levels in serum and liver homogenates were detected by ELISA. Signaling molecules in liver homogenates were analyzed by Western blotting.Ad-IL-18BP/IL-4 effectively expressed the IL-18BP/IL-4 fusion protein for more than 14 days in BNL.CL12 cells. Treatment of mice with Ad-IL-18BP/IL-4-BNL.CL2 before ConA injection significantly reduced the elevated plasma levels of transaminases compared with ConA control groups. TNF-α, IL-18, IL-12p70 and MCP-1 levels in serum and liver homogenates from mice transplanted with Ad-IL-18BP/IL-4-BNL.CL2 were lower and IL-4 and IL-10 levels were higher than control groups. Phosphorylation levels of NF-κB p65, AKT, p38 and JNK1/2 in liver homogenates were markedly suppressed by Ad-IL-18BP/IL-4.Ad-IL-18BP/IL-4 was effectively transfected into mouse BNL.CL2 cells. Intrasplenic transplantation of Ad-IL-18BP/IL-4-BNL.CL12 cells alleviated the severity of inflammation in ConA-induced experimental hepatitis and provides a useful basis for the targeted gene therapy of liver disease.

  9. Exercise Does Not Protect Against Peripheral and Central Effects of a High Cholesterol Diet Given Ad Libitum in Old ApoE-/- Mice

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    Vanessa Di Cataldo

    2016-10-01

    Full Text Available Aim:Advanced atherosclerosis increases inflammation and stroke risk in the cerebral vasculature. Exercise is known to improve cardio-metabolic profiles when associated with a caloric restriction, but it remains debated whether it is still beneficial without the dietary control. The aim of this study was to determine both the peripheral and central effects of exercise training combined with a cholesterol-rich diet given ad libitum in old ApoE-/- mice.Methods:45-weeks old obese ApoE-/-mice fed with a high cholesterol diet ad libitum were divided into Exercise-trained (EX; running wheel free access and Sedentary (SED groups. Insulin tolerance and brain imaging were performed before and after the twelve-weeks training. Tissue insulin resistance, oxidative stress and inflammation markers in plasma, aorta and brain were then assessed.Results:In EX ApoE-/- mice, no beneficial effect of exercise was observed on weight, abdominal fat, metabolic parameters, oxidative stress, or inflammation compared to SED. Despite the regular exercise training in ApoE-/- EX mice (mean of 12.5 km/week during twelve weeks, brain inflammation imaging score was significantly associated with increased blood brain barrier (BBB leakage evaluated by imaging follow-up (r²=0.87; p=0.049 with a faster evolution compared to SED ApoE-/-mice. Conclusion:We conclude that in a context of high cardio-metabolic risk, exercise does not provide any protective effect in old ApoE-/- animals under high cholesterol diet given ad libitum. Peripheral (insulin sensitivity and oxidative/inflammatory status but also central features (BBB preservation and protection against inflammation did not show any benefits of exercise. Indeed, there was a fast induction of irreversible brain damage that was more pronounced in exercise-trained ApoE-/- mice.

  10. Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice.

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    Carlo Corona

    Full Text Available BACKGROUND: The pathogenic road map leading to Alzheimer's disease (AD is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties. METHODOLOGY: In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Aβ- and tau-dependent pathology. PRINCIPAL FINDINGS: We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits. CONCLUSIONS AND SIGNIFICANCE: Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD.

  11. The Effect of Adding Fish Oil Sunflower Seed Oil in the Produce of Yogurt From Skim Milk on Cholesterol Level of Mice (Mus Musculus)

    OpenAIRE

    Purnama, A; Malaka, R; Ako, A

    2011-01-01

    This study aims to look at the effect of adding fish oil and sunflower seed oil in the produce of yogurt from skim milk as unsaturated fatty acids that can lower blood cholesterol levels are tested on mice (Mus musculus). Materials research is skim milk, lamuru fish oil, sunflower seed oil, starter plain yogurt Lb.delbrueckii subps. bulgaricus, penoptalin 1%, NaOH 0.1 N and experimental animals. Experimental animals used were 27 mice (Mus musculus) which 2-3 month old male and weighing 25-30 ...

  12. Abeta-mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61.

    Science.gov (United States)

    Kurup, Pradeep; Zhang, Yongfang; Xu, Jian; Venkitaramani, Deepa V; Haroutunian, Vahram; Greengard, Paul; Nairn, Angus C; Lombroso, Paul J

    2010-04-28

    Amyloid beta (Abeta) is involved in the etiology of Alzheimer's disease (AD) and may contribute to cognitive deficits by increasing internalization of ionotropic glutamate receptors. Striatal-enriched protein tyrosine phosphatase 61 (STEP(61)), which is targeted in part to the postsynaptic terminal, has been implicated in this process. Here we show that STEP(61) levels are progressively increased in the cortex of Tg2576 mice over the first year, as well as in prefrontal cortex of human AD brains. The increased STEP(61) was associated with greater STEP activity, dephosphorylation of phospho-tyr(1472) of the NR2B subunit, and decreased NR1 and NR2B subunits on neuronal membranes. Treatment with Abeta-enriched medium also increased STEP(61) levels and decreased NR1/NR2B abundance in mouse cortical cultures as determined by biotinylation experiments. In STEP knock-out cultures, Abeta treatment failed to induce NMDA receptor internalization. The mechanism for the increase in STEP(61) levels appears to involve the ubiquitin proteasome system. Blocking the proteasome resulted in elevated levels of STEP(61). Moreover, STEP(61)-ubiquitin conjugates were increased in wild-type cortical slices upon Abeta treatment as well as in 12 month Tg2576 cortex. These findings reveal a novel mechanism by which Abeta-mediated accumulation of STEP(61) results in increased internalization of NR1/NR2B receptor that may contribute to the cognitive deficits in AD.

  13. Aβ–mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61

    Science.gov (United States)

    Kurup, Pradeep; Zhang, Yongfang; Xu, Jian; Venkitaramani, Deepa V.; Haroutunian, Vahram; Greengard, Paul; Nairn, Angus C.; Lombroso, Paul J.

    2010-01-01

    Amyloid beta (Aβ) is involved in the etiology of Alzheimer's disease (AD) and may contribute to cognitive deficits by increasing internalization of ionotropic glutamate receptors. STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61), which is targeted in part to the postsynaptic terminal, has been implicated in this process. Here we show that STEP61 levels are progressively increased in the cortex of Tg2576 mice over the first year, as well as in prefrontal cortex of human AD brains. The increased STEP61 was associated with greater STEP activity, dephosphorylation of phospho-tyr1472 of the NR2B subunit, and decreased NR1 and NR2B subunits on neuronal membranes. Treatment with Aβ~-enriched medium also increased STEP61 levels and decreased NR1/NR2B abundance in mouse cortical cultures as determined by biotinylation experiments. In STEP knock-out cultures, Aβ treatment failed to induce NMDAR internalization. The mechanism for the increase in STEP61 levels appears to involve the ubiquitin proteasome system (UPS). Blocking the proteasome resulted in elevated levels of STEP61. Moreover, STEP61-ubiquitin conjugates were increased in wild-type cortical slices upon Aβ treatment as well as in 12-month Tg2576 cortex. These findings reveal a novel mechanism by which Aβ-mediated accumulation of STEP61 results in increased internalization of NR1/NR2B receptor that may contribute to the cognitive deficits in AD. PMID:20427654

  14. Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice.

    Science.gov (United States)

    Christensen, Amy; Pike, Christian J

    2017-01-01

    Depletion of ovarian hormones at menopause is associated with increased Alzheimer's disease (AD) risk. Hormone loss also increases central adiposity, which promotes AD development. One strategy to improve health outcomes in postmenopausal women is estrogen-based hormone therapy (HT), though its efficacy is controversial. The window of opportunity hypothesis posits that HT is beneficial only if initiated near the onset of menopause. Here, we tested this hypothesis by assessing the efficacy of HT against diet-induced obesity and AD-related pathology in female 3xTg-AD mice at early versus late middle-age. HT protected against obesity and reduced β-amyloid burden only at early middle-age. One mechanism that contributes to AD pathogenesis is microglial activation, which is increased by obesity and reduced by estrogens. In parallel to its effects on β-amyloid accumulation, we observed that HT reduced morphological evidence of microglial activation in early but not late middle-age. These findings suggest that HT may be effective during human perimenopause in reducing indices of obesity and AD-related pathology, a conclusion consistent with the window of opportunity hypothesis.

  15. The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice.

    Science.gov (United States)

    Chen, Yijing; Han, Shuangxue; Huang, Xiuxian; Ni, Jiazuan; He, Xiaoyang

    2016-01-27

    Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer's disease (AD) rats through inhibition of Aβ production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3× Tg) AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1α (PDHE1α), and the post synaptic density protein 95 (PSD95), was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Aβ and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1) and an increase in fusion protein Mitofusin 2 (Mfn2). These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction-related neuronal degenerative diseases.

  16. The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice

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    Yijing Chen

    2016-01-01

    Full Text Available Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer’s disease (AD rats through inhibition of Aβ production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3× Tg AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1α (PDHE1α, and the post synaptic density protein 95 (PSD95, was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Aβ and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1 and an increase in fusion protein Mitofusin 2 (Mfn2. These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction-related neuronal degenerative diseases.

  17. A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.

    Science.gov (United States)

    Yu, Yun-Zhou; Liu, Si; Wang, Hai-Chao; Shi, Dan-Yang; Xu, Qing; Zhou, Xiao-Wei; Sun, Zhi-Wei; Huang, Pei-Tang

    2016-06-03

    Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.

  18. Diet-induced obesity in ad libitum-fed mice: food texture overrides the effect of macronutrient composition.

    Science.gov (United States)

    Desmarchelier, Charles; Ludwig, Tobias; Scheundel, Ronny; Rink, Nadine; Bader, Bernhard L; Klingenspor, Martin; Daniel, Hannelore

    2013-04-28

    Diet-induced obesity in mice can be achieved through the use of diets with different macronutrient compositions and textures. We aimed at determining the contribution of macronutrient composition to obesity development and associated pathophysiological changes in mice. C57BL/6N mice were offered a control, a high-fat or a Western-style diet, either as pellet (H for hard) or with identical composition in powder form (S for soft), resulting in C-S, C-H, HF-H, HF-S, W-H and W-S groups, respectively. Body fat distribution, expression levels of selected target genes in adipose tissues, clinical chemistry and hormone concentration in the blood, as well as liver TAG content were measured. The most striking finding was that all mice fed the different powder diets developed obesity with similar weight gain, whereas among the mice fed the pellet diets, only those given the HF and W diets became obese. This allowed us to separate diet-specific effects from obesity-mediated effects. Irrespective of the food texture, the W diet induced a more severe hepatosteatosis and higher activities of serum transaminases compared with the two other diets. Adipose tissue gene expression analysis revealed that leptin and adiponectin levels were not affected by the dietary composition per se, whereas uncoupling protein 1 and 11β-hydroxysteroid dehydrogenase type 1 levels were decreased by both dietary composition and changes in body weight. In conclusion, diets differing in macronutrient composition elicit specific pathophysiological changes, independently of changes in body weight. A diet high in both fat and sugars seems to be more deleterious for the liver than a HF diet.

  19. [Antitumor effect of human recombinant interferon-alpha A/D in mice(I): Comparison between systemic and lesional treatment of meth-A sarcoma in BALB/c mice].

    Science.gov (United States)

    Nanjo, M; Yoshie, O; Aso, H; Ebina, T; Ishida, N

    1985-03-01

    Human recombinant interferon-alpha A/D (IFN-alpha A/D) is known to be as active on murine cells as on human cells. We studied the antitumor effect of pure IFN-alpha A/D on Meth-A sarcoma cells in vivo. When administered systemically (intraperitoneally), IFN-alpha A/D (total dosage: 7 X 10(5) units/mouse) was only marginally but significantly (p less than 0.05) effective in reducing the growth of Meth-A sarcoma cells transplanted subcutaneously into syngeneic BALB/c mice. By lesional (intra-tumor) administration (total dosage: 5 X 10(4) to 5 X 10(5) units/mouse), however, IFN-alpha A/D strongly inhibited the growth of Meth-A sarcoma cells and even led to a complete regression of tumor growth and subsequent immunity to Meth-A sarcoma cells in the host animals when treatment was started early after transplantation and at a high dose. Indomethacin or cyclophosphamide administered intraperitoneally at a dose at which, although not directly effective against tumor growth, both were expected to stimulate the host immune system by inhibiting suppressor macrophage function or suppressor T cells, respectively, showed neither enhancing nor suppressing effect on the above mentioned strong antitumor effect of locally administered IFN-alpha A/D.

  20. Improvements in a Mouse Model of Alzheimer's Disease through Sod2 Overexpression Are Due to Functional and Not Structural Alterations

    Directory of Open Access Journals (Sweden)

    Brittany R. Bitner

    2012-01-01

    Full Text Available Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease. We and others have shown that over expression of the mitochondrial antioxidant superoxide dismutase 2 (SOD-2 can improve many of the pathologies in the Tg2576 mouse model of Alzheimer's disease that harbors the Swedish mutation in the amyloid precursor protein. However, it is not clear if these improvements are due to functional improvements or structural/anatomical changes. To answer this question, we used diffusion tensor imaging (DTI to assess the structural integrity of white matter tracts in the control mice, Tg2576 mouse and Tg2576 mice over expressing SOD-2. We observed minimal differences in diffusion parameters with SOD-2 over expression in this model indicating that the improvements we previously reported are due to functional changes and not any alterations to the white matter tractography.

  1. The contrasting effects of ad libitum and restricted feeding of a diet very high in saturated fats on sex ratio and metabolic hormones in mice.

    Science.gov (United States)

    Alexenko, Andrei P; Mao, Jiude; Ellersieck, Mark R; Davis, Angela M; Whyte, Jeffrey J; Rosenfeld, Cheryl S; Roberts, R Michael

    2007-10-01

    Skewing of the sex ratio towards males occurs among pups born to mice fed a very high saturated fat (VHF) diet. In the present study, we tested whether the fat content of the VHF diet rather than the number of calories consumed is responsible for this effect. Eight-week-old NIH Swiss mice were placed on the VHF diet either ad libitum (VHF) or in a restricted manner (VHF-R). The VHF-R mice gained weight at a similar rate to controls fed a standard chow diet. Mice were bred at 15 wk and subsequently at 26 wk and 35 wk of age. Overall, the VHF, VHF-R, and control groups delivered 244, 242, and 274 pups, respectively, with male proportions of 0.60, 0.43, and 0.48, respectively. The pup sex ratios of the VHF group (favoring males) and VHF-R group (favoring females) each differed from 0.5 (P diet groups, maternal body weight had no effect on sex ratio. Serum leptin concentrations among the dams were similar in the VHF and VHF-R groups but higher than in the control group, while the IGF1 and corticosterone levels were comparable in all three groups. Therefore, the atypical sex ratios of offspring born to dams on the VHF diet seem to be influenced by the amount of fat consumed. Since males fed the VHF diet had neither more Y-sperm nor sired more sons than daughters, the dietary effects are manifested exclusively through the female.

  2. All-trans-retinoic Acid Reduces BACE1 Expression under Inflammatory Conditions via Modulation of Nuclear Factor κB (NFκB) Signaling*

    Science.gov (United States)

    Wang, Ruishan; Chen, Shaoya; Liu, Yingchun; Diao, Shiyong; Xue, Yueqiang; You, Xiaoqing; Park, Edwards A.; Liao, Francesca-Fang

    2015-01-01

    Insulin resistance and neuroinflammation have emerged as two likely key contributors in the pathogenesis of Alzheimer disease (AD), especially in those sporadic AD cases compromised by diabetes or cardiovascular disease. Amyloid-β (Aβ) deposition and its associated inflammatory response are hallmarks in sporadic AD brains. Elevated expression and activity of β-secretase 1 (BACE1), the rate-limiting enzyme responsible for the β-cleavage of amyloid precursor proteins to Aβ peptides, are also observed in sporadic AD brains. Previous studies have suggested that there is therapeutic potential for retinoic acid in treating neurodegeneration based on decreased Aβ. Here we discovered that BACE1 expression is elevated in the brains of both Tg2576 transgenic mice and mice on high fat diets. These conditions are associated with a neuroinflammatory response. We found that administration of all-trans-retinoic acid (atRA) down-regulated the expression of BACE1 in the brains of Tg2576 mice and in mice fed a high fat diet. Moreover, in LPS-treated mice and cultured neurons, BACE1 expression was repressed by the addition of atRA, correlating with the anti-inflammatory efficacy of atRA. Mutations of the NFκB binding site in BACE1 promoter abolished the suppressive effect of atRA. Furthermore, atRA disrupted LPS-induced nuclear translocation of NFκB and its binding to BACE1 promoter as well as promoting the recruitment of the corepressor NCoR. Our findings indicate that atRA represses BACE1 gene expression under inflammatory conditions via the modulation of NFκB signaling. PMID:26240147

  3. The effect of metals on spatial memory in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Railey, Angela M; Groeber, Caitlin M; Flinn, Jane M

    2011-01-01

    The amyloid-β protein (Aβ) is a metalloprotein with affinity for the metal ions zinc (Zn), copper (Cu), and iron (Fe), which are found in high concentrations in the plaques of Alzheimer's disease (AD). Increasing attention is focused on the role of these metals in AD, and much of the evidence suggests a dyshomeostasis between these metal ions may significantly affect Aβ aggregation and deposition in the brain. While the effect of these metals on Aβ has been shown in vitro, there is less behavioral data supporting a direct role in cognitive impairment. In order to investigate the cognitive consequences of metal dyshomeostasis, we sought to directly increase metal levels in the brain by dietary means in a transgenic mouse model (Tg2576). We have now examined the effect of increased Zn (10 ppm) and Fe (10 ppm) levels in the drinking water in the Tg2576 mouse. Since increased dietary Zn can lead to Cu deficiency, a Zn group supplemented with copper was also examined (Zn (10 ppm)+Cu (0.025 ppm)). Significant increases in latency and fewer platform crossings on probe trials, which are considered measures of spatial memory impairment, were seen in both Fe and Zn supplemented transgenic mice, compared to those raised on lab water. No significant differences were seen between the Zn + Cu group and in transgenic mice raised on lab water. These data suggest that the negative consequences of Zn may be due to a reduction in copper levels and, therefore, an imbalance between these metal ions rather than a direct effect of increased Zn.

  4. Peripheral Tumor Necrosis Factor-Alpha (TNF-α) Modulates Amyloid Pathology by Regulating Blood-Derived Immune Cells and Glial Response in the Brain of AD/TNF Transgenic Mice.

    Science.gov (United States)

    Paouri, Evi; Tzara, Ourania; Kartalou, Georgia-Ioanna; Zenelak, Sofia; Georgopoulos, Spiros

    2017-05-17

    Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the CNS can provide potential therapeutic targets. TNF-α is a proinflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases, such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear. To investigate the role of peripheral TNF-α as a mediator of RA in the pathogenesis of AD, we generated double-transgenic 5XFAD/Tg197 AD/TNF mice that develop amyloid deposits and inflammatory arthritis induced by human TNF-α (huTNF-α) expression. We found that 5XFAD/Tg197 mice display decreased amyloid deposition, compromised neuronal integrity, and robust brain inflammation characterized by extensive gliosis and elevated blood-derived immune cell populations, including phagocytic macrophages and microglia. To evaluate the contribution of peripheral huTNF-α in the observed brain phenotype, we treated 5XFAD/Tg197 mice systemically with infliximab, an anti-huTNF-α antibody that does not penetrate the blood-brain barrier and prevents arthritis. Peripheral inhibition of huTNF-α increases amyloid deposition, rescues neuronal impairment, and suppresses gliosis and recruitment of blood-derived immune cells, without affecting brain huTNF-α levels. Our data report, for the first time, a distinctive role for peripheral TNF-α in the modulation of the amyloid phenotype in mice by regulating blood-derived and local brain inflammatory cell populations involved in β-amyloid clearance. SIGNIFICANCE STATEMENT Mounting evidence supports the active involvement of systemic inflammation, in addition to local brain inflammation, in Alzheimer's disease (AD) progression. TNF-α is a

  5. NTP Toxicology and Carcinogenesis Studies of AZT (CAS No. 30516-87-1) and AZT/alpha-Interferon A/D B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1999-02-01

    3'-Azido-3'-deoxythymidine (AZT) is the most widely used and evaluated chemotherapeutic agent for the treatment of persons with acquired immune deficiency syndrome (AIDS) and persons seropositive for human immunodeficiency virus (HIV). The National Cancer Institute nominated AZT for toxicity and carcinogenicity studies because of the impending large-scale use of AZT in the treatment of adult patients with AIDS or AIDS-related complex. alpha-Interferon A/D, which displays antiviral activity in mice, is a hybrid molecule composed of the N-terminal portion of human alpha-interferon A and the C-terminal portion of human alpha-interferon D. AZT and alpha-interferon A/D combination studies were conducted because in vitro studies of AZT and alpha-interferon have demonstrated that the combination is more effective in blocking HIV infection than either agent alone. Male and female B6C3F1 mice received AZT (approximately 98% pure) in 0.5% aqueous methylcellulose by gavage for 14 weeks or 2 years. In addition, male and female B6C3F1 mice received alpha-interferon A or alpha-interferon A/D by subcutaneous injection for 2 years, and male and female B6C3F1 mice received AZT in 0.5%% aqueous methylcellulose by gavage in combination with alpha-interferon A/D by subcutaneous injection for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow erythrocytes, and mouse peripheral blood erythrocytes. 14-WEEK AZT STUDY: Groups of 10 male and 10 female mice received AZT in 0.5% methylcellulose by gavage at doses of 0, 50, 100, 200, 800, or 2,000 mg/kg daily for 14 weeks. Additional groups of 10 male and 10 female mice received AZT in 0.5% methylcellulose by gavage at doses of 0, 100, 800, or 2,000 mg/kg daily for 14 weeks and then were held without treatment for an additional 4 weeks before necropsy. One female receiving 100 mg/kg and two females receiving 200 mg/kg died during week 1 as a result of gavage

  6. Chronic Dietary Supplementation of 4% Figs on the Modification of Oxidative Stress in Alzheimer’s Disease Transgenic Mouse Model

    Directory of Open Access Journals (Sweden)

    Selvaraju Subash

    2014-01-01

    Full Text Available We assessed the changes in the plasma Aβ, oxidative stress/antioxidants, and membrane bound enzymes in the cerebral cortex and hippocampus of Alzheimer’s disease (AD transgenic mice (Tg2576 after dietary supplementation of Omani figs fruits for 15 months along with spatial memory and learning test. AD Tg mice on control diet without figs showed significant impairment in spatial learning ability compared to the wild-type mice on same diet and figs fed Tg mice as well. Significant increase in oxidative stress and reduced antioxidant status were observed in AD Tg mice. 4% figs treated AD Tg mice significantly attenuated oxidative damage, as evident by decreased lipid peroxidation and protein carbonyls and restoration of antioxidant status. Altered activities of membrane bound enzymes (Na+ K+ ATPase and acetylcholinesterase (AChE in AD Tg mice brain regions and was restored by figs treatment. Further, figs supplementation might be able to decrease the plasma levels of Aβ (1–40, 1–42 significantly in Tg mice suggesting a putative delay in the formation of plaques, which might be due to the presence of high natural antioxidants in figs. But this study warrants further extensive investigation to find a novel lead for a therapeutic target for AD from figs.

  7. Hairy AdS solitons

    Energy Technology Data Exchange (ETDEWEB)

    Anabalón, Andrés, E-mail: andres.anabalon@uai.cl [Departamento de Ciencias, Facultad de Artes Liberales and Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez, Av. Padre Hurtado 750, Viña del Mar (Chile); Astefanesei, Dumitru, E-mail: dumitru.astefanesei@pucv.cl [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Casilla 4059, Valparaíso (Chile); Choque, David, E-mail: brst1010123@gmail.com [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Casilla 4059, Valparaíso (Chile); Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso (Chile)

    2016-11-10

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We examine their thermodynamic properties and discuss the role of these solutions for the existence of first order phase transitions for hairy black holes. The negative energy density associated to hairy AdS solitons can be interpreted as the Casimir energy that is generated in the dual filed theory when the fermions are antiperiodic on the compact coordinate.

  8. Reduction of the immunostainable length of the hippocampal dentate granule cells' primary cilia in 3xAD-transgenic mice producing human A{beta}{sub 1-42} and tau

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarthy, Balu, E-mail: Balu.Chakravarthy@nrc-cnrc.gc.ca [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Gaudet, Chantal; Menard, Michel; Brown, Leslie; Atkinson, Trevor [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); LaFerla, Frank M. [Department of Neurobiology and Behavior, University of California, Irvine, CA (United States); Ito, Shingo [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Armato, Ubaldo; Dal Pra, Ilaria [Department of Life and Reproduction Sciences, University of Verona Medical School, Verona (Italy); Whitfield, James [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A{beta} and tau-induced neurofibrillary tangles play a key role in Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}{sub 1-42} and mutant tau protein together reduce the primary cilium length. Black-Right-Pointing-Pointer This shortening likely reduces cilium-dependent neurogenesis and memory function. Black-Right-Pointing-Pointer This provides a model of an A{beta}/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75{sup NTR}). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both A{beta}{sub 1-42} and the mutant human tau protein tau{sub P301L,} the dentate granule cells still had immunostainable SSTR3- and p75{sup NTR}-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A{beta}{sub 1-42} or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A{beta}{sub 1-42} and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  9. Vaccination to conserved influenza antigens in mice using a novel Simian adenovirus vector, PanAd3, derived from the bonobo Pan paniscus.

    Science.gov (United States)

    Vitelli, Alessandra; Quirion, Mary R; Lo, Chia-Yun; Misplon, Julia A; Grabowska, Agnieszka K; Pierantoni, Angiolo; Ammendola, Virginia; Price, Graeme E; Soboleski, Mark R; Cortese, Riccardo; Colloca, Stefano; Nicosia, Alfredo; Epstein, Suzanne L

    2013-01-01

    Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.

  10. Vaccination to conserved influenza antigens in mice using a novel Simian adenovirus vector, PanAd3, derived from the bonobo Pan paniscus.

    Directory of Open Access Journals (Sweden)

    Alessandra Vitelli

    Full Text Available Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP and matrix 1 (M1. We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.

  11. Adding Ajax

    CERN Document Server

    Powers, Shelley

    2007-01-01

    Ajax can bring many advantages to an existing web application without forcing you to redo the whole thing. This book explains how you can add Ajax to enhance, rather than replace, the way your application works. For instance, if you have a traditional web application based on submitting a form to update a table, you can enhance it by adding the capability to update the table with changes to the form fields, without actually having to submit the form. That's just one example.Adding Ajax is for those of you more interested in extending existing applications than in creating Rich Internet Applica

  12. Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice.

    Science.gov (United States)

    Qi, Yue; Dou, De-Qiang; Jiang, Hong; Zhang, Bing-Bing; Qin, Wen-Yan; Kang, Kai; Zhang, Na; Jia, Dong

    2017-01-01

    Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects both in vitro and in vivo in a Parkinson's disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloid β1-42 was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloid β1-42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid β1-42, the mice were sacrificed for biochemical analysis. Arctigenin (10-150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3β. Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3β signalling pathway. Georg Thieme Verlag KG Stuttgart · New York.

  13. Mitochondrial oxidative stress causes hyperphosphorylation of tau.

    Directory of Open Access Journals (Sweden)

    Simon Melov

    2007-06-01

    Full Text Available Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD: tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2 die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576 with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.

  14. Lipid Emulsion Added to a Liquid High-Carbohydrate Diet and Voluntary Running Exercise Reduce Lipogenesis and Ameliorate Early-Stage Hepatic Steatosis in Mice.

    Science.gov (United States)

    Huang, Kuan-Hsun; Hao, Lei; Smith, Philip B; Rogers, Connie J; Patterson, Andrew D; Ross, A Catharine

    2017-05-01

    Background: The use of parenteral nutrition formulas is often associated with the development of hepatic steatosis. We have shown previously that the addition of a lipid emulsion (LE) rich in n-6 (ω-6) fatty acids (FAs) ameliorated triglyceride (TG) accumulation in the livers of nonobese mice fed a high-carbohydrate diet (HCD) for 5 wk. However, it remains unclear how rapidly this condition develops and whether it can be prevented by LE with or without a running wheel for voluntary exercise (Exe).Objective: We investigated in an 8-d study whether mice develop steatosis and whether the administration of LE with or without Exe reduces the concentration of total FAs and prevents an increase in the expression of genes in the liver associated with lipogenesis.Methods: Male C57BL/6 mice aged 5 wk were randomized into 5 groups: standard feed pellet (SFP); a liquid HCD (77% of total energy from carbohydrates and 0.5% from fat); HCD + Exe; HCD + 13.5% LE (67% carbohydrates and 13.5% fat); or HCD + 13.5% LE + Exe. Hepatic TG concentration, lipogenic genes, and total FAs were measured on day 8.Results: Oil Red O staining and TG quantification showed hepatic TG accumulation on day 8; the addition of 13.5% LE either with or without Exe suppressed the TG accumulation compared with HCD (P < 0.005). With the use of quantitative reverse transcriptase-polymerase chain reaction analysis, the expression concentrations of lipogenic genes [ATP-citrate lyase, acetyl coenzyme A carboxylase 1, FA synthase (Fasn), and stearoyl coenzyme A desaturase 1 (Scd1)] in the HCD + 13.5% LE group were 26-60% of HCD (P < 0.01) and 11-38% of HCD in the HCD + 13.5% LE + Exe group (P < 0.001), with interactions for Fasn and Scd1 (P < 0.05). With the use of gas chromatography-mass spectrometry analysis, the HCD + 13.5% LE group had lower monounsaturated fatty acids (38.7% of HCD) but higher polyunsaturated fatty acids (164% of HCD) (P < 0.001).Conclusions: In short-term studies designed to resemble the

  15. PET imaging of brain with the {beta}-amyloid probe, [{sup 11}C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Hiroshi [Fujita Health University, Department of Radiology, Aichi (Japan); National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ye, Daniel; Cohen, Robert M. [National Institutes of Health, Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Jacobowitz, David [USUHS, Department of Anatomy, Physiology, and Genetics, Bethesda, Maryland (United States); Seidel, Jurgen; Green, Michael V. [National Institutes of Health, Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, Bethesda, Maryland (United States); Katada, Kazuhiro [Fujita Health University, Department of Radiology, Aichi (Japan)

    2005-04-01

    The purpose of this study was to evaluate the capacity of [{sup 11}C]6-OH-BTA-1 and positron emission tomography (PET) to quantify {beta}-amyloid (A{beta}) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0{+-}1.8 months; 23.6{+-}2.6 g) overexpressing a mutated form of human {beta}-amyloid precursor protein (APP) known to result in the production of A{beta} plaques, and in six elderly wild-type litter mates (age 21.8{+-}1.6 months; 29.5{+-}4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [{sup 11}C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [{sup 11}C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06{+-}0.04 vs 0.98{+-}0.07, p=0.04; 1.06{+-}0.09 vs 0.93{+-}0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A{beta} plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild

  16. Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease.

    Science.gov (United States)

    Velazquez, Ramon; Tran, An; Ishimwe, Egide; Denner, Larry; Dave, Nikhil; Oddo, Salvatore; Dineley, Kelly T

    2017-10-01

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We report that CNS insulin signaling abnormalities are evident months before peripheral insulin resistance. In addition, we find that brain energy metabolism is differentially altered in both mouse models, with 3xTg-AD mice showing more extensive changes. Collectively, our data suggest that early AD may reflect engagement of different signaling networks that influence CNS metabolism, which in turn may alter peripheral insulin signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. n-3 PUFA added to high-fat diets affect differently adiposity and inflammation when carried by phospholipids or triacylglycerols in mice

    Directory of Open Access Journals (Sweden)

    Awada Manar

    2013-02-01

    Full Text Available Abstract Background Dietary intake of n-3 polyunsaturated fatty acids (PUFA is primarily recognized to protect against cardiovascular diseases, cognitive dysfunctions and the onset of obesity and associated metabolic disorders. However, some of their properties such as bioavailability can depend on their chemical carriers. The objective of our study was to test the hypothesis that the nature of n-3 PUFA carrier results in different metabolic effects related to adiposity, oxidative stress and inflammation. Methods 4 groups of C57BL/6 mice were fed for 8 weeks low fat (LF diet or high-fat (HF, 20% diets. Two groups of high-fat diets were supplemented with long-chain n-3 PUFA either incorporated in the form of phospholipids (HF-ω3PL or triacylglycerols (HF-ω3TG. Results Both HF-ω3PL and HF-ω3TG diets reduced the plasma concentrations of (i inflammatory markers such as monocyte chemoattractant protein-1 (MCP-1 and interleukin 6 (IL-6, (ii leptin and (iii 4-hydroxy-2-nonenal (4-HNE, a marker of n-6 PUFA-derived oxidative stress compared with the control HF diet. Moreover, in both HF-ω3PL and HF-ω3TG groups, MCP-1 and IL-6 gene expressions were decreased in epididymal adipose tissue and the mRNA level of gastrointestinal glutathione peroxidase GPx2, an antioxidant enzyme, was decreased in the jejunum compared with the control HF diet. The type of n-3 PUFA carrier affected other outcomes. The phospholipid form of n-3 PUFA increased the level of tocopherols in epididymal adipose tissue compared with HF-ω3TG and resulted in smaller adipocytes than the two others HF groups. Adipocytes in the HF-ω3PL and LF groups were similar in size distribution. Conclusion Supplementation of mice diet with long-chain n-3 PUFA during long-term consumption of high-fat diets had the same lowering effects on inflammation regardless of triacyglycerol or phospholipid carrier, whereas the location of these fatty acids on a PL carrier had a major effect on decreasing

  18. Expression of the neuronal adaptor protein X11alpha protects against memory dysfunction in a transgenic mouse model of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Mitchell, Jacqueline C

    2010-01-01

    X11alpha is a neuronal-specific adaptor protein that binds to the amyloid-beta protein precursor (AbetaPP). Overexpression of X11alpha reduces Abeta production but whether X11alpha also protects against Abeta-related memory dysfunction is not known. To test this possibility, we crossed X11alpha transgenic mice with AbetaPP-Tg2576 mice. AbetaPP-Tg2576 mice produce high levels of brain Abeta and develop age-related defects in memory function that correlate with increasing Abeta load. Overexpression of X11alpha alone had no detectable adverse effect upon behavior. However, X11alpha reduced brain Abeta levels and corrected spatial reference memory defects in aged X11alpha\\/AbetaPP double transgenics. Thus, X11alpha may be a therapeutic target for Alzheimer\\'s disease.

  19. Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling.

    Science.gov (United States)

    Chen, Li-Ming; Xiong, Yan-Si; Kong, Fan-Li; Qu, Min; Wang, Qun; Chen, Xiao-Qian; Wang, Jian-Zhi; Zhu, Ling-Qiang

    2012-01-01

    Neuroglobin (Ngb) is a recently identified member of hemoglobin family, distributed mainly in central and peripheral nervous systems. Recent studies suggest that Ngb can protect neural cells from β-amyloid-induced toxicity in Alzheimer disease (AD). Hyperphosphorylation of tau is another characterized pathological hallmark in the AD brains; however, it is not reported whether Ngb also affects tau phosphorylation. In this study, we found that the level of Ngb was significantly reduced in Tg2576 mice (a recognized mouse model of AD) and TgMAPt mice, and the level of Ngb was negatively correlated with tau phosphorylation. Over-expression of Ngb attenuates tau hyperphosphorylation at multiple AD-related sites induced by up-regulation of glycogen synthase kinase-3β (GSK-3β), a crucial tau kinase. While Ngb activates Akt and thus inhibits GSK-3β, simultaneously inhibition of Akt abolishes the effects of Ngb on GSK-3β inhibition and tau hyperphosphorylation. Our data indicate that Ngb may attenuate tau hyperphosphorylation through activating Akt signaling pathway, implying a therapeutic target for AD. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  20. Reduced levels of the tyrosine phosphatase STEP block β amyloid-mediated GluA1/GluA2 receptor internalization.

    Science.gov (United States)

    Zhang, Yongfang; Kurup, Pradeep; Xu, Jian; Anderson, George M; Greengard, Paul; Nairn, Angus C; Lombroso, Paul J

    2011-11-01

    Striatal-Enriched protein tyrosine Phosphatase of MW 61 kDa (STEP(61)) is a protein tyrosine phosphatase recently implicated in the pathophysiology of Alzheimer's disease (AD). STEP(61) is elevated in human AD prefrontal cortex and in the cortex of several AD mouse models. The elevated levels of active STEP(61) down-regulate surface expression of GluN1/GluN2B (formerly NR1/NR2B) receptor complexes, while genetically reducing STEP levels rescues both the biochemical and cognitive deficits in a triple transgenic AD mouse model (3xTg-AD). Here, we show that increased STEP(61) also plays a role in beta amyloid (Aβ)-mediated internalization of the α-amino-3-hydroxy-5-methyl-4-(AMPA) receptor (AMPAR) subunits GluA1/GluA2 (formerly GluR1/GluR2). We purified Aβ oligomers and determined that oligomers, but not monomers, lead to endocytosis of GluA1/GluA2 receptors in cortical cultures. The decrease in GluA1/GluA2 receptors is reversed in the progeny of STEP knock-out (KO) mice crossed with Tg2576 mice, despite elevated levels of Aβ. These results provide strong support for the hypothesis that STEP(61) is required for Aβ-mediated internalization of GluA1/GluA2 receptors. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  1. Role of deferoxamine on enzymatic stress markers in an animal model of Alzheimer's disease after chronic aluminum exposure.

    Science.gov (United States)

    Esparza, José L; Garcia, Tania; Gómez, Mercedes; Nogués, M Rosa; Giralt, Montserrat; Domingo, José L

    2011-06-01

    The effect of the chelator deferoxamine (DFO) on the activity of enzymatic stress markers was assessed in amyloid beta peptide (AβPP) transgenic mice, an animal model of Alzheimer's disease, after oral aluminum (Al) exposure for 6 months. AβPP transgenic (Tg2576) and C57BL6/SJL wild-type mice of 5 months of age were fed a diet supplemented with Al lactate (1 mg of Al/g food). Four groups of Tg2576 and wild-type animals were used: control, Al only, DFO only, and Al plus DFO. Mice in the DFO-treated groups received also subcutaneous injections of 0.20 mmol/kg/d of this chelating agent twice a week until the end of the study at 11 months of age. The hippocampus, cerebellum, and cortex were removed and processed to examine a number of oxidative stress markers. Furthermore, the expression of Cu-Zn superoxide dismutase, glutathione reductase, and catalase was evaluated by quantitative reverse transcriptase polymerase chain reaction analysis. Aluminum levels in the hippocampus of Tg2576 mice were higher than those found in cerebellum and cortex, while the main oxidative effects were evidenced in the presence of DFO only. Oral Al exposure of AβPP transgenic mice would have some potential to promote pro-oxidant events, while DFO administration would not help in preventing these deleterious effects.

  2. Dysregulation of Elongation Factor 1A Expression is Correlated with Synaptic Plasticity Impairments in Alzheimer's Disease.

    Science.gov (United States)

    Beckelman, Brenna C; Day, Stephen; Zhou, Xueyan; Donohue, Maggie; Gouras, Gunnar K; Klann, Eric; Keene, C Dirk; Ma, Tao

    2016-09-06

    Synaptic dysfunction may represent an early and crucial pathophysiology in Alzheimer's disease (AD). Recent studies implicate a connection between synaptic plasticity deficits and compromised capacity of de novo protein synthesis in AD. The mRNA translational factor eukaryotic elongation factor 1A (eEF1A) is critically involved in several forms of long-lasting synaptic plasticity. By examining postmortem human brain samples, a transgenic mouse model, and application of synthetic human Aβ42 on mouse hippocampal slices, we demonstrated that eEF1A protein levels were significantly decreased in AD, particularly in the hippocampus. In contrast, brain levels of eukaryotic elongation factor 2 were unaltered in AD. Further, upregulation of eEF1A expression by the adenylyl cyclase activator forskolin, which induces long-lasting synaptic plasticity, was blunted in hippocampal slices derived from Tg2576 AD model mice. Finally, Aβ-induced hippocampal long-term potentiation defects were alleviated by upregulation of eEF1A signaling via brain-specific knockdown of the gene encoding tuberous sclerosis 2. In summary, our findings suggest a strong correlation between the dysregulation of eEF1A synthesis and AD-associated synaptic failure. These findings provide insights into the understanding of molecular mechanisms underlying AD etiology and may aid in identification of novel biomarkers and therapeutic targets.

  3. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease.

    Science.gov (United States)

    Garcia, Pierre; Youssef, Ihsen; Utvik, Jo K; Florent-Béchard, Sabrina; Barthélémy, Vanassa; Malaplate-Armand, Catherine; Kriem, Badreddine; Stenger, Christophe; Koziel, Violette; Olivier, Jean-Luc; Escanye, Marie-Christine; Hanse, Marine; Allouche, Ahmad; Desbène, Cédric; Yen, Frances T; Bjerkvig, Rolf; Oster, Thierry; Niclou, Simone P; Pillot, Thierry

    2010-06-02

    The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta (Abeta) oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure long-term administration of CNTF in the brain, we used recombinant cells secreting CNTF encapsulated in alginate polymers. The implantation of these bioreactors in the brain of Abeta oligomer-infused mice led to a continuous secretion of recombinant CNTF and was associated with the robust improvement of cognitive performances. Most importantly, CNTF led to full recovery of cognitive functions associated with the stabilization of synaptic protein levels in the Tg2576 AD mouse model. In vitro as well as in vivo, CNTF activated a Janus kinase/signal transducer and activator of transcription-mediated survival pathway that prevented synaptic and neuronal degeneration. These preclinical studies suggest that CNTF and/or CNTF receptor-associated pathways may have AD-modifying activity through protection against progressive Abeta-related memory deficits. Our data also encourage additional exploration of ex vivo gene transfer for the prevention and/or treatment of AD.

  4. No-carrier-added (NCA) N-(3-( sup 18 F)fluoropropyl)-N-norbuprenorphine and N-(3-( sup 18 F)fluoropropyl)-N-nordiprenorphine -synthesis, anatomical distribution in mice and rats, and tomographic studies in a baboon

    Energy Technology Data Exchange (ETDEWEB)

    Lanqin Bai; Renrui Teng; Chyngyann Shiue; Wolf, A.P.; Dewey, S.L. (Brookhaven National Lab., Upton, NY (USA)); Holland, M.J.; Simon, E.J. (New York Univ., NY (USA). Medical Center)

    1990-01-01

    N-(3-Fluoropropyl)-N-norbuprenorphine (3a) and N-(3-fluoropropyl)-N-nordiprenorphine (4a) were synthesized by N-alkylation of norbuprenorphine (1) and nordiprenorphine (2) with 1-bromo-3-fluoropropane. The corresponding no-carrier-added (NCA) N-(3-({sup 18}F)fluoropropyl)-N-norbuprenorphine (3b) and N-(3-({sup 18}F)fluoropropyl)-N-nordiprenorphine (4b) were synthesized by N-alkylation of 1 and 2 with NCA 1-({sup 18}F)fluoro-3-iodopropane. In vitro studies indicate that in the absence of sodium chloride, compounds 3a, 4a, N-propyl-N-norbuprenorphine (5), buprenorphine and diprenorphine are reasonably comparable in binding affinity for opioid receptors. In the presence of 100 mM sodium chloride, however, compounds 3a, 4a and 5, are clearly less potent than buprenorphine and diprenorphine. The anatomical distribution study of compound 3b in mice shows radioactivity accumulating in bone. Rat studies of both compounds 3b and 4b indicate the specific distribution of these two radioligands within certain cortical and subcortical regions of rat brain. However, the absolute uptake of compound 4b in rat brain was only half that of compound 3b. PET studies of 3b in a baboon revealed specific binding of compound 3b in striatum and cerebellum. At 1 h after injection, ratios of specific/non-specific binding of 3b in striatum and cerebellum of a baboon were 1.9 and 1.7 respectively. (author).

  5. Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Amala Soumyanath

    2012-01-01

    Full Text Available Centella asiatica (CA, commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD, we examined the effects of a water extract of CA (GKW in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.

  6. INDUCTION OF CYP1A1 AD CYP1B1 AND FORMATION OF DNA ADDUCTS IN C57BL/6, BALB/C, AND F1 MICE FOLLOWING IN UTERO EXPOSURE TO 3-METHYLCHOLANTHRENE

    Science.gov (United States)

    Fetal mice are more sensitive to chemical carcinogens than are adults. Previous studies from our laboratory demonstrated differences in the mutational spectrum induced in the Ki-ras gene from lung tumors isolated from [D2 x B6D2F1]F2 mice and Balb/c mice treated in utero with 3�m...

  7. Efeito da adição dietética de milho de alta qualidade protéica em camundongos Effect of adding high-quality protein maize to the diet of mice

    Directory of Open Access Journals (Sweden)

    Aline Castro Silva

    2007-06-01

    Full Text Available OBJETIVO: O objetivo do estudo consistiu em avaliar os efeitos da adição de milho quality protein maize BR473 sobre aspectos bioquímicos e fisiológicos. MÉTODOS: Camundongos Swiss, fêmeas, 6-7 semanas, foram alimentados com rações comerciais, rações comerciais com milho híbrido (1:1, rações comerciais com milho de alta qualidade protéica (1:1. Foram avaliados, durante 3 meses, o consumo de ração, o ganho de peso e de tecido adiposo retroperitoneal e os valores plasmáticos de proteínas, triglicerídeos, colesterol e glicose. RESULTADOS: A adição dietética de milho quality protein maize BR473 reduziu o consumo alimentar e o tecido adiposo retroperitoneal, porém manteve a glicemia e trigliceridemia em relação à adição de milho híbrido na ração comercial. CONCLUSÃO: A melhor eficiência alimentar e os impactos sobre os parâmetros bioquímicos do sangue sugerem o potencial do uso do milho quality protein maize BR473 como um importante complemento para garantir a segurança alimentar e nutricional.OBJECTIVE: The aim of this work was to evaluate the biochemical and physiological effects of adding quality protein maize BR473 to the diet of mice. METHODS:Female Swiss mice, 6-7 weeks old, were fed commercial diet alone or supplemented with either hybrid maize (1:1 or quality protein maize (1:1. Food intake, weight gain, abdominal obesity and plasma glucose, proteins, cholesterol and triglycerides levels were evaluated for 3 months. RESULTS: Dietary addition of the quality protein maize BR473 reduced food intake and abdominal fat, yet plasma glucose and triglycerides remained the same when compared with the addition of hybrid maize to the commercial feed. CONCLUSION: A better dietary efficiency and the impacts on the biochemical parameters of the blood suggest that the quality protein maize BR473 is an important complement to guarantee dietary and nutritional security.

  8. Resorufin analogs preferentially bind cerebrovascular amyloid: potential use as imaging ligands for cerebral amyloid angiopathy

    Directory of Open Access Journals (Sweden)

    Han Byung

    2011-12-01

    Full Text Available Abstract Background Cerebral amyloid angiopathy (CAA is characterized by deposition of fibrillar amyloid β (Aβ within cerebral vessels. It is commonly seen in the elderly and almost universally present in patients with Alzheimer's Disease (AD. In both patient populations, CAA is an independent risk factor for lobar hemorrhage, ischemic stroke, and dementia. To date, definitive diagnosis of CAA requires obtaining pathological tissues via brain biopsy (which is rarely clinically indicated or at autopsy. Though amyloid tracers labeled with positron-emitting radioligands such as [11C]PIB have shown promise for non-invasive amyloid imaging in AD patients, to date they have been unable to clarify whether the observed amyloid load represents neuritic plaques versus CAA due in large part to the low resolution of PET imaging and the almost equal affinity of these tracers for both vascular and parenchymal amyloid. Therefore, the development of a precise and specific non-invasive technique for diagnosing CAA in live patients is desired. Results We found that the phenoxazine derivative resorufin preferentially bound cerebrovascular amyloid deposits over neuritic plaques in the aged Tg2576 transgenic mouse model of AD/CAA, whereas the congophilic amyloid dye methoxy-X34 bound both cerebrovascular amyloid deposits and neuritic plaques. Similarly, resorufin-positive staining was predominantly noted in fibrillar Aβ-laden vessels in postmortem AD brain tissues. Fluorescent labeling and multi-photon microscopy further revealed that both resorufin- and methoxy-X34-positive staining is colocalized to the vascular smooth muscle (VSMC layer of vessel segments that have severe disruption of VSMC arrangement, a characteristic feature of CAA. Resorufin also selectively visualized vascular amyloid deposits in live Tg2576 mice when administered topically, though not systemically. Resorufin derivatives with chemical modification at the 7-OH position of resorufin also

  9. Selective antihypertensive dihydropyridines lower Aβ accumulation by targeting both the production and the clearance of Aβ across the blood-brain barrier.

    Science.gov (United States)

    Paris, Daniel; Bachmeier, Corbin; Patel, Nikunj; Quadros, Amita; Volmar, Claude-Henry; Laporte, Vincent; Ganey, Jim; Beaulieu-Abdelahad, David; Ait-Ghezala, Ghania; Crawford, Fiona; Mullan, Michael J

    2011-01-01

    Several large population-based or clinical trial studies have suggested that certain dihydropyridine (DHP) L-type calcium channel blockers (CCBs) used for the treatment of hypertension may confer protection against the development of Alzheimer disease (AD). However, other studies with drugs of the same class have shown no beneficial clinical effects. To determine whether certain DHPs are able to impact underlying disease processes in AD (specifically the accumulation of the Alzheimer Aβ peptide), we investigated the effect of several antihypertensive DHPs and non-DHP CCBs on Aβ production. Among the antihypertensive DHPs tested, a few, including nilvadipine, nitrendipine and amlodipine inhibited Aβ production in vitro, whereas others had no effect or raised Aβ levels. In vivo, nilvadipine and nitrendipine acutely reduced brain Aβ levels in a transgenic mouse model of AD (Tg PS1/APPsw) and improved Aβ clearance across the blood-brain barrier (BBB), whereas amlodipine and nifedipine were ineffective showing that the Aβ-lowering activity of the DHPs is independent of their antihypertensive activity. Chronic oral treatment with nilvadipine decreased Aβ burden in the brains of Tg APPsw (Tg2576) and Tg PS1/APPsw mice, and also improved learning abilities and spatial memory. Our data suggest that the clinical benefit conferred by certain antihypertensive DHPs against AD is unrelated to their antihypertensive activity, but rely on their ability to lower brain Aβ accumulation by affecting both Aβ production and Aβ clearance across the BBB.

  10. Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Darrell Sawmiller

    2014-01-01

    Full Text Available Traumatic brain injury (TBI occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer’s disease (AD. Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in Aβ depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3 activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.

  11. Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease.

    Directory of Open Access Journals (Sweden)

    Anna Parachikova

    2010-11-01

    Full Text Available Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ in the Tg2576 mouse model of the disease.The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.

  12. Axion wormholes in AdS compactifications

    Science.gov (United States)

    Hertog, Thomas; Trigiante, Mario; Van Riet, Thomas

    2017-06-01

    We find regular axionic Euclidean wormhole solutions in Type IIB string theory compactified on {AdS}_5× {S}^5/{Z}_k . AdS/CFT enables a precise derivation of the axion content of the Euclidean theory, placing the string theory embedding of the wormholes on firm footing. This further sharpens the paradox posed by these solutions.

  13. Polarised Black Holes in AdS

    CERN Document Server

    Costa, Miguel S.; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-05-03

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global $AdS_{4}$ with conformal boundary $S^{2}\\times\\mathbb{R}_{t}$. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic $AdS$ behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an $AdS$ soliton that includes the full backreaction of the electric field on the $AdS$ geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both $AdS$ soliton and black hole phases. The corresponding phase diagram generalizes the Hawkin...

  14. Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

    Science.gov (United States)

    Trushina, Eugenia; Nemutlu, Emirhan; Zhang, Song; Christensen, Trace; Camp, Jon; Mesa, Janny; Siddiqui, Ammar; Tamura, Yasushi; Sesaki, Hiromi; Wengenack, Thomas M.; Dzeja, Petras P.; Poduslo, Joseph F.

    2012-01-01

    Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated

  15. Current status of AdS instability

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    arXiv:1403.6471 and thoroughly developed in arXiv:1407.6273. On the other hand the negative cosmological constant allows for the existence of stable, time-periodic, asymptotically AdS solutions of Einstein equations [arXiv:1303.3186].

  16. AdS braneworld with Backreaction

    CERN Document Server

    Bilic, Neven

    2014-01-01

    We review the tachyon model derived from the dynamics of a 3-brane moving in the AdS5 bulk. The bulk geometry is based on the Randall-Sundrum II model extended to include the radion. The effective tachyon Lagrangian is modified due to the back-reaction of the brane on the bulk geometry.

  17. Lorentzian AdS, Wormholes and Holography

    CERN Document Server

    Arias, Raul E; Silva, Guillermo A

    2011-01-01

    We investigate the structure of two point functions for the QFT dual to an asymptotically Lorentzian AdS-wormhole. The bulk geometry is a solution of 5-dimensional second order Einstein Gauss Bonnet gravity and causally connects two asymptotically AdS space times. We revisit the GKPW prescription for computing two-point correlation functions for dual QFT operators O in Lorentzian signature and we propose to express the bulk fields in terms of the independent boundary values phi_0^\\pm at each of the two asymptotic AdS regions, along the way we exhibit how the ambiguity of normalizable modes in the bulk, related to initial and final states, show up in the computations. The independent boundary values are interpreted as sources for dual operators O^\\pm and we argue that, apart from the possibility of entanglement, there exists a coupling between the degrees of freedom leaving at each boundary. The AdS_(1+1) geometry is also discussed in view of its similar boundary structure. Based on the analysis, we propose a ...

  18. Baby Skyrmions in AdS

    Energy Technology Data Exchange (ETDEWEB)

    Elliot-Ripley, Matthew; Winyard, Thomas [Department of Mathematical Sciences, Durham University,South Rd, Durham (United Kingdom)

    2015-09-01

    We study the baby Skyrme model in a pure AdS background without a mass term. The tail decays and scalings of massless radial solutions are demonstrated to take a similar form to those of the massive flat space model, with the AdS curvature playing a similar role to the flat space pion mass. We also numerically find minimal energy solutions for a range of higher topological charges and find that they form concentric ring-like solutions. Popcorn transitions (named in analogy with studies of toy models of holographic QCD) from an n layer to an n+1-layer configuration are observed at topological charges 9 and 27 and further popcorn transitions for higher charges are predicted. Finally, a point-particle approximation for the model is derived and used to successfully predict the ring structures and popcorn transitions for higher charge solitons.

  19. AdS solutions through transgression

    Energy Technology Data Exchange (ETDEWEB)

    Donos, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Gauntlett, J.P. [Imperial College, London (United Kingdom). Blackett Lab.]|[Imperial College, London (United Kingdom). The Institute for Mathematical Sciences; Kim, Nakwoo [Kyung Hee Univ., Seoul (Korea). Dept. of Physics and Research Inst. of Basic Science

    2008-07-15

    We present new classes of explicit supersymmetric AdS{sub 3} solutions of type IIB supergravity with non-vanishing five-form flux and AdS{sub 2} solutions of D=11 supergravity with electric four-form flux. The former are dual to two-dimensional SCFTs with (0,2) supersymmetry and the latter to supersymmetric quantum mechanics with two supercharges. We also investigate more general classes of AdS{sub 3} solutions of type IIB supergravity and AdS{sub 2} solutions of D=11 supergravity which in addition have non-vanishing three-form flux and magnetic four-form flux, respectively. The construction of these more general solutions makes essential use of the Chern-Simons or ''transgression'' terms in the Bianchi identity or the equation of motion of the field strengths in the supergravity theories. We construct infinite new classes of explicit examples and for some of the type IIB solutions determine the central charge of the dual SCFTs. The type IIB solutions with non-vanishing three-form flux that we construct include a two-torus, and after two T-dualities and an S-duality, we obtain new AdS3 solutions with only the NS fields being non-trivial. (orig.)

  20. Predicting AD conversion

    DEFF Research Database (Denmark)

    Liu, Yawu; Mattila, Jussi; Ruiz, Miguel �ngel Mu�oz

    2013-01-01

    To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI...

  1. Adding more value to added-value

    DEFF Research Database (Denmark)

    Marian, Livia

    Recent studies reveal that consumers respond favourably to “organic plus” products with additional ethical attributes. The aim of the current study is to explore whether consumers would notice and value further improvements in the animal welfare standards than those imposed by the organic...... it is probably valued less than expected. The added attributes need to be thoroughly considered when developing and marketing “organic plus” products, as their effect on other product characteristics (e.g. high prices) can detract from their added value....

  2. The political attack ad

    Directory of Open Access Journals (Sweden)

    Palma Peña-Jiménez, Ph.D.

    2011-01-01

    Full Text Available During election campaigns the political spot has a clear objective: to win votes. This message is communicated to the electorate through television and Internet, and usually presents a negative approach, which includes a direct critical message against the opponent, rather than an exposition of proposals. This article is focused on the analysis of the campaign attack video ad purposely created to encourage the disapproval of the political opponent among voters. These ads focus on discrediting the opponent, many times, through the transmission of ad hominem messages, instead of disseminating the potential of the political party and the virtues and manifesto of its candidate. The article reviews the development of the attack ad since its first appearance, which in Spain dates back to 1996, when the famous Doberman ad was broadcast, and examines the most memorable campaign attack ads.

  3. Twistor methods for AdS$_5$

    CERN Document Server

    Adamo, Tim; Williams, Jack

    2016-01-01

    We consider the application of twistor theory to five-dimensional anti-de Sitter space. The twistor space of AdS$_5$ is the same as the ambitwistor space of the four-dimensional conformal boundary; the geometry of this correspondence is reviewed for both the bulk and boundary. A Penrose transform allows us to describe free bulk fields, with or without mass, in terms of data on twistor space. Explicit representatives for the bulk-to-boundary propagators of scalars and spinors are constructed, along with twistor action functionals for the free theories. Evaluating these twistor actions on bulk-to-boundary propagators is shown to produce the correct two-point functions.

  4. α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.

    Directory of Open Access Journals (Sweden)

    Tiina Maria Pirttimaki

    Full Text Available It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ, the toxic trigger for Alzheimer's disease (AD, interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs. Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT. The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.

  5. F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting A{beta} aggregates in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Wei [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Oya, Shunichi [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung Meiping [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Hou, Catherine [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Maier, Donna L. [Department of Neuroscience, AstraZeneca, Wilmington, DE 19850 (United States); Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States) and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)]. E-mail: kunghf@sunmac.spect.upenn.edu

    2005-11-01

    This paper describes a novel series of {sup 18}F-labeled polyethyleneglycol (PEG)-stilbene derivatives as potential {beta}-amyloid (A{beta}) plaque-specific imaging agents for positron emission tomography (PET). In these series of compounds, {sup 18}F is linked to the stilbene through a PEG chain, of which the number of ethoxy groups ranges from 2 to 5. The purpose of adding PEG groups is to lower the lipophilicity and improve bioavailability. The syntheses of the 'cold' compounds and the {sup 18}F-labeled PEG stilbene derivatives are successfully achieved. All of the fluorinated stilbenes displayed high binding affinities in an assay using postmortem AD brain homogenates (K {sub i}=2.9-6.7 nM). Labeling was successfully performed by a substitution of the mesylate group of 10a-d by [{sup 18}F]fluoride giving the target compounds [{sup 18}F]12a-d (EOS, specific activity, 900-1500 Ci/mmol; radiochemical purity >99%). In vivo biodistribution of these novel {sup 18}F ligands in normal mice exhibited excellent brain penetrations and rapid washouts after an intravenous injection (6.6-8.1 and 1.2-2.6% dose/g at 2 and 60 min, respectively). Autoradiography of postmortem AD brain sections of [{sup 18}F]12a-d confirmed the specific binding related to the presence of A{beta} plaques. In addition, in vivo plaque labeling can be clearly demonstrated with these {sup 18}F-labeled agents in transgenic mice (Tg2576), a useful animal model for Alzheimer's disease. In conclusion, the preliminary results strongly suggest these fluorinated PEG stilbene derivatives are suitable candidates as A{beta} plaque imaging agents for studying patients with Alzheimer's disease.

  6. Skil problemerne ad

    DEFF Research Database (Denmark)

    Kaspersen, Peter

    2007-01-01

    På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger.......På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger....

  7. Probing crunching AdS cosmologies

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S. Prem; Vaganov, Vladislav [Department of Physics, Swansea University,Singleton Park, Swansea SA2 8PP (United Kingdom)

    2016-02-03

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of N=8 supergravity on AdS{sub 4}, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor ã{sub max}. Radial geodesics connecting antipodal points necessarily have de Sitter energy E≲ã{sub max}, while geodesics with E>ã{sub max} terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved “outward” in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green’s function has a branch point determined by ã{sub max} which corresponds to the lowest quasinormal frequency.

  8. Progranulin gene delivery reduces plaque burden and synaptic atrophy in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Van Kampen, Jackalina M; Kay, Denis G

    2017-01-01

    Progranulin (PGRN) is a multifunctional protein that is widely expressed throughout the brain, where it has been shown to act as a critical regulator of CNS inflammation and also functions as an autocrine neuronal growth factor, important for long-term neuronal survival. PGRN has been shown to activate cell signaling pathways regulating excitoxicity, oxidative stress, and synaptogenesis, as well as amyloidogenesis. Together, these critical roles in the CNS suggest that PGRN has the potential to be an important therapeutic target for the treatment of various neurodegenerative disorders, particularly Alzheimer's disease (AD). AD is the leading cause of dementia and is marked by the appearance of extracellular plaques consisting of aggregates of amyloid-β (Aβ), as well as neuroinflammation, oxidative stress, neuronal loss and synaptic atrophy. The ability of PGRN to target multiple key features of AD pathophysiology suggests that enhancing its expression may benefit this disease. Here, we describe the application of PGRN gene transfer using in vivo delivery of lentiviral expression vectors in a transgenic mouse model of AD. Viral vector delivery of the PGRN gene effectively enhanced PGRN expression in the hippocampus of Tg2576 mice. This elevated PGRN expression significantly reduced amyloid plaque burden in these mice, accompanied by reductions in markers of inflammation and synaptic atrophy. The overexpression of PGRN was also found to increase activity of neprilysin, a key amyloid beta degrading enzyme. PGRN regulation of neprilysin activity could play a major role in the observed alterations in plaque burden. Thus, PGRN may be an effective therapeutic target for the treatment of AD.

  9. Mobile ad hoc networking

    CERN Document Server

    John Wiley & Sons

    2004-01-01

    "Assimilating the most up-to-date information on research and development activities in this rapidly growing area, Mobile Ad Hoc Networking covers physical, data link, network, and transport layers, as well as application, security, simulation, and power management issues in sensor, local area, personal, and mobile ad hoc networks. Each of the book's sixteen chapters has been written by a top expert and discusses in-depth the most important topics in the field. Mobile Ad Hoc Networking is an excellent reference and guide for professionals seeking an in-depth examination of topics that also provides a comprehensive overview of the current state-of-the-art."--Jacket.

  10. Antiproton-Decelerator (AD)

    CERN Multimedia

    Laurent Guiraud

    1998-01-01

    When the Low-Energy Antiproton Ring (LEAR) was stopped in 1996, because of its costly operation, a cheaper way of continuing low-energy antiproton physics was sought. The Antiproton-Collector (AC), added in 1987 to the Antiproton Accumulator (AA) to provide a tenfold intensity increase, was converted into the Antiproton-Decelerator (AD). Antiprotons from the target at 3.5 GeV/c are decelerated to 100 MeV/c, and fast-ejected to the experiments. Major changes were necessary. Above all, the conversion from a constant-field machine to one with a magnetic cycle, modulating the field by an impressive factor 35. New systems for stochastic and electron cooling had to be added. Beam diagnostics at an intensity of only 2E7 antiprotons was a challenge. In 2000, the AD began delivery of antiprotons to the experiments.

  11. Effects of oral aluminum exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Ribes, D; Colomina, M T; Vicens, P; Domingo, J L

    2008-12-01

    The effects of a very low oral dose of Al on spatial learning and neurogenesis were evaluated in a transgenic mouse (Tg 2576) model of Alzheimer disease. At 5 months of age, wild and Tg 2576 mice received a diet supplemented with Al lactate at 0 and 1 mg/g of diet for 120 days. The experimental groups (n=7-8) were: control wild, Al-treated wild, control transgenic, and Al-treated transgenic. After 3 months of Al exposure, activity in an open-field and learning in a water maze were evaluated. At the end of the behavioral testing, in order to study cell proliferation and differentiation in the hippocampus, mice were injected with 5-bromo-2-deoxyuridine (BrdU) and sacrificed 1 or 28 days after the last BrdU injection. Tg 2576 mice were impaired in both acquisition and retention of the water maze task, showing higher amounts of beta-amyloid fragments in brain. Aluminum exposure impaired learning and memory in wild mice and increased the total number of proliferating cells in the dentate gyrus of hippocampus. The low Al doses here experimented suggest that this element might impair cognition in the general population at doses comparable to current levels of human exposure. Although these doses are not enough to interact with the amyloidogenic pathway, an increase in cell proliferation can indicate a reactive response of the brain to Al insult. Further investigations should be performed to corroborate the effects observed at very low doses of Al and to study the potential effects derived from a longer exposure period.

  12. Minocycline reduces spontaneous hemorrhage in mouse models of cerebral amyloid angiopathy.

    Science.gov (United States)

    Yan, Ping; Zhu, Alec; Liao, Fan; Xiao, Qingli; Kraft, Andrew; Gonzales, Ernie; Perez, Ron; Greenberg, Steven M; Holtzman, David; Lee, Jin-Moo

    2015-06-01

    Cerebral amyloid angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine whether spontaneous intracerebral hemorrhage could be reduced. Tg2576 (n=16) and 5xFAD/ApoE4 knockin mice (n=16), aged 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, IP) or saline every other day for 2 months. Brains were extracted and stained with X-34 (to quantify amyloid), Perls' blue (to quantify hemorrhage), and immunostained to examined β-amyloid peptide load, gliosis (glial fibrillary acidic protein [GFAP], Iba-1), and vascular markers of blood-brain barrier integrity (zonula occludins-1 [ZO-1] and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes. Minocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5xFAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (matrix metalloproteinase-9, NOX4, CD45, S-100b, and Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls. Minocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in 2 different mouse models of CAA, supporting the importance of matrix metalloproteinase-related and inflammatory pathways in intracerebral hemorrhage pathogenesis. As a Food and Drug Administration-approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related intracerebral hemorrhage. © 2015 American

  13. Dynamic ad hoc networks

    CERN Document Server

    Rashvand, Habib

    2013-01-01

    Motivated by the exciting new application paradigm of using amalgamated technologies of the Internet and wireless, the next generation communication networks (also called 'ubiquitous', 'complex' and 'unstructured' networking) are changing the way we develop and apply our future systems and services at home and on local, national and global scales. Whatever the interconnection - a WiMAX enabled networked mobile vehicle, MEMS or nanotechnology enabled distributed sensor systems, Vehicular Ad hoc Networking (VANET) or Mobile Ad hoc Networking (MANET) - all can be classified under new networking s

  14. Adding and Deleting Images

    Science.gov (United States)

    Images are added via the Drupal WebCMS Editor. Once an image is uploaded onto a page, it is available via the Library and your files. You can edit the metadata, delete the image permanently, and/or replace images on the Files tab.

  15. What Value "Value Added"?

    Science.gov (United States)

    Richards, Andrew

    2015-01-01

    Two quantitative measures of school performance are currently used, the average points score (APS) at Key Stage 2 and value-added (VA), which measures the rate of academic improvement between Key Stage 1 and 2. These figures are used by parents and the Office for Standards in Education to make judgements and comparisons. However, simple…

  16. Adding an extra storey

    DEFF Research Database (Denmark)

    Engelmark, Jesper; Dahl, Torben; Melgaard, Ebbe

    2007-01-01

    of them had to be renovated after a shorter period. In stead of just replacing the original roof with a new one, it is now a days rather common to ad an extra storey where that is possible according to local planning. The reason is as a rule based on economical benefits, but very often this extra storey...

  17. Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is stimulus-dependent

    DEFF Research Database (Denmark)

    Hartlage-Rübsamen, Maike; Zeitschel, Ulrike; Apelt, Jenny

    2003-01-01

    The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental...... paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1-immunoreactive astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients....

  18. Ads in Indonesia

    Directory of Open Access Journals (Sweden)

    Wulan Roro Retno

    2017-01-01

    Full Text Available Cosmetics industry created the beauty myth for women through advertising. A cosmetic ad in Indonesia has spread a new concept of white skin: East Asia beauty myth. The white concept of Asia white skin basically derived from colonial legacy. The purpose of the research was analyzing the beauty myth in Indonesia ads using postcolonial perspective. The principal result brought the discourse analysis and postcolonial perspective a new insight in communication research. Particularly on media and cultural studies. Major conclusions showed that the beauty myth since the Dutch colonial period never been change. The main concept is always in colonialism’s idea: “white is better”. The West is better than the East.

  19. Management job ads

    DEFF Research Database (Denmark)

    Holmgreen, Lise-Lotte

    2014-01-01

    jobs by discursively constructing job ads that appeal to both sexes. This argument is part of the broader field of corporate social responsibility, corporate citizenship, and stakeholder management, which involves discussions of the obligations of corporations to acknowledge and mitigate......The article asks whether it is not the responsibility of corporations to address the issue of women being underrepresented in Danish management jobs. In other words, it is argued that corporations should be encouraged to engage more actively in the recruitment of both men and women for management...... the increasingly widespread impact that their activities have on communities and social structures. The article emphasises the need for more active engagement on the part of corporations by analysing the discursive construction of preferred candidates in a small sample of Danish management job ads. By means...

  20. Philosophia ad bellum

    Directory of Open Access Journals (Sweden)

    Yu. O. Loboda

    2014-06-01

    Full Text Available In the paper «Philosophia ad bellum» is being realized an attempt to classify philosophic approaches to the study of phenomenon of war by the analogy with the structure of «Just war theory» – 1. Philosophia ad bellum – «philosophy for war», where are investigated ways of using of philosophic methods of cognition in applied military sciences; 2. Philosophia supra bello – «philosophy above war», which investigates world­view, historic­philosophic, existential, logic­epistemological aspects of war; 3. Philosophia contra belli – «philosophy against war», where research of the essence of war gets its logical conclusion in grounding of the absurdity of thinking schemes which justify war as an act of violence. In the article was made historic­philosophic overview of the part «Philosophia ad bellum», where were showed tangent questions, which are considered by philosophic logic and theory of strategic intelligence. It was stated, that specialists if military intelligence admit the important role of researches in logic and theory of cognition in their professional work; were defined basic questions, which have the most essential interest for military professionals. There were analyzed ways of using of philosophic methods in developing military strategies, was made a conclusion that philosophy can be a basis of strategic failures and victories as well.

  1. Hod mice and the mouse set conjecture

    CERN Document Server

    Sargsyan, Grigor

    2015-01-01

    The author develops the theory of Hod mice below AD_{\\mathbb{R}}+ "\\Theta is regular". He uses this theory to show that HOD of the minimal model of AD_{\\mathbb{R}}+ "\\Theta is regular" satisfies GCH. Moreover, he shows that the Mouse Set Conjecture is true in the minimal model of AD_{\\mathbb{R}}+ "\\Theta is regular".

  2. AdS 3-manifolds and Higgs bundles

    DEFF Research Database (Denmark)

    Alessandrini, Daniele; Li, Qiongling

    2017-01-01

    In this paper we investigate the relationships between closed AdS $3$-manifolds and Higgs bundles. We have a new way to construct AdS structures that allows us to see many of their properties explicitly, for example we can recover the very recent formula by Tholozan for their volume. We give natu...

  3. Dressing phases of AdS3/CFT2

    NARCIS (Netherlands)

    Borsato, R.; Olsson Sax, O.E.; Sfondrini, A.; Stefanski, B.; Torrielli, A.

    2013-01-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3×S3×T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones

  4. Rapamycin promotes β-amyloid production via ADAM-10 inhibition

    Science.gov (United States)

    Zhang, Sheqing; Salemi, Jon; Hou, Huayan; Zhu, Yuyan; Mori, Takashi; Giunta, Brian; Obregon, Demian; Tan, Jun

    2010-01-01

    Rapamycin is a well known immunosuppressant drug for rejection prevention in organ transplantation. Numerous clinical trials using rapamycin analogs, involving both children and adults with various disorders are currently ongoing worldwide. Most recently, rapamycin gained much attention for what appears to be life-span extending properties when administered to mice. The risk for Alzheimer disease (AD) is strongly and positively correlated with advancing age and is characterized by deposition of β-amyloid peptides (Aβ) as senile plaques in the brain. We report that rapamycin (2.5 μM), significantly increases Aβ generation in murine neuron-like cells (N2a) transfected with the human “Swedish” mutant amyloid precursor protein (APP). In concert with these observations, we found rapamycin significantly decreases the neuroprotective amino-terminal APP (amyloid precursor protein) cleavage product, soluble APP-α (sAPP-α) while increasing production of the β-carboxyl-terminal fragment of APP (β-CTF). These cleavage events are associated with decreased activation of a disintegrin and metallopeptidase domain-10 (ADAM-10), an important candidate α-secretase which opposes Aβ generation. To validate these findings in vivo, we intraperitoneal (i.p.) injected Tg2576 Aβ-overproducing transgenic mice with rapamycin (3 mg/kg/day) for 2 weeks. We found increased Aβ levels associated with decreased sAPP-α at an average rapamycin plasma concentration of 169.7 ± 23.5 ng/mL by high performance liquid chromatography (HPLC). These data suggest that although rapamycin may increase the lifespan in some mouse models, it may not decrease the risk for age-associated neurodegenerative disorders such as AD. PMID:20542014

  5. A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.

    Science.gov (United States)

    Spencer, Brian; Verma, Inder; Desplats, Paula; Morvinski, Dinorah; Rockenstein, Ed; Adame, Anthony; Masliah, Eliezer

    2014-06-20

    Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Value-Added Exchange Rates

    OpenAIRE

    Rudolfs Bems; Robert C. Johnson

    2012-01-01

    This paper updates the conceptual foundations for measuring real effective exchange rates (REERs) to allow for vertical specialization in trade. We derive a value-added REER describing how demand for the value added that a country produces changes as the price of its value added changes relative to competitors. We then compute this index for 42 countries from 1970-2009 using trade measured in value added terms and GDP deflators. There are substantial differences between value-added and conven...

  7. Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Hong-Chuan Yang

    2007-01-01

    Full Text Available We study the energy-efficient configuration of multihop paths with automatic repeat request (ARQ mechanism in wireless ad hoc networks. We adopt a cross-layer design approach and take both the quality of each radio hop and the battery capacity of each transmitting node into consideration. Under certain constraints on the maximum tolerable transmission delay and the required packet delivery ratio, we solve optimization problems to jointly schedule the transmitting power of each transmitting node and the retransmission limit over each hop. Numerical results demonstrate that the path configuration methods can either significantly reduce the average energy consumption per packet delivery or considerably extend the average lifetime of the multihop route.

  8. Hypothetical atopic dermatitis-myeloproliferative neoplasm (AD-MPN syndrome

    Directory of Open Access Journals (Sweden)

    Toshiaki eKawakami

    2015-08-01

    Full Text Available Atopic dermatitis (AD is a chronic inflammatory skin disease. Myeloproliferative neoplasms (MPNs are hematopoietic malignancies caused by uncontrolled proliferation of hematopoietic stem/progenitor cells. Recent studies have described several mutant mice exhibiting both AD-like skin inflammation and MPN. Common pathways for skin inflammation encompass overexpression of thymic stromal lymphopoietin and reduced signaling of epidermal growth factor receptor in the epidermis, while overproduction of granulocyte-colony stimulating factor by keratinocytes and constitutive activation of Stat5 in hematopoietic stem cells are important for the development of MPN. The murine studies suggest the existence of a similar human disease tentatively termed the AD-MPN syndrome.

  9. Value Added in English Schools

    OpenAIRE

    Andrew Ray; Tanya McCormack; Helen Evans

    2009-01-01

    Value-added indicators are now a central part of school accountability in England, and value-added information is routinely used in school improvement at both the national and the local levels. This article describes the value-added models that are being used in the academic year 2007–8 by schools, parents, school inspectors, and other professionals in local and national governments. The article outlines the development of value-added models in England following the introduction of national t...

  10. Value Added in English Schools

    Science.gov (United States)

    Ray, Andrew; McCormack, Tanya; Evans, Helen

    2009-01-01

    Value-added indicators are now a central part of school accountability in England, and value-added information is routinely used in school improvement at both the national and the local levels. This article describes the value-added models that are being used in the academic year 2007-8 by schools, parents, school inspectors, and other…

  11. AdS Black Hole with Phantom Scalar Field

    Directory of Open Access Journals (Sweden)

    Limei Zhang

    2017-01-01

    Full Text Available We present an AdS black hole solution with Ricci flat horizon in Einstein-phantom scalar theory. The phantom scalar fields just depend on the transverse coordinates x and y, which are parameterized by the parameter α. We study the thermodynamics of the AdS phantom black hole. Although its horizon is a Ricci flat Euclidean space, we find that the thermodynamical properties of the black hole solution are qualitatively the same as those of AdS Schwarzschild black hole. Namely, there exists a minimal temperature and the large black hole is thermodynamically stable, while the smaller one is unstable, so there is a so-called Hawking-Page phase transition between the large black hole and the thermal gas solution in the AdS space-time in Poincare coordinates. We also calculate the entanglement entropy for a strip geometry dual to the AdS phantom black holes and find that the behavior of the entanglement entropy is qualitatively the same as that of the black hole thermodynamical entropy.

  12. Revisiting the thermodynamic relations in AdS /CMT models

    Science.gov (United States)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2017-03-01

    Motivated by the recent unified approach to the Smarr-like relation of anti-de Sitter (AdS) planar black holes in conjunction with the quasilocal formalism on conserved charges, we revisit the quantum statistical and thermodynamic relations of hairy AdS planar black holes. By extending the previous results, we identify the hairy contribution in the bulk and show that the holographic computation can be improved so that it is consistent with the bulk computation. We argue that the first law can be retained in its universal form and that the relation between the on-shell renormalized Euclidean action and its free energy interpretation in gravity may also be undeformed even with the hairy contribution in hairy AdS black holes.

  13. Asymptotically AdS spacetimes with a timelike Kasner singularity

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jie [Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel)

    2016-07-21

    Exact solutions to Einstein’s equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution’s appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  14. Centella asiatica Attenuates Mitochondrial Dysfunction and Oxidative Stress in Aβ-Exposed Hippocampal Neurons

    Science.gov (United States)

    Zweig, Jonathan A.; Matthews, Donald G.; Caruso, Maya; Quinn, Joseph F.; Soumyanath, Amala

    2017-01-01

    Centella asiatica has been used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) protects against the deleterious effects of amyloid-β (Aβ) in neuroblastoma cells and attenuates Aβ-induced cognitive deficits in mice. Yet, the neuroprotective mechanism of CAW has yet to be thoroughly explored in neurons from these animals. This study investigates the effects of CAW on neuronal metabolism and oxidative stress in isolated Aβ-expressing neurons. Hippocampal neurons from amyloid precursor protein overexpressing Tg2576 mice and wild-type (WT) littermates were treated with CAW. In both genotypes, CAW increased the expression of antioxidant response genes which attenuated the Aβ-induced elevations in reactive oxygen species (ROS) and lipid peroxidation in Tg2576 neurons. CAW also improved mitochondrial function in both genotypes and increased the expression of electron transport chain enzymes and mitochondrial labeling, suggesting an increase in mitochondrial content. These data show that CAW protects against mitochondrial dysfunction and oxidative stress in Aβ-exposed hippocampal neurons which could contribute to the beneficial effects of the extract observed in vivo. Since CAW also improved mitochondrial function in the absence of Aβ, these results suggest a broader utility for other conditions where neuronal mitochondrial dysfunction occurs. PMID:28883904

  15. Affinity of nat/68Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers

    Directory of Open Access Journals (Sweden)

    Sara Rubagotti

    2016-09-01

    Full Text Available Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer’s disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide. Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three nat/68Ga-labelled curcumin analogues, namely curcumin curcumin (CUR, bis-dehydroxy-curcumin (bDHC and diacetyl-curcumin (DAC, was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of 68Ga(CUR2+, 68Ga(DAC2+, and 68Ga(bDHC2+ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood–brain barrier. Like curcumin, all nat/68Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo.

  16. Holography in Lovelock Chern-Simons AdS gravity

    Science.gov (United States)

    Cvetković, Branislav; Miskovic, Olivera; Simić, Dejan

    2017-08-01

    We analyze holographic field theory dual to Lovelock Chern-Simons anti-de Sitter (AdS) gravity in higher dimensions using first order formalism. We first find asymptotic symmetries in the AdS sector showing that they consist of local translations, local Lorentz rotations, dilatations and non-Abelian gauge transformations. Then, we compute 1-point functions of energy-momentum and spin currents in a dual conformal field theory and write Ward identities. We find that the holographic theory possesses Weyl anomaly and also breaks non-Abelian gauge symmetry at the quantum level.

  17. AdS5 magnetized solutions in minimal gauged supergravity

    Science.gov (United States)

    Blázquez-Salcedo, Jose Luis; Kunz, Jutta; Navarro-Lérida, Francisco; Radu, Eugen

    2017-08-01

    We construct a generalization of the AdS charged rotating black holes with two equal magnitude angular momenta in five-dimensional minimal gauged supergravity. In addition to the mass, electric charge and angular momentum, the new solutions possess an extra-parameter associated with a non-zero magnitude of the magnetic potential at infinity. In contrast with the known cases, these new black holes possess a non-trivial zero-horizon size limit which describes a one parameter family of spinning charged solitons. All configurations reported in this work approach asymptotically an AdS5 spacetime in global coordinates and are free of pathologies.

  18. AdS5 magnetized solutions in minimal gauged supergravity

    Directory of Open Access Journals (Sweden)

    Jose Luis Blázquez-Salcedo

    2017-08-01

    Full Text Available We construct a generalization of the AdS charged rotating black holes with two equal magnitude angular momenta in five-dimensional minimal gauged supergravity. In addition to the mass, electric charge and angular momentum, the new solutions possess an extra-parameter associated with a non-zero magnitude of the magnetic potential at infinity. In contrast with the known cases, these new black holes possess a non-trivial zero-horizon size limit which describes a one parameter family of spinning charged solitons. All configurations reported in this work approach asymptotically an AdS5 spacetime in global coordinates and are free of pathologies.

  19. Loops in AdS from conformal field theory

    Science.gov (United States)

    Aharony, Ofer; Alday, Luis F.; Bissi, Agnese; Perlmutter, Eric

    2017-07-01

    We propose and demonstrate a new use for conformal field theory (CFT) crossing equations in the context of AdS/CFT: the computation of loop amplitudes in AdS, dual to non-planar correlators in holographic CFTs. Loops in AdS are largely unexplored, mostly due to technical difficulties in direct calculations. We revisit this problem, and the dual 1 /N expansion of CFTs, in two independent ways. The first is to show how to explicitly solve the crossing equations to the first subleading order in 1 /N 2, given a leading order solution. This is done as a systematic expansion in inverse powers of the spin, to all orders. These expansions can be resummed, leading to the CFT data for finite values of the spin. Our second approach involves Mellin space. We show how the polar part of the four-point, loop-level Mellin amplitudes can be fully reconstructed from the leading-order data. The anomalous dimensions computed with both methods agree. In the case of ϕ 4 theory in AdS, our crossing solution reproduces a previous computation of the one-loop bubble diagram. We can go further, deriving the four-point scalar triangle diagram in AdS, which had never been computed. In the process, we show how to analytically derive anomalous dimensions from Mellin amplitudes with an infinite series of poles, and discuss applications to more complicated cases such as the N = 4 super-Yang-Mills theory.

  20. Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Subash, Selvaraju; Essa, Musthafa Mohamed; Braidy, Nady; Awlad-Thani, Kathyia; Vaishnav, Ragini; Al-Adawi, Samir; Al-Asmi, Abdullah; Guillemin, Gilles J

    2015-01-01

    At present, the treatment options available to delay the onset or slow down the progression of Alzheimer's disease (AD) are not effective. Recent studies have suggested that diet and lifestyle factors may represent protective strategies to minimize the risk of developing AD. Date palm fruits are a good source of dietary fiber and are rich in total phenolics and natural antioxidants, such as anthocyanins, ferulic acid, protocatechuic acid and caffeic acid. These polyphenolic compounds have been shown to be neuroprotective in different model systems. We investigated whether dietary supplementation with 2% and 4% date palm fruits (grown in Oman) could reduce cognitive and behavioral deficits in a transgenic mouse model for AD (amyloid precursor protein [APPsw]/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% date fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in all the animals at the age of 4 months and after 14 months of treatment using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. We have also analyzed the levels of amyloid beta (Aβ) protein (1-40 and 1-42) in plasma of control and experimental animals. Standard diet-fed Tg mice showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination when compared to wild-type on the same diet and Tg mice fed 2% and 4% date supplementation at the age of 18 months. The levels of both Aβ proteins were significantly lowered in date fruits supplemented groups than the Tg mice without the diet supplement. The neuroprotective effect offered by 4% date fruits diet to AD mice is higher than 2% date fruits diet. Our results suggest that date fruits dietary supplementation may have beneficial effects in lowering the

  1. Black Hole Astrophysics in AdS Braneworlds

    CERN Document Server

    Emparan, R; Kaloper, Nemanja; Emparan, Roberto; Garcia-Bellido, Juan; Kaloper, Nemanja

    2003-01-01

    We consider astrophysics of large black holes localized on the brane in the infinite Randall-Sundrum model. Using their description in terms of a conformal field theory (CFT) coupled to gravity, deduced in Ref. [1], we show that they undergo a period of rapid decay via Hawking radiation of CFT modes. For example, a black hole of mass ${\\rm few} \\times M_\\odot$ would shed most of its mass in $\\sim 10^4 - 10^5$ years if the AdS radius is $L \\sim 10^{-1}$ mm, currently the upper bound from table-top experiments. Since this is within the mass range of X-ray binary systems containing a black hole, the evaporation enhanced by the hidden sector CFT modes could cause the disappearance of X-ray sources on the sky. This would be a striking signature of RS2 with a large AdS radius. Alternatively, for shorter AdS radii, the evaporation would be slower. In such cases, the persistence of X-ray binaries with black holes already implies an upper bound on the AdS radius of $L \\la 10^{-2}$ mm, an order of magnitude better than...

  2. Logarithmic AdS waves and Zwei-Dreibein gravity

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Goya, Andres F.; Merbis, Wout; Rosseel, Jan

    2014-01-01

    We show that the parameter space of Zwei-Dreibein Gravity (ZDG) in AdS(3) exhibits critical points, where massive graviton modes coincide with pure gauge modes and new 'logarithmic' modes appear, similar to what happens in New Massive Gravity. The existence of critical points is shown both at the

  3. Internet Advertising. Google AdWords versus Facebook Ads

    OpenAIRE

    Paul PAŞCU

    2014-01-01

    This article describes how to use the applications for Internet advertising, Google AdWords and Facebook Ads. Our attempt is to present the advantages and disadvantages of each of them, the costs and benefits, a useful aspect for companies that plan to start advertising campaigns on the Internet.

  4. Internet Advertising. Google AdWords versus Facebook Ads

    Directory of Open Access Journals (Sweden)

    Paul PAŞCU

    2014-05-01

    Full Text Available This article describes how to use the applications for Internet advertising, Google AdWords and Facebook Ads. Our attempt is to present the advantages and disadvantages of each of them, the costs and benefits, a useful aspect for companies that plan to start advertising campaigns on the Internet.

  5. Ultraviolet asymptotics for quasiperiodic AdS_4 perturbations

    CERN Document Server

    Craps, Ben; Jai-akson, Puttarak; Vanhoof, Joris

    2015-01-01

    Spherically symmetric perturbations in AdS-scalar field systems of small amplitude epsilon approximately periodic on time scales of order 1/epsilon^2 (in the sense that no significant transfer of energy between the AdS normal modes occurs) have played an important role in considerations of AdS stability. They are seen as anchors of stability islands where collapse of small perturbations to black holes does not occur. (This collapse, if it happens, typically develops on time scales of the order 1/epsilon^2.) We construct an analytic treatment of the frequency spectra of such quasiperiodic perturbations, paying special attention to the large frequency asymptotics. For the case of a self-interacting phi^4 scalar field in a non-dynamical AdS background, we arrive at a fairly complete analytic picture involving quasiperiodic spectra with an exponential suppression modulated by a power law at large mode numbers. For the case of dynamical gravity, the structure of the large frequency asymptotics is more complicated....

  6. Radiosynthesis and evaluation of [{sup 11}C]BTA-1 and [{sup 11}C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of {beta}-amyloid plaques

    Energy Technology Data Exchange (ETDEWEB)

    Neumaier, B.; Deisenhofer, S.; Fuerst, D.; Thees, S.; Buck, A.K.; Glatting, G.; Landwehrmeyer, G.B.; Krause, B.J.; Reske, S.N.; Mottaghy, F.M. [Dept. of Nuclear Medicine, Univ. Hospital Ulm (Germany); Arnim, C.A.F. von [Dept. of Neurology, Univ. Hospital Ulm (Germany); Mueller, H.D.; Sommer, C. [Dept. of Neuropathology, Univ. of Mainz (Germany)

    2007-07-01

    Aim: To evaluate the in vitro and in vivo characteristics of [N-methyl-{sup 11}C]2-(4'-(methylaminophenyl))-benzothiazole ([{sup 11}C]BTA-1) as well as [N-methyl-{sup 11}C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([{sup 11}C]3'-Me-BTA-1) as diagnostic markers of amyloid-{beta} (A{beta}) in Alzheimer's disease (AD). Material, methods: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K{sub i}) of [{sup 11}C]BTA-1 and [{sup 11}C]3'-Me-BTA-1 for aggregated A{beta}(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [{sup 11}C]BTA-1 PET study of an AD patient and a healthy control was performed. Results: In mice brain uptake and clearance of [{sup 11}C]BTA-1 is compatible with the half life of {sup 11}C (2 min: 12.7% ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [{sup 11}C]3'-Me-BTA-1 is too slow (2 mm 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K{sub i} of [{sup 11}C]BTA-1 is 11 nmol/l and that of [{sup 11}C]3'-Me-BTA-1 27 nmol/l. Both radioligands label A{beta} selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of A{beta} plaques. The AD patient has a higher pre-frontal, parietal and striatal [{sup 11}C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [{sup 11}C]BTA-1 after 30min in plasma. [{sup 11}C]BTA-1 is favourable for in vivo imaging of A{beta} due to its rapid brain entry, sufficient clearance and good binding affinity for A{beta}. Conclusion: The ability to label A{beta} plaques in vivo in human subjects supports the suitability of [{sup 11}C]BTA-1 as a plaque imaging agent. (orig.)

  7. Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: a cross-sectional study.

    Science.gov (United States)

    Stevens, Leanne M; Brown, Richard E

    2015-02-01

    Impairments in working memory (WM) can predict the shift from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the rate at which AD progresses with age. The 3xTg-AD mouse model develops both Aβ plaques and neurofibrillary tangles, the neuro-pathological hallmarks of AD, by 6 months of age, but no research has investigated the age-related changes in WM in these mice. Using a cross-sectional design, we tested male and female 3xTg-AD and wildtype control (B6129SF2/J) mice between 2 and 15 months of age for reference and working memory errors in the 8-arm radial maze. The 3xTg-AD mice had deficits in both working and reference memory across the ages tested, rather than showing the predicted age-related memory deficits. Male 3xTg-AD mice showed more working and reference memory errors than females, but there were no sex differences in wildtype control mice. These results indicate that the 3xTg-AD mouse replicates the impairments in WM found in patients with AD. However, these mice show memory deficits as early as two months of age, suggesting that the genes underlying reference and working memory in these mice cause deficits from an early age. The finding that males were affected more than females suggests that more attention should be paid to sex differences in transgenic AD mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. AdS sub 2 supergravity and superconformal quantum mechanics

    CERN Document Server

    Astorino, M; Klemm, D; Zanon, D

    2003-01-01

    We investigate the asymptotic dynamics of topological anti-de Sitter supergravity in two dimensions. Starting from the formulation as a BF theory, it is shown that the AdS sub 2 boundary conditions imply that the asymptotic symmetries form a super-Virasoro algebra. Using the central charge of this algebra in Cardy's formula, we exactly reproduce the thermodynamical entropy of AdS sub 2 black holes. Furthermore, we show that the dynamics of the dilaton and its superpartner reduces to that of superconformal transformations that leave invariant one chiral component of the stress tensor supercurrent of a two-dimensional conformal field theory. This dynamics is governed by a supersymmetric extension of the de Alfaro-Fubini-Furlan model of conformal quantum mechanics. Finally, two-dimensional de Sitter gravity is also considered, and the dS sub 2 entropy is computed by counting CFT states.

  9. Entropy function and attractors for AdS black holes

    CERN Document Server

    Morales, J F; Morales, Jose F.; Samtleben, Henning

    2006-01-01

    We apply Sen's entropy formalism to the study of the near horizon geometry and the entropy of asymptotically AdS black holes in gauged supergravities. In particular, we consider non-supersymmetric electrically charged black holes with AdS_2 xS^{d-2} horizons in U(1)^4 and U(1)^3 gauged supergravities in d=4 and d=5 dimensions, respectively. We study several cases including static/rotating, BPS and non-BPS black holes in Einstein as well as in Gauss-Bonnet gravity. In all examples, the near horizon geometry and black hole entropy are derived by extremizing the entropy function and are given entirely in terms of the gauge coupling, the electric charges and the angular momentum of the black hole.

  10. AdS gravity and the scalar glueball spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Vento, Vicente [Departament de Fisica Teorica, Universitat de Valencia y Institut de Fisica Corpuscular, Consejo Superior de Investigaciones Cientificas, Burjassot (Valencia) (Spain)

    2017-09-15

    The scalar glueball spectrum has attracted much attention since the formulation of Quantum Chromodynamics. Different approaches give very different results for the glueball masses. We revisit the problem from the perspective of the AdS/CFT correspondence. (orig.)

  11. The Mixed Phase of Charged AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Piyabut Burikham

    2016-01-01

    Full Text Available We study the mixed phase of charged AdS black hole and radiation when the total energy is fixed below the threshold to produce a stable charged black hole branch. The coexistence conditions for the charged AdS black hole and radiation are derived for the generic case when radiation particles carry charge. The phase diagram of the mixed phase is demonstrated for both fixed potential and charge ensemble. In the dual gauge picture, they correspond to the mixed phase of quark-gluon plasma (QGP and hadron gas in the fixed chemical potential and density ensemble, respectively. In the nuclei and heavy-ion collisions at intermediate energies, the mixed phase of exotic QGP and hadron gas could be produced. The mixed phase will condense and evaporate into the hadron gas as the fireball expands.

  12. Conserved higher-spin charges in AdS4

    Directory of Open Access Journals (Sweden)

    O.A. Gelfond

    2016-03-01

    Full Text Available Gauge invariant conserved conformal currents built from massless fields of all spins in 4d Minkowski space–time and AdS4 are described in the unfolded dynamics approach. The current cohomology associated with non-zero conserved charges is found. The resulting list of charges is shown to match the space of parameters of the conformal higher-spin symmetry algebra in four dimensions.

  13. Generalised structures for N=1 AdS backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Coimbra, André [Institut für Theoretische Physik & Center for Quantum Engineering and Spacetime Research,Leibniz Universität Hannover,Appelstraße 2, 30167 Hannover (Germany); Strickland-Constable, Charles [Institut de physique théorique, Université Paris Saclay, CEA, CNRS, Orme des Merisiers, F-91191 Gif-sur-Yvette (France)

    2016-11-16

    We expand upon a claim made in a recent paper [http://arxiv.org/abs/1411.5721] that generic minimally supersymmetric AdS backgrounds of warped flux compactifications of Type II and M theory can be understood as satisfying a straightforward weak integrability condition in the language of E{sub d(d)}×ℝ{sup +} generalised geometry. Namely, they are spaces admitting a generalised G-structure set by the Killing spinor and with constant singlet generalised intrinsic torsion.

  14. ADS Bumblebee comes of age

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, Michael J.; Henneken, Edwin; Grant, Carolyn S.; Thompson, Donna M.; Chyla, Roman; McDonald, Steven; Shaulis, Taylor J.; Blanco-Cuaresma, Sergi; Shapurian, Golnaz; Hostetler, Timothy W.; Templeton, Matthew R.; Lockhart, Kelly E.

    2018-01-01

    The ADS Team has been working on a new system architecture and user interface named “ADS Bumblebee” since 2015. The new system presents many advantages over the traditional ADS interface and search engine (“ADS Classic”). A new, state of the art search engine features a number of new capabilities such as full-text search, advanced citation queries, filtering of results and scalable analytics for any search results. Its services are built on a cloud computing platform which can be easily scaled to match user demand. The Bumblebee user interface is a rich javascript application which leverages the features of the search engine and integrates a number of additional visualizations such as co-author and co-citation networks which provide a hierarchical view of research groups and research topics, respectively. Displays of paper analytics provide views of the basic article metrics (citations, reads, and age). All visualizations are interactive and provide ways to further refine search results. This new search system, which has been in beta for the past three years, has now matured to the point that it provides feature and content parity with ADS Classic, and has become the recommended way to access ADS content and services. Following a successful transition to Bumblebee, the use of ADS Classic will be discouraged starting in 2018 and phased out in 2019. You can access our new interface at https://ui.adsabs.harvard.edu

  15. Ad skepticisms: Antecedents and consequences

    Directory of Open Access Journals (Sweden)

    Rafique Ahmed

    2016-11-01

    Full Text Available Engaging customer is the burning issue for companies especially the service sector, either online or offline. Minimizing the customer disengagement is the same like reducing dissatisfaction or churn. Customer disengagement may be caused by many factors, ad skepticism is one of them; ad skepticism has two main antecedents personality variable and consumption/influencing varia-bles. This research explores the relationship of ad skepticism with customer disengagement through personality variables which are cynicism, reactance and self-esteem. The unit of analysis is the telecom and banking industry of Pakistan which is foreseeing an era of virtual currency and both are customer oriented industries. Only offline disengagement is researched and data is collected from the Business centers of telecom and banking branches dealing with virtual curren-cy in Pakistan. Hypothetical model is given after digging the relevant literature; model is tested through confirmatory factor analysis and structural equation modeling. Eight hypotheses were purposed from the connections of model, all hypotheses are accepted except the cynicism posi-tive effect on social ad skepticism. This can be due to commonality of social and charity in Paki-stani society, Muslims consider charity as a pious act and they do not think for cynic behavior in charity or social related works. The results manifest that customers in telecom industry are hav-ing ad skepticism and that is becoming the cause of their disengagement. Further, social ad skep-ticism has more impact on the customer disengagement than the general ad skepticism. While the reactance has more effect on general ad skepticism than other antecedents and cynicism has the lowest impact on social ad skepticism than other antecedents.

  16. ADS/CFT and QCD

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, Stanley J.; /SLAC; de Teramond, Guy F.; /Costa Rica U. /SLAC

    2007-02-21

    The AdS/CFT correspondence between string theory in AdS space and conformal .eld theories in physical spacetime leads to an analytic, semi-classical model for strongly-coupled QCD which has scale invariance and dimensional counting at short distances and color confinement at large distances. Although QCD is not conformally invariant, one can nevertheless use the mathematical representation of the conformal group in five-dimensional anti-de Sitter space to construct a first approximation to the theory. The AdS/CFT correspondence also provides insights into the inherently non-perturbative aspects of QCD, such as the orbital and radial spectra of hadrons and the form of hadronic wavefunctions. In particular, we show that there is an exact correspondence between the fifth-dimensional coordinate of AdS space z and a specific impact variable {zeta} which measures the separation of the quark and gluonic constituents within the hadron in ordinary space-time. This connection allows one to compute the analytic form of the frame-independent light-front wavefunctions, the fundamental entities which encode hadron properties and allow the computation of decay constants, form factors, and other exclusive scattering amplitudes. New relativistic lightfront equations in ordinary space-time are found which reproduce the results obtained using the 5-dimensional theory. The effective light-front equations possess remarkable algebraic structures and integrability properties. Since they are complete and orthonormal, the AdS/CFT model wavefunctions can also be used as a basis for the diagonalization of the full light-front QCD Hamiltonian, thus systematically improving the AdS/CFT approximation.

  17. Maximal temperature of a gas in AdS spacetime

    Science.gov (United States)

    Dai, De-Chang; Stojkovic, Dejan

    2017-04-01

    Assuming only statistical mechanics and general relativity, we calculate the maximal temperature of gas of particles placed in anti-de Sitter (AdS) spacetime. If two particles with a given center of mass energy come close enough, according to classical gravity, they will form a black hole. We focus only on the black holes with a Hawking temperature lower than the environment, because they do not disappear. The number density of such black holes grows with the temperature in the system. At a certain finite temperature, the thermodynamical system will be dominated by black holes. This critical temperature is lower than the Planck temperature for the values of the AdS vacuum energy density below the Planck density. This result might be interesting from the AdS/CFT correspondence point of view, since it is different from the Hawking-Page phase transition, and it is not immediately clear what effect dynamically limits the maximal temperature of the thermal state on the CFT side of the correspondence.

  18. Use of agar-based diet to fulfil the food and water requirements of mice.

    Science.gov (United States)

    Lang, J A; Lang, C M; White, W J

    1984-01-01

    Mice were fed an agar-based diet without an additional source of water for 5 weeks. In comparison with a similar group of mice fed a commercial diet and water ad libitum, there were no significant changes in bodyweight.

  19. Fermionic currents in AdS spacetime with compact dimensions

    Science.gov (United States)

    Bellucci, S.; Saharian, A. A.; Vardanyan, V.

    2017-09-01

    We derive a closed expression for the vacuum expectation value (VEV) of the fermionic current density in a (D +1 )-dimensional locally AdS spacetime with an arbitrary number of toroidally compactified Poincaré spatial dimensions and in the presence of a constant gauge field. The latter can be formally interpreted in terms of a magnetic flux treading the compact dimensions. In the compact subspace, the field operator obeys quasiperiodicity conditions with arbitrary phases. The VEV of the charge density is zero and the current density has nonzero components along the compact dimensions only. They are periodic functions of the magnetic flux with the period equal to the flux quantum and tend to zero on the AdS boundary. Near the horizon, the effect of the background gravitational field is small and the leading term in the corresponding asymptotic expansion coincides with the VEV for a massless field in the locally Minkowski bulk. Unlike the Minkowskian case, in the system consisting of an equal number of fermionic and scalar degrees of freedom, with same masses, charges and phases in the periodicity conditions, the total current density does not vanish. In these systems, the leading divergences in the scalar and fermionic contributions on the horizon are canceled and, as a consequence of that, the charge flux, integrated over the coordinate perpendicular to the AdS boundary, becomes finite. We show that in odd spacetime dimensions the fermionic fields realizing two inequivalent representations of the Clifford algebra and having equal phases in the periodicity conditions give the same contribution to the VEV of the current density. Combining the contributions from these fields, the current density in odd-dimensional C -,P - and T -symmetric models are obtained. As an application, we consider the ground state current density in curved carbon nanotubes described in terms of a (2 +1 )-dimensional effective Dirac model.

  20. New Features in ADS Labs

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Di Milia, G.; Luker, J.; Murray, S. S.

    2013-01-01

    The NASA Astrophysics Data System (ADS) has been working hard on updating its services and interfaces to better support our community's research needs. ADS Labs is a new interface built on the old tried-and-true ADS Abstract Databases, so all of ADS's content is available through it. In this presentation we highlight the new features that have been developed in ADS Labs over the last year: new recommendations, metrics, a citation tool and enhanced fulltext search. ADS Labs has long been providing article-level recommendations based on keyword similarity, co-readership and co-citation analysis of its corpus. We have now introduced personal recommendations, which provide a list of articles to be considered based on a individual user's readership history. A new metrics interface provides a summary of the basic impact indicators for a list of records. These include the total and normalized number of papers, citations, reads, and downloads. Also included are some of the popular indices such as the h, g and i10 index. The citation helper tool allows one to submit a set of records and obtain a list of top 10 papers which cite and/or are cited by papers in the original list (but which are not in it). The process closely resembles the network approach of establishing "friends of friends" via an analysis of the citation network. The full-text search service now covers more than 2.5 million documents, including all the major astronomy journals, as well as physics journals published by Springer, Elsevier, the American Physical Society, the American Geophysical Union, and all of the arXiv eprints. The full-text search interface interface allows users and librarians to dig deep and find words or phrases in the body of the indexed articles. ADS Labs is available at http://adslabs.org

  1. Entanglement entropy and duality in AdS4

    Directory of Open Access Journals (Sweden)

    Ioannis Bakas

    2015-07-01

    Full Text Available Small variations of the entanglement entropy δS and the expectation value of the modular Hamiltonian δE are computed holographically for circular entangling curves in the boundary of AdS4, using gravitational perturbations with general boundary conditions in spherical coordinates. Agreement with the first law of thermodynamics, δS=δE, requires that the line element of the entangling curve remains constant. In this context, we also find a manifestation of electric–magnetic duality for the entanglement entropy and the corresponding modular Hamiltonian, following from the holographic energy–momentum/Cotton tensor duality.

  2. Fermionic continuous spin gauge field in (AdS space

    Directory of Open Access Journals (Sweden)

    R.R. Metsaev

    2017-10-01

    Full Text Available Fermionic continuous spin field propagating in (AdS space–time is studied. Gauge invariant Lagrangian formulation for such fermionic field is developed. Lagrangian of the fermionic continuous spin field is constructed in terms of triple gamma-traceless tensor–spinor Dirac fields, while gauge symmetries are realized by using gamma-traceless gauge transformation parameters. It is demonstrated that partition function of fermionic continuous spin field is equal to one. Modified de Donder gauge condition that considerably simplifies analysis of equations of motion is found. Decoupling limits leading to arbitrary spin massless, partial-massless, and massive fermionic fields are studied.

  3. S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10.

    Directory of Open Access Journals (Sweden)

    Weiping Qin

    Full Text Available Alzheimer's disease (AD is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral-S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of beta-amyloid (Abeta(1-42 and Abeta(1-40 peptides, coincidental with a selective promotion of "non- amyloidogenic" alpha-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of alpha-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote alpha-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker of therapeutic efficacy in the characterization of novel drug agents for

  4. Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo.

    Directory of Open Access Journals (Sweden)

    Katherine E Davis

    Full Text Available Mouse Alzheimer's disease (AD models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct' and long-latency (presumably polysynaptic: 're-entrant' responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice

  5. Introducing ADS 2.0

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Luker, J.; Chyla, R.; Murray, S. S.

    2014-01-01

    In the spring of 1993, the Smithsonian/NASA Astrophysics Data System (ADS) first launched its bibliographic search system. It was known then as the ADS Abstract Service, a component of the larger Astrophysics Data System effort which had developed an interoperable data system now seen as a precursor of the Virtual Observatory. As a result of the massive technological and sociological changes in the field of scholarly communication, the ADS is now completing the most ambitious technological upgrade in its twenty-year history. Code-named ADS 2.0, the new system features: an IT platform built on web and digital library standards; a new, extensible, industrial strength search engine; a public API with various access control capabilities; a set of applications supporting search, export, visualization, analysis; a collaborative, open source development model; and enhanced indexing of content which includes the full-text of astronomy and physics publications. The changes in the ADS platform affect all aspects of the system and its operations, including: the process through which data and metadata are harvested, curated and indexed; the interface and paradigm used for searching the database; and the follow-up analysis capabilities available to the users. This poster describes the choices behind the technical overhaul of the system, the technology stack used, and the opportunities which the upgrade is providing us with, namely gains in productivity and enhancements in our system capabilities.

  6. AdS nonlinear instability: moving beyond spherical symmetry

    Science.gov (United States)

    Dias, Óscar J. C.; Santos, Jorge E.

    2016-12-01

    Anti-de Sitter (AdS) is conjectured to be nonlinear unstable to a weakly turbulent mechanism that develops a cascade towards high frequencies, leading to black hole formation (Dafermos and Holzegel 2006 Seminar at DAMTP (University of Cambridge) available at https://dpmms.cam.ac.uk/~md384/ADSinstability.pdf, Bizon and Rostworowski 2011 Phys. Rev. Lett. 107 031102). We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied by Bizon and Rostworowski. In contrast with Bizon and Rostworowski, we find that not all gravitational normal modes of AdS can be nonlinearly extended into periodic horizonless smooth solutions of the Einstein equation. In particular, we show that even seeds with a single normal mode can develop secular resonances, unlike the spherically symmetric scalar field collapse studied by Bizon and Rostworowski. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of Bizon and Rostworowski. We also show that weak turbulent perturbative theory predicts the existence of direct and inverse cascades, with the former dominating the latter for equal energy two-mode seeds.

  7. AdS pure spinor superstring in constant backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Chandia, Osvaldo [Departamento de Ciencias, Facultad de Artes Liberales, Universidad Adolfo Ibáñez,Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez,Diagonal Las Torres 2640, Peñalolén, Santiago (Chile); Bevilaqua, L. Ibiapina [Escola de Ciências e Tecnologia, Universidade Federal do Rio Grande do Norte,Caixa Postal 1524, 59072-970, Natal, RN (Brazil); Vallilo, Brenno Carlini [Facultad de Ciencias Exactas, Departamento de Ciencias Físicas, Universidad Andres Bello,Republica 220, Santiago (Chile)

    2014-06-05

    In this paper we study the pure spinor formulation of the superstring in AdS{sub 5}×S{sup 5} around point particle solutions of the classical equations of motion. As a particular example we quantize the pure spinor string in the BMN background.

  8. Numerical Simulations of Asymptotically AdS Spacetimes

    Science.gov (United States)

    Bantilan, Hans

    In this dissertation, we introduce a numerical scheme to construct asymptotically anti-de Sitter spacetimes with Lorentzian signature, focusing on cases that preserve five-dimensional axisymmetry. We study the field theories that are dual to these spacetimes by appealing to the AdS/CFT correspondence in the regime where the gravity dual is completely described by Einstein gravity. The numerical scheme is based on generalized harmonic evolution, and we begin by obtaining initial data defined on some Cauchy hypersurface. For the study described in this dissertation, we use a scalar field to source deviations from pure AdS5, and obtain data that correspond to highly deformed black holes. We evolve this initial data forward in time, and follow the subsequent ringdown. What is novel about this study is that the initial horizon geometry cannot be considered a small perturbation of the final static horizon, and hence we are probing an initial non-linear phase of the evolution of the bulk spacetime. On the boundary, we find that the dual CFT stress tensor behaves like that of a thermalized N = 4 SYM fluid. We find that the equation of state of this fluid is consistent with conformal invariance, and that its transport coefficients match those previously calculated for an N = 4 SYM fluid via holographic methods. Modulo a brief transient that is numerical in nature, this matching appears to hold from the initial time onwards. We transform these solutions computed in global AdS onto a Minkowski piece of the boundary, and examine the temperature of the corresponding fluid flows. Under this transformation, the spatial profile of temperature at the initial time resembles a Lorentz-flattened pancake centered at the origin of Minkowski space. By interpreting the direction along which the data is flattened as the beam-line direction, our initial data can be thought of as approximating a head-on heavy ion collision at its moment of impact.

  9. Smooth causal patches for AdS black holes

    Science.gov (United States)

    Raju, Suvrat

    2017-06-01

    We review the paradox of low energy excitations of a black hole in anti-de Sitter space (AdS). An appropriately chosen unitary operator in the boundary theory can create a locally strong excitation near the black hole horizon, whose global energy is small as a result of the gravitational redshift. The paradox is that this seems to violate a general rule of statistical mechanics, which states that an operator with energy parametrically smaller than k T cannot create a significant excitation in a thermal system. When we carefully examine the position dependence of the boundary unitary operator that produces the excitation and the bulk observable necessary to detect the anomalously large effect, we find that they do not both fit in a single causal patch. This follows from a remarkable property of position-space AdS correlators that we establish explicitly and resolves the paradox in a generic state of the system, since no combination of observers can both create the excitation and observe its effect. As a special case of our analysis, we show how this resolves the "Born rule" paradox of Marolf and Polchinski [J. High Energy Phys. 01 (2016) 008, 10.1007/JHEP01(2016)008] and we verify our solution using an independent calculation. We then consider boundary states that are finely tuned to display a spontaneous excitation outside the causal patch of the infalling observer, and we propose a version of causal patch complementarity in AdS/CFT that resolves the paradox for such states as well.

  10. ADS-B in space

    DEFF Research Database (Denmark)

    Knudsen, Bjarke Gosvig; Jensen, Morten; Birklykke, Alex

    2014-01-01

    them to the terrestrial receivers. This paper gives an overview of the GATOSS mission and of its highly-sensitive ADS-B software-defined radio receiver payload. Details of the design and implementation of the receiver's decoder are introduced. The first real-life, space-based results show that ADS......-B signals are indeed successfully received in space and retransmitted to a terrestrial station by the GATOSS nano-satellite orbiting at 700+ km altitudes, thus showing that GATOSS is capable of tracking flights, including transoceanic ones, from space....

  11. Pharmacokinetics of [{sup 18}F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Snellman, Anniina; Lopez-Picon, Francisco R.; Haaparanta-Solin, Merja [University of Turku, MediCity/PET Preclinical Laboratory, Turku PET Centre, Turku (Finland); Rokka, Johanna; Eskola, Olli [University of Turku, Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, Turku (Finland); Wilson, Ian; Farrar, Gill [GE Healthcare Medical Diagnostics, Little Chalfont, Buckinghamshire (United Kingdom); Scheinin, Mika [University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Turku University Hospital, Unit of Clinical Pharmacology, Turku (Finland); Solin, Olof [University of Turku, Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, Turku (Finland); Aabo Akademi University, Accelerator Laboratory, Turku PET Centre, Turku (Finland); Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland)

    2012-11-15

    The aim of this study was to investigate the potential of [{sup 18}F]flutemetamol as a preclinical PET tracer for imaging {beta}-amyloid (A{beta}) deposition by comparing its pharmacokinetics to those of [{sup 11}C]Pittsburgh compound B ([{sup 11}C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [{sup 18}F]flutemetamol to A{beta} deposits was studied in the Tg2576 transgenic mouse model of Alzheimer's disease. [{sup 18}F]Flutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wild-type rats and mice. Metabolism and binding of [{sup 11}C]PIB and [{sup 18}F]flutemetamol to plasma proteins were analysed using thin-layer chromatography and ultrafiltration methods, respectively. Radiation dose estimates were calculated from rat ex vivo biodistribution data. The binding of [{sup 18}F]flutemetamol to A{beta} deposits was also studied using ex vivo and in vitro autoradiography. The location of A{beta} deposits in the brain was determined with thioflavine S staining and immunohistochemistry. The pharmacokinetics of [{sup 18}F]flutemetamol resembled that of [{sup 11}C]PIB in rats and mice. In vivo studies showed that both tracers readily entered the brain, and were excreted via the hepatobiliary pathway in both rats and mice. The metabolism of [{sup 18}F]flutemetamol into radioactive metabolites was faster than that of [{sup 11}C]PIB. [{sup 18}F]Flutemetamol cleared more slowly from the brain than [{sup 11}C]PIB, particularly from white matter, in line with its higher lipophilicity. Effective dose estimates for [{sup 11}C]PIB and [{sup 18}F]flutemetamol were 2.28 and 6.65 {mu}Sv/MBq, respectively. Autoradiographs showed [{sup 18}F]flutemetamol binding to fibrillar A{beta} deposits in the brain of Tg2576 mice. Based on its pharmacokinetic profile, [{sup 18}F]flutemetamol showed potential as a PET tracer for preclinical imaging. It showed good brain uptake and was bound to A{beta} deposits in the

  12. Intracellular clusterin interacts with brain isoforms of the bridging integrator 1 and with the microtubule-associated protein Tau in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Yuan Zhou

    Full Text Available Sporadic or late-onset Alzheimer's disease (AD is expected to affect 50% of individuals reaching 85 years of age. The most significant genetic risk factor for late-onset AD is the e4 allele of APOE gene encoding apolipoprotein E, a lipid carrier shown to modulate brain amyloid burden. Recent genome-wide association studies have uncovered additional single nucleotide polymorphisms (SNPs linked to AD susceptibility, including those in the CLU and BIN1 genes encoding for clusterin (CLU and the bridging integrator 1 (BIN1 proteins, respectively. Because CLU has been implicated in brain amyloid-β (Aβ clearance in mouse models of amyloid deposition, we sought to investigate whether an AD-linked SNP in the CLU gene altered Aβ42 biomarker levels in the cerebrospinal fluid (CSF. Instead, we found that the CLU rs11136000 SNP modified CSF levels of the microtubule-associated protein Tau in AD patients. We also found that an intracellular form of CLU (iCLU was upregulated in the brain of Tau overexpressing Tg4510 mice, but not in Tg2576 amyloid mouse model. By overexpressing iCLU and Tau in cell culture systems we discovered that iCLU was a Tau-interacting protein and that iCLU associated with brain-specific isoforms of BIN1, also recently identified as a Tau-binding protein. Through expression analysis of CLU and BIN1 variants, we found that CLU and BIN1 interacted via their coiled-coil motifs. In co-immunoprecipitation studies using human brain tissue, we showed that iCLU and the major BIN1 isoform expressed in neurons were associated with modified Tau species found in AD. Finally, we showed that expression of certain coding CLU variants linked to AD risk led to increased levels of iCLU. Together, our findings suggest that iCLU and BIN1 interaction might impact Tau function in neurons and uncover potential new mechanisms underlying the etiology of Tau pathology in AD.

  13. Adding Value to Indiana's Commodities.

    Science.gov (United States)

    Welch, Mary A., Ed.

    1995-01-01

    Food processing plants are adding value to bulk and intermediate products to sell overseas. The Asian Pacific Rim economies constituted the largest market for consumer food products in 1993. This shift toward consumer food imports in this area is due to more women working outside the home, the internationalization of populations, and dramatic…

  14. Facilities Management and Added Value

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2010-01-01

    Aim: This paper aims to present different models of the concept of the added value of Facilities Management (FM), including the FM Value Map, which forms the basis of research group in EuroFM, and to present some of the results of this research collaboration. Approach and methodology: The paper i...

  15. Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept).

    Science.gov (United States)

    Romberg, Carola; Mattson, Mark P; Mughal, Mohamed R; Bussey, Timothy J; Saksida, Lisa M

    2011-03-02

    Several mouse models of Alzheimer's disease (AD) with abundant β-amyloid and/or aberrantly phosphorylated tau develop memory impairments. However, multiple non-mnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals. Currently, it is unclear whether mutations in the β-amyloid precursor protein (APP) and tau are sufficient to cause similar, AD-like attention deficits in mouse models of the disease. To address this question, we tested 3xTgAD mice (which express APPswe, PS1M146V, and tauP301L mutations) and wild-type control mice on a newly developed touchscreen-based 5-choice serial reaction time test of attention and response control. The 3xTgAD mice attended less accurately to short, spatially unpredictable stimuli when the attentional demand of the task was high, and also showed a general tendency to make more perseverative responses than wild-type mice. The attentional impairment of 3xTgAD mice was comparable to that of AD patients in two aspects: first, although 3xTgAD mice initially responded as accurately as wild-type mice, they subsequently failed to sustain their attention over the duration of the task; second, the ability to sustain attention was enhanced by the cholinesterase inhibitor donepezil (Aricept). These findings demonstrate that familial AD mutations not only affect memory, but also cause significant impairments in attention, a cognitive domain supported by the prefrontal cortex and its afferents. Because attention deficits are likely to affect memory encoding and other cognitive abilities, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD.

  16. Black holes as bubbles of AdS

    Science.gov (United States)

    Danielsson, U. H.; Dibitetto, G.; Giri, S.

    2017-10-01

    In this paper we propose that bubbles of AdS within Minkowski spacetime, stabilized at a finite radius by stiff matter and an electromagnetic gas, can be an alternative endpoint of gravitational collapse. The bubbles are horizonless with a size up to 12.5% larger than their Schwarzschild radius depending on their charge. We argue that they are stable against small perturbations, and have thermodynamical properties similar to those of real black holes. We provide a realization of the bubbles within string theory that relies on a specific brane intersection giving rise to a shell carrying dissolved charges from lower dimensional D-branes as well as a gas of open strings. We also note that our construction provides a new way of understanding the entropy of Reissner-Nordström black holes in the extremal limit.

  17. Colliding waves on a string in AdS$_3$

    CERN Document Server

    Vegh, David

    2015-01-01

    This paper is concerned with the classical motion of a string in global AdS$_3$. The initially static string stretches between two antipodal points on the boundary circle. Both endpoints are perturbed which creates cusps at a steady rate. The cusps propagate towards the interior where they collide. The behavior of the string depends on the strength of forcing. Three qualitatively different phases can be distinguished: transparent, gray, and black. The transparent region is analogous to a standing wave. In the black phase, there is a horizon on the worldsheet and cusps never reach the other endpoint. The string keeps folding and its length grows linearly over time. In the gray phase, the string still grows linearly. However, cusps do cross to the other side. The transparent and gray regions are separated by a transition point where a logarithmic accumulation of cusps is numerically observed. A simple model reproduces the qualitative behavior of the string in the three phases.

  18. Massless AdS 2 scattering and Bethe ansatz

    Science.gov (United States)

    Fontanella, A.; Torrielli, A.

    2017-09-01

    We first analyse the integrable scattering theory describing the massless excitations of AdS 2 × S 2 × T 6 superstrings in the relativistic limit. The matrix part of the S-matrix is obtained in the BMN limit from the conjectured exact expression, and compared to known S-matrices with N=1 supersymmetry in 1 + 1 dimensions. A dressing factor, yet unknown for the complete theory, is here constructed based on relativistic crossing symmetry. We derive a Bethe-ansatz condition by employing a transfer-matrix technique based on the so-called free-fermion condition. This is known to overcome the problem of lack of a reference state. We then generalise the method to the massless non-relativistic case, and compare the resulting Bethe-ansatz condition with a simple massless limit of the one conjectured by Sorokin, Tseytlin, Wulff and Zarembo.

  19. Thermodynamics of charged Lovelock: AdS black holes

    Energy Technology Data Exchange (ETDEWEB)

    Prasobh, C.B.; Suresh, Jishnu; Kuriakose, V.C. [Cochin University of Science and Technology, Department of Physics, Cochin (India)

    2016-04-15

    We investigate the thermodynamic behavior of maximally symmetric charged, asymptotically AdS black hole solutions of Lovelock gravity. We explore the thermodynamic stability of such solutions by the ordinary method of calculating the specific heat of the black holes and investigating its divergences which signal second-order phase transitions between black hole states. We then utilize the methods of thermodynamic geometry of black hole spacetimes in order to explain the origin of these points of divergence. We calculate the curvature scalar corresponding to a Legendre-invariant thermodynamic metric of these spacetimes and find that the divergences in the black hole specific heat correspond to singularities in the thermodynamic phase space. We also calculate the area spectrum for large black holes in the model by applying the Bohr-Sommerfeld quantization to the adiabatic invariant calculated for the spacetime. (orig.)

  20. Adiabatic pumping solutions in global AdS

    Science.gov (United States)

    Carracedo, Pablo; Mas, Javier; Musso, Daniele; Serantes, Alexandre

    2017-05-01

    We construct a family of very simple stationary solutions to gravity coupled to a massless scalar field in global AdS. They involve a constantly rising source for the scalar field at the boundary and thereby we name them pumping solutions. We construct them numerically in D = 4. They are regular and, generically, have negative mass. We perform a study of linear and nonlinear stability and find both stable and unstable branches. In the latter case, solutions belonging to different sub-branches can either decay to black holes or to limiting cycles. This observation motivates the search for non-stationary exactly timeperiodic solutions which we actually construct. We clarify the role of pumping solutions in the context of quasistatic adiabatic quenches. In D = 3 the pumping solutions can be related to other previously known solutions, like magnetic or translationally-breaking backgrounds. From this we derive an analytic expression.

  1. Worldsheet dilatation operator for the AdS superstring

    Energy Technology Data Exchange (ETDEWEB)

    Ramírez, Israel [Departamento de Física, Universidad Técnica Federico Santa María,Casilla 110-V, Valparaíso (Chile); Institut für Mathematik und Institut für Physik, Humboldt-Universität zu Berlin,IRIS Haus, Zum Großen Windkanal 6, 12489 Berlin (Germany); Vallilo, Brenno Carlini [Departamento de Ciencias Físicas, Universidad Andres Bello,Republica 220, Santiago (Chile)

    2016-05-23

    In this work we propose a systematic way to compute the logarithmic divergences of composite operators in the pure spinor description of the AdS{sub 5}×S{sup 5} superstring. The computations of these divergences can be summarized in terms of a dilatation operator acting on the local operators. We check our results with some important composite operators of the formalism.

  2. Brownian motion in AdS/CFT

    NARCIS (Netherlands)

    de Boer, J.; Hubeny, V.E.; Rangamani, M.; Shigemori, M.

    2009-01-01

    We study Brownian motion and the associated Langevin equation in AdS/CFT. The Brownian particle is realized in the bulk spacetime as a probe fundamental string in an asymptotically AdS black hole background, stretching between the AdS boundary and the horizon. The modes on the string are excited by

  3. AdDelta24 and the p53-expressing variant AdDelta24-p53 achieve potent anti-tumor activity in glioma when combined with radiotherapy.

    Science.gov (United States)

    Idema, Sander; Lamfers, Martine L M; van Beusechem, Victor W; Noske, David P; Heukelom, Stan; Moeniralm, Sharif; Gerritsen, Winald R; Vandertop, W Peter; Dirven, Clemens M F

    2007-12-01

    The conditionally replicating adenovirus (CRAd) AdDelta24-p53 replicates selectively in Rb mutant cells, and encodes the p53 suppressor protein. It has shown improved oncolytic potency compared to the parental control AdDelta24. As exogenous p53 has been shown to enhance radiosensitivity, the combination of AdDelta24-p53 and AdDelta24 with radiotherapy was assessed in vitro and in vivo against the therapy resistant gliomas. In glioma cells, multicellular spheroids and animal xenografts the efficacy of combination therapy was assessed. P53 phosphorylation, induction of apoptosis and viral replication were determined following single or combination therapies. In vitro, AdDelta24-p53 was more effective against glioma cells than the control AdDelta24. Addition of irradiation equally increased the efficacy of both AdDelta24-p53 and AdDelta24 resulting in improved oncolysis compared to single agent treatment. Radiotherapy did not significantly change the replication kinetics of AdDelta24-p53 or AdDelta24. No detectable increase in p53 phosphorylation was observed but combination of radiotherapy and AdDelta24-p53 caused an increase in the percentage of apoptotic cells. In vivo, combination therapy with either AdDelta24 or AdDelta24-p53 significantly increased the number of mice demonstrating tumor regression (100%) as well as long-term survival (50%). No differences between viruses were noted. Exogenous p53 expression does not appear to increase the synergistic interaction of CRAds combined with radiotherapy. These results however do indicate that radiotherapy provides the time frame in which AdDelta24 and AdDelta24-p53 can eradicate established tumors that would otherwise escape treatment, and establishes the need to combine these modalities to form an effective anti-cancer treatment.

  4. Lessons from Tau-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Yazi D. Ke

    2012-01-01

    Full Text Available Both Alzheimer's disease (AD and frontotemporal dementia (FTD are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to the umbrella term “tauopathies” for these conditions, also emphasizing the central role of tau in AD and FTD. Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease. To reveal the physiological functions of tau in vivo, several knockout mouse strains with deletion of the tau-encoding MAPT gene have been established over the past decade, using different gene targeting constructs. Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations. The number of publications using tau knockout mice has recently markedly increased, and both behavioural changes and motor deficits have been identified in aged mice of certain strains. Moreover, tau knockout mice have been instrumental in identifying novel functions of tau, both in cultured neurons and in vivo. Importantly, tau knockout mice have significantly contributed to the understanding of the pathophysiological interplay between Aβ and tau in AD. Here, we review the literature that involves tau knockout mice to summarize what we have learned so far from depleting tau in vivo.

  5. Realizing "value-added" metrology

    Science.gov (United States)

    Bunday, Benjamin; Lipscomb, Pete; Allgair, John; Patel, Dilip; Caldwell, Mark; Solecky, Eric; Archie, Chas; Morningstar, Jennifer; Rice, Bryan J.; Singh, Bhanwar; Cain, Jason; Emami, Iraj; Banke, Bill, Jr.; Herrera, Alfredo; Ukraintsev, Vladamir; Schlessinger, Jerry; Ritchison, Jeff

    2007-03-01

    The conventional premise that metrology is a "non-value-added necessary evil" is a misleading and dangerous assertion, which must be viewed as obsolete thinking. Many metrology applications are key enablers to traditionally labeled "value-added" processing steps in lithography and etch, such that they can be considered integral parts of the processes. Various key trends in modern, state-of-the-art processing such as optical proximity correction (OPC), design for manufacturability (DFM), and advanced process control (APC) are based, at their hearts, on the assumption of fine-tuned metrology, in terms of uncertainty and accuracy. These trends are vehicles where metrology thus has large opportunities to create value through the engineering of tight and targetable process distributions. Such distributions make possible predictability in speed-sorts and in other parameters, which results in high-end product. Additionally, significant reliance has also been placed on defect metrology to predict, improve, and reduce yield variability. The necessary quality metrology is strongly influenced by not only the choice of equipment, but also the quality application of these tools in a production environment. The ultimate value added by metrology is a result of quality tools run by a quality metrology team using quality practices. This paper will explore the relationships among present and future trends and challenges in metrology, including equipment, key applications, and metrology deployment in the manufacturing flow. Of key importance are metrology personnel, with their expertise, practices, and metrics in achieving and maintaining the required level of metrology performance, including where precision, matching, and accuracy fit into these considerations. The value of metrology will be demonstrated to have shifted to "key enabler of large revenues," debunking the out-of-date premise that metrology is "non-value-added." Examples used will be from critical dimension (CD

  6. Quantum Black Holes as Holograms in AdS Braneworlds

    CERN Document Server

    Emparan, R; Kaloper, Nemanja; Emparan, Roberto; Fabbri, Alessandro; Kaloper, Nemanja

    2002-01-01

    We propose a new approach for using the AdS/CFT correspondence to study quantum black hole physics. The black holes on a brane in an AdS$_{D+1}$ braneworld that solve the classical bulk equations are interpreted as duals of {\\it quantum-corrected} $D$-dimensional black holes, rather than classical ones, of a conformal field theory coupled to gravity. We check this explicitly in D=3 and D=4. In D=3 we reinterpret the existing exact solutions on a flat membrane as states of the dual 2+1 CFT. We show that states with a sufficiently large mass really are 2+1 black holes where the quantum corrections dress the classical conical singularity with a horizon and censor it from the outside. On a negatively curved membrane, we reinterpret the classical bulk solutions as quantum-corrected BTZ black holes. In D=4 we argue that the bulk solution for the brane black hole should include a radiation component in order to describe a quantum-corrected black hole in the 3+1 dual. Hawking radiation of the conformal field is then ...

  7. Role of Liver X Receptor in AD Pathophysiology.

    Directory of Open Access Journals (Sweden)

    Adrián G Sandoval-Hernández

    Full Text Available Alzheimer's disease (AD is the major cause of dementia worldwide. The pharmacological activation of nuclear receptors (Liver X receptors: LXRs or Retinoid X receptors: RXR has been shown to induce overexpression of the ATP-Binding Cassette A1 (ABCA1 and Apolipoprotein E (ApoE, changes that are associated with improvement in cognition and reduction of amyloid beta pathology in amyloidogenic AD mouse models (i.e. APP, PS1: 2tg-AD. Here we investigated whether treatment with a specific LXR agonist has a measurable impact on the cognitive impairment in an amyloid and Tau AD mouse model (3xTg-AD: 12-months-old; three months treatment. The data suggests that the LXR agonist GW3965 is associated with increased expression of ApoE and ABCA1 in the hippocampus and cerebral cortex without a detectable reduction of the amyloid load. We also report that most cells overexpressing ApoE (86±12% are neurons localized in the granular cell layer of the hippocampus and entorhinal cortex. In the GW3965 treated 3xTg-AD mice we also observed reduction in astrogliosis and increased number of stem and proliferating cells in the subgranular zone of the dentate gyrus. Additionally, we show that GW3965 rescued hippocampus long term synaptic plasticity, which had been disrupted by oligomeric amyloid beta peptides. The effect of GW3965 on synaptic function was protein synthesis dependent. Our findings identify alternative functional/molecular mechanisms by which LXR agonists may exert their potential benefits as a therapeutic strategy against AD.

  8. Role of Liver X Receptor in AD Pathophysiology

    Science.gov (United States)

    Sandoval-Hernández, Adrián G.; Buitrago, Luna; Moreno, Herman; Cardona-Gómez, Gloria Patricia; Arboleda, Gonzalo

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia worldwide. The pharmacological activation of nuclear receptors (Liver X receptors: LXRs or Retinoid X receptors: RXR) has been shown to induce overexpression of the ATP-Binding Cassette A1 (ABCA1) and Apolipoprotein E (ApoE), changes that are associated with improvement in cognition and reduction of amyloid beta pathology in amyloidogenic AD mouse models (i.e. APP, PS1: 2tg-AD). Here we investigated whether treatment with a specific LXR agonist has a measurable impact on the cognitive impairment in an amyloid and Tau AD mouse model (3xTg-AD: 12-months-old; three months treatment). The data suggests that the LXR agonist GW3965 is associated with increased expression of ApoE and ABCA1 in the hippocampus and cerebral cortex without a detectable reduction of the amyloid load. We also report that most cells overexpressing ApoE (86±12%) are neurons localized in the granular cell layer of the hippocampus and entorhinal cortex. In the GW3965 treated 3xTg-AD mice we also observed reduction in astrogliosis and increased number of stem and proliferating cells in the subgranular zone of the dentate gyrus. Additionally, we show that GW3965 rescued hippocampus long term synaptic plasticity, which had been disrupted by oligomeric amyloid beta peptides. The effect of GW3965 on synaptic function was protein synthesis dependent. Our findings identify alternative functional/molecular mechanisms by which LXR agonists may exert their potential benefits as a therapeutic strategy against AD. PMID:26720273

  9. Effects of ovariectomy on autophagy and senile plaques in the brain of adult APP/PS1 double transgenic mice

    Directory of Open Access Journals (Sweden)

    Ming-liang XU

    2015-04-01

    Full Text Available Objective To investigate the effect of ovarian estrogen on autophagy and senile plaques (SP in the brain of adult APP/PS1 double transgenic mice, and inquire into the mechanism of Alzheimer disease (AD neuropathogenesis due to estrogen deficiency. Methods APP/PS1 AD mice (3-month old were divided into ovariectomy group (OVX-AD and sham group (sham-AD. Two months after operation, transmission electron microscopy (TEM was employed to observe the morphological structures of the brains of AD model mice, and immunohistochemical staining was performed to examine the changes in SP and autophagy-related proteins LC3 and Beclin-1 in the brain of AD model mice. Results Immunohistochemical staining showed that the number of SP in the brain of OVX-AD mice incrcased significantly compared with that in sham-AD mice, and distribution of SP was observed more extensively, including the cortex and hippocampus. The autophagy related proteins LC3 and Beclin-1 positive neurons were decreased greatly in the OVX-AD mice brain compared with that of sham-AD mice. TEM revealed a larger number of swollen and dark neurons in hippocampus of OVX-AD mice, while more autophagosome was observed around the neuronal processes in OVX-AD mice brain compared with sham-AD mice. Conclusion Estrogen deficiency may lead to delayed maturation of autophagy, decrease the activity and weaken the function of autophagy, which in turn may result in aggravation of pathological features of AD. DOI: 10.11855/j.issn.0577-7402.2015.01.06

  10. Chronic Anatabine Treatment Reduces Alzheimer's Disease (AD-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD.

    Directory of Open Access Journals (Sweden)

    Megha Verma

    Full Text Available Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with anatabine in a transgenic mouse model (Tg PS1/APPswe of Alzheimer's disease (AD which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the anatabine treatment. We found that anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with anatabine. This is the first study to investigate the impact of chronic anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of anatabine as a possible disease modifying agent for the treatment of AD.

  11. Entanglement Entropy of AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Maurizio Melis

    2010-11-01

    Full Text Available We review recent progress in understanding the entanglement entropy of gravitational configurations for anti-de Sitter gravity in two and three spacetime dimensions using the AdS/CFT correspondence. We derive simple expressions for the entanglement entropy of two- and three-dimensional black holes. In both cases, the leading term of the entanglement entropy in the large black hole mass expansion reproduces exactly the Bekenstein-Hawking entropy, whereas the subleading term behaves logarithmically. In particular, for the BTZ black hole the leading term of the entanglement entropy can be obtained from the large temperature expansion of the partition function of a broad class of 2D CFTs on the torus.

  12. Sputnik: ad hoc distributed computation.

    Science.gov (United States)

    Völkel, Gunnar; Lausser, Ludwig; Schmid, Florian; Kraus, Johann M; Kestler, Hans A

    2015-04-15

    In bioinformatic applications, computationally demanding algorithms are often parallelized to speed up computation. Nevertheless, setting up computational environments for distributed computation is often tedious. Aim of this project were the lightweight ad hoc set up and fault-tolerant computation requiring only a Java runtime, no administrator rights, while utilizing all CPU cores most effectively. The Sputnik framework provides ad hoc distributed computation on the Java Virtual Machine which uses all supplied CPU cores fully. It provides a graphical user interface for deployment setup and a web user interface displaying the current status of current computation jobs. Neither a permanent setup nor administrator privileges are required. We demonstrate the utility of our approach on feature selection of microarray data. The Sputnik framework is available on Github http://github.com/sysbio-bioinf/sputnik under the Eclipse Public License. hkestler@fli-leibniz.de or hans.kestler@uni-ulm.de Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant.

    Science.gov (United States)

    Ophorst, Olga J A E; Radosević, Katarina; Klap, Jaco M; Sijtsma, Jeroen; Gillissen, Gert; Mintardjo, Ratna; van Ooij, Mark J M; Holterman, Lennart; Companjen, Arjen; Goudsmit, Jaap; Havenga, Menzo J E

    2007-08-29

    Previously, we have shown the potency of recombinant Adenovirus serotype 35 viral vaccines (rAd35) to induce strong immune response against the circumsporozoite protein (CS) of the plasmodium parasite. To further optimize immunogenicity of Ad35-based malaria vaccines we formulated rAd35.CS vaccine with aluminium phosphate adjuvant (AlPO(4)). In contrast to the conventional protein based vaccines no absorption to aluminium adjuvant was observed and rAd35 viral in vitro infectivity in mammalian cells was preserved. Immunization with Ad35.CS formulated with AlPO(4) resulted in significantly higher CS specific T and B cell responses in mice upon either single or prime-boost vaccination regimens as compared to rAd35.CS alone. With these results we report for the first time the feasibility of using an AlPO(4) adjuvant to increase the potency of a live adenovirus serotype 35-based vaccine.

  14. Antismoking Ads at the Point of Sale: The Influence of Ad Type and Context on Ad Reactions.

    Science.gov (United States)

    Kim, Annice; Nonnemaker, James; Guillory, Jamie; Shafer, Paul; Parvanta, Sarah; Holloway, John; Farrelly, Matthew

    2017-06-01

    Efforts are underway to educate consumers about the dangers of smoking at the point of sale (POS). Research is limited about the efficacy of POS antismoking ads to guide campaign development. This study experimentally tests whether the type of antismoking ad and the context in which ads are viewed influence people's reactions to the ads. A national convenience sample of 7,812 adult current smokers and recent quitters was randomized to 1 of 39 conditions. Participants viewed one of the four types of antismoking ads (negative health consequences-graphic, negative social consequences-intended emotive, benefits of quitting-informational, benefits of quitting-graphic) in one of the three contexts (alone, next to a cigarette ad, POS tobacco display). We assessed participants' reactions to the ads, including perceived effectiveness, negative emotion, affective dissonance, and motivational reaction. Graphic ads elicited more negative emotion and affective dissonance than benefits of quitting ads. Graphic ads elicited higher perceived effectiveness and more affective dissonance than intended emotive ads. Antismoking ads fared best when viewed alone, and graphic ads were least influenced by the context in which they were viewed. These results suggest that in developing POS campaigns, it is important to consider the competitive pro-tobacco context in which antismoking ads will be viewed.

  15. Intratumoral delivery of CD154 homolog (Ad-ISF35) induces tumor regression: analysis of vector biodistribution, persistence and gene expression.

    Science.gov (United States)

    Melo-Cardenas, J; Urquiza, M; Kipps, T J; Castro, J E

    2012-05-01

    Ad-ISF35 is an adenovirus (Ad) vector that encodes a mouse-human chimeric CD154. Ad-ISF35 induces activation of chronic lymphocytic leukemia (CLL) cells converting them into CLL cells capable of promoting immune recognition and anti-leukemia T-cell activation. Clinical trials in humans treated with Ad-ISF35-transduced leukemia cells or intranodal injection of Ad-ISF35 have shown objective clinical responses. To better understand the biology of Ad-ISF35 and to contribute to its clinical development, we preformed studies to evaluate biodistribution, persistence and toxicity of repeat dose intratumoral administration of Ad-ISF35 in a mouse model. Ad-ISF35 intratumoral administration induced tumor regression in more than 80% of mice bearing A20 tumors. There were no abnormalities in the serum chemistry. Mice receiving Ad-ISF35 presented severe extramedullary hematopoiesis and follicular hyperplasia in the spleen and extramedullary hematopoiesis with lymphoid hyperplasia in lymph nodes. After Ad-ISF35 injection, the vector was found primarily in the injected tumors with a biodistribution pattern that showed a rapid clearance with no evidence of Ad-ISF35 accumulation or persistence in the injected tumor or peripheral organs. Furthermore, pre-existing antibodies against Ad-5 did not abrogate Ad-ISF35 anti-tumor activity. In conclusion, intratumoral administration of Ad-ISF35 induced tumor regression in A20 tumor bearing mice without toxicities and with no evidence of vector accumulation or persistence.

  16. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions.

    Science.gov (United States)

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li

    2014-08-18

    Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

  17. Ad valorem versus unit taxes

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Sørensen, Allan

    2010-01-01

    Real-world industries are composed from heterogeneous firms and substantial intra-industry reallocations take place, i.e. high productivity firms squeeze out low productivity firms. Previous tax-tool comparisons have not included these central forces of industry structure. This paper examines...... a general equilibrium monopolistic competition model with heterogeneous firms and intra-industry reallocations. We show that the welfare superiority of ad valorem over unit taxes under imperfect competition is not only preserved but amplified. The additional difference between the tools arises because unit...... taxes distort relative prices, which in turn reduces average industry productivity through reallocations (the survival and increased market share of lower productivity firms). Importantly, numerical solutions of the model reveal that the relative welfare loss from using the unit tax increases...

  18. MUSICAL ARRANGEMENT OF MEDIA ADS

    Directory of Open Access Journals (Sweden)

    Chernyshov Alexander V.

    2015-01-01

    Full Text Available The music-compositional principles of commercial and political advertising and also the self-promotion of electronic media (radio, television, Internet are considered in this mediatext: from the elementary beeps, symbolic functions, emblems/logos and musical brands to the sound engineering technology to underscore the product's name and the complex synthesis between music and intra movements and color-light design of frames. Simultaneously examines, how the musical arrangement of ethereal advertising is involved in creation the emotional drama or bravado which reach the level of explicit or associative counterpoint 'music with the advertised object or subject' and which extend to expression of cultural image of all the broadcast channel. The article explores the works of the next genres like infomercial, teleshopping, film-ad, and autonomous commercials that have been produced in European countries or USA.

  19. Adding timing to the VELO

    CERN Document Server

    Mitreska, Biljana

    2017-01-01

    The LHCb experiment is designed to perform high precision measurements of matter-antimatter asymmetries and searches for rare and forbidden decays, with the aim of discovering new and unexpected particles and forces. In 2030 the LHC beam intensity will increase by a factor of 50 compared to current operations. This means increased samples of the particles we need to study, but it also presents experimental challenges. In particular, with current technology it becomes impossible to differentiate the many (>50) separate proton-proton collisions which occur for each bunch crossing.\\\\ In this project a Monte Carlo simulation was developed to model the operation of a silicon pixel vertex detector surrounding the collision region at LHCb, under the conditions expected after 2030, after the second upgrade of the Vertex Locator(VELO).The main goal was studying the effect of adding '4D' detectors which save high-precision timing information, in addition to the usual three spatial coordinates, as charged particles pas...

  20. Topological AdS/CFT

    Science.gov (United States)

    Genolini, Pietro Benetti; Richmond, Paul; Sparks, James

    2017-12-01

    We define a holographic dual to the Donaldson-Witten topological twist of N=2 gauge theories on a Riemannian four-manifold. This is described by a class of asymptotically locally hyperbolic solutions to N=4 gauged supergravity in five dimensions, with the four-manifold as conformal boundary. Under AdS/CFT, minus the logarithm of the partition function of the gauge theory is identified with the holographically renormalized supergravity action. We show that the latter is independent of the metric on the boundary four-manifold, as required for a topological theory. Supersymmetric solutions in the bulk satisfy first order differential equations for a twisted Sp(1) structure, which extends the quaternionic Kähler structure that exists on any Riemannian four-manifold boundary. We comment on applications and extensions, including generalizations to other topological twists.

  1. III Adli Bilimler Kongresi - Posterler

    Directory of Open Access Journals (Sweden)

    Adli Tıp Uzmanları Derneği ATUD

    2000-08-01

    Full Text Available POSTER ÖZETLERİ OTOPSİ UYGULAMASINA TOPLUMSAL YAKLAŞIM C. Haluk İNCE*, Nurhan İNCE** ***, Şebnem Korur FİNCANCI*, Yıldız TÜMERDEM**. ÖZET Otopsi sayısı, bir ülkenin sağlık ve yargı yönünden gelişmişliğinin kriterlerinden biridir. Çalışma bireylerin konu ile ilgili bilgi ve davranışları öğrenildiği takdirde otopsi ile ilgili olumsuz davranışlarının da en aza indirgenecek bir yöntemle eğitilmelerinin sağlanabileceği savı ile gerçekleştirilmiştir. Verileri İstanbul kentinde farklı sosyoekonomik kültürel (SEK düzeyli toplum yapısının gözlendiği ilçelerden rastlantısal örnekleme ile seçilen 342 katılıcıdan çok sorulu anketi (ön seçimli yüzyüze uygulama yöntemi ile toplanmıştır. 342 katılımcının %6l.4 (n=210'ü kadın, %38.6 (n=132'si erkektir. % 9.1 kişinin ailesinde bir otopsi deneyimi yaşamıştır. %76.9 (n:263 kişi otopsinin gerekli olduğunu ifade etmiştir. Bireylerin eğitim durumlarına göre otopsiye izin verme konusundaki görüşlerinin arasında öğrenim düzeyi yüksek olanların lehine istatistiksi açıdan anlamlı sonuç çıkmıştır. Her iki cinste de ailelerinde hangi birey olursa olsun otopsiye rıza konusundaki görüşlerinde farklılığın olmaması dikkat çekici bulunmuştur. % 16.1 (n:5' i ise dini inançlarına aykırı olduğu için otopsiye asla izin veremeyeceklerini ifade etmiştir. Toplumun SEK yapısından kaynaklanan yetersiz bilgi ülkemizdeki otopsi sayısının gelişmiş ülkelere oranla olumsuz etkilemektedir. Ancak hekim ve hekim dışı sağlık çalışanlarının da otopsi konusunda bilgi ve donanımlarını geliştirmeleri gerekmektedir. Bu çalışma otopsi sayısındaki düşüklüğün rolünü araştırmak üzere düzenlenmiştir. Anahtar Kelimeler: Otopsi, toplumsal yargı, bilgilendirme. TRAKTÖR KAZALARINDA ÖLEN OLGULARIN DEĞERLENDİRİLMESİ M.Selim ÖZKÖK*, Ufuk KATKICI. ÖZET Trafik kazaları adli tıp pratiğinde

  2. Thinking outside the box about COX-1 in Alzheimer's disease.

    Science.gov (United States)

    Frautschy, Sally A

    2010-06-01

    This article from Coma et al. shows that a salicylic acid derivative Triflusal, a platelet aggregation inhibitor and irreversible inhibitor of COX-1, can correct defects in axonal curvature and cognition in an AD transgenic mouse model (Tg2576) (Coma et al., 2010). Here we discuss the controversy over the role of COX-1 in AD, which has not been considered carefully in part due to the presumed adverse gastrointestinal effects of COX-1 antagonism. However, recent clinical data from this group as well as other groups challenges this assumption that COX-1 antagonism will be associated with side effects. Most importantly this article raises critical questions about the role of COX-1, versus COX-2 versus both in Abeta pathogenesis. The animal model data in this article as well as the recently published trial data suggest that COX-1 may play an important role in early pathogenesis and should not be ignored as a potential target for early intervention.

  3. Impaired structural correlates of memory in Alzheimer's disease mice ?

    OpenAIRE

    Badhwar, AmanPreet; Lerch, Jason P.; Hamel, Edith; Sled, John G.

    2013-01-01

    The healthy adult brain demonstrates robust learning-induced neuroanatomical plasticity. While altered neuroanatomical plasticity is suspected to be a factor mitigating the progressive cognitive decline in Alzheimer's disease (AD), it is not known to what extent this plasticity is affected by AD. We evaluated whether spatial learning and memory-induced neuroanatomical plasticity are diminished in an adult mouse model of AD (APP mice) featuring amyloid beta-driven cognitive and cerebrovascular...

  4. Recurring Anomaly Detection System (ReADS)

    Data.gov (United States)

    National Aeronautics and Space Administration — Overview: ReADS can analyze text reports, such as aviation reports and problem or maintenance records. ReADS uses text clustering algorithms to group loosely related...

  5. VALUE ADDED IN A LOGISTICS CENTER

    OpenAIRE

    Beata Skowron-Grabowska

    2010-01-01

    In the paper, the author has shown possibilities of creating added value in logistics centre from the theoretical point of view. Value creation in the supply literature commonly builds on the added value models One of such possibilities is preparing hierarchical model of creating added value through prediction of customers’ and enterprises’ in supply chain expectations. Another possibility pointed in the paper is creation of added value due to building special department of transportation and...

  6. Effective ads: new technology answers old questions

    NARCIS (Netherlands)

    L.E. Couwenberg (Linda)

    2017-01-01

    markdownabstractMarketing experts commonly refer to ads as either “emotional” or “rational” in their appeal to consumers. This dichotomy of “thinking versus feeling” is most evident when it comes to discussions around what makes an ad effective. Some studies suggest that an ad that pulls on the

  7. Automated Experiments on Ad Privacy Settings

    Directory of Open Access Journals (Sweden)

    Datta Amit

    2015-04-01

    Full Text Available To partly address people’s concerns over web tracking, Google has created the Ad Settings webpage to provide information about and some choice over the profiles Google creates on users. We present AdFisher, an automated tool that explores how user behaviors, Google’s ads, and Ad Settings interact. AdFisher can run browser-based experiments and analyze data using machine learning and significance tests. Our tool uses a rigorous experimental design and statistical analysis to ensure the statistical soundness of our results. We use AdFisher to find that the Ad Settings was opaque about some features of a user’s profile, that it does provide some choice on ads, and that these choices can lead to seemingly discriminatory ads. In particular, we found that visiting webpages associated with substance abuse changed the ads shown but not the settings page. We also found that setting the gender to female resulted in getting fewer instances of an ad related to high paying jobs than setting it to male. We cannot determine who caused these findings due to our limited visibility into the ad ecosystem, which includes Google, advertisers, websites, and users. Nevertheless, these results can form the starting point for deeper investigations by either the companies themselves or by regulatory bodies.

  8. Contextual advertising using Google AdWords and Google AdSense

    OpenAIRE

    Mihok, Radovan

    2008-01-01

    The thesis introduces contextual advertising on internet using Google AdWords. The paper describes individual steps of an ad campaign (product choosing, ad types, keywords), its management and success evaluation (calculation of ROI and modified ROI).

  9. Thermodynamic Volume in AdS/CFT

    Science.gov (United States)

    Kim, Kyung Kiu; Ahn, Byoungjoon

    2018-01-01

    In this note, we study on extended thermodynamics of AdS black holes by varying cosmological constant. We found and discussed pressure and volume of both bulk and boundary physics through AdS/CFT correspondence. In particular, we derive the relation between thermodynamic volume and a chemical potential for M2 brane dual to four dimensional AdS space. In addition, we show that thermodynamic volume of hyperbolic black hole is related to `entanglement pressure' coming from a generalized first law of entanglement entropy.

  10. Ad-hoc networking towards seamless communications

    CERN Document Server

    Gavrilovska, Liljana

    2006-01-01

    Ad-Hoc Networking Towards Seamless Communications is dedicated to an area that attracts growing interest in academia and industry and concentrates on wireless ad hoc networking paradigm. The persistent efforts to acquire the ability to establish dynamic wireless connections from anywhere to anyone with any device without prerequisite imbedded infrastructure move the communications boundaries towards ad-hoc networks. Recently, ad hoc networking has attracted growing interest due to advances in wireless communications, and developed framework for running IP based protocols. The expected degree of penetration of these networks will depend on the successful resolution of the key features. Ad-hoc networks pose many complex and open problems for researchers. Ad-Hoc Networking Towards Seamless Communications reveals the state-of-the-art in wireless ad-hoc networking and discusses some of the key research topics that are expected to promote and accelerate the commercial applications of these networks (e.g., MAC, rout...

  11. Alzheimer’s Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Maria José Menal

    2018-01-01

    Full Text Available BackgroundEvidence from patients and animal models suggests that obstructive sleep apnea (OSA may increase the risk of Alzheimer’s disease (AD and that AD is associated with reduced brain tissue stiffness.AimTo investigate whether intermittent hypoxia (IH alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA.MethodsSix-eight month old (B6C3-Tg(APPswe,PSEN1dE985Dbo/J AD mutant mice and wild-type (WT littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day or normoxia for 8 weeks. After euthanasia, the stiffness (E of 200-μm brain cortex slices was measured by atomic force microscopy.ResultsTwo-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT, but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice.ConclusionAD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

  12. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  13. p62 improves AD-like pathology by increasing autophagy.

    Science.gov (United States)

    Caccamo, A; Ferreira, E; Branca, C; Oddo, S

    2017-06-01

    The multifunctional protein p62 is associated with neuropathological inclusions in several neurodegenerative disorders, including frontotemporal lobar degeneration, amyotrophic lateral sclerosis and Alzheimer's disease (AD). Strong evidence shows that in AD, p62 immunoreactivity is associated with neurofibrillary tangles and is involved in tau degradation. However, it remains to be determined whether p62 also plays a role in regulating amyloid-β (Aβ) aggregation and degradation. Using a gene therapy approach, here we show that increasing brain p62 expression rescues cognitive deficits in APP/PS1 mice, a widely used animal model of AD. The cognitive improvement was associated with a decrease in Aβ levels and plaque load. Using complementary genetic and pharmacologic approaches, we found that the p62-mediated changes in Aβ were due to an increase in autophagy. To this end, we showed that removing the LC3-interacting region of p62, which facilitates p62-mediated selective autophagy, or blocking autophagy with a pharmacological inhibitor, was sufficient to prevent the decrease in Aβ. Overall, we believe these data provide the first direct in vivo evidence showing that p62 regulates Aβ turnover.

  14. p62 improves AD-like pathology by increasing autophagy

    Science.gov (United States)

    Caccamo, Antonella; Ferreira, Eric; Branca, Caterina; Oddo, Salvatore

    2016-01-01

    The multifunctional protein p62 is associated with neuropathological inclusions in several neurodegenerative disorders, including frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Alzheimer’s disease (AD). Strong evidence shows that in AD, p62 immunoreactivity is associated with neurofibrillary tangles and is involved in tau degradation. However, it remains to be determined whether p62 also plays a role in regulating amyloid-β aggregation and degradation. Using a gene therapy approach, here we show that increasing brain p62 expression rescues cognitive deficits in APP/PS1 mice, a widely used animal model of AD. The cognitive improvement was associated with a decrease in amyloid-β levels and plaque load. Using complementary genetic and pharmacologic approaches, we found that the p62-mediated changes in Aβ were due to an increase in autophagy. To this end, we showed that removing the LIR domain of p62, which facilitates p62-mediated selective autophagy, or blocking autophagy with a pharmacological inhibitor, was sufficient to prevent the decrease in Aβ. Overall, these data provide the first direct in vivo evidence showing that p62 regulates Aβ turnover. PMID:27573878

  15. III Adli Bilimler Kongresi - Posterler

    Directory of Open Access Journals (Sweden)

    Adli Tıp Uzmanları Derneği ATUD

    1999-12-01

    Full Text Available POSTER ÖZETLERİ ADLİ ÇOCUK OTOPSİLERİ Y.Mustafa KARAGÖZ*, Mehmet ATILGAN*, Sema (Demirçin KARAGÖZ**, Refik AKMAN*. ÖZET Çocukluk döneminde meydana gelen ölümlerin aydınlatılması, sağlık hizmetlerinin yönlendirilmesinde olduğu kadar, yasal açıdan da farklı yaklaşımları gerektirdiğinden büyük önem taşımaktadır. Bu çalışmada çocuk otopsilerine ait verilerden yararlanılarak özellikle ölüm orijinleri ve yöresel farklılıklar açısından çocuk ölümlerinin irdelenmesi amaçlanmıştır. 1987-1996 yılları arasındaki 10 yıllık süre içinde Adli Tıp Kurumu Antalya Şube Müdürlüğü’nde otopsisi yapılan 940 olgudan 18 yaş ve altındaki 172 olgu çalışma kapsamına alınarak yaş grupları, cinsiyet, ölüm nedenleri ve orijinler açısından değerlendirilmiştir. Olguların % 58.1’i erkek, % 4l.9’u kadındır. Ölüm orijinleri arasında ilk sırada kazalar (%34.3 bulunmakta, ardından intiharlar (% 19.2 gelmektedir. Kazalarda % 40.6, intiharlarda % 72.8 olmak üzere her iki gruptaki ölüm nedenleri arasında da pestisit intoksikasyonları ilk sıradadır. Doğal ölümler % 16.9 oranında olup solunum sistemi hastalıkları ön plandadır. 0-4, 5-9, ve 10-14 yaş gruplarında kazalar, 15-18 yaş grubunda ise % 36.7 lik bir oranla intihar orijinli ölümler ilk sırada yer almıştır. GÖĞÜS VE BATINA NAFİZ KESİCİ DELİCİ ALET YARALANMALARINA BAĞLI ÖLÜMLERİN RETROSPEKTİF OLARAK DEĞERLENDİRİLMESİ Süleyman GÖREN, Yaşar TIRAŞÇI. ÖZET Kesici delici aletler günümüzde çok yaygın olarak, çeşitli tip ve nitelikte evlerde ve birçok iş yerinde meslek ve sanat icrası için kullanılmaktadır. Bu aletlerin tip ve nitelikleri salt saldırı ve savunma silahı olarak kullanılan aletleri aratmayacak özelliktedir. Bu nedenle bölgedeki kesici delici alet yaralanması ile ölümler ve demografik özellikleri araştırılmaya değer görülmüştür. 1989 - 1996 y

  16. Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer's disease.

    Science.gov (United States)

    Ye, Minsook; Chung, Hwan-Suck; Lee, Chanju; Yoon, Moon Sik; Yu, A Ram; Kim, Jin Su; Hwang, Deok-Sang; Shim, Insop; Bae, Hyunsu

    2016-01-16

    Alzheimer's disease (AD) is a severe neuroinflammatory disease. CD4(+)Foxp3(+) regulatory T cells (Tregs) modulate various inflammatory diseases via suppressing Th cell activation. There are increasing evidences that Tregs have beneficial roles in neurodegenerative diseases. Previously, we found the population of Treg cells was significantly increased by bee venom phospholipase A2 (bvPLA2) treatment in vivo and in vitro. To examine the effects of bvPLA2 on AD, bvPLA2 was administered to 3xTg-AD mice, mouse model of Alzheimer's disease. The levels of amyloid beta (Aβ) deposits in the hippocampus, glucose metabolism in the brain, microglia activation, and CD4(+) T cell infiltration were analyzed to evaluate the neuroprotective effect of bvPLA2. bvPLA2 treatment significantly enhanced the cognitive function of the 3xTg-AD mice and increased glucose metabolism, as assessed with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET). The levels of Aβ deposits in the hippocampus were dramatically decreased by bvPLA2 treatment. This neuroprotective effect of bvPLA2 was associated with microglial deactivation and reduction in CD4(+) T cell infiltration. Interestingly, the neuroprotective effects of bvPLA2 were abolished in Treg-depleted mice. The present studies strongly suggest that the increase of Treg population by bvPLA2 treatment might inhibit progression of AD in the 3xTg AD mice.

  17. Joule-Thomson Expansion of Charged AdS Black Holes

    CERN Document Server

    Ökcü, Özgür

    2016-01-01

    In this paper, we study Joule-Thomson effects for charged AdS black holes. We obtain inversion temperatures and curves. We investigate similarities and differences between van der Waals fluids and charged AdS black holes for the expansion. We obtain isenthalpic curves for both systems in $T-P$ plane and determine the cooling-heating regions.

  18. Joule-Thomson expansion of the charged AdS black holes

    Energy Technology Data Exchange (ETDEWEB)

    Oekcue, Oezguer; Aydiner, Ekrem [Istanbul University, Department of Physics, Faculty of Science, Vezneciler, Istanbul (Turkey)

    2017-01-15

    In this paper, we study Joule-Thomson effects for charged AdS black holes. We obtain inversion temperatures and curves. We investigate similarities and differences between van der Waals fluids and charged AdS black holes for the expansion. We obtain isenthalpic curves for both systems in the T-P plane and determine the cooling-heating regions. (orig.)

  19. Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.

    Science.gov (United States)

    Gray, Nora E; Zweig, Jonathan A; Murchison, Charles; Caruso, Maya; Matthews, Donald G; Kawamoto, Colleen; Harris, Christopher J; Quinn, Joseph F; Soumyanath, Amala

    2017-04-12

    The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer's disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. LRRTM3 interacts with APP and BACE1 and has variants associating with late-onset Alzheimer's disease (LOAD.

    Directory of Open Access Journals (Sweden)

    Sarah Lincoln

    Full Text Available Leucine rich repeat transmembrane protein 3 (LRRTM3 is member of a synaptic protein family. LRRTM3 is a nested gene within α-T catenin (CTNNA3 and resides at the linkage peak for late-onset Alzheimer's disease (LOAD risk and plasma amyloid β (Aβ levels. In-vitro knock-down of LRRTM3 was previously shown to decrease secreted Aβ, although the mechanism of this is unclear. In SH-SY5Y cells overexpressing APP and transiently transfected with LRRTM3 alone or with BACE1, we showed that LRRTM3 co-localizes with both APP and BACE1 in early endosomes, where BACE1 processing of APP occurs. Additionally, LRRTM3 co-localizes with APP in primary neuronal cultures from Tg2576 mice transduced with LRRTM3-expressing adeno-associated virus. Moreover, LRRTM3 co-immunoprecipitates with both endogenous APP and overexpressed BACE1, in HEK293T cells transfected with LRRTM3. SH-SY5Y cells with knock-down of LRRTM3 had lower BACE1 and higher CTNNA3 mRNA levels, but no change in APP. Brain mRNA levels of LRRTM3 showed significant correlations with BACE1, CTNNA3 and APP in ∼400 humans, but not in LRRTM3 knock-out mice. Finally, we assessed 69 single nucleotide polymorphisms (SNPs within and flanking LRRTM3 in 1,567 LOADs and 2,082 controls and identified 8 SNPs within a linkage disequilibrium block encompassing 5'UTR-Intron 1 of LRRTM3 that formed multilocus genotypes (MLG with suggestive global association with LOAD risk (p = 0.06, and significant individual MLGs. These 8 SNPs were genotyped in an independent series (1,258 LOADs and 718 controls and had significant global and individual MLG associations in the combined dataset (p = 0.02-0.05. Collectively, these results suggest that protein interactions between LRRTM3, APP and BACE1, as well as complex associations between mRNA levels of LRRTM3, CTNNA3, APP and BACE1 in humans might influence APP metabolism and ultimately risk of AD.

  1. Static Einstein-Maxwell Black Holes with No Spatial Isometries in AdS Space.

    Science.gov (United States)

    Herdeiro, Carlos A R; Radu, Eugen

    2016-11-25

    We explicitly construct static black hole solutions to the fully nonlinear, D=4, Einstein-Maxwell-anti-de Sitter (AdS) equations that have no continuous spatial symmetries. These black holes have a smooth, topologically spherical horizon (section), but without isometries, and approach, asymptotically, global AdS spacetime. They are interpreted as bound states of a horizon with the Einstein-Maxwell-AdS solitons recently discovered, for appropriate boundary data. In sharp contrast to the uniqueness results for a Minkowski electrovacuum, the existence of these black holes shows that single, equilibrium, black hole solutions in an AdS electrovacuum admit an arbitrary multipole structure.

  2. Effects of ad placement and type on consumer responses to podcast ads.

    Science.gov (United States)

    Ritter, Eric A; Cho, Chang-Hoan

    2009-10-01

    The purpose of this study was to understand the effects of podcast ad placement and podcast ad type on consumers' perceived intrusiveness, perceived irritation, attitude toward the ad, and ad avoidance. Our 2 x 2 (traditional ad vs. sponsorship by beginning vs. middle) experimental study found that sponsorships generated better consumer responses than did traditional ads and that podcast ads placed at the beginning of audio podcasts yielded better consumer responses than those placed in the middle. Implications for marketers and advertisers are discussed.

  3. Oral lactoferrin protects against experimental candidiasis in mice.

    Science.gov (United States)

    Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

    2015-01-01

    To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

  4. Depletion of coagulation factor XII ameliorates brain pathology and cognitive impairment in Alzheimer disease mice.

    Science.gov (United States)

    Chen, Zu-Lin; Revenko, Alexey S; Singh, Pradeep; MacLeod, A Robert; Norris, Erin H; Strickland, Sidney

    2017-05-04

    Vascular abnormalities and inflammation are found in many Alzheimer disease (AD) patients, but whether these changes play a causative role in AD is not clear. The factor XII (FXII) -initiated contact system can trigger both vascular pathology and inflammation and is activated in AD patients and AD mice. We have investigated the role of the contact system in AD pathogenesis. Cleavage of high-molecular-weight kininogen (HK), a marker for activation of the inflammatory arm of the contact system, is increased in a mouse model of AD, and this cleavage is temporally correlated with the onset of brain inflammation. Depletion of FXII in AD mice inhibited HK cleavage in plasma and reduced neuroinflammation, fibrinogen deposition, and neurodegeneration in the brain. Moreover, FXII-depleted AD mice showed better cognitive function than untreated AD mice. These results indicate that FXII-mediated contact system activation contributes to AD pathogenesis, and therefore this system may offer novel targets for AD treatment. © 2017 by The American Society of Hematology.

  5. Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

    Science.gov (United States)

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li

    2014-01-01

    Alzheimer’s disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and d-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics. PMID:25196440

  6. Alzheimer's disease-like impaired cognition in endothelial-specific megalin-null mice.

    Science.gov (United States)

    Dietrich, Marcelo; Antequera, Desiree; Pascual, Consuelo; Castro, Nerea; Bolos, Marta; Carro, Eva

    2014-01-01

    Megalin has been suggested to be involved in Alzheimer's disease (AD), mediating blood-brain barrier (BBB) transport of multiple ligands, including amyloid-β peptide (Aβ), but also neuroprotective factors. Because no transgenic model is currently available to study this concept, we have obtained transgenic mice blocking megalin expression at the BBB. These endothelial megalin deficient (EMD) mice developed increased anxiety behavior and impaired learning ability and recognition memory, similar to symptoms described in AD. Degenerating neurons were also observed in the cerebral cortex of EMD mice. In view of our findings we suggest that, in mice, megalin deficiency at the BBB leads to neurodegeneration.

  7. Mitochondrial Dysfunction in Neocortex and Hippocampus of Olfactory Bulbectomized Mice, a Model of Alzheimer's Disease.

    Science.gov (United States)

    Avetisyan, A V; Samokhin, A N; Alexandrova, I Y; Zinovkin, R A; Simonyan, R A; Bobkova, N V

    2016-06-01

    Structural and functional impairments of mitochondria in brain tissues in the pathogenesis of Alzheimer's disease (AD) cause energy deficiency, increased generation of reactive oxygen species (ROS), and premature neuronal death. However, the causal relations between accumulation of beta-amyloid (Aβ) peptide in mitochondria and mitochondrial dysfunction, as well as molecular mechanisms underlying deleterious effects of both these factors in sporadic AD, the most common form in humans, remain unknown. Here we used olfactory bulbectomized (OBX) mice of NMRI strain as a model for sporadic AD. Five weeks after surgery, the OBX mice developed major behavioral and biochemical features of AD neurodegeneration, including spatial memory loss, increased brain levels of Aβ, and energy deficiency. Mitochondria isolated from the neocortex and hippocampus of OBX mice displayed severe functional impairments, such as low NADH oxidation rate, reduced transmembrane potential, and decreased cytochrome c oxidase (complex IV) activity that correlated with high levels of soluble Aβ1-40. Mitochondria from OBX mice showed increased contents of lipid peroxidation products, indicative of the development of oxidative stress. We found that neurodegeneration caused by olfactory bulbectomy is accompanied by energy metabolism disturbances and oxidative stress in brain mitochondria similar to those occurring in transgenic animals - familial AD models and patients with sporadic AD. Therefore, OBX mice can serve as a valid AD model for investigating the mechanisms of AD neurodegeneration, drug testing, and development of therapeutic strategies for AD treatment.

  8. Scrutiny Heightens for "Value Added" Research Methods

    Science.gov (United States)

    Viadero, Debra

    2008-01-01

    As value-added research designs gain in popularity and undergo increasing scrutiny, experts are beginning to wave cautionary flags about how best to make use of them in education. Value-added techniques for measuring student achievement appeal to administrators and policymakers at all levels of education because they quantify the gains that…

  9. Queueing Models for Mobile Ad Hoc Networks

    NARCIS (Netherlands)

    de Haan, Roland

    2009-01-01

    This thesis presents models for the performance analysis of a recent communication paradigm: \\emph{mobile ad hoc networking}. The objective of mobile ad hoc networking is to provide wireless connectivity between stations in a highly dynamic environment. These dynamics are driven by the mobility of

  10. Validity of Maxwell equal area law for black holes conformally coupled to scalar fields in $$\\text {AdS}_5$$ AdS 5 spacetime

    National Research Council Canada - National Science Library

    Miao, Yan-Gang; Xu, Zhen-Ming

    2017-01-01

    We investigate the $$P{-}V$$ P - V criticality and the Maxwell equal area law for a five-dimensional spherically symmetric AdS black hole with a scalar hair in the absence of and in the presence of a Maxwell field, respectively...

  11. Holographic complexity and fidelity susceptibility as holographic information dual to different volumes in AdS

    Directory of Open Access Journals (Sweden)

    N.S. Mazhari

    2017-03-01

    Full Text Available The holographic complexity and fidelity susceptibility have been defined as new quantities dual to different volumes in AdS. In this paper, we will use these new proposals to calculate both of these quantities for a variety of interesting deformations of AdS. We obtain the holographic complexity and fidelity susceptibility for an AdS black hole, Janus solution, a solution with cylindrical symmetry, an inhomogeneous background and a hyperscaling violating background. It is observed that the holographic complexity depends on the size of the subsystem for all these solutions and the fidelity susceptibility does not have any such dependence.

  12. Holographic complexity and fidelity susceptibility as holographic information dual to different volumes in AdS

    Energy Technology Data Exchange (ETDEWEB)

    Mazhari, N.S., E-mail: najmemazhari86@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Momeni, Davood, E-mail: davoodmomeni78@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Bahamonde, Sebastian, E-mail: sebastian.beltran.14@ucl.ac.uk [Department of Mathematics, University College London, Gower Street, London, WC1E 6BT (United Kingdom); Faizal, Mir, E-mail: mirfaizalmir@googlemail.com [Irving K. Barber School of Arts and Sciences, University of British Columbia - Okanagan, 3333 University Way, Kelowna, British Columbia, V1V 1V7 (Canada); Department of Physics and Astronomy, University of Lethbridge, Lethbridge, Alberta, T1K 3M4 (Canada); Myrzakulov, Ratbay, E-mail: rmyrzakulov@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan)

    2017-03-10

    The holographic complexity and fidelity susceptibility have been defined as new quantities dual to different volumes in AdS. In this paper, we will use these new proposals to calculate both of these quantities for a variety of interesting deformations of AdS. We obtain the holographic complexity and fidelity susceptibility for an AdS black hole, Janus solution, a solution with cylindrical symmetry, an inhomogeneous background and a hyperscaling violating background. It is observed that the holographic complexity depends on the size of the subsystem for all these solutions and the fidelity susceptibility does not have any such dependence.

  13. Thermodynamic geometry and phase transitions of AdS braneworld black holes

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Pankaj, E-mail: cpankaj@iitk.ac.in; Sengupta, Gautam, E-mail: sengupta@iitk.ac.in

    2017-02-10

    The thermodynamics and phase transitions of charged RN–AdS and rotating Kerr–AdS black holes in a generalized Randall–Sundrum braneworld are investigated in the framework of thermodynamic geometry. A detailed analysis of the thermodynamics, stability and phase structures in the canonical and the grand canonical ensembles for these AdS braneworld black holes are described. The thermodynamic curvatures for both these AdS braneworld black holes are computed and studied as a function of the thermodynamic variables. Through this analysis we illustrate an interesting dependence of the phase structures on the braneworld parameter for these black holes.

  14. Google Advertising Tools Cashing in with AdSense and AdWords

    CERN Document Server

    Davis, Harold

    2010-01-01

    With this book, you'll learn how to take full advantage of Google AdWords and AdSense, the sophisticated online advertising tools used by thousands of large and small businesses. This new edition provides a substantially updated guide to advertising on the Web, including how it works in general, and how Google's advertising programs in particular help you make money. You'll find everything you need to work with AdWords, which lets you generate text ads to accompany specific search term results, and AdSense, which automatically delivers precisely targeted text and image ads to your website.

  15. Inflation in AdS/CFT

    Energy Technology Data Exchange (ETDEWEB)

    Freivogel, Ben; /Stanford U., Phys. Dept. /LBL, Berkeley; Hubeny, Veronika E.; /LBL, Berkeley /Durham U., Dept. of Math.; Maloney, Alexander; /Stanford U., Phys. Dept.; Myers, Rob; /Perimeter Inst. Theor. Phys. /Waterloo U.; Rangamani, Mukund; /LBL, Berkeley /Durham U., Dept. of Math.; Shenker, Stephen; /Stanford U., Phys. Dept.

    2005-10-07

    We study the realization of inflation within the AdS/CFT correspondence. We assume the existence of a string landscape containing at least one stable AdS vacuum and a (nearby) metastable de Sitter state. Standard arguments imply that the bulk physics in the vicinity of the AdS minimum is described by a boundary CFT. We argue that large enough bubbles of the dS phase, including those able to inflate, are described by mixed states in the CFT. Inflating degrees of freedom are traced over and do not appear explicitly in the boundary description. They nevertheless leave a distinct imprint on the mixed state. Analytic continuation allows us, in principle, to recover a large amount of nonperturbatively defined information about the inflating regime. Our work also shows that no scattering process can create an inflating region, even by quantum tunneling, since a pure state can never evolve into a mixed state under unitary evolution.We study the realization of inflation within the AdS/CFT correspondence. We assume the existence of a string landscape containing at least one stable AdS vacuum and a (nearby) metastable de Sitter state. Standard arguments imply that the bulk physics in the vicinity of the AdS minimum is described by a boundary CFT. We argue that large enough bubbles of the dS phase, including those able to inflate, are described by mixed states in the CFT. Inflating degrees of freedom are traced over and do not appear explicitly in the boundary description. They nevertheless leave a distinct imprint on the mixed state. Analytic continuation allows us, in principle, to recover a large amount of nonperturbatively defined information about the inflating regime. Our work also shows that no scattering process can create an inflating region, even by quantum tunneling, since a pure state can never evolve into a mixed state under unitary evolution.

  16. [Premature immunosenescence in triple-transgenic mice for Alzheimer's disease].

    Science.gov (United States)

    Mate, Ianire; Cruces, Julia; Vida, Carmen; Sanfeliu, Coral; Manassra, Rashed; Giménez-Llort, Lydia; De la Fuente, Mónica

    2014-01-01

    A deterioration of the neuroimmunoendocrine network has been observed in Alzheimer's disease (AD). However, the peripheral immune response has hardly been investigated in this pathology. Since some immune function parameters have been established as good markers of the rate of ageing, and can predict longevity, the aim of the present work was to study some of these functions in splenic leucocytes in transgenic mice for AD of different ages. Young female (4 ± 1 months), adult (9 ± 1 months), and mature (12 ± 1 months) triple-transgenic mice for AD (3 xTgAD) and non-transgenic (NTg) control mice of the same ages were used. The chemotaxis, the anti-tumour activity of « natural killer » (NK) cells and the lymphoproliferative response in the presence of the mitogens concanavalin A and lipopolysaccharide, functions that decrease with age, were determined in splenic leucocytes. In addition, the differences in lifespan between 3 xTgAD and NTg were studied in parallel using other animals, until their death through natural causes. In 3 xTgAD, with respect to NTg, chemotaxis decreased at all ages studied, whereas in lymphoproliferative response this reduction was shown at 4 months and 9 months. NK activity was diminished only in young 3 xTgAD with respect to NTg. The 3 xTgAD showed a shorter lifespan than the NTg control group. The 3 xTgAD mice show a premature immunosenescence, which could explain their early mortality. The determination of these immune functions at peripheral level could serve as a marker of the progression of the Alzheimer's disease. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

  17. Notch activation drives adipocyte dedifferentiation and tumorigenic transformation in mice.

    Science.gov (United States)

    Bi, Pengpeng; Yue, Feng; Karki, Anju; Castro, Beatriz; Wirbisky, Sara E; Wang, Chao; Durkes, Abigail; Elzey, Bennett D; Andrisani, Ourania M; Bidwell, Christopher A; Freeman, Jennifer L; Konieczny, Stephen F; Kuang, Shihuan

    2016-09-19

    Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of the lack of animal models, the cellular origin and molecular regulation of LPS remain unclear. Here, we report that mice with adipocyte-specific activation of Notch signaling (Ad/N1ICD) develop LPS with complete penetrance. Lineage tracing confirms the adipocyte origin of Ad/N1ICD LPS. The Ad/N1ICD LPS resembles human dedifferentiated LPS in histological appearance, anatomical localization, and gene expression signature. Before transformation, Ad/N1ICD adipocytes undergo dedifferentiation that leads to lipodystrophy and metabolic dysfunction. Although concomitant Pten deletion normalizes the glucose metabolism of Ad/N1ICD mice, it dramatically accelerates the LPS prognosis and malignancy. Transcriptomes and lipidomics analyses indicate that Notch activation suppresses lipid metabolism pathways that supply ligands to Pparγ, the master regulator of adipocyte homeostasis. Accordingly, synthetic Pparγ ligand supplementation induces redifferentiation of Ad/N1ICD adipocytes and tumor cells, and prevents LPS development in Ad/N1ICD mice. Importantly, the Notch target HES1 is abundantly expressed in human LPS, and Notch inhibition suppresses the growth of human dedifferentiated LPS xenografts. Collectively, ectopic Notch activation is sufficient to induce dedifferentiation and tumorigenic transformation of mature adipocytes in mouse. © 2016 Bi et al.

  18. Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cheng Cheng

    2007-02-01

    Full Text Available Recombinant adenoviral (rAd vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5 vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs was independent of the coxsackievirus and adenovirus receptor (CAR, its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines.

  19. Intravenous administration of the conditionally replicative adenovirus Ad5-Δ24RGD induces regression of osteosarcoma lung metastases

    Directory of Open Access Journals (Sweden)

    Gerritsen Winald R

    2008-01-01

    Full Text Available Abstract Metastatic osteosarcoma (OS has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Δ24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Δ24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Δ24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1–3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of >158 in PBS-treated control mice to 58 in Ad5-Δ24RGD-treated mice (p = 0.15. Moreover, mice treated at weeks 5–7 showed a significantly reduced lung weight (decrease of tumor mass, p 149, p = 0.12 compared to PBS treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Δ24RGD might be a promising new treatment strategy for metastatic osteosarcoma.

  20. Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social tasks.

    Science.gov (United States)

    Hsieh, Lawrence S; Wen, John H; Miyares, Laura; Lombroso, Paul J; Bordey, Angélique

    2017-01-10

    Inbred mouse strains have been used preferentially for behavioral testing over outbred counterparts, even though outbred mice reflect the genetic diversity in the human population better. Here, we compare the sociability of widely available outbred CD1 mice with the commonly used inbred C57BL/6J (C57) mice in the one-chamber social interaction test and the three-chamber sociability test. In the one-chamber task, intra-strain pairs of juvenile, non-littermate, male CD1 or C57 mice display a series of social and aggressive behaviors. While CD1 and C57 pairs spend equal amount of time socializing, CD1 pairs spend significantly more time engaged in aggressive behaviors than C57 mice. In the three-chamber task, sociability of C57 mice was less dependent on acclimation paradigms than CD1 mice. Following acclimation to all three chambers, both groups of age-matched male mice spent more time in the chamber containing a stranger mouse than in the empty chamber, suggesting that CD1 mice are sociable like C57 mice. However, the observed power suggests that it is easier to achieve statistical significance with C57 than CD1 mice. Because the stranger mouse could be considered as a novel object, we assessed for a novelty effect by adding an object. CD1 mice spend more time in the chamber with a stranger mouse than that a novel object, suggesting that their preference is social in nature. Thus, outbred CD1 mice are as appropriate as inbred C57 mice for studying social behavior using either the single or the three-chamber test using a specific acclimation paradigm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Evaluation of polymer shielding for adenovirus serotype 6 (Ad6 for systemic virotherapy against human prostate cancers

    Directory of Open Access Journals (Sweden)

    Tien V Nguyen

    2016-01-01

    Full Text Available Oncolytic viruses hold promise as “self-amplifying” cancer therapies wherein a virally killed cell can produce thousands of new viral “drugs” that can kill more cancer cells. Adenoviruses (Ads are one family of oncolytic viruses. Most human studies have used human Ad serotype 5 (Ad5. Unfortunately, most patients are already immune to Ad5 increasing the likelihood that the agent will be neutralized if used as a cancer therapy. In this work, lower seroprevalence Ad6 was tested as a systemic therapy for prostate cancer. Ad5 and Ad6 were injected intravenously a single time in nude mice bearing human prostate tumors, and toxicity and efficacy were assessed. Ad6 was chemically shielded with polyethylene glycol (PEG to test if this would further improve its pharmacology. Ad6 produced 30-fold lower liver damage and less toxicity than Ad5. Ad6 significantly repressed the growth of androgen-resistant human DU145 prostate tumors and androgen-sensitive LNCaP tumors after single intravenous injection. PEGylation did not change virus distribution, but blunted liver damage and cytokine production by Ad6. PEGylated Ad6 eradicated LNCaP tumors and maintained body mass, but lost potency against the more challenging DU145 tumors. These and other data suggest that low seroprevalent Ad6 has better efficacy and safety than the benchmark oncolytic virus Ad5 for systemic therapy of prostate cancer. These data also indicate that PEGylation may improve Ad6 safety, but that this shielding may reduce oncolytic efficacy after intravenous treatment.

  2. Collapse and Nonlinear Instability of AdS Space with Angular Momentum

    Science.gov (United States)

    Choptuik, Matthew W.; Dias, Óscar J. C.; Santos, Jorge E.; Way, Benson

    2017-11-01

    We present a numerical study of rotational dynamics in AdS5 with equal angular momenta in the presence of a complex doublet scalar field. We determine that the endpoint of gravitational collapse is a Myers-Perry black hole for high energies and a hairy black hole for low energies. We investigate the time scale for collapse at low energies E , keeping the angular momenta J ∝E in anti-de Sitter (AdS) length units. We find that the inclusion of angular momenta delays the collapse time, but retains a t ˜1 /E scaling. We perturb and evolve rotating boson stars, and find that boson stars near AdS space appear stable, but those sufficiently far from AdS space are unstable. We find that the dynamics of the boson star instability depend on the perturbation, resulting either in collapse to a Myers-Perry black hole, or development towards a stable oscillating solution.

  3. Quantum corrections to short folded superstring in AdS × S × M

    DEFF Research Database (Denmark)

    Beccaria, M.; Macorini, G.

    2013-01-01

    We consider integrable superstring theory on AdS × S × M where M = T or M = S × S with generic ratio of the radii of the two 3-spheres. We compute the one-loop energy of a short folded string spinning in AdS and rotating in S. The computation is performed by world-sheet small spin perturbation...... in the Bethe Ansatz. Remarkably, this contribution E turns out to be independent on the radii ratio. In the M = T limit, we discuss how E relates to a recent proposal for the dressing phase tested in the su(2) sector. We point out some difficulties suggesting that quantization of the AdS classical finite......-gap equations could be subtler than the easier AdS × S case....

  4. Impaired cognition in depression and Alzheimer (AD: a gradient from depression to depression in AD

    Directory of Open Access Journals (Sweden)

    Narahyana Bom de Araujo

    2014-09-01

    Full Text Available Objective To assess cognition in major depressed (MD, Alzheimer's disease (AD, and depression in AD elderly. Method Subjects were evaluated by Mini Mental, Rey Auditory Verbal Learning Test, Rey Complex Figure, Digit Span, Similarities, Trail Making A/B, Verbal Fluency and Stroop. One-way ANOVA and multivariate models were used to compare the performance of each group on neuropsychological tests. Results We evaluated 212 subjects. Compared to MD, attention, working memory, processing speed and recall showed significantly better in controls. Controls showed significantly higher performance in all cognitive measures, except in attention compared to AD. Verbal fluency, memory, processing speed and abstract reasoning in MD was significantly higher compared to AD. AD was significantly better in general cognitive state than depression in AD. All other cognitive domains were similar. Conclusion A decreasing gradient in cognition appeared from the control to depression in AD, with MD and AD in an intermediate position.

  5. Orbiting strings in AdS black holes and N=4 SYM at finite temperature

    CERN Document Server

    Armoni, Adi; Petkou, Anastasios C

    2002-01-01

    Following Gubser, Klebanov and Polyakov [hep-th/0204051], we study strings in AdS black hole backgrounds. With respect to the pure AdS case, rotating strings are replaced by orbiting strings. We interpret these orbiting strings as CFT states of large spin similar to glueballs propagating through a gluon plasma. The energy and the spin of the orbiting string configurations are associated with the energy and the spin of states in the dual finite temperature N=4 SYM theory. We analyse in particular the limiting cases of short and long strings. Moreover, we perform a thermodynamic study of the angular momentum transfer from the glueball to the plasma by considering string orbits around rotating AdS black holes. We find that standard expectations, such as the complete thermal dissociation of the glueball, are borne out after subtle properties of rotating AdS black holes are taken into account.

  6. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Directory of Open Access Journals (Sweden)

    Jun Kurai

    Full Text Available An Asian dust storm (ADS contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil in asthma model mice.Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df, and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF were measured, and airway inflammation was examined histopathologically.Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles.These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  7. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Science.gov (United States)

    Kurai, Jun; Watanabe, Masanari; Tomita, Katsuyuki; Sano, Hiroyuki; Yamasaki, Hiroyuki Sano Akira; Yamasaki, Akira; Shimizu, Eiji

    2014-01-01

    An Asian dust storm (ADS) contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil) in asthma model mice. Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df), and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured, and airway inflammation was examined histopathologically. Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL)-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles. These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  8. Anxiety-like behavior and dysregulation of miR-34a in triple transgenic mice of Alzheimer's disease.

    Science.gov (United States)

    Zhang, Y-L; Xing, R-Z; Luo, X-B; Xu, H; Chang, R C-C; Zou, L-Y; Liu, J-J; Yang, X-F

    2016-07-01

    MicroRNAs (miRNAs) play an important role in the development of the brain and also implicated in the pathogenesis of neurological diseases such as Alzheimer's disease (AD). Recent studies implied that dysregulation of miRNAs is involved in neuropsychiatric disorders such as anxiety disorder in AD. In this study, behavioral experiments such as open field test, elevated plus maze test and light-dark box test were performed to evaluate anxiety-like behaviors in a triple transgenic mouse model of AD (3xTg-AD mice), and Q-PCR was used to measure the change of miR-34a expression. Behavioral tests revealed anxiety-like behaviors in 3xTg-AD mice. Q-PCR assay showed significantly elevated expression of miR-34a in the hippocampus of 3xTg-AD mice compared with the age- and gender-matched wild-type mice. Western-blot analysis showed that the expression of metabotropic glutamate receptor 7 (GRM7) but not fibroblast growth factor-2 (FGF2), two anxiety disorder-related target genes of miR-34a, was significantly decreased in hippocampus of 3xTg-AD mice compared with the wild-type mice. We concluded that anxiety-like behavior occurred in 3xTg-AD mice with an involvement of miR-34a/GRM7.

  9. Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.

    Science.gov (United States)

    Vandal, Milene; White, Philip J; Tournissac, Marine; Tremblay, Cyntia; St-Amour, Isabelle; Drouin-Ouellet, Janelle; Bousquet, Melanie; Traversy, Marie-Thérèse; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2016-07-01

    The sharp rise in the incidence of Alzheimer's disease (AD) at an old age coincides with a reduction in energy metabolism and core body temperature. We found that the triple-transgenic mouse model of AD (3×Tg-AD) spontaneously develops a lower basal body temperature and is more vulnerable to a cold environment compared with age-matched controls. This was despite higher nonshivering thermogenic activity, as evidenced by brown adipose tissue norepinephrine content and uncoupling protein 1 expression. A 24-hour exposure to cold (4 °C) aggravated key neuropathologic markers of AD such as: tau phosphorylation, soluble amyloid beta concentrations, and synaptic protein loss in the cortex of 3×Tg-AD mice. Strikingly, raising the body temperature of aged 3×Tg-AD mice via exposure to a thermoneutral environment improved memory function and reduced amyloid and synaptic pathologies within a week. Our results suggest the presence of a vicious cycle between impaired thermoregulation and AD-like neuropathology, and it is proposed that correcting thermoregulatory deficits might be therapeutic in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 27 CFR 19.456 - Adding denaturants.

    Science.gov (United States)

    2010-04-01

    ... Denaturation § 19.456 Adding denaturants. Denaturants and spirits shall be mixed in packages, tanks, or bulk... methods of mixing denaturants and spirits if he deems such denaturation will not hinder effective...

  11. The contribution of technology to added value

    CERN Document Server

    Fernandes, António S C

    2013-01-01

    There is a wide consensus that introduction of technology to the production process contributes to an overall economic value, however, confusion between technology, knowledge and capital often makes value calculations ambiguous and non-objective. The Contribution of Technology to Added Value addresses not only this issue of definition but also provides a production model to assess the value contribution of technology within the production process. A clarification  of fundamental semantics  provides a significant taxonomy for technology dependence, and allows understanding and modeling of how knowledge, technology and capital individually contribute to production and to value adding. A new technology dependence taxonomy is proposed and assessed following chapters explaining growth models, the KTC model and technology index values. Balancing theoretical knowledge with real-world data and applications The Contribution of Technology to Added Value clarifies the issue of value adding for a range of different vie...

  12. Hypoglycaemia when adding sulphonylurea to metformin

    DEFF Research Database (Denmark)

    Andersen, Stig Ejdrup; Christensen, Mikkel

    2016-01-01

    when added to metformin. METHODS: A systematic review identified RCTs lasting 12-52 weeks and evaluating SUs added to inadequate metformin monotherapy (≥1000 mg/day) in type 2 diabetes. Adding RCTs investigating the active comparators from the identified SU trials, we established a coherent network...... of hypoglycaemia was lowest with gliclazide compared to glipizide (OR 0.22, CrI: 0.05 to 0.96), glimepiride (OR 0.40, CrI: 0.13 to 1.27), and glibenclamide (OR 0.21, CrI: 0.03 to 1.48). A major limitation is varying definitions of hypoglycaemia across studies. CONCLUSIONS: When added to metformin, gliclazide...

  13. An Alternative Path to the Boundary - the CFT as the Fourier Space of AdS

    OpenAIRE

    Tolfree, Ian M.

    2008-01-01

    In this paper we shed new light on the AdS/CFT duality by interpreting the CFT as the Fourier space of AdS. We make use of well known integral geometry techniques to derive the Fourier transformation of a function defined on the AdS hyperboloid. We show that the Fourier Transformation of a function on the hyperboloid is a function defined on the boundary. We find that the Green's functions from the literature are actually the Fourier weights (i.e. plane wave solutions) of the transformation a...

  14. The Tetrahedral Zamolodchikov Algebra and the {AdS_5× S^5} S-matrix

    Science.gov (United States)

    Mitev, Vladimir; Staudacher, Matthias; Tsuboi, Zengo

    2017-08-01

    The S-matrix of the {AdS_5× S^5} string theory is a tensor product of two centrally extended su{(2|2)\\ltimes R^2 S-matrices, each of which is related to the R-matrix of the Hubbard model. The R-matrix of the Hubbard model was first found by Shastry, who ingeniously exploited the fact that, for zero coupling, the Hubbard model can be decomposed into two XX models. In this article, we review and clarify this construction from the AdS/CFT perspective and investigate the implications this has for the {AdS_5× S^5} S-matrix.

  15. Countering A2/AD with Swarming

    Science.gov (United States)

    2016-04-01

    inferior force can deny or delay a decisive engagement through time or attrition ultimately changing the political calculus.6 Using chess as an...deterrence in a non-nuclear scenario. Conventional deterrence is largely based on perceptions . Creating the wrong perception can cause conventional...necessarily defeat an enemy’s A2/AD strategy. Rather, the swarm needs to only create a perception that the U.S. is willing to fight within the A2/AD

  16. Mobile Offloading in Wireless Ad Hoc Networks

    OpenAIRE

    Kalejaiye, Gabriel B. T.; Rondina, João A. S. R.; Albuquerque, Leonardo V. V. L.; Pereira, Taís L.; Campos, Luiz F. O.; Melo, Raphael A. S.; Mascarenhas, Daniel S.; Carvalho, Marcelo M.

    2014-01-01

    This paper describes a strategy that was designed, implemented, and presented at the {\\it Mobile Ad Hoc Networking Interoperability and Cooperation (MANIAC) Challenge 2013}. The theme of the MANIAC Challenge 2013 was ``Mobile Data Offloading,'' and consisted on developing and comparatively evaluating strategies to offload infrastructure access points via customer ad hoc forwarding using handheld devices (e.g., tablets and smartphones). According to the challenge rules, a hop-by-hop bidding co...

  17. New Features in the ADS Abstract Service

    Science.gov (United States)

    Eichhorn, G.; Accomazzi, A.; Grant, C. S.; Henneken, E.; Kurtz, M. J.; Murray, S. S.

    2004-12-01

    The ADS now provides a search system for close to 4 million records. The data are organized in 4 databases, Astronomy/Planetary Sciences, Physics/Geophysics, Instrumentation, and ArXiv Preprints. The ADS is a NASA funded project and is free to use for everybody world-wide. We have recently extracted a large number of references from article reference lists. We now have over 16 million citing/cited reference pairs. This provides a very comprehensive citation database. During the last year we implemented a full text search system. This allows you to search the full text of all journals that we have scanned. This provides a unique way to find information, especially from the older literature. We recently implemented a customized notification service, called myADS. This service lets you specify several queries that are executed against new entries in the database whenever the database is updated. It also informs about new citations to your articles and new preprints, as well as what other articles are of interest to the users of the ADS. The ADS can be accessed at http://ads.harvard.edu

  18. Gauge symmetries and holographic anomalies of Chern-Simons and transgression AdS gravity

    Energy Technology Data Exchange (ETDEWEB)

    Mora, Pablo [Centro Universitario Regional Este (CURE), Universidad de la República, Uruguay,Ruta 9 Km 207, Rocha (Uruguay)

    2015-04-20

    We review the issue of gauge and gravitational anomalies with backgrounds, offering a new outlook on some aspects of these questions. We compute the holographic anomalies of hypothetical theories dual, in the sense of the AdS-CFT correspondence, to Chern-Simons AdS gravity. Those anomalies are either gauge anomalies, associated to the AdS gauge group of the theory, or diffeomorphism anomalies, with each kind related to the other. AdS gauge anomalies include Weyl, Lorentz (gravitational) and gauge translations while diffeomorphism anomalies include gravitational and Weyl (or scale) anomalies. Our results therefore go beyond previous investigations on Chern-Simons AdS gravity holograpic anomalies, that dealt only with Weyl anomalies. Furthermore, our calculations were done allowing a non vanishing torsion, unlike previous works that considered only the zero torsion, or metric, case. As a result of using suitable action principles for Chern-Simons AdS gravity, coming from Transgression forms, we obtain finite results without the need for further regularization. Our results are of potential interest for Lovelock gravity theories, as it has been shown that the boundary terms dictated by the transgressions for Chern-Simons gravity are also suitable to regularize Lovelock theories. The Wess-Zumino consistency condition ensures that anomalies of the generic form computed here should appear for these and other theories.

  19. Supersymmetric AdS_2× Σ _2 solutions from tri-sasakian truncation

    Science.gov (United States)

    Karndumri, Parinya

    2017-10-01

    A class of AdS_2× Σ _2, with Σ _2 being a two-sphere or a hyperbolic space, solutions within four-dimensional N=4 gauged supergravity coupled to three-vector multiplets with dyonic gauging is identified. The gauged supergravity has a non-semisimple SO(3)\\ltimes (T^3,\\hat{T}^3) gauge group and can be obtained from a consistent truncation of 11-dimensional supergravity on a tri-sasakian manifold. The maximally symmetric vacua contain AdS_4 geometries with N=1,3 supersymmetry corresponding to N=1 and N=3 superconformal field theories (SCFTs) in three dimensions. We find supersymmetric solutions of the form AdS_2× Σ _2 preserving two supercharges. These solutions describe twisted compactifications of the dual N=1 and N=3 SCFTs and should arise as near horizon geometries of dyonic black holes in asymptotically AdS_4 space-time. Most solutions have hyperbolic horizons although some of them exhibit spherical horizons. These provide a new class of AdS_2× Σ _2 geometries with known M-theory origin.

  20. Age-related changes of dopamine, noradrenaline and adrenaline in adrenal glands of mice.

    Science.gov (United States)

    Amano, Akiko; Tsunoda, Makoto; Aigaki, Toshiro; Maruyama, Naoki; Ishigami, Akihito

    2013-04-01

    Catecholamines, which are physiologically important neurotransmitters and hormones, apparently decrease in the brain and plasma as some species age. Because this observation has engendered controversy, we used mice to investigate whether age-related changes occur in adrenal catecholamine levels and in the expression of catecholamine synthetic enzymes. Adrenal glands were collected from male C57BL/6NCr mice at the ages of 6, 12 and 24 months. Catecholamines, such as dopamine (DA), noradrenaline (NA) and adrenaline (AD) from those glands, were measured by using a highly sensitive liquid chromatographic method with peroxyoxalate chemiluminescence reaction detection. Tyrosine hydroxylase (TH), dopa decarboxylase, dopamine beta hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression levels were measured by quantitative real-time polymerase chain reaction. Although DA levels in the adrenals of 24-month-old mice were higher than in 6- and 12-month-old mice, the AD content decreased with age. In such mice, the ratio of DA to NA at 24 months was lower than at 12 months, and the ratio of NA to AD content at 24 months was significantly lower than at 6 months. The mRNA expression ratios in TH, DBH and PNMT in 24-month-old mice were all lower than in 12-month-old mice. These results strongly suggest that catecholamine synthesis, in general, declines with aging in the adrenal glands of mice and that AD, in particular, undergoes a significant decrease with advancing age. © 2012 Japan Geriatrics Society.

  1. AdS/CFT duality user guide

    CERN Document Server

    Natsuume, Makoto

    2015-01-01

    This book describes applications of the AdS/CFT duality to the "real world." The AdS/CFT duality is an idea that originated from string theory and is a powerful tool for analyzing strongly-coupled gauge theories using classical gravitational theories. In recent years, it has been shown that one prediction of AdS/CFT is indeed close to the experimental result of the real quark–gluon plasma. Since then, the AdS/CFT duality has been applied to various fields of physics; examples are QCD, nuclear physics, condensed-matter physics, and nonequilibrium physics.   The aim of this book is to provide background materials such as string theory, black holes, nuclear physics, condensed-matter physics, and nonequilibrium physics as well as key applications of the AdS/CFT duality in a single volume. The emphasis throughout the book is on a pedagogical and intuitive approach focusing on the underlying physical concepts. It also includes step-by-step computations for important results, which are useful for beginners.   Th...

  2. Non-spherical collapse in AdS and early thermalization in RHIC

    Science.gov (United States)

    Oh, Eunseok; Sin, Sang-Jin

    2013-10-01

    In the flat space, non-spherical shells collapse to give globular cluster after many oscillations. We show that in anti de Sitter space, they form black holes in one dynamical time. We propose that this is the mechanism of early thermalization in strong quark-gluon plasma in gravity dual. This is traced back to the a remarkable property of AdS: the period in radial motion is amplitude independent in spite of the non-linearity of the equation of motion. We investigate the interaction effect numerically and observe the same qualitative behavior for the attractive forces. For repulsive interactions, particles halt at a small but finite radius for long time due to the specific structure of the bulk AdS propagator. It helps hair creation in the AdS black hole.

  3. Thermal stability analysis of nonlinearly charged asymptotic AdS black hole solutions

    Science.gov (United States)

    Dehghani, M.; Hamidi, S. F.

    2017-08-01

    In this paper, the four-dimensional nonlinearly charged black hole solutions have been considered in the presence of the power Maxwell invariant electrodynamics. Two new classes of anti-de Sitter (AdS) black hole solutions have been introduced according to different amounts of the parameters in the nonlinear theory of electrodynamics. The conserved and thermodynamical quantities of either of the black hole classes have been calculated from geometrical and thermodynamical approaches, separately. It has been shown that the first law of black hole thermodynamics is satisfied for either of the AdS black hole solutions we just obtained. Through the canonical and grand canonical ensemble methods, the black hole thermal stability or phase transitions have been analyzed by considering the heat capacities with the fixed black hole charge and fixed electric potential, respectively. It has been found that the new AdS black holes are stable if some simple conditions are satisfied.

  4. On thermodynamics of AdS black holes in M-theory

    Energy Technology Data Exchange (ETDEWEB)

    Belhaj, A. [Universite Sultan Moulay Slimane, Departement de Physique, LIRST, Faculte Polydisciplinaire, Beni Mellal (Morocco); Cadi Ayyad University, High Energy Physics and Astrophysics Laboratory, FSSM, Marrakesh (Morocco); Chabab, M.; Masmar, K. [Cadi Ayyad University, High Energy Physics and Astrophysics Laboratory, FSSM, Marrakesh (Morocco); El Moumni, H. [Cadi Ayyad University, High Energy Physics and Astrophysics Laboratory, FSSM, Marrakesh (Morocco); Universite Ibn Zohr, Departement de Physique, Faculte des Sciences, Agadir (Morocco); Sedra, M.B. [Universite Ibn Tofail, Departement de Physique, LASIMO, Faculte des Sciences, Kenitra (Morocco)

    2016-02-15

    Motivated by recent work on asymptotically AdS{sub 4} black holes in M-theory, we investigate the thermodynamics and thermodynamical geometry of AdS black holes from M2- and M5-branes. Concretely, we consider AdS black holes in AdS{sub p+2} x S{sup 11-p-2}, where p = 2,5 by interpreting the number of M2- (and M5-branes) as a thermodynamical variable. More precisely, we study the corresponding phase transition to examine their stabilities by calculating and discussing various thermodynamical quantities including the chemical potential. Then we compute the thermodynamical curvatures from the Quevedo metric for M2- and M5-branes geometries to reconsider the stability of such black holes. The Quevedo metric singularities recover similar stability results provided by the phase-transition program. It has been shown that similar behaviors are also present in the limit of large N. (orig.)

  5. Spinning strings in AdS3×S3 with NS–NS flux

    Directory of Open Access Journals (Sweden)

    Rafael Hernández

    2014-11-01

    Full Text Available The sigma model describing closed strings rotating in AdS3×S3 is known to reduce to the one-dimensional Neumann–Rosochatius integrable system. In this article we show that closed spinning strings in AdS3×S3×T4 in the presence of NS–NS three-form flux can be described by an extension of the Neumann–Rosochatius system. We consider closed strings rotating with one spin in AdS3 and two different angular momenta in S3. For a class of solutions with constant radii we find the dependence of the classical energy on the spin and the angular momenta as an expansion in the square of the 't Hooft coupling of the theory.

  6. QCD Condensates and Holographic Wilson Loops for Asymptotically AdS Spaces

    Energy Technology Data Exchange (ETDEWEB)

    Quevedo, R. Carcasses [Instituto Balseiro, Centro Atomico Bariloche, 8400 San Carlos de Bariloche (Argentina); CONICET, Rivadavia 1917, 1033 Buenos Aires (Argentina); Goity, Jose L. [Hampton University, Hampton, VA 23668 (United States); Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Trinchero, Roberto C. [Instituto Balseiro, Centro Atomico Bariloche, 8400 San Carlos de Bariloche (Argentina); CONICET, Rivadavia 1917, 1033 Buenos Aires (Argentina)

    2014-02-01

    The minimization of the Nambu-Goto (NG) action for a surface whose contour defines a circular Wilson loop of radius a placed at a finite value of the coordinate orthogonal to the border is considered. This is done for asymptotically AdS spaces. The condensates of dimension n = 2, 4, 6, 8, and 10 are calculated in terms of the coefficients in the expansion in powers of the radius a of the on-shell subtracted NG action for small a->0. The subtraction employed is such that it presents no conflict with conformal invariance in the AdS case and need not introduce an additional infrared scale for the case of confining geometries. It is shown that the UV value of the gluon condensates is universal in the sense that it only depends on the first coefficients of the difference with the AdS case.

  7. Extended Hamiltonian action for arbitrary spin fields in flat and AdS space

    Science.gov (United States)

    Metsaev, R. R.

    2013-05-01

    Totally symmetric, arbitrary spin massless and massive free fields in flat and AdS space and conformal fields in flat space are studied. An extended gauge-invariant Hamiltonian action for such fields is obtained. The action is constructed out of phase space fields and Lagrangian multipliers which are free of algebraic constraints. Gauge transformations of the phase space fields and Lagrangian multipliers are derived. Use of the Poincaré parametrization of AdS space allows us to treat fields in flat space and AdS space on an equal footing. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Higher spin theories and holography’.

  8. Introduction to AdS/CFT correspondence

    CERN Document Server

    Nastase, Horatiu

    2015-01-01

    Providing a pedagogical introduction to the rapidly developing field of AdS/CFT correspondence, this is one of the first texts to provide an accessible introduction to all the necessary concepts needed to engage with the methods, tools and applications of AdS/CFT. Without assuming anything beyond an introductory course in quantum field theory, it begins by guiding the reader through the basic concepts of field theory and gauge theory, general relativity, supersymmetry, supergravity, string theory and conformal field theory, before moving on to give a clear and rigorous account of AdS/CFT correspondence. The final section discusses the more specialised applications, including QCD, quark-gluon plasma and condensed matter. This book is self-contained and learner-focused, featuring numerous exercises and examples. It is essential reading for both students and researchers across the fields of particle, nuclear and condensed matter physics.

  9. Value added meat marketing around the globe

    DEFF Research Database (Denmark)

    Grebitus, Carola; Mueller Loose, Simone

    In highly competitive meat markets it is important to offer value added products to consumers. Thus, we need to understand which attributes are especially valued by consumers. This track session will contribute to a better understanding of consumer preferences for value added meats across different...... countries and simultaneously address different stages of the food chain by acknowledging factors such as breeding, forage (fat content), meat cuts as well as product labelling and packaging. Comparing consumers’ choices for value added pork and beef across different countries is the main theme and focus...... practices will be examined and the economic and technological dimensions of meat packaging will be related to each other presenting work from the US and Germany. Lastly, we will uncover the competitive nature between different beef cuts for Italian consumers....

  10. Pengukuran Kinerja Keuangan dengan Pendekatan Egonomic Value Added dan Financial Value Added

    OpenAIRE

    Felisia

    2011-01-01

    Performance measurement has become an important indicator not only for companies but also for investors. It indicates the capability of companies in managing their capital. Performance measurement can be divided into financial and non-financial performance measurement. This article will discuss further about financial performance measurement using Economic Value Added (EVA) and Financial Value Added (FVA) Economic Value Added was developed by Stern, Stewart & Company, while Financial Value...

  11. Alternative path to the boundary: The CFT as the Fourier transform in AdS space

    Science.gov (United States)

    Tolfree, Ian M.

    2008-11-01

    In this paper we shed new light on the AdS/CFT duality by interpreting the CFT as the Fourier transform in AdS space. We make use of well-known integral geometry techniques to derive the Fourier transformation of a function defined on the AdS hyperboloid. We show that the Fourier transformation of a function on the hyperboloid is a function defined on the boundary. We find that the Green’s functions from the literature are actually the Fourier weights (i.e. plane wave solutions) of the transformation and that the boundary values of fields appearing in the correspondence are the Fourier components of the transformation. One is thus left to interpret the CFT as the quantized version of a classical theory in AdS and the dual operator as the Fourier coefficients. Group theoretic considerations are discussed in relation to the transformation and its potential use in constructing QCD-like theories. In addition, we consider possible implications involving understanding the dual of AdS black holes.

  12. iAd Production Beginner's Guide

    CERN Document Server

    Collier, Ben

    2012-01-01

    This beginner's guide focuses on getting you through all the major learning points in a smooth, logical order. You'll also see how to avoid some common pitfalls. This book is for brands, advertisers and developers who want to create compelling, emotive, iAd advertisements that generate revenue and increase brand awareness. You don't need previous experience of creating adverts or apps for iPhone and iPad, as you'll be taken through the entire process to make motion-rich, beautiful ads.

  13. Ad hoc networks telecommunications and game theory

    CERN Document Server

    Benslama, Malek; Batatia, Hadj

    2015-01-01

    Random SALOHA and CSMA protocols that are used to access MAC in ad hoc networks are very small compared to the multiple and spontaneous use of the transmission channel. So they have low immunity to the problems of packet collisions. Indeed, the transmission time is the critical factor in the operation of such networks. The simulations demonstrate the positive impact of erasure codes on the throughput of the transmission in ad hoc networks. However, the network still suffers from the intermittency and volatility of its efficiency throughout its operation, and it switches quickly to the satura

  14. Tribunales arbitrales ad hoc en el Mercosur

    OpenAIRE

    Bou Franch, Valentín

    2011-01-01

    El Mercosur tiene establecido un procedimiento obligatorio de solución de controversias comerciales entre sus Estados miembros. No obstante, en caso de surgir una controversia, el Estado demandante y el demandado pueden pactar de mutuo acuerdo que la misma no se someta al procedimiento ordinario de solución, sino a un Tribunal arbitral ad hoc. En este trabajo, se analiza la elaboración de las dos listas de árbitros, la constitución de cada Tribunal arbitral ad hoc, el procedimiento y la oblig...

  15. Adding value to corporate ventures through governance

    DEFF Research Database (Denmark)

    Skat-Rørdam, Peter

    2005-01-01

    This working paper examines the governance of corporate ventures based upon a qualitative interview based case study of a European industrial conglomerate. The purpose is to explore the value adding mechanisms of governance, that are considered more critical to the success of corporate ventures...... than the control mechanisms widely explored in connection with the governance of large public corporations. The paper provides examples of how value can be added as well as perspectives on the challenges and effectivenes here-off as evaluated by venture CEO's and venture board members...

  16. Vehicular ad hoc network security and privacy

    CERN Document Server

    Lin, X

    2015-01-01

    Unlike any other book in this area, this book provides innovative solutions to security issues, making this book a must read for anyone working with or studying security measures. Vehicular Ad Hoc Network Security and Privacy mainly focuses on security and privacy issues related to vehicular communication systems. It begins with a comprehensive introduction to vehicular ad hoc network and its unique security threats and privacy concerns and then illustrates how to address those challenges in highly dynamic and large size wireless network environments from multiple perspectives. This book is richly illustrated with detailed designs and results for approaching security and privacy threats.

  17. QCD condensates in ADS/QCD

    DEFF Research Database (Denmark)

    Bechi, Jacopo

    2009-01-01

    This paper focuses on some issues about condensates and renormalization in AdS/QCD models. In particular we consider the consistency of the AdS/QCD approach for scale dependent quantities as the chiral condensate questioned in some recent papers and the 4D meaning of the 5D cosmological constant...... in a model in which the QCD is dual to a 5D gravity theory. We will be able to give some arguments that the cosmological constant is related to the QCD gluon condensate....

  18. Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice.

    Science.gov (United States)

    Chen, Yi-Jing; Zheng, Hai-Yang; Huang, Xiu-Xian; Han, Shuang-Xue; Zhang, Dong-Sheng; Ni, Jia-Zuan; He, Xiao-Yang

    2016-01-01

    This study investigated the neuroprotective properties of icariin (an effective component of traditional Chinese herbal medicine Epimedium) on neuronal function and brain energy metabolism maintenance in a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD). 3 × Tg-AD mice as well as primary neurons were subjected to icariin treatment. Morris water maze assay, magnetic resonance spectroscopy (MRS), Western blotting, ELISA, and immunohistochemistry analysis were used to evaluate the effects of icariin administration. Icariin significantly improved spatial learning and memory retention in 3 × Tg-AD mice, promoted neuronal cell activity as identified by the enhancement of brain metabolite N-acetylaspartate level and ATP production in AD mice, preserved the expressions of mitochondrial key enzymes COX IV, PDHE1α, and synaptic protein PSD95, reduced Aβ plaque deposition in the cortex and hippocampus of AD mice, and inhibited β-site APP cleavage enzyme 1 (BACE1) expression. Icariin treatment also decreased the levels of extracellular and intracellular Aβ1-42 in 3 × Tg-AD primary neurons, modulated the distribution of Aβ along the neurites, and protected against mitochondrial fragmentation in 3 × Tg-AD neurons. Icariin shows neuroprotective effects in 3 × Tg-AD mice and may be a promising multitarget drug in the prevention/protection against AD. © 2015 John Wiley & Sons Ltd.

  19. ENEA presenta sistema ADS per trattamento scorie

    CERN Multimedia

    2002-01-01

    "Arriva il sistema Ads (Accelerator driven system) per il trattamento dei rifiuti radioattivi. Lo studio di fattibilita' per l' innovativa tecnologia, realizzato da un gruppo di lavoro congiunto Enea, Cea, Cern e Ansaldo, e' stato presentato oggi nel corso di un workshop presieduto dal premio Nobel per la fisica, Carlo Rubbia" (1/2 page).

  20. Added value: The differences that count

    Directory of Open Access Journals (Sweden)

    Dominique Bouchet

    2012-08-01

    Full Text Available Clinging to a simplistic conceptualization of the concept of added value might impair our capability to develop insights to what really matters today when companies seek to make differences within the global market. Today it is more necessary than ever to take into account the importance of language and culture as competitive factors.

  1. Accelerator development in India for ADS programme

    Indian Academy of Sciences (India)

    LEHIPA), as front-end injector of the 1 GeV accelerator for the ADS programme, has been initiated. The major components of LEHIPA (20 MeV, 30 mA) are a 50 keV ECR ion source, a 3 MeV Radio Frequency Quadrupole (RFQ) and a 20 MeV drift ...

  2. "Value Added" Gauge of Teaching Probed

    Science.gov (United States)

    Viadero, Debra

    2009-01-01

    A new study by a public and labor economist suggests that "value added" methods for determining the effectiveness of classroom teachers are built on some shaky assumptions and may be misleading. The study, due to be published in February in the "Quarterly Journal of Economics," is the first of a handful of papers now in the…

  3. CERN Enters the Second Year AD

    CERN Multimedia

    2001-01-01

    2001 is the year that physics at CERN's new Antiproton Decelerator (AD) really gets up to speed. Changes to the AD since 2000 mean that this year the three experiments, ASACUSA, ATHENA, and ATRAP have had more intense antiproton beams to work with since physics started on 7 May. CERN's Antiproton Decelerator - major improvements for 2001. The AD is a unique machine. Its job is to decelerate not accelerate particle beams, and it has to handle beam energies that vary by an unprecedented factor of 35 from injection to ejection. Since the machine was designed to operate at fixed energy in its first incarnation as a collector of antiprotons for CERN's 1980s proton antiproton collider, this factor of 35 presented a big challenge to the AD team. The team's design goal was to hang onto a quarter of the injected antiprotons through their vertiginous fall in energy, and to repeat the deceleration cycle once per minute. Improvements to the machine over the winter shutdown and through the first four weeks of 2001 run...

  4. Adding Test Generation to the Teaching Machine

    Science.gov (United States)

    Bruce-Lockhart, Michael; Norvell, Theodore; Crescenzi, Pierluigi

    2009-01-01

    We propose an extension of the Teaching Machine project, called Quiz Generator, that allows instructors to produce assessment quizzes in the field of algorithm and data structures quite easily. This extension makes use of visualization techniques and is based on new features of the Teaching Machine that allow third-party visualizers to be added as…

  5. Ad-Hoc Transient Communities Simulation

    NARCIS (Netherlands)

    Van den Berg, Bert; Van Rosmalen, Peter; Sloep, Peter; Brouns, Francis; Fetter, Sibren; Berlanga, Adriana

    2009-01-01

    Van den Berg, B., Van Rosmalen, P., Sloep, P. B., Brouns, F., Fetter, S., & Berlanga, A. J. (2009). Ad-Hoc Transient Communities Simulation. The Netlogo application is distributed as a java applet and for that matter part of an archive which contains also the NetlogoLiteJar and the index.htm to

  6. Adding calcium improves lithium ferrite core

    Science.gov (United States)

    Lessoff, H.

    1969-01-01

    Adding calcium increases uniformity of grain growth over a wide range of sintering temperatures and reduces porosity within the grain. Ferrite cores containing calcium have square hysteresis loops and high curie temperatures, making them useful in coincident current memories of digital electronic computers.

  7. The foresight of AD de Groot

    NARCIS (Netherlands)

    Jansen, E. P. W. A.; Nieuwenhuis, A. F. M.

    2013-01-01

    Study success rates in higher education were already described in an article in Pedagogische Studien in 1959. Professor A.D. de Groot, internationally well-known by his research on Thought and choice in chess, analysed the success rate figures provided by Statistics Netherlands. Based on the

  8. Epidemiological studies on cutaneous leishmaniasis in Ad ...

    African Journals Online (AJOL)

    Dawadimi region of Saudi Arabia. Methods: Data from the patients included in this retrospective study were collected from the Leishmaniasis Control Center of Ad-Dawadimi District of Saudi Arabia. A total of 370 patients with CL were recorded from ...

  9. Anomaly Detection Techniques for Ad Hoc Networks

    Science.gov (United States)

    Cai, Chaoli

    2009-01-01

    Anomaly detection is an important and indispensable aspect of any computer security mechanism. Ad hoc and mobile networks consist of a number of peer mobile nodes that are capable of communicating with each other absent a fixed infrastructure. Arbitrary node movements and lack of centralized control make them vulnerable to a wide variety of…

  10. Value-Added Analysis in Instruction

    Science.gov (United States)

    Nicholson, Michael R.; Brown, Jeffrey R.

    2010-01-01

    Value-added data provide a viable alternative for gauging school effectiveness--one virtually free of the confounding effects of student demographics and other factors relating to student learning. How is it different from other measuring methods? It concentrates on growth, rather than attainment. This strengthens the concept and measurement of…

  11. Value Added School Review Field Guide

    Science.gov (United States)

    Alberta Education, 2009

    2009-01-01

    The "Value-Added School Review (VSR)" is an analytical model designed to assist schools in identifying and addressing opportunities for school improvement. The model works best when it is focused purposefully on students and the student learning outcomes as defined in the "Guide to Education". It complements the processes…

  12. Value-Added Modeling in Physical Education

    Science.gov (United States)

    Hushman, Glenn; Hushman, Carolyn

    2015-01-01

    The educational reform movement in the United States has resulted in a variety of states moving toward a system of value-added modeling (VAM) to measure a teacher's contribution to student achievement. Recently, many states have begun using VAM scores as part of a larger system to evaluate teacher performance. In the past decade, only "core…

  13. DAWN: Dynamic Ad-hoc Wireless Network

    Science.gov (United States)

    2016-06-19

    Wireless Network 1 Introduction The network-centric battlefield includes sensors, troop carriers, unmanned air vehicle (UAV), aircraft, smart ...Bellman Control Heritage Award. • Honorary Doctorate at Technical University of Crete. • Best paper award at 2008 IEEE International Conference on Mobile Ad-hoc and Sensor Systems.

  14. Ad-Coop Positioning System (ACPS)

    DEFF Research Database (Denmark)

    Frattasi, Simone; Monti, Marco

    2008-01-01

    -hoc connections among pairs of mobiles. Specifically, peer-to-peer (P2P) communications are exploited in a mesh fashion within cellular-established clusters for cooperation-aided localization purposes (from that, the word ad-coop is derived). The major contribution of this work is the design of the data fusion...

  15. Swift Trust in Distributed Ad Hoc Teams

    Science.gov (United States)

    2007-10-04

    not visible or likely to be in close proximity . Page 22 Swift Trust in Distributed Ad hoc Teams Humansystems® mission ended, the servers were...simply allow less “ poetic license” when making judgements about other people. Perhaps asking about a more ambiguous behaviour or task would have yielded

  16. Redox Proteomic Profiling of Specifically Carbonylated Proteins in the Serum of Triple Transgenic Alzheimer’s Disease Mice

    Directory of Open Access Journals (Sweden)

    Liming Shen

    2016-04-01

    Full Text Available Oxidative stress is a key event in the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD. To investigate the role of oxidative stress in AD and to search for potential biomarkers in peripheral blood, serums were collected in this study from the 3-, 6-, and 12-month-old triple transgenic AD mice (3×Tg-AD mice and the age- and sex-matched non-transgenic (non-Tg littermates. The serum oxidized proteins were quantified by slot-blot analysis and enzyme-linked immunosorbent assay (ELISA to investigate the total levels of serum protein carbonyl groups. Western blotting, in conjunction with two-dimensional gel electrophoresis (2D-Oxyblot, was employed to identify and quantify the specifically-carbonylated proteins in the serum of 3×Tg-AD mice. The results showed that the levels of serum protein carbonyls were increased in the three month old 3×Tg-AD mice compared with the non-Tg control mice, whereas no significant differences were observed in the six and 12 months old AD mice, suggesting that oxidative stress is an early event in AD progression. With the application of 2D-Oxyblot analysis, (immunoglobin Ig gamma-2B chain C region (IGH-3, Ig lambda-2 chain C region (IGLC2, Ig kappa chain C region (IGKC, and Ig kappa chain V-V region HP R16.7 were identified as significantly oxidized proteins compared with the control. Among them IGH-3 and IGKC were validated via immunoprecipitation and Western blot analysis. Identification of oxidized proteins in the serums of 3×Tg-AD mice can not only reveal potential roles of those proteins in the pathogenesis of AD but also provide potential biomarkers of AD at the early stage.

  17. Curing color blindness--mice and nonhuman primates.

    Science.gov (United States)

    Neitz, Maureen; Neitz, Jay

    2014-08-21

    It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  18. Curing Color Blindness—Mice and Nonhuman Primates

    Science.gov (United States)

    Neitz, Maureen; Neitz, Jay

    2014-01-01

    It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. PMID:25147187

  19. An alternative perspective to observe the critical phenomena of dilaton AdS black holes

    CERN Document Server

    Mo, Jie-Xiong

    2016-01-01

    The critical phenomena of dilaton AdS black holes are probed from a totally different perspective other than the $P-v$ criticality and the $q-U$ criticality discussed in the former literature. We investigate not only the two point correlation function but also the entanglement entropy of dilaton AdS black holes. We achieve this goal by solving the equation of motion constrained by the boundary condition numerically and we concentrate on $\\delta L$ and $\\delta S$ which have been regularized by subtracting the terms in pure AdS with the same boundary region. For both the two point correlation function and the entanglement entropy, we consider $4\\times2\\times2=16$ cases due to different choices of parameters. The van der Waals like behavior can be clearly witnessed from all the $T-\\delta L$ ($T-\\delta S$) graphs for $qAdS black holes are disclosed. Furthermore, we discuss the stability of dilaton...

  20. Value Added to What? How a Ceiling in the Testing Instrument Influences Value-Added Estimation

    Science.gov (United States)

    Koedel, Cory; Betts, Julian

    2010-01-01

    Value-added measures of teacher quality may be sensitive to the quantitative properties of the student tests upon which they are based. This article focuses on the sensitivity of value added to test score ceiling effects. Test score ceilings are increasingly common in testing instruments across the country as education policy continues to…

  1. Integrability of the AdS_5 x S^5 superstring and its deformations

    NARCIS (Netherlands)

    van Tongeren, S.J.

    2013-01-01

    Based on the author's PhD thesis, this article reviews the application of integrability to the spectral problem of strings on AdS_5 x S^5 and its deformations. We begin with a pedagogical introduction to integrable field theories culminating in the description of their finite-volume spectra through

  2. On Critical Massive (Super)Gravity in adS(3)

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Hohm, Olaf; Rosseel, Jan; Sezgin, Ergin; Townsend, Paul K.; Aldaya,; Barcelo, C; Jaramillo, JL

    2011-01-01

    We review the status of three-dimensional "general massive gravity" (GMG) in its linearization about an anti-de Sitter (adS) vacuum, focusing on critical points in parameter space that yield generalizations of "chiral gravity". We then show how these results extend to,N = 1 super-GMG, expanded about

  3. The differential effects of position, ad and reader characteristics on readers' processing of newspaper ads

    NARCIS (Netherlands)

    Smit, E.G.; Neijens, P.C.; Heath, R.

    2013-01-01

    Building on previous research on the processing of newspaper ads, this comprehensive field study, with 26,556 newspaper readers and 290 unique advertisements, investigated the combined effects of position in the newspaper, ad characteristics and reader characteristics. The results show a

  4. Near horizon data and physical charges of extremal AdS black holes

    NARCIS (Netherlands)

    Astefanesei, D.; Banerjee, N.; Dutta, S.

    2011-01-01

    We compute the physical charges and discuss the properties of a large class of five-dimensional extremal AdS black holes by using the near horizon data. Our examples include baryonic and electromagnetic black branes, as well as supersymmetric spinning black holes. In the presence of the gauge

  5. Multi-Skyrmions on AdS2 × S2, rational maps and popcorn transitions

    Science.gov (United States)

    Canfora, Fabrizio; Tallarita, Gianni

    2017-08-01

    By combining two different techniques to construct multi-soliton solutions of the (3 + 1)-dimensional Skyrme model, the generalized hedgehog and the rational map ansatz, we find multi-Skyrmion configurations in AdS2 ×S2. We construct Skyrmionic multi-layered configurations such that the total Baryon charge is the product of the number of kinks along the radial AdS2 direction and the degree of the rational map. We show that, for fixed total Baryon charge, as one increases the charge density on ∂ (AdS2 ×S2) , it becomes increasingly convenient energetically to have configurations with more peaks in the radial AdS2 direction but a lower degree of the rational map. This has a direct relation with the so-called holographic popcorn transitions in which, when the charge density is high, multi-layered configurations with low charge on each layer are favored over configurations with few layers but with higher charge on each layer. The case in which the geometry is M2 ×S2 can also be analyzed.

  6. Avoiding Ad Avoidance: Factors Affecting the Perception of Online Banner Ads

    Science.gov (United States)

    Portnoy, Felix

    2012-01-01

    This dissertation examined the effect of search type, ad saliency, and ad repetition on the perception of online banner advertisements. In the first study, 48 student participants conducted simulated search tasks using mixed factorial design where search type (known-item vs. exploratory) was manipulated within-subject and the banner saliency level…

  7. Geometry and supersymmetry of heterotic warped flux AdS backgrounds

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2015-07-01

    We classify the geometries of the most general warped, flux AdS backgrounds of heterotic supergravity up to two loop order in sigma model perturbation theory. We show under some mild assumptions that there are no AdS n backgrounds with n ≠ 3. Moreover the warp factor of AdS3 backgrounds is constant, the geometry is a product AdS 3 × M 7 and such solutions preserve, 2, 4, 6 and 8 supersymmetries. The geometry of M 7 has been specified in all cases. For 2 supersymmetries, it has been found that M 7 admits a suitably restricted G 2 structure. For 4 supersymmetries, M 7 has an SU(3) structure and can be described locally as a circle fibration over a 6-dimensional KT manifold. For 6 and 8 supersymmetries, M 7 has an SU(2) structure and can be described locally as a S 3 fibration over a 4-dimensional manifold which either has an anti-self dual Weyl tensor or a hyper-Kähler structure, respectively. We also demonstrate a new Lichnerowicz type theorem in the presence of α' corrections.

  8. The complete AdS_3 x S^3 x T^4 worldsheet S-matrix

    NARCIS (Netherlands)

    Borsato, Riccardo|info:eu-repo/dai/nl/370952170; Sax, Olof Ohlsson; Sfondrini, Alessandro|info:eu-repo/dai/nl/330983083; jr, Bogdan Stefanski

    2014-01-01

    We derive the non-perturbative worldsheet S matrix for fundamental excitations of Type IIB superstring theory on AdS_3 x S^3 x T^4 with Ramond-Ramond flux. To this end, we study the off-shell symmetry algebra of the theory and its representations. We use these to determine the S matrix up to scalar

  9. The bound state S-matrix for AdS5×S5 superstring

    NARCIS (Netherlands)

    Arutyunov, G.E.; de Leeuw, M.; Torrielli, A.

    2009-01-01

    We determine the S-matrix that describes scattering of arbitrary bound states in the light-cone string theory in AdS5×S5. The corresponding construction relies on the Yangian symmetry and the superspace formalism for the bound state representations. The basic analytic structure supporting the

  10. S-matrix for strings on η-deformed AdS5 x S5

    NARCIS (Netherlands)

    Arutyunov, Gleb; Borsato, Riccardo; Frolov, Sergey

    2013-01-01

    We determine the bosonic part of the superstring sigma model Lagrangian on η-deformed AdS5 × S5, and use it to compute the perturbative world-sheet scattering matrix of bosonic particles of the model. We then compare it with the large string tension limit of the q-deformed S-matrix and find exact

  11. The S-matrix of the AdS5xS5 superstring

    NARCIS (Netherlands)

    de Leeuw, M.

    2010-01-01

    According to the gauge-string duality conjecture, the spectrum of scaling dimensions of composite gauge invariant operators of the planar maximally supersymmetric Yang-Mills theory in four dimensions should be equivalent to the energy spectrum of superstrings propagating in the AdS5 x S5 space-time,

  12. S-matrix for strings on η-deformed AdS5 x S5

    NARCIS (Netherlands)

    Arutyunov, G.E.|info:eu-repo/dai/nl/326372822; Borsato, R.|info:eu-repo/dai/nl/370952170; Frolov, S.

    2013-01-01

    We determine the bosonic part of the superstring sigma model Lagrangian on η-deformed AdS5 x S5, and use it to compute the perturbative world-sheet scattering matrix of bosonic particles of the model. We then compare it with the large string tension limit of the q-deformed S-matrix and find exact

  13. Characterization of cells transformed by Ad5/Ad12 hybrid early region I plasmids

    NARCIS (Netherlands)

    Bernards, R.A.; Houweling, A.; Schrier, P.I.; Bos, J.L.; Eb, A.J. van der

    1982-01-01

    Early region I (EI) of the human adenoviruses consists of two transcriptional units, EIa and EIb. We have constructed plasmids containing hybrid EI regions from the nononcogenic adenovirus type 5 (Ad5) and the highly oncogenic Ad12. Each plasmid essentially contains the EIa region of one serotype

  14. Covariant anomalies and Hawking radiation from Kaluza–Klein AdS ...

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics; Volume 80; Issue 2. Covariant anomalies and Hawking radiation from Kaluza–Klein AdS ... angular momentum and energy momentum tensor are derived here. Our results support the common view that Hawking radiation is the quantum effect arising at the event horizon.

  15. Of mice and men

    CERN Multimedia

    1973-01-01

    At the end of March , sixty mice were irradiated at the synchro-cyclotron in the course of an experimental programme studying radiation effects on mice and plants (Vicia faba bean roots) being carried out by the CERN Health Physics Group.

  16. Black hole formation in AdS Einstein-Gauss-Bonnet gravity

    Science.gov (United States)

    Deppe, Nils; Kolly, Allison; Frey, Andrew R.; Kunstatter, Gabor

    2016-10-01

    AdS spacetime has been shown numerically to be unstable against a large class of arbitrarily small perturbations. In [1], the authors presented a preliminary study of the effects on stability of changing the local dynamics by adding a Gauss-Bonnet term to the Einstein action. Here we provide further details as well as new results with improved numerical methods. In particular, we elucidate new structure in Choptuik scaling plots. We also provide evidence of chaotic behavior at the transition between immediate horizon formation and horizon formation after the matter pulse reflects from the AdS conformal boundary. Finally, we present data suggesting the formation of naked singularities in spacetimes with ADM mass below the algebraic bound for black hole formation.

  17. Black hole formation in AdS Einstein-Gauss-Bonnet gravity

    Energy Technology Data Exchange (ETDEWEB)

    Deppe, Nils [Cornell Center for Astrophysics and Planetary Science andDepartment of Physics, Cornell University,122 Sciences Drive, Ithaca, New York 14853 (United States); Kolly, Allison [Department of Atmospheric and Oceanic Sciences, McGill University,805 Sherbrooke Street West, Montréal, Québec H3A 0B9 (Canada); Frey, Andrew R.; Kunstatter, Gabor [Department of Physics and Winnipeg Institute for Theoretical Physics, University of Winnipeg,515 Portage Avenue, Winnipeg, Manitoba R3B 2E9 (Canada)

    2016-10-17

    AdS spacetime has been shown numerically to be unstable against a large class of arbitrarily small perturbations. In http://dx.doi.org/10.1103/PhysRevLett.114.071102, the authors presented a preliminary study of the effects on stability of changing the local dynamics by adding a Gauss-Bonnet term to the Einstein action. Here we provide further details as well as new results with improved numerical methods. In particular, we elucidate new structure in Choptuik scaling plots. We also provide evidence of chaotic behavior at the transition between immediate horizon formation and horizon formation after the matter pulse reflects from the AdS conformal boundary. Finally, we present data suggesting the formation of naked singularities in spacetimes with ADM mass below the algebraic bound for black hole formation.

  18. The MICE Online Systems

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) is designed to test transverse cooling of a muon beam, demonstrating an important step along the path toward creating future high intensity muon beam facilities. Protons in the ISIS synchrotron impact a titanium target, producing pions which decay into muons that propagate through the beam line to the MICE cooling channel. Along the beam line, particle identification (PID) detectors, scintillating fiber tracking detectors, and beam diagnostic tools identify and measure individual muons moving through the cooling channel. The MICE Online Systems encompass all tools; including hardware, software, and documentation, within the MLCR (MICE Local Control Room) that allow the experiment to efficiently record high quality data. Controls and Monitoring (C&M), Data Acquisition (DAQ), Online Monitoring and Reconstruction, Data Transfer, and Networking all fall under the Online Systems umbrella. C&M controls all MICE systems including the target, conventional an...

  19. Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rats.

    Science.gov (United States)

    Widjojoatmodjo, Myra N; Bogaert, Lies; Meek, Bob; Zahn, Roland; Vellinga, Jort; Custers, Jerome; Serroyen, Jan; Radošević, Katarina; Schuitemaker, Hanneke

    2015-10-05

    RSV is an important cause of lower respiratory tract infections in children, the elderly and in those with underlying medical conditions. Although the high disease burden indicates an urgent need for a vaccine against RSV, no licensed RSV vaccine is currently available. We developed an RSV vaccine candidate based on the low-seroprevalent human adenovirus serotypes 26 and 35 (Ad26 and Ad35) encoding the RSV fusion (F) gene. Single immunization of mice with either one of these vectors induced high titers of RSV neutralizing antibodies and high levels of F specific interferon-gamma-producing T cells. A Th1-type immune response was indicated by a high IgG2a/IgG1 ratio of RSV-specific antibodies, strong induction of RSV-specific interferon-gamma and tumor necrosis factor-alpha cytokine producing CD8 Tcells, and low RSV-specific CD4 T-cell induction. Both humoral and cellular responses were increased upon a boost with RSV-F expressing heterologous adenovirus vector (Ad35 boost after Ad26 prime or vice versa). Both single immunization and prime-boost immunization of cotton rats induced high and long-lasting RSV neutralizing antibody titers and protective immunity against lung and nasal RSV A2 virus load up to at least 30 weeks after immunization. Cotton rats were also completely protected against challenge with a RSV B strain (B15/97) after heterologous prime-boost immunization. Lungs from vaccinated animals showed minimal damage or inflammatory infiltrates post-challenge, in contrast to animals vaccinated with formalin-inactivated virus. Our results suggest that recombinant human adenoviral Ad26 and Ad35 vectors encoding the RSV F gene have the potential to provide broad and durable protection against RSV in humans, and appear safe to be investigated in infants. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Prevalence, proximity and predictors of alcohol ads in Central Harlem

    National Research Council Canada - National Science Library

    Kwate, Naa Oyo A; Jernigan, Meghan; Lee, Tammy

    2007-01-01

    Aims: This study examined the prevalence of alcohol ads, the spatial relationship between alcohol ads and schools, churches and playgrounds, and area-level determinants of alcohol ad density in Central Harlem, New York City. Methods...

  1. Evolutionary algorithms for mobile ad hoc networks

    CERN Document Server

    Dorronsoro, Bernabé; Danoy, Grégoire; Pigné, Yoann; Bouvry, Pascal

    2014-01-01

    Describes how evolutionary algorithms (EAs) can be used to identify, model, and minimize day-to-day problems that arise for researchers in optimization and mobile networking. Mobile ad hoc networks (MANETs), vehicular networks (VANETs), sensor networks (SNs), and hybrid networks—each of these require a designer’s keen sense and knowledge of evolutionary algorithms in order to help with the common issues that plague professionals involved in optimization and mobile networking. This book introduces readers to both mobile ad hoc networks and evolutionary algorithms, presenting basic concepts as well as detailed descriptions of each. It demonstrates how metaheuristics and evolutionary algorithms (EAs) can be used to help provide low-cost operations in the optimization process—allowing designers to put some “intelligence” or sophistication into the design. It also offers efficient and accurate information on dissemination algorithms topology management, and mobility models to address challenges in the ...

  2. Quantum load balancing in ad hoc networks

    Science.gov (United States)

    Hasanpour, M.; Shariat, S.; Barnaghi, P.; Hoseinitabatabaei, S. A.; Vahid, S.; Tafazolli, R.

    2017-06-01

    This paper presents a novel approach in targeting load balancing in ad hoc networks utilizing the properties of quantum game theory. This approach benefits from the instantaneous and information-less capability of entangled particles to synchronize the load balancing strategies in ad hoc networks. The quantum load balancing (QLB) algorithm proposed by this work is implemented on top of OLSR as the baseline routing protocol; its performance is analyzed against the baseline OLSR, and considerable gain is reported regarding some of the main QoS metrics such as delay and jitter. Furthermore, it is shown that QLB algorithm supports a solid stability gain in terms of throughput which stands a proof of concept for the load balancing properties of the proposed theory.

  3. Constrained Delaunay Triangulation for Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    D. Satyanarayana

    2008-01-01

    Full Text Available Geometric spanners can be used for efficient routing in wireless ad hoc networks. Computation of existing spanners for ad hoc networks primarily focused on geometric properties without considering network requirements. In this paper, we propose a new spanner called constrained Delaunay triangulation (CDT which considers both geometric properties and network requirements. The CDT is formed by introducing a small set of constraint edges into local Delaunay triangulation (LDel to reduce the number of hops between nodes in the network graph. We have simulated the CDT using network simulator (ns-2.28 and compared with Gabriel graph (GG, relative neighborhood graph (RNG, local Delaunay triangulation (LDel, and planarized local Delaunay triangulation (PLDel. The simulation results show that the minimum number of hops from source to destination is less than other spanners. We also observed the decrease in delay, jitter, and improvement in throughput.

  4. Supporting Dynamic Ad hoc Collaboration Capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Deborah A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Berket, Karlo [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2003-07-14

    Modern HENP experiments such as CMS and Atlas involve as many as 2000 collaborators around the world. Collaborations this large will be unable to meet often enough to support working closely together. Many of the tools currently available for collaboration focus on heavy-weight applications such as videoconferencing tools. While these are important, there is a more basic need for tools that support connecting physicists to work together on an ad hoc or continuous basis. Tools that support the day-to-day connectivity and underlying needs of a group of collaborators are important for providing light-weight, non-intrusive, and flexible ways to work collaboratively. Some example tools include messaging, file-sharing, and shared plot viewers. An important component of the environment is a scalable underlying communication framework. In this paper we will describe our current progress on building a dynamic and ad hoc collaboration environment and our vision for its evolution into a HENP collaboration environment.

  5. AD/HD: POSSIBLE DIAGNOSIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    Karl REICHELT

    2008-12-01

    Full Text Available The purpose of this paper is to show that a more exact diagnosis and dietary intervention in AD/HD (Attention Deficit/Hyperactivity Di­sor­der is possible and probable. The clinical symptom based diagnosis we suggest may be supplemented with physiological tests. A ge­netic and environmental inter-action is clearly involved and explainable using phenyl­ke­tonuria as a model.Method: Examining peer reviewed published papers on gut to blood, blood to brain inter­action and effect of interventions in AD/HD and our own studies in the field. The various treatment options are discussed.Results: It can be shown that a gut to brain activity is possible and probable, and dietary intervention is useful and probably safer than drugs. Preliminary data on a small five year follow up of dietary intervention is shown.

  6. Accelerator development in India for ADS programme

    Indian Academy of Sciences (India)

    Abstract. At BARC, development of a Low Energy High Intensity Proton Accelerator. (LEHIPA), as front-end injector of the 1 GeV accelerator for the ADS programme, has been initiated. The major components of LEHIPA (20 MeV, 30 mA) are a 50 keV ECR ion source, a 3 MeV Radio Frequency Quadrupole (RFQ) and a 20 ...

  7. AdS-Flows and Weyl Gravity

    CERN Document Server

    Schmidhuber, C

    2000-01-01

    An analogy is noted between RG flow equations in 4-dimensional gauge theory, as derived from the AdS/CFT correspondence, and the RG flow equations in 4-dimensional field theory coupled to a particular limit of Weyl supergravity. This suggests a possible theory of dynamical 3-branes with fluctuating 4-dimensional conformal factor. The argument involves a map from flows in 4-dimensional gauge theories to flows in a class of 2-dimensional sigma models.

  8. Drag cancellation by added-mass pumping

    CERN Document Server

    Giorgio-Serchi, F

    2016-01-01

    A submerged body subject to a sudden shape-change experiences large forces due to the variation of added-mass energy. While this phenomenon has been studied for single actuation events, application to sustained propulsion requires studying \\textit{periodic} shape-change. We do so in this work by investigating a spring-mass oscillator submerged in quiescent fluid subject to periodic changes in its volume. We develop an analytical model to investigate the relationship between added-mass variation and viscous damping and demonstrate its range of application with fully coupled fluid-solid Navier-Stokes simulations at large Stokes number. Our results demonstrate that the recovery of added-mass kinetic energy can be used to completely cancel the viscous damping of the fluid, driving the onset of sustained oscillations with amplitudes as large as four times the average body radius $r_0$. A quasi-linear relationship is found to link the terminal amplitude of the oscillations $X$, to the extent of size change $a$, wit...

  9. Transmission Strategies in MIMO Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Fakih Khalil

    2009-01-01

    Full Text Available Abstract Precoding problem in multiple-input multiple-output (MIMO ad hoc networks is addressed in this work. Firstly, we consider the problem of maximizing the system mutual information under a power constraint. In this context, we give a brief overview of the nonlinear optimization methods, and systematically we compare their performances. Then, we propose a fast and distributed algorithm based on the quasi-Newton methods to give a lower bound of the system capacity of MIMO ad hoc networks. Our proposed algorithm solves the maximization problem while diminishing the amount of information in the feedback links needed in the cooperative optimization. Secondly, we propose a different problem formulation, which consists in minimizing the total transmit power under a quality of signal constraint. This novel problem design is motivated since the packets are captured in ad hoc networks based on their signal-to-interference-plus-noise ratio (SINR values. We convert the proposed formulation into semidefinite optimization problem, which can be solved numerically using interior point methods. Finally, an extensive set of simulations validates the proposed algorithms.

  10. PERBEDAAN PERUSAHAN PENCIPTA ECONOMIC VALUE ADDED POSITIF DENGAN ECONOMIC VALUE ADDED NEGATIF

    Directory of Open Access Journals (Sweden)

    Suripto Suripto

    2017-03-01

    Full Text Available This research was to explain and analyze the different variable of Inflation Rate,Exchange Rate, Interest Rate, Ratio Plant Asset, Size Measure Company, Profitability, Growth ,LD / E, TD / TA, Stock of Return, Book To Market between company having Economic ValueAdded ( Positive and company having Economic Value Added ( Negative . Analysis which wasused in this research was multivariate analysis of variant (MANOVA. There was different variableof Inflation Rate, Exchange Rate, Interest Rate, Ratio Plant Asset, Size Measure Company,Profitability, Growth , LD / E, TD / TA, Stock of Return, Book To Market between companyhaving Economic Value Added ( Positive and negative EVA. However, by partial, only differentsale size was significant

  11. AD HOC Networks for the Autonomous Car

    Science.gov (United States)

    Ron, Davidescu; Negrus, Eugen

    2017-10-01

    The future of the vehicle is made of cars, roads and infrastructures connected in a two way automated communication in a holistic system. It is a mandatory to use Encryption to maintain Confidentiality, Integrity and Availability in an ad hoc vehicle network. Vehicle to Vehicle communication, requires multichannel interaction between mobile, moving and changing parties to insure the full benefit from data sharing and real time decision making, a network of such users referred as mobile ad hoc network (MANET), however as ad hoc networks were not implemented in such a scale, it is not clear what is the best method and protocol to apply. Furthermore the visibility of secure preferred asymmetric encrypted ad hoc networks in a real time environment of dense moving autonomous vehicles has to be demonstrated, In order to evaluate the performance of Ad Hoc networks in changing conditions a simulation of multiple protocols was performed on large number of mobile nodes. The following common routing protocols were tested, DSDV is a proactive protocol, every mobile station maintains a routing table with all available destinations, DSR is a reactive routing protocol which allows nodes in the MANET to dynamically discover a source route across multiple network hops, AODV is a reactive routing protocol Instead of being proactive. It minimizes the number of broadcasts by creating routes based on demand, SAODV is a secure version of AODV, requires heavyweight asymmetric cryptographic, ARIANDE is a routing protocol that relies on highly efficient symmetric cryptography the concept is primarily based on DSR. A methodical evolution was performed in a various density of transportation, based on known communication bench mark parameters including, Throughput Vs. time, Routing Load per packets and bytes. Out of the none encrypted protocols, It is clear that in terms of performance of throughput and routing load DSR protocol has a clear advantage the high node number mode. The encrypted

  12. A reference accelerator scheme for ADS applications

    Science.gov (United States)

    Biarrotte, Jean-Luc; Bousson, Sébastien; Junquera, Tomas; Mueller, Alex C.; Olivier, Aurélia

    2006-06-01

    Accelerator Driven Systems (ADS) for transmutation of nuclear waste typically require 350 MeV-1 GeV accelerators delivering proton fluxes of 5-10 mA for demonstrators, and 20-50 mA for large industrial systems. Thus, such machines belong to the category of the so-called HPPA (High-Power Proton Accelerators), with multi-megawatt beam power. HPPA are presently developed and constructed at great pace for their broad utility in fundamental or applied science. Compared to other HPPA, many features and requirements are similar for the ADS driver. However, there is a need for exceptional reliability: because of the induced thermal stress to the sub-critical core, the number of unwanted "beam-trips" should not exceed a few per year, a requirement that is several orders of magnitude above usual performance. Consecutive to the work of the European Technical Working Group (ETWG) on ADS, the Preliminary Design Study of an Experimental ADS (PDS-XADS) was launched in 2001 as a 5th Framework Program EC project. A special Working Package (WP3) was dedicated to the accelerator design, taking especially into account that the issue of "beam-trips" could be a potential "show-stopper" for ADS technology in general. A reference solution, based on a linear superconducting accelerator with its associated doubly achromatic beam line, has been worked out to some detail. For high reliability, the proposed design is intrinsically fault tolerant, relying on highly modular "de-rated" components associated to a fast digital feedback system. The proposed solution also appears to be robust concerning operational aspects like maintenance and radioprotection. A roadmap for construction as well as the required consolidated budget was elaborated. A program for the remaining R&D, focused on experimental reliability demonstration of prototypical components has been elaborated. This R&D will be performed in the 6th Framework Program EC project EUROTRANS, which presently is just starting. EC Contract No

  13. D-instanton in AdS sub 5 and instanton in SYM sub 4

    CERN Document Server

    Chu, C S; Wu, Y Y

    1999-01-01

    Following the observation of Banks and Green that the D-instantons in AdS sub 5 correspond to the instantons in four-dimensional supersymmetric Yang-Mills theory, we study in more detail this correspondence for individual instantons. The supergravity solution for a D-instanton in AdS sub 5 is found using the ansatz used previously for D-instantons in flat space. We check that the actions and supersymmetries match between the D-instanton solution and the Yang-Mills instanton. Generalizing this result, we propose that any supergravity solution satisfying the ansatz corresponds to a (anti-) self-dual Yang-Mills configuration. Using this ansatz a family of identities for correlation functions in the supersymmetric Yang-Mills theory are derived.

  14. AdS5 vacua from type IIB supergravity on T 1 ,1

    Science.gov (United States)

    Louis, Jan; Muranaka, Constantin

    2017-06-01

    We study maximally supersymmetric Anti-de Sitter backgrounds in consistent \\mathcal{N}=2 truncations of type IIB supergravity compactified on the Sasaki-Einstein manifold T 1,1. In particular, we focus on truncations that contain fields coming from the nontrivial second and third cohomology forms on T 1,1. These give rise to \\mathcal{N}=2 super-gravity coupled to two vector- and two hypermultiplets (Betti-vector truncation) or one vector- and three hypermultiplets (Betti-hyper truncation), respectively. We find that both truncations admit AdS5 backgrounds with the gauge group always being broken but containing at least an U(1) R factor. Moreover, in both cases we show that the moduli space of AdS vacua is nontrivial and of maximal dimension. Finally, we explicitly compute the metrics on these moduli spaces.

  15. P-V criticality of AdS black holes in a general framework

    CERN Document Server

    Majhi, Bibhas Ranjan

    2016-01-01

    Interpreting the cosmological constant as pressure, it has been observed that AdS black holes behave as van der Waals system. The critical exponents for the phase transition for all AdS black holes are exactly same as those for the van der Waals system. Till now this has been observed case by case. Here, without using any specific form of the black hole metric, we present a general framework based on just two universal inputs. These are the general forms of the Smarr formula and the first law of thermodynamics. We find that the same values of the critical exponents can be obtained by this general analysis. Therefore there is no need to investigate for a particular metric. The importance of our analysis is that it highlights the observed universality, as well as revels the reason for such universality.

  16. Free field realization of superstring theory on AdS3

    Energy Technology Data Exchange (ETDEWEB)

    Hofman, Diego M. E-mail: dmhof@yahoo.com.ar; Nunez, Carmen A

    2004-07-01

    The Coulomb gas representation of expectation values in SU(2) conformal field theory developed by Dotsenko is extended to the SL(2,R) WZW model and applied to bosonic string theory on AdS3 and to Type II superstrings on AdS3 x N. The spectral flow symmetry is included in the free field realization of vertex operators creating superstring states of both Ramond and Neveu-Schwarz sectors. Conjugate representations for these operators are constructed and a background charge prescription is designed to compute correlation functions. Two and three point functions of bosonic and fermionic string states in arbitrary winding sectors are calculated. Scattering amplitudes that violate winding number conservation are also discussed. (author)

  17. AdS5 compactifications with punctures in massive IIA supergravity

    Science.gov (United States)

    Bah, Ibrahima; Passias, Achilleas; Tomasiello, Alessandro

    2017-11-01

    We find AdS5 solutions holographically dual to compactifications of six- dimensional N = (1, 0) supersymmetric field theories on Riemann surfaces with punctures. We simplify a previous analysis of supersymmetric AdS5 IIA solutions, and with a suitable Ansatz we find explicit solutions organized in three classes, where an O8-D8 stack, D6-and D4-branes are simultaneously present, localized and partially localized. The D4-branes are smeared over the Riemann surface and this is interpreted as the presence of a uniform distribution of punctures. For the first class we identify the corresponding six-dimensional theory as an E-string theory coupled to a quiver gauge theory. The second class of solutions lacks D6-branes and its central charge scales as n 5/2, suggesting a five-dimensional origin for the dual field theory. The last class has elements of the previous two.

  18. Bulk Fields and Supersymmetry in a Slice of AdS

    CERN Document Server

    Gherghetta, Tony; Gherghetta, Tony; Pomarol, Alex

    2000-01-01

    Five-dimensional models where the bulk is a slice of AdS have the virtue of solving the hierarchy problem. The electroweak scale is generated by a ``warp'' factor of the induced metric on the brane where the standard model fields live. However, it is not necessary to confine the standard model fields on the brane and we analyze the possibility of having the fields actually living in the slice of AdS. Specifically, we study the behaviour of fermions, gauge bosons and scalars in this geometry and their implications on electroweak physics. These scenarios can provide an explanation of the fermion mass hierarchy by warp factors. We also consider the case of supersymmetry in the bulk, and analyze the conditions on the mass spectrum. Finally, a model is proposed where the warp factor generates a small (TeV) supersymmetry-breaking scale, with the gauge interactions mediating the breaking to the scalar sector.

  19. Comments on Penrose Limit of AdS_4 x M^{1,1,1}

    OpenAIRE

    Ahn, Changhyun

    2002-01-01

    We construct a Penrose limit of AdS_4 x M^{1,1,1} where M^{1,1,1}= SU(3) x SU(2) x U(1)/(SU(2) x U(1) x U(1)) that provides the pp-wave geometry equal to the one in the Penrose limit of AdS_4 x S^7. There exists a subsector of three dimensional N=2 dual gauge theory which has enhanced N=8 maximal supersymmetry. We identify operators in the N=2 gauge theory with supergravity KK excitations in the pp-wave geometry and describe how the gauge theory operators made out of two kinds of chiral field...

  20. Non-Supersymmetric CS-Matter Theories with Known AdS Duals

    Directory of Open Access Journals (Sweden)

    Davide Forcella

    2011-01-01

    Full Text Available We consider three-dimensional conformal field theories living on a stack of N anti-M2 branes at the tip of eight-dimensional supersymmetric cones. The corresponding supergravity solution is obtained by changing sign to the four-form in the Freund-Rubin solution representing M2 branes (“skew-whiffing” transformation and it is known to be stable. The existence of these non-supersymmetric, stable field theories, at least in the large N limit, is a peculiarity of the AdS 4 / CFT 3 correspondence with respect to the usual AdS 5 / CFT 4 , and it is worthwhile to study it. We analyze in detail the KK spectrum of the skew-whiffed solution associated with S 7 / ℤ k and we speculate on the natural field content for a candidate non-supersymmetric dual field theory.

  1. Weak field collapse in AdS: introducing a charge density

    Energy Technology Data Exchange (ETDEWEB)

    Caceres, Elena [Facultad de Ciencias, Universidad de Colima,Bernal Diaz del Castillo 340, Colima (Mexico); Theory Group, Department of Physics and Texas Cosmology Center,The University of Texas at Austin,2515 Speedway Stop C1608, Austin, TX 78712 (United States); Kundu, Arnab [Department de Física Fondamental & Institut de Ciències del Cosmos,Universitat de Barcelona,Martí i Franquès 1, E-08028 Barcelona (Spain); Saha Institute of Nuclear Physics,1/AF Bidhannagar, Kolkata 700064 (India); Pedraza, Juan F. [Theory Group, Department of Physics and Texas Cosmology Center,The University of Texas at Austin,2515 Speedway Stop C1608, Austin, TX 78712 (United States); Perimeter Institute for Theoretical Physics,31 Caroline Street North Waterloo, Ontario N2L 2Y5 (Canada); Yang, Di-Lun [Crete Center for Theoretical Physics, Department of physics, University of Crete,71003, Heraklion (Greece); Department of physics, Chung-Yuan Christian University,Chung Pei Road, Chung-Li 32023, Taiwan (China)

    2015-06-17

    We study the effect of a non-vanishing chemical potential on the thermalization time of a strongly coupled large N{sub c} gauge theory in (2+1)-dimensions, using a specific bottom-up gravity model in asymptotically AdS space. We first construct a perturbative solution to the gravity-equations, which dynamically interpolates between two AdS black hole backgrounds with different temperatures and chemical potentials, in a perturbative expansion of a bulk neutral scalar field. In the dual field theory, this corresponds to a quench dynamics by a marginal operator, where the corresponding coupling serves as the small parameter in which the perturbation is carried out. The evolution of non-local observables, such as the entanglement entropy, suggests that thermalization time decreases with increasing chemical potential. We also comment on the validity of our perturbative analysis.

  2. Hawking Radiation-Quasinormal Modes Correspondence for Large AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Dao-Quan Sun

    2017-01-01

    Full Text Available It is well-known that the nonstrictly thermal character of the Hawking radiation spectrum generates a natural correspondence between Hawking radiation and black hole quasinormal modes. This main issue has been analyzed in the framework of Schwarzschild black holes, Kerr black holes, and nonextremal Reissner-Nordstrom black holes. In this paper, by introducing the effective temperature, we reanalyze the nonstrictly thermal character of large AdS black holes. The results show that the effective mass corresponding to the effective temperature is approximatively the average one in any dimension. And the other effective quantities can also be obtained. Based on the known forms of frequency in quasinormal modes, we reanalyze the asymptotic frequencies of the large AdS black hole in three and five dimensions. Then we get the formulas of the Bekenstein-Hawking entropy and the horizon’s area quantization with functions of the quantum “overtone” number n.

  3. Correlation functions in the CFT sub d /AdS sub d sub + sub 1 correspondence

    CERN Document Server

    Freedman, D Z; Matusis, A; Rastelli, L

    1999-01-01

    Conformal techniques are applied to the calculation of integrals on AdS sub d sub + sub 1 space which define correlators of composite operators in the superconformal field theory on the d-dimensional boundary. The 3-point amplitudes for scalar fields of arbitrary mass and gauge fields in the AdS supergravity are calculated explicitly. For three gauge fields we compare in detail with the known conformal structure of the SU(4) flavor current correlator of the N = 4, d = 4 SU(N) SYM theory. Results agree with the free field approximation as would be expected from superconformal non-renormalization theorems. In studying the Ward identity relating to for (non-marginal) scalar composite operators O sup I , we find that there is a subtlety in obtaining the normalization of from the supergravity action integral.

  4. Symmetry operators of Killing spinors and superalgebras in AdS5

    Science.gov (United States)

    Ertem, Ümit

    2016-04-01

    We construct the first-order symmetry operators of Killing spinor equation in terms of odd Killing-Yano forms. By modifying the Schouten-Nijenhuis bracket of Killing-Yano forms, we show that the symmetry operators of Killing spinors close into an algebra in AdS5 spacetime. Since the symmetry operator algebra of Killing spinors corresponds to a Jacobi identity in extended Killing superalgebras, we investigate the possible extensions of Killing superalgebras to include higher-degree Killing-Yano forms. We found that there is a superalgebra extension but no Lie superalgebra extension of the Killing superalgebra constructed out of Killing spinors and odd Killing-Yano forms in AdS5 background.

  5. Phases of planar AdS black holes with axionic charge

    Science.gov (United States)

    Caldarelli, Marco M.; Christodoulou, Ariana; Papadimitriou, Ioannis; Skenderis, Kostas

    2017-04-01

    Planar AdS black holes with axionic charge have finite DC conductivity due to momentum relaxation. We obtain a new family of exact asymptotically AdS4 black branes with scalar hair, carrying magnetic and axion charge, and we study the thermodynamics and dynamic stability of these, as well as of a number of previously known electric and dyonic solutions with axion charge and scalar hair. The scalar hair for all solutions satisfy mixed boundary conditions, which lead to modified holographic Ward identities, conserved charges and free energy, relative to those following from the more standard Dirichlet boundary conditions. We show that properly accounting for the scalar boundary conditions leads to well defined first law and other thermodynamic relations. Finally, we compute the holographic quantum effective potential for the dual scalar operator and show that dynamical stability of the hairy black branes is equivalent to positivity of the energy density.

  6. Finite-size corrections for quantum strings on AdS4 x CP3

    DEFF Research Database (Denmark)

    Astolfi, D.; Puletti, V.G.M.; Grignani, G.

    2011-01-01

    We revisit the calculation of curvature corrections to the pp-wave energy of type IIA string states on AdS4×CP3 initiated in arXiv:0807.1527. Using the near pp-wave Hamiltonian found in arXiv:0912.2257, we compute the first non-vanishing correction to the energy of a set of bosonic string states...

  7. Logarithmic corrections to entropy of magnetically charged AdS4 black holes

    Science.gov (United States)

    Jeon, Imtak; Lal, Shailesh

    2017-11-01

    Logarithmic terms are quantum corrections to black hole entropy determined completely from classical data, thus providing a strong check for candidate theories of quantum gravity purely from physics in the infrared. We compute these terms in the entropy associated to the horizon of a magnetically charged extremal black hole in AdS4×S7 using the quantum entropy function and discuss the possibility of matching against recently derived microscopic expressions.

  8. Generalized thermodynamic identity and new Maxwell's law for charged AdS black hole

    CERN Document Server

    Zhao, Zixu

    2016-01-01

    We study the thermodynamic properties of the RN-AdS black hole in full phase space and propose a generalized thermodynamic identity. As an example, we use it to find relations of thermodynamical coefficients between the grand canonical and canonical ensembles. We also show, for the first order phase transition, that the usual Maxwell's equal area law should be extended to a new form for the RN-AdS black hole.

  9. State Operator Correspondence and Entanglement in AdS2/CFT1

    Directory of Open Access Journals (Sweden)

    Ashoke Sen

    2011-07-01

    Full Text Available Since Euclidean global AdS2 space represented as a strip has two boundaries, the state-operator correspondence in the dual CFT1 reduces to the standard map from the operators acting on a single copy of the Hilbert space to states in the tensor product of two copies of the Hilbert space. Using this picture we argue that the corresponding states in the dual string theory living on AdS2 × K are described by the twisted version of the Hartle–Hawking states, the twists being generated by a large unitary group of symmetries that this string theory must possess. This formalism makes natural the dual interpretation of the black hole entropy—as the logarithm of the degeneracy of ground states of the quantum mechanics describing the low energy dynamics of the black hole, and also as an entanglement entropy between the two copies of the same quantum theory living on the two boundaries of global AdS2 separated by the event horizon.

  10. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    Science.gov (United States)

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-05-27

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.

  11. Assessment of dental fluorosis in Mmp20 +/- mice.

    Science.gov (United States)

    Sharma, R; Tye, C E; Arun, A; MacDonald, D; Chatterjee, A; Abrazinski, T; Everett, E T; Whitford, G M; Bartlett, J D

    2011-06-01

    The molecular mechanisms that underlie dental fluorosis are poorly understood. The retention of enamel proteins hallmarking fluorotic enamel may result from impaired hydrolysis and/or removal of enamel proteins. Previous studies have suggested that partial inhibition of Mmp20 expression is involved in the etiology of dental fluorosis. Here we ask if mice expressing only one functional Mmp20 allele are more susceptible to fluorosis. We demonstrate that Mmp20 (+/-) mice express approximately half the amount of MMP20 as do wild-type mice. The Mmp20 heterozygous mice have normal-appearing enamel, with Vickers microhardness values similar to those of wild-type control enamel. Therefore, reduced MMP20 expression is not solely responsible for dental fluorosis. With 50-ppm-fluoride (F(-)) treatment ad libitum, the Mmp20 (+/-) mice had F(-) tissue levels similar to those of Mmp20 (+/+) mice. No significant difference in enamel hardness was observed between the F(-)-treated heterozygous and wild-type mice. Interestingly, we did find a small but significant difference in quantitative fluorescence between these two groups, which may be attributable to slightly higher protein content in the Mmp20 (+/-) mouse enamel. We conclude that MMP20 plays a nominal role in dental enamel fluorosis.

  12. Assessment of Dental Fluorosis in Mmp20+/− Mice

    Science.gov (United States)

    Sharma, R.; Tye, C.E.; Arun, A.; MacDonald, D.; Chatterjee, A.; Abrazinski, T.; Everett, E.T.; Whitford, G.M.; Bartlett, J.D.

    2011-01-01

    The molecular mechanisms that underlie dental fluorosis are poorly understood. The retention of enamel proteins hallmarking fluorotic enamel may result from impaired hydrolysis and/or removal of enamel proteins. Previous studies have suggested that partial inhibition of Mmp20 expression is involved in the etiology of dental fluorosis. Here we ask if mice expressing only one functional Mmp20 allele are more susceptible to fluorosis. We demonstrate that Mmp20+/− mice express approximately half the amount of MMP20 as do wild-type mice. The Mmp20 heterozygous mice have normal-appearing enamel, with Vickers microhardness values similar to those of wild-type control enamel. Therefore, reduced MMP20 expression is not solely responsible for dental fluorosis. With 50-ppm-fluoride (F−) treatment ad libitum, the Mmp20+/− mice had F− tissue levels similar to those of Mmp20+/+ mice. No significant difference in enamel hardness was observed between the F−-treated heterozygous and wild-type mice. Interestingly, we did find a small but significant difference in quantitative fluorescence between these two groups, which may be attributable to slightly higher protein content in the Mmp20+/− mouse enamel. We conclude that MMP20 plays a nominal role in dental enamel fluorosis. PMID:21386097

  13. Plastik Sanatlarda Adli Vaka İmgeleri

    Directory of Open Access Journals (Sweden)

    Necla Rüzgar Kayıran

    2014-04-01

    Full Text Available Resim sanatıyla adli tıp arasındaki ilişkiye baktığımızda en temelde şu ayrımı görürüz: Adli tıp bir cinayeti kurban üzerinden değil, katil üzerinden düşünme eğilimindedir. Oysa resim sanatı bir cinayeti konu ederken kurban üzerinden düşünme, söz konusu katil bile olsa katili de “kurban” olarak imgeselleştirme eğilimindedir. Örneğin Caravaggio cinayet işlemiş bir sanatçıdır. Bu cinayetten duyduğu pişmanlığı “Goliath'ın Başını Kesen Davud” adlı resimle imgeselleştirir. Sanatçı, otoportresinde katil-kurban imgelerinin yer değiştiren döngüsüyle mücadele içindedir. Kesik kulağıyla Van Gogh’un, şiddete uğramış haliyle Nan Goldin’in otoportreleri yine sanatçıların kurban olarak kendilerini ifadelerinin çarpıcı birer örneğidir. Gericault’nun öldürülen suçluların kesik başlarına gizli ve derin bir şefkat eklemesi, Goya’nın parçalanarak terkedilmiş beden parçalarına resimleri aracılığıyla sahip çıkması sanatçıların cezalandırılmış suçlulara başka bir açıdan bakmamızı öneren yapıtlarına örnektir. Karakteristik adli vaka örnekleri olarak David’in “Marat’ın Ölümü” ya da Magritte’in “Tehdit Altındaki Katil” adlı resimlerinin “olay yeri” bulgularının imgesel dizilimiyle dolu olduklarını görebiliriz. Rembrandt’ın “Dr. Nicolaes Tulp’un Anatomi Dersi” adlı resmi, doktorlarla sanatçıların bakış açısındaki farkı göstermek açısından sembolik bir örnektir. Rembrandt, Aris Kindt’in elini değil, ayak ucunda duran anatomi atlasındaki eli resmetmiştir. Doktorların tümü anatomi atlasına bakarken, sanatçı, izleyicileri ölü bedene yöneltir ve bu noktadan görünen artık bir kurbana dönüşmüş olan Aris Kindt’dir. Adli tıp’ta incelenen “deliller/sonuçlar” bizi “katile/suçluya” ulaşırken, sanat tarihindeki imgeler bizi “kurbana” ulaştırır. Anahtar Kelimeler

  14. Adília Lopes – ironista

    Directory of Open Access Journals (Sweden)

    Rosa Maria Martelo

    2004-10-01

    Full Text Available O nome Adília Lopes tanto designa uma leitora profundamente interessada pela tradição poética erudita como uma assumida “poetisa pop”. E enquanto a primeira gosta de recordar referências fundamentais da Modernidade, de Rimbaud a Apollinaire, de Cesário a Pessoa, derivando para Sophia, Herberto Helder ou Sylvia Plath, ou facilmente recua no tempo literário ocidental até Diderot, S. João da Cruz e Virgílio, a segunda parece valorizar mais todo um outro universo de escrita, no qual avultam os contos infantis, as leituras da adolescência, o folhetinesco e o fait-divers das revistas femininas. Sem nunca pôr de parte as referências literárias de Adília-leitoraerudita, é sobretudo este o mundo que a “poetisa pop” gosta de reescrever, mostrando até que ponto ele é atravessado por uma insidiosa crueldade e tornando indistintas as fronteiras que o separavam (separam? da Literatura. Entre cultura erudita e cultura de massas, entre referências eruditas e uma linguagem muito próxima dos registros orais pouco vigiados, usando um verso que, por vezes, parece premeditadamente distraído num ritmo muito fácil, Adília Lopes faz apelo à memória de um mundo adolescente onde o bem e o mal, o alto e o baixo, o bom e o mau gosto pareciam irredutivelmente distintos, para tudo indiferenciar, agora, com dessacralizadora ironia. 

  15. Interpolated Sounding Value-Added Product

    Energy Technology Data Exchange (ETDEWEB)

    Troyan, D [Brookhaven National Laboratory

    2013-04-01

    The Interpolated Sounding (INTERPSONDE) value-added product (VAP) uses a combination of observations from radiosonde soundings, the microwave radiometer (MWR), and surface meteorological instruments in order to define profiles of the atmospheric thermodynamic state at one-minute temporal intervals and a total of at least 266 altitude levels. This VAP is part of the Merged Sounding (MERGESONDE) suite of VAPs. INTERPSONDE is the profile of the atmospheric thermodynamic state created using the algorithms of MERGESONDE without including the model data from the European Centre for Medium-range Weather Forecasting (ECMWF). More specifically, INTERPSONDE VAP represents an intermediate step within the larger MERGESONDE process.

  16. ADS-B- Automatic Dependent Surveillance- Broadcast

    Directory of Open Access Journals (Sweden)

    Borivoj Galović

    2002-01-01

    Full Text Available The CU/Tent system of air traffic is facing many drawbacksand problems that restrict its further development and makes itdifficult to follow the trends of increase in the traffic volume.By means of their technology, the systems such as ADS-8create rhe basis for further building, upgrading, improving anddeveloping of a completely new concept of the air traffic system.Through their functions they fully fit into and support the basicfunctions of communication, navigation and swveillancewhich form the basis of the new concept that needs to be implementedas soon as possible.

  17. The concept of added value of FM

    DEFF Research Database (Denmark)

    Jensen, Per Anker; van der Voordt, Theo; Coenen, Christian

    2012-01-01

    Management (CREM) and Business to Business Marketing (B2B Marketing). Findings: The research shows different definitions and focus points, dependent on the academic field and the area of application. The different research perspectives explored a holistic view on the added value of FM by the integration...... of an external market based view (with a focus on the aimed output) and the internal resource based view (with a focus on the input from FM and real estate). Good relationship management and building on trust shows to be equally important as delivering the agreed services. Practical implications: A clear...

  18. Visual attention: the interplay between ad characteristics and context factors

    NARCIS (Netherlands)

    Boerman, S.; Smit, E.; van Meurs, A.

    2011-01-01

    Using eye-tracking data, we tested what elements of the ad are able to catch the eye and whether the context of the ad can draw visual attention away. Characteristics of 183 magazine ads and their direct context were systematically coded and linked to eye-tracking data. Results showed that indeed ad

  19. Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice.

    Science.gov (United States)

    Couch, Brian A; Kerrisk, Meghan E; Kaufman, Adam C; Nygaard, Haakon B; Strittmatter, Stephen M; Koleske, Anthony J

    2013-04-15

    Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4-9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment is delayed considerably in outcrossed AβPP/PS1 mice relative to inbred mice on a C57BL/6 background. While inbred AβPP/PS1 mice develop deficits in radial-arm water maze performance and novel object recognition as early as 8 months, outcrossed AβPP/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred AβPP/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed AβPP/PS1 mice of the same age. Surprisingly, inbred AβPP/PS1 mice at 8 months have low plaque burden, suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of AβPP processing revealed that elevated levels of soluble Aβ correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and AβPP processing are sensitive to genetic differences between mouse strains. Copyright © 2012 Wiley Periodicals, Inc.

  20. Evaluation of FITC-Induced Atopic Dermatitis-Like Disease in NC/Nga Mice and BALB/c Mice Using Computer-Assisted Stereological Toolbox, a Computer-Aided Morphometric System

    DEFF Research Database (Denmark)

    Hvid, Malene; Jensen, Helene; Deleuran, Bent

    2009-01-01

    , as this is mandatory for research animals in many countries. Methods: We evaluated the use of the hapten FITC as an inducer of AD-like disease in NC/Nga and BALB/c mice maintained under SPF conditions. Mice were either untreated or treated with tacrolimus or betamethasone. Using the software Computer Assisted...

  1. Recent highlights from the CERN-AD

    CERN Document Server

    Tranquille, Gerard

    2004-01-01

    The Antiproton Decelerator and cooling ring (AD) provides dense and cold beams of antiprotons to low energy experiments for the study of basic properties of antiprotons and antihydrogen. It combines stochastic cooling (at 3.5 and 2GeV/c) with electron cooling at 0.3 and 0.1GeV/c. In 2002 the AD gave beam during more than 1900h to its three experiments (ASACUSA, ATHENA and ATRAP) with beam properties meeting, and often exceeding design specification. Stochastic cooling with cool-down times of 18s works as aimed for in the design. Electron cooling using the "old LEAR cooler" reaches the very small equilibrium emittances required but still takes more time (12s instead of 6s anticipated in the 1996 design). However the increase in cycle length is made up for by the higher deceleration efficiency. ASACUSA has very successfully continued the program of antiprotonic helium 3 spectroscopy and ATHENA and ATRAP have reported last autumn the synthesis of copious numbers of cold antihydrogen atoms.

  2. Added values of photovoltaic power systems

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-15

    The structure, ownership and operation of electricity systems around the world are changing in response to industry restructuring, the availability of new technologies and increasing environmental awareness. At the same time, many countries have yet to provide basic energy services for their populations, particularly in areas not served by the electricity grid. Large-scale, central power generation and distribution which characterized the electricity industry for much of the 20{sup th} century is being challenged by new technologies, which are cleaner, faster to deploy and better matched to local requirements. Higher values are being placed on ancillary services, such as power system reliability and voltage stability, so that a simple comparison of energy cost is no longer appropriate as a measure of competitiveness. Solar photovoltaic electricity is unique amongst the new energy sources for the wide range of energy and non-energy benefits which can be provided, while the use of photovoltaic power systems as an integral part of a building provides the greatest opportunity for exploiting non-energy benefits and for adding value to the photovoltaic power system. This report documents the potential added values or non-energy benefits photovoltaic power systems can provide, the current state of market development and the key barriers faced by renewable energy technologies generally and photovoltaic power systems in particular. Means by which non-energy benefits may be used to overcome barriers to the use of photovoltaic power systems are then discussed, with specific attention to the use of building integrated photovoltaics. (author)

  3. POSSIBLE CHROMOSPHERIC ACTIVITY CYCLES IN AD LEO

    Energy Technology Data Exchange (ETDEWEB)

    Buccino, Andrea P.; Petrucci, Romina; Mauas, Pablo J. D. [Instituto de Astronomía y Física del Espacio (CONICET-UBA), C.C. 67 Sucursal 28, C1428EHA-Buenos Aires (Argentina); Jofré, Emiliano [Observatorio Astronómico de Córdoba, Córdoba (Argentina)

    2014-01-20

    AD Leo (GJ 388) is an active dM3 flare star that has been extensively observed both in the quiescent and flaring states. Since this active star is near the fully convective boundary, studying its long-term chromospheric activity in detail could be an appreciable contribution to dynamo theory. Here, using the Lomb-Scargle periodogram, we analyze the Ca II K line-core fluxes derived from CASLEO spectra obtained between 2001 and 2013 and the V magnitude from the ASAS database between 2004 and 2010. From both of these totally independent time series, we obtain a possible activity cycle with a period of approximately seven years and a less significant shorter cycle of approximately two years. A tentative interpretation is that a dynamo operating near the surface could be generating the longer cycle, while a second dynamo operating in the deep convection zone could be responsible for the shorter one. Based on the long duration of our observing program at CASLEO and the fact that we observe different spectral features simultaneously, we also analyze the relation between simultaneous measurements of the Na I index (R{sub D}{sup ′}), Hα, and Ca II K fluxes at different activity levels of AD Leo, including flares.

  4. AD Consolidation for operation beyond 2010

    CERN Document Server

    Eriksson, T

    2008-01-01

    The Antiproton Decelerator (AD), which started up for physics in 2000 and today supplies low-energy antiprotons to the ATRAP, ALPHA, ASACUSA and ACE experiments is based on the ACOL machine from which it still retains most of the components. ACOL construction was completed in 1986 at a total cost of approximately 80 MCHF (excluding infrastructure) which today would correspond to a value of around 160 MCHF. During recent years, a reduction of maintenance and modernisation has been unavoidable due to budgetary restraints. In order to identify the resources needed for continued AD operation beyond 2010 with a reasonably low risk of failures and to avoid increasing maintenance and repair costs, a study has been conducted involving groups from the AB, AT and TS departments. Analysis of breakdown risks, identification of items and costs for consolidation has been done as well as a risk score classification. To be noted is the relatively modest cost of the proposed items in view of the value of the facility and in c...

  5. The AD: The unique anti-accelerator

    CERN Multimedia

    Slide show by Maximilien Brice. Voice (French only): Jacques Fichet. Content: Paola Catapano, Django Manglunki, CERN Bulletin

    2011-01-01

    Unlike other machines whose performance is measured in terms of energy records, AD's uniqueness resides in the fact that it can very effectively decelerate beams. At the hearth of antimatter production at CERN, the AD is making headlines in the world's press. This provides an excellent opportunity for us to retrace its history in images.   var flash_video_player=get_video_player_path(); insert_player_for_external('Video/Public/Movies/2011/CERN-MOVIE-2011-083/CERN-MOVIE-2011-083-0753-kbps-480x360-25-fps-audio-64-kbps-44-kHz-stereo', 'mms://mediastream.cern.ch/MediaArchive/Video/Public/Movies/2011/CERN-MOVIE-2011-083/CERN-MOVIE-2011-083-0480-kbps-384x288-25-fps-audio-128-kbps-48-kHz-stereo.wmv', 'false', 480, 360, 'http://mediaarchive.cern.ch/MediaArchive/Video/Public/Movies/2011/CERN-MOVIE-2011-083/CERN-MOVIE-2011-083-posterframe-480x360-at-5-percent.jpg', '1357551', true, '');  

  6. An alternative path to the boundary: The CFT as the Fourier space of AdS

    Science.gov (United States)

    Tolfree, Ian M.

    2009-12-01

    In this thesis we shed new light on the conjectured duality between an n + 1 dimensional theory of gravity in anti de Sitter space (AdS) and an n dimensional conformal field theory (CFT) by showing that the CFT can be interpreted as the Fourier space of AdS. We then make use of this to gain insight into the nature of black hole entropy. In the first part of this thesis, we give an introduction to the ideas of and review the basics of the AdS/CFT. In the next section we make use of well known integral geometry techniques to derive the Fourier transformation of a function on AdS and see it is a function with compact support on the boundary. Comparing this to the literature, we find that the Green's functions from the literature are actually the Fourier weights of the transformation and that the boundary values of fields appearing in the correspondence are the Fourier coefficients of the transformation. One is thus left to interpret the CFT as the quantized version of a classical theory in AdS and the dual operator as the Fourier coefficients. Group theoretic considerations are discussed in relation to the transformation and its potential use in constructing QCD like theories. In the last section, we then build upon this to study the BTZ black hole. Named after its authors, Banados, Teitelboim and Zanelli, the BTZ black hole is a three dimensional (two space plus one time dimension) black hole in anti de Sitter space. Following standard procedures for modifying Fourier Transformations to accommodate quotient spaces we arrive at a mapping in a black hole background consistent with known results that yields the exact micro-states of a scalar field in a black hole background. We find that the micro-states are the Fourier coefficients on the boundary, which transform under the principal series representation of SL(2, R). Using the knowledge of how to represent a bulk scalar field in the CFT, and knowing how a black hole interacts with a scalar field, we deduce the

  7. Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice

    Science.gov (United States)

    IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote Th2 while suppressing Th1 and Th17 cytokine responses. We investigated the contribution of endogenous IL-25 to DSS-induced colitis in mice. Mice were exposed to DSS in drinking water ad li...

  8. REST/NRSF-induced changes of ChAT protein expression in the neocortex and hippocampus of the 3xTg-AD mouse model for Alzheimer's disease.

    Science.gov (United States)

    Orta-Salazar, E; Aguilar-Vázquez, A; Martínez-Coria, H; Luquín-De Anda, S; Rivera-Cervantes, M; Beas-Zarate, C; Feria-Velasco, A; Díaz-Cintra, S

    2014-10-29

    The cholinergic system is one of the neurotransmitter systems altered in Alzheimer's disease (AD), the most common form of human dementia. The objective of this work was to determine the REST/NRSF involvement in altered ChAT expression in the neocortex and hippocampus of an AD transgenic mouse (homozygous 3xTg-AD) that over-expresses 3 proteins, amyloid-β precursor protein, presenilin-1, and tau, all of which are associated with AD and cause cellular degeneration. Two groups (WT and 3xTg-AD) of 11-month-old female mice were analyzed and compared. Half of the brains of each group were used for ChAT immunohistochemistry, and Western Blot analyses of ChAT and REST/NRSF were performed on the other half. We observed significant decreases in the number of ChAT-immunoreactive cells in the Meynert nucleus and of fibers in the frontal motor cortex and hippocampal CA1 area in transgenic mice compared with control mice. An increased level of REST/NRSF protein and a reduction of ChAT protein expression in the 3xTg-AD mice compared with their controls were also found in both in the latter two cerebral regions. The increased REST/NRSF expression reported here and its effect on the regulatory region for ChAT transcription could explain the decreased expression of ChAT in the 3xTg-AD mouse; these findings may be associated with the degeneration observed in AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

    Directory of Open Access Journals (Sweden)

    Maximilian Richter

    2016-01-01

    Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

  10. Critical Phenomena in Higher Curvature Charged AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Arindam Lala

    2013-01-01

    Full Text Available In this paper, we have studied the critical phenomena in higher curvature charged AdS black holes. We have considered Lovelock-Born-Infeld-AdS black hole as an example. The thermodynamics of the black hole have been studied which reveals the onset of a higher-order phase transition in the black hole in the canonical ensemble (fixed charge ensemble framework. We have analytically derived the critical exponents associated with these thermodynamic quantities. We find that our results fit well with the thermodynamic scaling laws and consistent with the mean field theory approximation. The suggestive values of the other two critical exponents associated with the correlation function and correlation length on the critical surface have been derived.

  11. Phases of planar AdS black holes with axionic charge

    Energy Technology Data Exchange (ETDEWEB)

    Caldarelli, Marco M.; Christodoulou, Ariana [Mathematical Sciences and STAG Research Centre, University of Southampton,Highfield, Southampton SO17 1BJ (United Kingdom); Papadimitriou, Ioannis [SISSA and INFN - Sezione di Trieste,Via Bonomea 265, I 34136 Trieste (Italy); Skenderis, Kostas [Mathematical Sciences and STAG Research Centre, University of Southampton,Highfield, Southampton SO17 1BJ (United Kingdom)

    2017-04-03

    Planar AdS black holes with axionic charge have finite DC conductivity due to momentum relaxation. We obtain a new family of exact asymptotically AdS{sub 4} black branes with scalar hair, carrying magnetic and axion charge, and we study the thermodynamics and dynamic stability of these, as well as of a number of previously known electric and dyonic solutions with axion charge and scalar hair. The scalar hair for all solutions satisfy mixed boundary conditions, which lead to modified holographic Ward identities, conserved charges and free energy, relative to those following from the more standard Dirichlet boundary conditions. We show that properly accounting for the scalar boundary conditions leads to well defined first law and other thermodynamic relations. Finally, we compute the holographic quantum effective potential for the dual scalar operator and show that dynamical stability of the hairy black branes is equivalent to positivity of the energy density.

  12. Implementation of Economic Value Added and Market Value Added Analysis as Valuation Tools of Invest Feasibility

    Directory of Open Access Journals (Sweden)

    Achmad Daengs GS

    2017-09-01

    Full Text Available For the investors, financial statement is a benchmark of investors in assessing the company's performance. In fact, investors are not always receiving the accurate company's financial statements information and its levels of fairness are in doubt. The financial statement analysis with using financial ratios is not enough. The investors may need to use alternatives financial statement analyses techniques that reflect the actual company's performance. Therefore, both of the investors and the prospective can use Economic Value Added (EVA and Market Value Added (MVA analysis. With these technical analyses, the investors may know the company's performance where they are invested or to be used as a place to invest whether it has value added or not. With the results of these analyses, it is the expected for the investors to be more confident in making decision whether to buy, sell or hold the ownership in the company.

  13. CART treatment improves memory and synaptic structure in APP/PS1 mice.

    Science.gov (United States)

    Jin, Jia-li; Liou, Anthony K F; Shi, Yejie; Yin, Kai-lin; Chen, Ling; Li, Ling-ling; Zhu, Xiao-lei; Qian, Lai; Yang, Rong; Chen, Jun; Xu, Yun

    2015-05-11

    Major characteristics of Alzheimer's disease (AD) include deposits of β-amyloid (Aβ) peptide in the brain, loss of synapses, and cognitive dysfunction. Cocaine- and amphetamine-regulated transcript (CART) has recently been reported to attenuate Aβ-induced toxicity. In this study, CART localization in APP/PS1 mice was characterized and the protective effects of exogenous CART treatment were examined. Compared to age-matched wild type mice, 8-month-old APP/PS1 mice had significantly greater CART immunoreactivity in the hippocampus and cortex. A strikingly similar pattern of Aβ plaque-associated CART immunoreactivity was observed in the cortex of AD cases. Treatment of APP/PS1 mice with exogenous CART ameliorated memory deficits; this effect was associated with improvements in synaptic ultrastructure and long-term potentiation, but not a reduction of the Aβ plaques. Exogenous CART treatment in APP/PS1 mice prevented depolarization of the mitochondrial membrane and stimulated mitochondrial complex I and II activities, resulting in an increase in ATP levels. CART treatment of APP/PS1 mice also reduced reactive oxygen species and 4-hydroxynonenal, and mitigated oxidative DNA damage. In summary, CART treatment reduced multiple neuropathological measures and improved memory in APP/PS1 mice, and may therefore be a promising and novel therapy for AD.

  14. Ginsenoside Rg1 Ameliorates Behavioral Abnormalities and Modulates the Hippocampal Proteomic Change in Triple Transgenic Mice of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Lulin Nie

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is one of the most common neurodegenerative diseases, so far, there are no effective measures to prevent and cure this deadly condition. Ginsenoside Rg1 (Rg1 was shown to improve behavioral abnormalities in AD; however, the potential mechanisms remain unclear. In this study, we pretreated 7-month-old 3xTg-AD mice for 6 weeks with Rg1 and evaluated the effects of Rg1 on the behaviors and the protein expression of hippocampal tissues. The behavioral tests showed that Rg1 could improve the memory impairment and ameliorate the depression-like behaviors of 3xTg-AD mice. Proteomic results revealed a total of 28 differentially expressed hippocampal proteins between Rg1-treated and nontreated 3xTg-AD mice. Among these proteins, complexin-2 (CPLX2, synapsin-2 (SYN2, and synaptosomal-associated protein 25 (SNP25 were significantly downregulated in the hippocampus of 3xTg-AD mice compared with the WT mice, and the treatment of Rg1 modulated the expression of CPLX2 and SNP25 in the hippocampus of 3xTg-AD mice. The expression of CPLX2, SYN2, and SNP25 was further validated by Western blot analysis. Taken together, we concluded that Rg1 could be a potential candidate drug to improve the behavioral deficits in AD via modulating the expression of the proteins (i.e., CPLX2, SYN2, and SNP25.

  15. Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice.

    Science.gov (United States)

    Trevino, Michelle B; Mazur-Hart, David; Machida, Yui; King, Timothy; Nadler, Joseph; Galkina, Elena V; Poddar, Arjun; Dutta, Sucharita; Imai, Yumi

    2015-10-01

    Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-α was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity.

  16. Super 0-brane and GS superstring actions on AdS sub 2 x S sup 2

    CERN Document Server

    Zhou Jian Ge

    1999-01-01

    The super 0-brane and GS superstring actions on AdS sub 2 x S sup 2 background with 2-form flux are constructed by taking a supercoset approach. We find that the super 0-brane action contains two parameters which are interpreted as the electric and magnetic charges of the super 0-brane. The obtained super 0-brane action describes the BPS saturated dyonic superparticle moving on AdS sub 2 x S sup 2 background. The WZ action contains the required coupling with 2-form flux. For GS superstring, we find the string action on AdS sub 2 x S sup 2 takes the same form as those in AdS sub 3 x S sup 3 and AdS sub 5 x S sup 5 with RR field background.

  17. Feeding-elicited cataplexy in orexin knockout mice

    Science.gov (United States)

    Clark, Erika L.; Baumann, Christian R.; Cano, Georgina; Scammell, Thomas E.; Mochizuki, Takatoshi

    2009-01-01

    Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad lib regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 hr after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy. PMID:19362119

  18. Climate Since A.D. 1500

    Science.gov (United States)

    Fleming, James R.

    The editors of this impressive volume are to be congratulated for gathering a stellar collection of thirty-three authoritative papers on the most recent period of climate history. In addition to providing thirty-three pages of introduction and conclusion, the editors also coauthored two important papers for the volume. This book will become a standard reference for the interdisciplinary climatic change community.Climate Since A.D. 1500 is divided into four sections: documentary evidence, dendroclimatic evidence, ice-core evidence, and forcing factors. In all, there are twelve papers using documentary evidence, eleven using dendroclimatic evidence, five on ice-core evidence, and three on forcing factors. The documentary papers cover Canada, the northeastern United States, Ireland, central Europe, northern Italy, the former Soviet Union, China, and Japan, with temporal coverage ranging from 1500 to very near the present.

  19. Adding crumb rubber into exterior wall materials.

    Science.gov (United States)

    Zhu, Han; Thong-On, Norasit; Zhang, Xiong

    2002-10-01

    In Arizona US, most houses are built with walls covered by stuccos/coatings/mortars. This paper presents an explorative investigation of adding crumb rubber into stuccos/coatings/mortars. A series of experiments are conducted to examine the thermal and mechanical performance of the crumb rubber mixes. The results show that, the mixes with crumb rubber do exhibit more desirable performances like being high in crack-resistance and thermal insulation, and low in thermal expansion/contraction. The drawback for the crumb rubber mixes is the reduction in compressive strength, but which can be compensated by other means. As a site experiment, an area of 100 square-feet of crumb rubber coatings for two mix designs is sprayed on a tire-adobe wall. After being sprayed more than 14 months, the coatings apparently are in good condition. Significance of this study is that this practice, if accepted, will yield improved products that consume large quantities of crumb rubber.

  20. AORTA: Adding Organizational Reasoning to Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia

    2014-01-01

    the expected behavior of the agents. Agents need to be able to reason about the regulations, so that they can act within the expected boundaries and work towards the objectives of the organization. This extended abstract introduces AORTA, a component that can be integrated into agents’ reasoning mechanism......Open systems are characterized by a diversity of heterogeneous and autonomous agents that act according to private goals, and with a behavior that is hard to predict. They can be regulated through organizations similar to human organizations, which regulate the agents’ behavior space and describe......, allowing them to reason about (and act upon) regulations specified by an organizational model using simple reasoning rules. The added value is that the organizational model is independent of that of the agents, and that the approach is not tied to a specific organizational model....

  1. [Did Henrik Wergeland have AD/HD?].

    Science.gov (United States)

    Aanonsen, Nils Olav

    2008-12-18

    Henrik Wergeland (1808 - 45) is one of Norwegian cultural history's most notable figures. He is honoured as a national symbol during this year's 200-year jubilee for his birth. Biographies and numerous academic publications have been written about him for more than 100 years. His life was short and diverse; on one hand he continuously worked to give people general education, he was an author and a poet and on the other hand he was always in a dispute with someone and involved in endless court cases and scandals. After his death it was said that Wergeland was one who . As I see it, his life is so full of events that indicate hyperactivity and impulsivity that I think it is legitimate to ask whether he would have received the diagnosis AD/HD (attention-deficit/ hyperactivity disorder) today.

  2. Quantum states of the spacetime, and formation of black holes in AdS

    CERN Document Server

    Botta Cantcheff, Marcelo

    2012-01-01

    We argue that a non-perturbative description of quantum gravity should involve two (non-interacting) copies of a dual field theory on the boundary, and describe the states of the spacetimes accordingly. So, for instance, a complete description of the asymptotically Anti-de-Sitter spacetimes is given by two copies of the conformal field theory associated to the global AdS spacetime. We also argue that, in this context, gravitational collapse and formation of a black hole may be described by unitary evolution of the dual non-perturbative degrees of freedom.

  3. Ehrenfest's scheme and thermodynamic geometry in Born-Infeld AdS black holes

    CERN Document Server

    Lala, Arindam

    2011-01-01

    In this paper we analyze the phase transition phenomena in Born-Infeld AdS black holes using Ehrenfest's scheme of standard thermodynamics. The critical points are marked by the divergences in the heat capacity. In order to investigate the nature of the phase transition, we analytically check both the Ehrenfest's equations near the critical points. Our analysis reveals that this is indeed a second order phase transition. Finally, we analyze the nature of the phase transition using state space geometry approach. This is found to be compatible with the Ehrenfest's scheme.

  4. On heat properties of AdS black holes in higher dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Belhaj, A. [Département de Physique, Faculté Polydisciplinaire, Université Sultan M. Slimane,Béni Mellal (Morocco); High Energy Physics and Astrophysics Laboratory, FSSM, Cadi Ayyad University,Marrakesh (Morocco); Chabab, M.; Moumni, H. El; Masmar, K. [High Energy Physics and Astrophysics Laboratory, FSSM, Cadi Ayyad University,Marrakesh (Morocco); Sedra, M.B. [Université Mohammed Premier, Ecole Nationale des Sciences Appliquées,Al Hoceima (Morocco); Département de Physique, LHESIR, Faculté des Sciences, Université Ibn Tofail,Kénitra (Morocco); Segui, A. [Departamento de Física Teórica, Universidad de Zaragoza,E-50009-Zaragoza (Spain)

    2015-05-28

    We investigate the heat properties of AdS Black Holes in higher dimensions. We consider the study of the corresponding thermodynamical properties including the heat capacity explored in the determination of the black hole stability. In particular, we compute the heat latent. To overcome the instability problem, the Maxwell construction, in the (T,S)-plane, is elaborated. This method is used to modify the the Hawking-Page phase structure by removing the negative heat capacity regions. Then, we discuss the thermodynamic cycle and the heat engines using the way based on the extraction of the work from a black hole solution.

  5. Bounds on CFTs with W3 algebras and AdS3 higher spin theories

    Science.gov (United States)

    Apolo, Luis

    2017-10-01

    The scaling dimension of the first excited state in two-dimensional conformal field theories (CFTs) satisfies a universal upper bound. Using the modular bootstrap, we extend this result to CFTs with W3 algebras which are generically dual to higher spin theories in AdS3 . Assuming unitarity and modular invariance, we show that the conformal weights h , h ¯ of the lightest charged state satisfy h 4 |h -c /24 |/√{10 π c }+O (1 ) . We discuss hints on the existence of stronger bounds and comment on the interpretation of our results in the dual higher spin theory.

  6. Frozen yogurt with added inulin and isomalt.

    Science.gov (United States)

    Isik, U; Boyacioglu, D; Capanoglu, E; Erdil, D Nilufer

    2011-04-01

    The objective of this study was to produce a frozen yogurt containing low fat and no added sugar. Samples containing 5% polydextrose, 0.065% aspartame and acesulfame-K mixture, and different levels of inulin and isomalt (5.0, 6.5, and 8.0%) were produced at pilot scale and analyzed for their physical and chemical properties including proximate composition, viscosity, acidity, overrun, melting rate, heat shock stability, as well as sensory characteristics, and viability of lactic acid bacteria. With the addition of inulin and isomalt, viscosity increased by 19 to 52% compared with that of sample B (reduced-fat control). The average calorie values of samples substituted with sweeteners were about 43% lower than that of original sample. Low-calorie frozen yogurt samples melted about 33 to 48% slower than the reduced-fat control sample at 45 min. Based on quantitative descriptive profile test results, statistically significant differences among products were observed for hardness, iciness, foamy melting, whey separation, and sweetness characteristics. The results of principal component analysis showed that the sensory properties of the sample containing 6.5% inulin and 6.5% isomalt were similar to those of control. Lactic acid bacteria counts of frozen yogurt were found to be between 8.12 and 8.49 log values, 3 mo after the production. The overall results showed that it is possible to produce an attractive frozen yogurt product with the incorporation of inulin and isomalt with no added sugar and reduced fat. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Detecting Anti Ad-blockers in the Wild

    Directory of Open Access Journals (Sweden)

    Mughees Muhammad Haris

    2017-07-01

    Full Text Available The rise of ad-blockers is viewed as an economic threat by online publishers who primarily rely on online advertising to monetize their services. To address this threat, publishers have started to retaliate by employing anti ad-blockers, which scout for ad-block users and react to them by pushing users to whitelist the website or disable ad-blockers altogether. The clash between ad-blockers and anti ad-blockers has resulted in a new arms race on the Web. In this paper, we present an automated machine learning based approach to identify anti ad-blockers that detect and react to ad-block users. The approach is promising with precision of 94.8% and recall of 93.1%. Our automated approach allows us to conduct a large-scale measurement study of anti ad-blockers on Alexa top-100K websites. We identify 686 websites that make visible changes to their page content in response to ad-block detection. We characterize the spectrum of different strategies used by anti ad-blockers. We find that a majority of publishers use fairly simple first-party anti ad-block scripts. However, we also note the use of third-party anti ad-block services that use more sophisticated tactics to detect and respond to ad-blockers.

  8. Zoopharmacognosy in diseased laboratory mice: conflicting evidence.

    Directory of Open Access Journals (Sweden)

    Minesh Kapadia

    Full Text Available Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY, an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors.

  9. Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice.

    Science.gov (United States)

    Amano, Akiko; Kondo, Yoshitaka; Noda, Yoshihiro; Ohta, Mitsuhiro; Kawanishi, Noriaki; Machida, Shuichi; Mitsuhashi, Kazuteru; Senmaru, Takafumi; Fukui, Michiaki; Takaoka, Osamu; Mori, Taisuke; Kitawaki, Jo; Ono, Masafumi; Saibara, Toshiji; Obayashi, Hiroshi; Ishigami, Akihito

    2017-05-15

    Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein 1 (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. II Infused Mice

    Directory of Open Access Journals (Sweden)

    Justin L. Wilson

    2012-01-01

    Full Text Available The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min. Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161±4 mmHg versus 145±4 mmHg and fenofibrate (145 mg/kg/day reduced MAP in WT + Ang II mice (134±7 mmHg. Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30±4 versus 8±2 pg/mL and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL. Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.

  11. Phenomenology on a slice of AdS sub 5 xM supdelta spacetime

    CERN Document Server

    Davoudiasl, H; Hewett, J L

    2003-01-01

    We study the phenomenology resulting from backgrounds of the form AdS sub 5 xM supdelta, where M supdelta denotes a generic manifold of dimension subdelta>= 1, and AdS sub 5 is the slice of 5-dimensional anti-de Sitter space which generates the hierarchy in the Randall-Sundrum (RS) model. The delta additional dimensions may be required when the RS model is embedded into a more fundamental theory. We analyze two classes of delta-dimensional manifolds: flat and curved geometries. In the first case, the additional flat dimensions may accommodate localized fermions which in turn could resolve issues, such as proton decay and flavor, that were not addressed in the original RS proposal. In the latter case, the positive curvature of an S supdelta manifold with delta>1 can geometrically provide the 5-dimensional warping of the RS model. We demonstrate the key features of these two classes of models by presenting the background solutions, the spectra of the Kaluza-Klein (KK) gravitons, and their 4-dimensional coupling...

  12. Critical phenomena in higher curvature charged AdS black holes

    CERN Document Server

    Lala, Arindam

    2012-01-01

    In this paper we have studied the critical phenomena in higher curvature charged black holes in the anti-de Sitter (AdS) space-time. As an example we have considered the third order Lovelock-Born-Infeld black holes in AdS space-time. We have analytically derived the thermodynamic quantities of the system. Our analysis revealed the onset of a higher order phase transition in the black hole leading to an infinite discontinuity in the specific heat at constant charge at the critical points. Our entire analysis is based on the canonical framework where we have fixed the charge of the black hole. In an attempt to study the behavior of the thermodynamic quantities near the critical points we have derived the critical exponents of the system explicitly. Although the values of the critical points have been determined numerically, the critical exponents are calculated analytically. Our results fit well with the thermodynamic scaling laws. The scaling hypothesis is also seen to be consistent with these scaling laws. We...

  13. P-V criticality of AdS black holes in a general framework

    Science.gov (United States)

    Majhi, Bibhas Ranjan; Samanta, Saurav

    2017-10-01

    In black hole thermodynamics, it has been observed that AdS black holes behave as van der Waals system if one interprets the cosmological constant as a pressure term. Also the critical exponents for the phase transition of AdS black holes and the van der Waals systems are same. Till now this type of analysis is done by two steps. In the first step one shows that a particular metric allows phase transition and in the second step, using this information, one calculates the exponents. Here, we present a different approach based on two universal inputs (the general forms of the Smarr formula and the first law of thermodynamics) and one assumption regarding the existence of van der Waals like critical point for a metric. We find that the same values of the critical exponents can be obtained by this approach. Thus we demonstrate that, though the existence of van der Waals like phase transition depends on specific metrics, the values of critical exponents are then fixed for that set of metrics.

  14. P-V criticality of AdS black holes in a general framework

    Directory of Open Access Journals (Sweden)

    Bibhas Ranjan Majhi

    2017-10-01

    Full Text Available In black hole thermodynamics, it has been observed that AdS black holes behave as van der Waals system if one interprets the cosmological constant as a pressure term. Also the critical exponents for the phase transition of AdS black holes and the van der Waals systems are same. Till now this type of analysis is done by two steps. In the first step one shows that a particular metric allows phase transition and in the second step, using this information, one calculates the exponents. Here, we present a different approach based on two universal inputs (the general forms of the Smarr formula and the first law of thermodynamics and one assumption regarding the existence of van der Waals like critical point for a metric. We find that the same values of the critical exponents can be obtained by this approach. Thus we demonstrate that, though the existence of van der Waals like phase transition depends on specific metrics, the values of critical exponents are then fixed for that set of metrics.

  15. Proper temperature of the Schwarzschild AdS black hole revisited

    Science.gov (United States)

    Eune, Myungseok; Kim, Wontae

    2017-10-01

    The Unruh temperature calculated by using the global embedding of the Schwarzschild AdS spacetime into the Minkowski spacetime was identified with the local proper temperature; however, it became imaginary in a certain region outside the event horizon. So, the temperature was assumed to be zero of non-thermal radiation for that region. In this work, we revisit this issue in an exactly soluble two-dimensional Schwarzschild AdS black hole and present an alternative resolution to this problem in terms of the Tolman's procedure. However, the process appears to be non-trivial in the sense that the original procedure assuming the traceless energy-momentum tensor should be extended in such a way that it should cover the non-vanishing case of the energy-momentum tensor in the presence of the trace anomaly. Consequently, we show that the proper temperature turns out to be real everywhere outside the event horizon without any imaginary value, in particular, it vanishes at both the horizon and the asymptotic infinity.

  16. Covariant anomalies and Hawking radiation from Kaluza–Klein AdS ...

    Indian Academy of Sciences (India)

    The KK-AdS black hole considered is a non-extremal charged rotating solution in the theory of 4D gauged supergravity. Its Hawking fluxes of electric charge, angular momentum and energy momentum tensor are derived here. Our results support the common view that Hawking radiation is the quantum effect arising at the ...

  17. A mosaic adenovirus possessing serotype Ad5 and serotype Ad3 knobs exhibits expanded tropism

    NARCIS (Netherlands)

    Takayama, K; Reynolds, PN; Short, JS; Kawakami, Y; Adachi, Y; Glasgow, JN; Rots, MG; Krasnykh, VN; Douglas, JT; Curiel, DT

    2003-01-01

    The efficiency of cancer gene therapy with recombinant adenoviruses based on serotype 5 (Ad5) has been limited partly because of variable, and often low, expression by human primary cancer cells of the primary cellular-receptor which recognizes the knob domain of the fiber protein, the coxsackie and

  18. Non-Abelian fields in AdS4 spacetime: Axially symmetric, composite configurations

    Science.gov (United States)

    Kichakova, Olga; Kunz, Jutta; Radu, Eugen; Shnir, Yasha

    2014-12-01

    We construct new finite-energy regular solutions in Einstein-Yang-Mills-SU(2) theory. They are static, axially symmetric and approach at infinity the anti-de Sitter spacetime background. These configurations are characterized by a pair of integers (m ,n ), where m is related to the polar angle and n to the azimuthal angle, being related to the known flat-space monopole-antimonopole chains and vortex rings. Generically, they describe composite configurations with several individual components, possessing a nonzero magnetic charge, even in the absence of a Higgs field. Such Yang-Mills configurations exist already in the probe limit, with the AdS geometry supplying the attractive force needed to balance the repulsive force of Yang-Mills gauge interactions. The gravitating solutions are constructed by numerically solving the elliptic Einstein-DeTurck-Yang-Mills equations. The variation of the gravitational coupling constant α reveals the existence of two branches of gravitating solutions which bifurcate at some critical value of α . The lower-energy branch connects to the solutions in the global AdS spacetime, while the upper branch is linked to the generalized Bartnik-McKinnon solutions in asymptotically flat spacetime. Also, a spherically symmetric, closed-form solution is found as a perturbation around the globally anti-de Sitter vacuum state.

  19. On the Pulsating Strings in AdS4×ℂℙ3

    Directory of Open Access Journals (Sweden)

    H. Dimov

    2009-01-01

    we quasiclassically quantize the theory and obtain the first corrections to the energy. The latter, due to AdS/CFT correspondence, is supposed to give the anomalous dimensions of operators of the gauge theory dual 𝒩=6 Chern-Simons theory.

  20. AdS{sub 2} holographic dictionary

    Energy Technology Data Exchange (ETDEWEB)

    Cvetič, Mirjam [Department of Physics and Astronomy, University of Pennsylvania,Philadelphia, PA 19104-6396 (United States); Center for Applied Mathematics and Theoretical Physics,University of Maribor, SI2000 Maribor (Slovenia); Papadimitriou, Ioannis [SISSA and INFN - Sezione di Trieste,Via Bonomea 265, 34136 Trieste (Italy)

    2016-12-02

    We construct the holographic dictionary for both running and constant dilaton solutions of the two dimensional Einstein-Maxwell-Dilaton theory that is obtained by a circle reduction from Einstein-Hilbert gravity with negative cosmological constant in three dimensions. This specific model ensures that the dual theory has a well defined ultraviolet completion in terms of a two dimensional conformal field theory, but our results apply qualitatively to a wider class of two dimensional dilaton gravity theories. For each type of solutions we perform holographic renormalization, compute the exact renormalized one-point functions in the presence of arbitrary sources, and derive the asymptotic symmetries and the corresponding conserved charges. In both cases we find that the scalar operator dual to the dilaton plays a crucial role in the description of the dynamics. Its source gives rise to a matter conformal anomaly for the running dilaton solutions, while its expectation value is the only non trivial observable for constant dilaton solutions. The role of this operator has been largely overlooked in the literature. We further show that the only non trivial conserved charges for running dilaton solutions are the mass and the electric charge, while for constant dilaton solutions only the electric charge is non zero. However, by uplifting the solutions to three dimensions we show that constant dilaton solutions can support non trivial extended symmetry algebras, including the one found by Compère, Song and Strominger http://dx.doi.org/10.1007/JHEP05(2013)152, in agreement with the results of Castro and Song http://arxiv.org/abs/1411.1948. Finally, we demonstrate that any solution of this specific dilaton gravity model can be uplifted to a family of asymptotically AdS{sub 2}×S{sup 2} or conformally AdS{sub 2}×S{sup 2} solutions of the STU model in four dimensions, including non extremal black holes. The four dimensional solutions obtained by uplifting the running dilaton

  1. [Morphological analysis of the hippocampal region associated with an innate behaviour task in the transgenic mouse model (3xTg-AD) for Alzheimer disease].

    Science.gov (United States)

    Orta-Salazar, E; Feria-Velasco, A; Medina-Aguirre, G I; Díaz-Cintra, S

    2013-10-01

    Different animal models for Alzheimer disease (AD) have been designed to support the hypothesis that the neurodegeneration (loss of neurons and synapses with reactive gliosis) associated with Aβ and tau deposition in these models is similar to that in the human brain. These alterations produce functional changes beginning with decreased ability to carry out daily and social life activities, memory loss, and neuropsychiatric disorders in general. Neuronal alteration plays an important role in early stages of the disease, especially in the CA1 area of hippocampus in both human and animal models. Two groups (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis (nest building) and a morphometric analysis of the CA1 region of the dorsal hippocampus. The 3xTg-AD mice showed a 50% reduction in nest quality associated with a significant increase in damaged neurons in the CA1 hippocampal area (26%±6%, P<.05) compared to the WT group. The decreased ability to carry out activities of daily living (humans) or nest building (3xTg-AD mice) is related to the neuronal alterations observed in AD. These alterations are controlled by the hippocampus. Post-mortem analyses of the human hippocampus, and the CA1 region in 3xTg-AD mice, show that these areas are associated with alterations in the deposition of Aβ and tau proteins, which start accumulating in the early stages of AD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  2. Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.

    Science.gov (United States)

    Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu

    2013-08-07

    Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

  3. Toxoplasma gondii Infection Suppresses House Dust Mite Extract-Induced Atopic Dermatitis in NC/Nga Mice.

    Science.gov (United States)

    Jeong, Young Il; Hong, Sung Hee; Cho, Shin Hyeong; Lee, Won Ja; Lee, Sang Eun

    2015-11-01

    Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects humans and animals via congenital or postnatal routes, and it is found worldwide. Modulation of the immune system by parasite infection is proposed to suppress allergic inflammation. Growing evidences have shown that interleukin (IL)-10-producing regulatory B cells (B(regs)) and CD4+CD25+FoxP3+ regulatory T cells (T(regs)) induced by parasite infection play a critical role in allergic or autoimmune diseases because these cells regulate negatively cellular immune responses and inflammation. Currently, the role of IL-10-producing regulatory B cells in host immune response during T. gondii infection is unknown. In this study, we investigate whether T. gondii infection can suppress the development of unrelated atopic dermatitis (AD)-like lesions. AD is a chronically relapsing inflammatory skin disease accompanied by severe itching; for this, we used NC/Nga mice, a well-known experimental model of systemic AD. Repeated exposure to Dermatophagoides farinae crude extract (DfE), known as a major environmental allergen, evokes AD-like skin lesions in NC/Nga mice under specific pathogen-free conditions. NC/Nga mice were intraperitoneally infected with 10 cysts of T. gondii. T. gondii infection significantly ameliorated AD-like skin lesions in NC/Nga mice. The subpopulation of B(regs) and T(regs) in the AD mice was expanded in the course of T. gondii infection. In addition, T. gondii infection inhibited Th2 and enhanced Th1 immune response in the DfE-treated AD mice. We have experimentally demonstrated for the first time that T. gondii infection ameliorated AD-like skin lesions in a mouse model of AD. Our study could in part explain the mechanisms of how parasite infection prevents the development of allergic disorder. Therefore, these immunemechanisms induced by T. gondii infection may be beneficial for the host in terms of reduced risk of allergic immune reactions.

  4. Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice.

    Science.gov (United States)

    Berrigan, David; Perkins, Susan N; Haines, Diana C; Hursting, Stephen D

    2002-05-01

    Heterozygous p53-deficient (p53(+/-)) mice, a potential model for human Li-Fraumeni Syndrome, have one functional allele of the p53 tumor suppressor gene. These mice are prone to spontaneous neoplasms, most commonly sarcoma and lymphoma; the median time to death of p53+/- mice is 18 months. We have shown previously that juvenile-onset calorie restriction (CR) to 60% of ad libitum (AL) intake delays tumor development in young p53-null (-/-) mice by a p53-independent and insulin-like growth factor 1 (IGF-1)-related mechanism. To determine whether CR is effective when started in adult p53-deficient mice, and to compare chronic CR with an intermittent fasting regimen, male p53+/- mice (7-10 months old, 31-32 mice/group) were randomly assigned to the following regimens: (i) AL (AIN-76A diet), (ii) CR to 60% of AL intake or (iii) 1 day/week fast. Food availability on non-fasting days was controlled to prevent compensatory over feeding. Relative to the AL group, CR significantly delayed (P = 0.001) the onset of tumors in adult mice, whereas the 1 day/week fast caused a moderate delay (P = 0.039). Substantial variation in longevity and maximum body weight within treatments was not correlated with variation in growth characteristics of individual mice. In a separate group of p53+/- mice treated for 4 weeks (n = five mice per treatment), plasma IGF-1 levels in CR versus AL mice were reduced by 20% (P fasted mice had intermediate levels of leptin and IGF-1. Our findings that CR or a 1 day/week fast suppressed carcinogenesis-even when started late in life in mice predestined to develop tumors due to decreased p53 gene dosage-support efforts to identify suitable interventions influencing energy balance in humans as a tool for cancer prevention.

  5. Superstring Theory on $AdS_{3} x G/H$ and Boundary N=3 Superconformal Symmetry

    CERN Document Server

    Argurio, R; Shomer, A; Argurio, Riccardo; Giveon, Amit; Shomer, Assaf

    2000-01-01

    Superstrings propagating on backgrounds of the form AdS_3 x G/H are studiedusing the coset CFT approach. We focus on seven dimensional cosets which have asemiclassical limit, and which give rise to N=3 superconformal symmetry in thedual CFT. This is realized for the two cases AdS_3 x SU(3)/U(1) and AdS_3 xSO(5)/SO(3), for which we present an explicit construction. We also providesufficient conditions on a CFT background to enable a similar construction, andcomment on the geometrical interpretation of our results.

  6. Acupuncture upregulates G protein coupled activity in SAMP8 mice.

    Science.gov (United States)

    Luo, Benhua; Zhao, Lan; Zhang, Xuezhu; Kan, Bohong; Liu, Yunhe; Jia, Yujie; Han, Jingxian; Yu, Jianchun

    2017-08-01

    Transmembrane and intracellular signal transduction of G protein is closely related to the pathophysiology of Alzheimer's disease (AD). To explore the effects of Sanjiao acupuncture on G protein signal transduction pathways in the pathogenesis of AD. 36 senescence-accelerated (SAM) prone 8 mice were divided into three groups that remained untreated (SAMP8, n=12) or received Sanjiao acupuncture (SAMP8+SA, n=12) or control acupuncture (SAMP8+CA, n=12). An additional control group of SAM resistant 1 mice was included (SAMR1 group, n=12). Morris water maze tests were used to investigate learning and memory abilities. Immunoprecipitation and Western blotting were used to study expression of G protein subunits and their activities in the cortex/hippocampus. Behavioural analysis showed that acupuncture attenuated the severe cognitive deficits observed in untreated/CA-treated SAMP8 mice. The findings of the G protein activation assays via immunoprecipitation and Western blots were that the physiologically coupled activation rate (PCAR) and maximal coupled activation rate (MCAR) of Gα s and Gα i were decreased in the cortex of SAMP8 vs SAMR1 mice. Sanjiao acupuncture induced an upregulation in the PCAR of Gα s and Gα i . In the hippocampus of untreated SAMP8 mice, the PCAR of Gα s and MCAR of both Gα s and Gα i declined, and Sanjiao acupuncture was associated with an upregulation in the MCAR of Gα s and Gα i . There were no significant differences in Gα s and Gα i expression between the groups. Sanjiao acupuncture attenuates cognitive deficits in a mouse model of AD via upregulation of G protein activity and stabilisation of the cellular signal. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Spontaneous ad hoc mobile cloud computing network.

    Science.gov (United States)

    Lacuesta, Raquel; Lloret, Jaime; Sendra, Sandra; Peñalver, Lourdes

    2014-01-01

    Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

  8. The AD vacuum system construction and commissioning

    CERN Document Server

    Brouet, M; Klette, H; Strubin, Pierre M

    1999-01-01

    CERN has built a new experimental facility, called the Antiproton Decelerator (AD), by transforming two existing machines: the "Antiproton Collector" (AC) and the "Antiproton Accumulator" (AA). To achieve adequate beam performance once the antiproton beam is decelerated to its final value of 0.1 GeV/c, it was necessary to lower the average pressure by nearly two orders of magnitude. For this purpose, a large number of additional pumps were installed and a very careful preparation was applied to a variety of special machine equipment which, in its original construction, was not designed for ultra-high vacuum operation. An important improvement in the outgassing rates was achieved through an extended, mild bake-out of tanks and vacuum vessels containing large amounts of ferrite material and multi-layer thermal insulation. This paper describes the necessary modifications of the vacuum system and in more detail the various steps taken to obtain the required pressure in the low 10/sup -10/ mbar range. It will also...

  9. The AD Vacuum System Construction and Commissioning

    CERN Document Server

    Brouet, M; Klette, H; Strubin, Pierre M

    1999-01-01

    CERN has built a new experimental facility, called the Antiproton Decelerator (AD), by transforming two existing machines: the "Antiproton Collector" (AC) and the "Antiproton Accumulator" (AA). To achieve adequate beam performance once the antiproton beam is decelerated to its final value of 0.1 GeV/c, it was necessary to lower the average pressure by nearly two orders of magnitude. For this purpose, a large number of additional pumps were installed and a very careful preparation was applied to a variety of special machine equipment which, in its original construction, was not designed for ultra-high vacuum operation. An important improvement in the outgassing rates was achieved through an extended, mild bake-out of tanks and vacuum vessels containing large amounts of ferrite material and multi-layer thermal insulation. This paper describes the necessary modifications of the vacuum system and in more detail the various steps taken to obtain the required pressure in the low 10-10 mbar range. It will also repor...

  10. Adding intelligence to a scientific database

    Directory of Open Access Journals (Sweden)

    F J Smith

    2006-01-01

    Full Text Available An experimental system called QPS (Quantitative Problem Solver has shown that a numerical database of quantities in the physical sciences can be enhanced by adding intelligence for problem-solving. The system needs to store not only numerical data but also the formulae that operate on the data. It needs also the logical software that enables the system to find and combine together data and formulae to solve problems. It is shown that this logical software is similar to the backward-chaining algorithm used in expert systems with factual data. It has been successfully tested on a large number of problems, including many taken from textbooks in physics and chemistry and some taken from practical problems in engineering, including problems that need the solution of simultaneous equations, and including a novel solution to the problem of choosing the optimum material for a component. It has an interface based on the well known symbols used in equations; it can work with any system of units and it can check the accuracy of the calculations. The principle can be used in any numerical database that contains data which can be manipulated using formulae, not just in the physical sciences.

  11. Spontaneous Ad Hoc Mobile Cloud Computing Network

    Directory of Open Access Journals (Sweden)

    Raquel Lacuesta

    2014-01-01

    Full Text Available Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

  12. SILAGE CANE SUGAR ADDED WITH DRIED BREWER

    Directory of Open Access Journals (Sweden)

    W. J. R. Castro

    2015-02-01

    Full Text Available The objective of this experiment was to evaluate the fermentative parameters and chemical composition of silage cane sugar added with residue dried brewery. The experimental design was completely randomized with four treatments and four replications: 100% cane sugar; 90% of cane sugar + 10% residue dried brewer; 80% of cane sugar + 20% residue dried brewer and 70% cane sugar + 30% dried brewer based on natural matter, composed silages. The sugar cane was chopped in a stationary machine with forage particle size of approximately 2 cm, and homogenized manually with the additives. For storage chopped fresh weight were used in experimental silos capacity of about 4 liters. The results showed that the contents of dry matter and crude protein showed positive linear (P0.05 with mean value of 3.81, while for ether extract and ash results were positive linear (P0.05 for N ammonia presented average value of 4.18. It is concluded that the addition of brewer dehydrated improves the fermentation process of silage cane sugar, in addition to improving their nutritional characteristics.

  13. Adding Four- Dimensional Data Assimilation (aka grid ...

    Science.gov (United States)

    Adding four-dimensional data assimilation (a.k.a. grid nudging) to MPAS.The U.S. Environmental Protection Agency is investigating the use of MPAS as the meteorological driver for its next-generation air quality model. To function as such, MPAS needs to operate in a diagnostic mode in much the same manner as the current meteorological driver, the Weather Research and Forecasting (WRF) model. The WRF operates in diagnostic mode using Four-Dimensional Data Assimilation, also known as "grid nudging". MPAS version 4.0 has been modified with the addition of an FDDA routine to the standard physics drivers to nudge the state variables for wind, temperature and water vapor towards MPAS initialization fields defined at 6-hour intervals from GFS-derived data. The results to be shown demonstrate the ability to constrain MPAS simulations to known historical conditions and thus provide the U.S. EPA with a practical meteorological driver for global-scale air quality simulations. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use bo

  14. Immunomodulatory properties of Alternanthera tenella Colla aqueous extracts in mice

    OpenAIRE

    Guerra R.N.M.; Pereira H.-A.W.; Silveira L.M.S.; Olea R.S.G.

    2003-01-01

    Plants from the genus Alternanthera are thought to possess antimicrobial and antiviral properties. In Brazilian folk medicine, the aqueous extract of A. tenella Colla is used for its anti-inflammatory activity. The present study investigated the immunomodulatory property of A. tenella extract by evaluating the antibody production in male albino Swiss mice weighing 20-25 g (10 per group). The animals received standard laboratory diet and water ad libitum. The effect of A. tenella extract (5 an...

  15. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

    Science.gov (United States)

    Seimon, Radhika V; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A; Nguyen, Amy D; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F; Lau, Jackie; Herzog, Herbert; Sainsbury, Amanda

    2016-01-01

    Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)-(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, Pindex. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, Penergy-restricted groups. Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative to energy deficit in mice.

  16. APP/PS1 transgenic mice treated with aluminum: an update of Alzheimer's disease model.

    Science.gov (United States)

    Zhang, Q L; Jia, L; Jiao, X; Guo, W L; Ji, J W; Yang, H L; Niu, Q

    2012-01-01

    There is still no animal model available that can mimic all the cognitive, behavioral, biochemical, and histopathological abnormalities observed in patients with Alzheimer's disease (AD). We undertook to consider the interaction between genetic factors, including amyloid precursor protein (APP) and presenilin-1 (PS1), and environmental factors, such as Aluminum (Al) in determining susceptibility outcomes when studying the pathogenesis of AD. In this article, we provide an AD model in APP/PS1 transgenic mice triggered by Al. The animal model was established via intracerebral ventricular microinjection of aluminum chloride once a day for 5 days in APP/PS1 transgenic mice. Twenty wild type (WT) mice and 20 APP/PS1 transgenic (TG) mice were separately divided into 2 groups (control and Al group), and a stainless steel injector with stopper was used for microinjection into the left-lateral cerebral ventricle of each mouse. The Morris water maze task was used to evaluate behavioral function of learning and memory ability on the 20th day after the last injection. This AD model's brain was analyzed by: (1) amyloid beta immunohistochemical staining; (2) Tunnel staining; (3) apoptotic rates; (4) caspase-3 gene expression. Here, decrease of cognitive ability and neural cells loss were shown in APP/PS1 transgenic mice exposed to Al, which were more extensive than those in APP/PS1 TG alone and WT mice exposed to Al alone. These findings indicate that there is a close relationship between over-expression of APP and PS1 genes and Al overload. It is also suggested that APP/PS1 TG mice exposed to Al have potential value for improving AD models.

  17. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

    Science.gov (United States)

    Seimon, Radhika V.; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A.; Nguyen, Amy D.; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F.; Lau, Jackie

    2016-01-01

    Background Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Methods Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Results Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, Pweight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, Pweight loss relative to energy deficit in mice. PMID:26784324

  18. Pemanfaatan Facebook Ads Untuk meningkatkan Brand Awareness pada Produk Lokal

    OpenAIRE

    Gita Aprinta

    2016-01-01

    Facebook ads is the most recent feature ad in facebook. Its simply stated as paid advertisment to help products in increasing their brand awareness.  The objective is to optimazing brands who want to reach thousands of costumers, by maximzing promotion through facebook ads.  Brand awareness is quite important for costumer to help them recalling brand, doing the purchasing, and have loyal to specific brand. Facebook ads providing huge opportunity for  each costumer to know, recall, involve and...

  19. Instantons and quark zero modes in AdS/QCD

    DEFF Research Database (Denmark)

    Bechi, Jacopo

    2009-01-01

    In this paper the quark zero modes creation effect is studied in the context of the AdS/QCD approach. This effect is generated, in presence of instantons, by a new that can be added in the bulk.......In this paper the quark zero modes creation effect is studied in the context of the AdS/QCD approach. This effect is generated, in presence of instantons, by a new that can be added in the bulk....

  20. Determining Positions and Desired Applicant Characteristics in Sports Job Ads

    Science.gov (United States)

    Atali, Levent

    2015-01-01

    The purpose of this study is to determine the diversity of positions occurring in sports job ads and reveal the characteristics requested from applicants for each position. This study examined 103 sports-related job ads obtained from four human resources websites. Using content analysis, job ads were examined in terms of job titles, and the…

  1. Comparative analysis of ADS gene promoter in seven Artemisia ...

    Indian Academy of Sciences (India)

    Artemisinin is the most effective antimalarial drug that is derived from Artemisia annua. Amorpha-4,11-diene synthase (ADS) controls the first committed step in artemisinin biosynthesis. The ADS gene expression is regulated by transcription factors which bind to the cis-acting elements on the ADS promoter and are probably ...

  2. RNA Interference Silencing of Glycogen Synthase Kinase 3β Inhibites Tau Phosphorylation in Mice with Alzheimer Disease.

    Science.gov (United States)

    Bian, Hong; Bian, Wei; Lin, Xiaoying; Ma, Zhaoyin; Chen, Wen; Pu, Ying

    2016-09-01

    To explore the effect of glycogen synthase kinase 3β (GSK-3β) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3β was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3β was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3β silencing system was successfully developed and silencing GSK-3β at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3β silence significantly improved the memory ability of AD mice in LV group compared with AD group (P silence. Silencing GSK-3β may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.

  3. Holography and AdS 2 gravity with a dynamical aether

    Science.gov (United States)

    Eling, Christopher

    2017-07-01

    We study two-dimensional Einstein-aether (or equivalently Hořava-Lifshitz) gravity, which has an AdS 2 solution. We examine various properties of this solution in the context of holography. We first show that the asymptotic symmetry group is the full set of time reparametrizations, the one-dimensional conformal group. At the same time there are configurations with finite energy and temperature, which indicate a violation of the Ward identity associated with one-dimensional conformal invariance. These solutions are characterized by a universal causal horizon and we show that the associated entropy of the universal horizon scales with the logarithm of the temperature. We discuss the puzzles associated with this result and argue that the violation of the Ward identity is associated with a type of explicit breaking of time reparametrizations in the hypothetical 0 + 1 dimensional dual system.

  4. P-V criticality in AdS black holes of massive gravity

    CERN Document Server

    Fernando, Sharmanthie

    2016-01-01

    In this paper we have studied the extended phase space thermodynamics in the canonical ensemble of black holes in massive gravity in AdS space. The black holes considered here belong to a theory of massive gravity where the graviton gain a mass due to Lorenz symmetry breaking. We have computed various thermodynamical quantities such as temperature, pressure, Gibbs free energy and specific heat capacity. The local and the global thermodynamical stability of the black holes are studied in detail. For a specific value of the parameter in the theory, the black holes undergo a first order phase transition similar to the Van der Waals phase transitions between gas and liquid under constant temperature. This transition is between the small and the large black hole. The critical exponents are computed at the critical values and shown to be the same as for the Van der Waals critical exponents.

  5. Testing quantum gravity effects through Dyonic charged AdS black hole

    CERN Document Server

    Sadeghi, J; Rostami, M

    2016-01-01

    In this paper, we consider dyonic charged AdS black hole which is holographic dual of a van der Waals fluid. We use logarithmic corrected entropy and study thermodynamics of the black hole and show that holographic picture is still valid. Critical behaviors and stability also discussed. Logarithmic corrections arises due to thermal fluctuations which are important when size of black hole be small. So, thermal fluctuations interpreted as quantum effect. It means that we can see quantum effect of a black hole which is a gravitational system. Hence, one can use result of this paper to compare with that of van der Waals fluid in the lab and see quantum gravity effects.

  6. Holographic microstate counting for AdS4 black holes in massive IIA supergravity

    Science.gov (United States)

    Hosseini, Seyed Morteza; Hristov, Kiril; Passias, Achilleas

    2017-10-01

    We derive the Bekenstein-Hawking entropy for a class of BPS black holes in the massive type IIA supergravity background AdS4 × S 6 from a microscopic counting of supersymmetric ground states in a holographically dual field theory. The counting is performed by evaluating the topologically twisted index of three-dimensional N=2 Chern-Simons-matter gauge theories in the large N limit. The I-extremization principle is shown to match the attractor mechanism for the near-horizon geometries constructed in the four-dimensional dyonic N=2 gauged supergravity, that arises as a consistent truncation of massive type IIA supergravity on S 6. In particular, our results prove that the imaginary part of the three-dimensional partition functions plays a crucial rôle in holography.

  7. Holographic fermionic spectrum from Born–Infeld AdS black hole

    Directory of Open Access Journals (Sweden)

    Jian-Pin Wu

    2016-07-01

    Full Text Available In this letter, we systematically explore the holographic (non-relativistic fermionic spectrum without/with dipole coupling dual to Born–Infeld anti-de Sitter (BI-AdS black hole. For the relativistic fermionic fixed point, this holographic fermionic system exhibits non-Fermi liquid behavior. Also, with the increase of BI parameter γ, the non-Fermi liquid becomes even “more non-Fermi”. When the dipole coupling term is included, we find that the BI term makes it a lot tougher to form the gap. While for the non-relativistic fermionic system with large dipole coupling in BI-AdS background, with the increase of BI parameter, the gap comes into being again.

  8. Thermodynamic geometry and phase transitions of dyonic charged AdS black holes

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Pankaj; Sengupta, Gautam [Indian Institute of Technology Kanpur, Department of Physics, Kanpur (India); Das, Anirban [Tata Institute of Fundamental Research, Department of Theoretical Physics, Mumbai (India)

    2017-02-15

    We investigate phase transitions and critical phenomena of four dimensional dyonic charged AdS black holes in the framework of thermodynamic geometry. In a mixed canonical-grand canonical ensemble with a fixed electric charge and varying magnetic charge these black holes exhibit a liquid-gas like first order phase transition culminating in a second order critical point similar to the van der Waals gas. We show that the thermodynamic scalar curvature R for these black holes follow our proposed geometrical characterization of the R-crossing Method for the first order liquid-gas like phase transition and exhibits a divergence at the second order critical point. The pattern of R crossing and divergence exactly corresponds to those of a van der Waals gas described by us in an earlier work. (orig.)

  9. Non-Abelian fields in AdS$_4$ spacetime: axially symmetric, composite configurations

    CERN Document Server

    Kichakova, Olga; Radu, Eugen; Shnir, Yasha

    2014-01-01

    We construct new finite energy regular solutions in Einstein-Yang-Mills-SU(2) theory. They are static, axially symmetric and approach at infinity the anti-de Sitter spacetime background. These configurations are characterized by a pair of integers $(m, n)$, where $m$ is related to the polar angle and $n$ to the azimuthal angle, being related to the known flat space monopole-antimonopole chains and vortex rings. Generically, they describe composite configurations with several individual components, possesing a nonzero magnetic charge, even in the absence of a Higgs field. Such Yang-Mills configurations exist already in the probe limit, the AdS geometry supplying the attractive force needed to balance the repulsive force of Yang-Mills gauge interactions. The gravitating solutions are constructed by numerically solving the elliptic Einstein-DeTurck--Yang-Mills equations. The variation of the gravitational coupling constant $\\alpha$ reveals the existence of two branches of gravitating solutions which bifurcate at...

  10. Three-spin Strings on AdS_5 x S^5 from N=4 SYM

    DEFF Research Database (Denmark)

    Kristjansen, C.

    2004-01-01

    the analyticity structure encoded in the Bethe equations for various distributions of Bethe roots. In a certain region of the parameter space our operators reduce to the gauge theory duals of the folded string with two large angular momenta and in another region to the duals of the circular string with angular...... momentum assignment (J,J',J'), J>J'. In between we locate a critical line. We propose that the operators above the critical line are the gauge theory duals of the circular elliptic string with three different spins and support this by a perturbative calculation.......Using the integrable spin chain picture we study the one-loop anomalous dimension of certain single trace scalar operators of N=4 SYM expected to correspond to semi-classical string states on AdS_5 x S^5 with three large angular momenta (J_1,J_2,J_3) on S^5. In particular, we investigate...

  11. On \\boldsymbol {AdS_2/CFT_1} transfer matrices, Bethe ansatz and scale invariance

    Science.gov (United States)

    Torrielli, Alessandro

    2018-01-01

    We explicitly calculate the \\renewcommand{\\r}ρ \\renewcommand{\\t}τ AdS2 × S2 × T6 transfer-matrix eigenvalues in the massless sector using the exact integrable S-matrix, for up to 5 particles. This enables us to conjecture the general pattern. We use the conjectured form of the eigenvalues to write down a set of massless Bethe ansatz equations. The same procedure applies to the relativistic as well as to the non-relativistic situation. In the relativistic case, the right and left modes decouple. We speculate that the relativistic massless Bethe ansatz we obtain in that case might capture the integrable structure of an underlying 2D critical theory. We finally take advantage of some remarkable simplifications to make progress in the massive case as well.

  12. A Crossing-Symmetric Phase for $AdS_{5} x S^{5}$ Strings

    CERN Document Server

    Beisert, N; López, E; Beisert, Niklas; Hernandez, Rafael; Lopez, Esperanza

    2006-01-01

    We propose an all-order perturbative expression for the dressing phase of the AdS_5 x S^5 string S-matrix at strong coupling. Moreover, we are able to sum up large parts of this expression. This allows us to start the investigation of the analytic structure of the phase at finite coupling revealing a few surprising features. The phase obeys all known constraints including the crossing relation and it matches with the known physical data at strong coupling. In particular, we recover the bound states of giant magnons recently found by Hofman and Maldacena as poles of the scattering matrix. At weak coupling our proposal seems to differ with gauge theory. A possible solution to this disagreement is the inclusion of additional pieces in the phase not contributing to crossing, which we also study.

  13. Charge Loss (or the Lack Thereof) for AdS Black Holes

    CERN Document Server

    Ong, Yen Chin

    2014-01-01

    The evolution of evaporating charged black holes is complicated to model in general, but is nevertheless important since the hints to the Information Loss Paradox and its recent firewall incarnation may lie in understanding more generic geometries than that of Schwarzschild spacetime. Fortunately, for sufficiently large asymptotically flat Reissner-Nordstrom black holes, the evaporation process can be modeled via a system of coupled linear ordinary differential equations, with charge loss rate governed by Schwinger pair-production process. The same model can be generalized to study the evaporation of AdS Reissner-Nordstrom black holes with flat horizon. It was recently found that such black holes always evolve towards extremality since charge loss is inefficient. This property is completely opposite to the asymptotically flat case in which the black hole eventually loses its charges and tends towards Schwarzschild limit. We clarify the underlying reason for this different behavior.

  14. Localized AdS_{5}×S^{5} Black Holes.

    Science.gov (United States)

    Dias, Óscar J C; Santos, Jorge E; Way, Benson

    2016-10-07

    According to heuristic arguments, global AdS_{5}×S^{5} black holes are expected to undergo a phase transition in the microcanonical ensemble. At high energies, one expects black holes that respect the symmetries of the S^{5}; at low energies, one expects "localized" black holes that appear pointlike on the S^{5}. According to anti-de Sitter/conformal field theory correspondence, N=4 supersymmetric Yang-Mills (SYM) theory on a 3-sphere should therefore exhibit spontaneous R-symmetry breaking at strong coupling. In this Letter, we numerically construct these localized black holes. We extrapolate the location of this phase transition, and compute the expectation value of the broken scalar operator with lowest conformal dimension. Via the correspondence, these results offer quantitative predictions for N=4 SYM theory.

  15. Regge limit of R-current correlators in AdS supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Bartels, J.; Kotanski, J.; Mischler, A.M. [II. Inst. fuer Theoretische Physik, Univ. Hamburg (Germany); Schomerus, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-08-15

    Four-point functions of R-currents are discussed within Anti-de Sitter supergravity. In particular, we compute Witten diagrams with graviton and gauge boson exchange in the high energy Regge limit. Assuming validity of the AdS/CFT correspondence, our results apply to R-current four-point functions of N=4 super Yang-Mills theory at strong coupling. (orig.)

  16. Logarithmic corrections to entropy of magnetically charged AdS4 black holes

    Directory of Open Access Journals (Sweden)

    Imtak Jeon

    2017-11-01

    Full Text Available Logarithmic terms are quantum corrections to black hole entropy determined completely from classical data, thus providing a strong check for candidate theories of quantum gravity purely from physics in the infrared. We compute these terms in the entropy associated to the horizon of a magnetically charged extremal black hole in AdS×4S7 using the quantum entropy function and discuss the possibility of matching against recently derived microscopic expressions.

  17. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

    DEFF Research Database (Denmark)

    Von Linstow, C. U.; Severino, Maurizio; Metaxas, Athanasios

    2017-01-01

    Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD......, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APPSWE/PS1δE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild......-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels...

  18. Added value of convection-permitting reanalyses

    Science.gov (United States)

    Wahl, S.; Keller, J. D.; Ohlwein, C.; Hense, A.; Friederichs, P.; Crewell, S.

    2016-12-01

    Atmospheric reanalyses are a state-of-the-art tool to generate consistent and realistic state estimates of the atmospheric system. They are used for validation of meteorological and hydrological models, climate monitoring, and renewable energy applications, amongst others. Current reanalyses are mainly global, while regional reanalyses are emerging for North America, the polar region, and most recently for Europe. Due to the horizontal resolution used, deep convection is still parameterized even in the regional reanalyses. However, convective parameterization is a major source of errors and uncertainties in atmospheric models. Therefore, it is expected that convection permitting reanalysis systems are able to adequately simulate the mechanisms leading to high-impact weather, notably heavy precipitation and winds related to deep moist convection. A novel convective-scale regional reanalysis system for Central Europe (COSMO-REA2) has been developed by the Hans-Ertel Center for Weather Research - Climate Monitoring Branch. The system is based on the COSMO model and uses a nudging scheme for the assimilation of observational data. In addition, radar-derived rain rates are assimilated through a latent heat nudging scheme. With a horizontal grid-spacing of 2 km, the model parameterization for deep moist convective processes is turned off. As we expect the largest benefit of the convection-permitting system for precipitation, the evaluation focuses on this essential climate variable (ECV). Furthermore, precipitation is crucial for climate monitoring purposes, e.g., in the form of extreme precipitation which is an major cause of severe damages and societal costs in Europe. This study illustrates the added value of the convective-scale reanalysis compared to coarser gridded regional European and global reanalyses.

  19. Value Added Products from Renewable Biofuels

    Energy Technology Data Exchange (ETDEWEB)

    Blum, Paul [Univ. of Nebraska, Lincoln, NE (United States)

    2014-07-31

    Cellulosic ethanol is an emerging biofuel that will make strong contributions to American domestic energy needs. In the US midwest the standard method for pretreatment of biomass uses hot acid to deconstruct lignocellulose. While other methods work, they are not in common use. Therefore it is necessary to work within this context to achieve process improvements and reductions in biofuel cost. Technology underlying this process could supplement and even replace commodity enzymes with engineered microbes to convert biomass-derived lignocellulose feedstocks into biofuels and valueadded chemicals. The approach that was used here was based on consolidated bioprocessing. Thermoacidophilic microbes belonging to the Domain Archaea were evaluated and modfied to promote deconvolution and saccharification of lignocellulose. Biomass pretreatment (hot acid) was combined with fermentation using an extremely thermoacidophilic microbial platform. The identity and fate of released sugars was controlled using metabolic blocks combined with added biochemical traits where needed. LC/MS analysis supported through the newly established Nebraska Bioenergy Facility provided general support for bioenergy researchers at the University of Nebraska. The primary project strategy was to use microbes that naturally flourish in hot acid (thermoacidophiles) with conventional biomass pretreatment that uses hot acid. The specific objectives were: to screen thermoacidophilic taxa for the ability to deconvolute lignocellulose and depolymerize associated carbohydrates; evaluate and respond to formation of “inhibitors” that arose during incubation of lignocellulose under heated acidic conditions; identify and engineer “sugar flux channeling and catabolic blocks” that redirect metabolic pathways to maximize sugar concentrations; expand the hydrolytic capacity of extremely thermoacidophilic microbes through the addition of deconvolution traits; and establish the Nebraska Bioenergy Facility (NBF

  20. Notes on worldvolume supersymmetries for D-branes on AdS5×S5 background

    Science.gov (United States)

    Park, Jaemo; Shin, Hyeonjoon

    2017-09-01

    We revisit the 1/2-BPS D-branes on the AdS5×S5 background. Based only on the classification of 1/2-BPS D-branes obtained by the covariant open string description, we consider various purely static configurations of D-branes without any worldvolume flux on the AdS5×S5 background. Under the covariant κ symmetry fixing condition, we investigate which part the spacetime supersymmetries is preserved on the D-brane worldvolume and obtain the associated worldvolume supersymmetry transformation rules to leading order in the worldvolume fluctuating fields. It is shown that, for purely static configurations without any worldvolume flux, only the AdS type D-branes, in which the AdS radial direction is one of worldvolume coordinates, are 1/2-BPS.

  1. Receiver-Based Ad Hoc On Demand Multipath Routing Protocol for Mobile Ad Hoc Networks.

    Directory of Open Access Journals (Sweden)

    Abdulaziz Al-Nahari

    Full Text Available Decreasing the route rediscovery time process in reactive routing protocols is challenging in mobile ad hoc networks. Links between nodes are continuously established and broken because of the characteristics of the network. Finding multiple routes to increase the reliability is also important but requires a fast update, especially in high traffic load and high mobility where paths can be broken as well. The sender node keeps re-establishing path discovery to find new paths, which makes for long time delay. In this paper we propose an improved multipath routing protocol, called Receiver-based ad hoc on demand multipath routing protocol (RB-AOMDV, which takes advantage of the reliability of the state of the art ad hoc on demand multipath distance vector (AOMDV protocol with less re-established discovery time. The receiver node assumes the role of discovering paths when finding data packets that have not been received after a period of time. Simulation results show the delay and delivery ratio performances are improved compared with AOMDV.

  2. AdS and ds Entropy from String Junctions or the Function of Junction Conjunctions

    Science.gov (United States)

    Silverstein, Eva

    Flux compactifications of string theory exhibiting the possibility of discretely tuning the cosmological constant to small values have been constructed. The highly tuned vacua in this discretuum have curvature radii which scale as large powers of the flux quantum numbers, exponential in the number of cycles in the compactiflcation. By the arguments of Susskind/Witten (in the AdS case) and Gibbons/Hawking (in the dS case), we expect correspondingly large entropies associated with these vacua. If they are to provide a dual description of these vacua on their Coulomb branch, branes traded for the flux need to account for this entropy at the appropriate energy scale. In this note, we argue that simple string junctions and webs ending on the branes can account for this large entropy, obtaining a rough estimate for junction entropy that agrees with the existing rough estimates for the spacing of the discretuum. In particular, the brane entropy can account for the (A)dS entropy far away from string scale correspondence limits.

  3. ECONOMIC VALUE ADDED AND MARKET VALUE ADDED - MODERN INDICATORS FOR ASSESSMENT THE FIRM’S VALUE

    Directory of Open Access Journals (Sweden)

    NICOLAE SICHIGEA

    2015-12-01

    Full Text Available The financial theory developed different categories of indicators - traditional and modern - in order to evaluate the firm’s value creation. The shareholders are directly interested by the value added in the company. The value creation is a complex process that implies correct decisions, common responsibility (managers and shareholders and actions towards an efficient and profitable activity. The traditional indicators of performance are not teoritically correlated with the the value creation and in these circumstances, should be used appropriate financial indicators in order to reflect the value of the company. Therefore, the modern indicators used in the value based management framework offer a greater flexibility and efficiency and represent a good alternative for companies. Such performance indicators used to measure the financial results correlated with shareholder wealth are the Economic Value Added (EVA, as a measure of internal performance and the Market Value Added (MVA as a measure of external performance of the company. Starting from the main deficiencies of the accounting indicators, the objective of this this study is to present the relationship between EVA and MVA and their implications on firms’valuation. Thus, the presentation and analysis of these indicators – EVA and MVA - will underline the main features, their correlations, and influence factors but also the main advantage and disadvantage of each indicator, which will enable the managers to make the correct choice and subsequently the best decision regarding the performance measures.

  4. Effect of Canavalia gladiata Extract Fermented with Aspergillus oryzae on the Development of Atopic Dermatitis in NC/Nga Mice.

    Science.gov (United States)

    Kim, Ok-Kyung; Chang, Jee-Yun; Nam, Da-Eun; Park, Yoo Kyoung; Jun, Woojin; Lee, Jeongmin

    2015-01-01

    Canavalia gladiata has been used as a Chinese traditional folk medicine for its anti-inflammatory properties. However, the use of C. gladiata is limited because it contains antinutritional and allergy-causing proteins. We fermented C. gladiata with Aspergillus oryzae and investigated the effects of fermented C. gladiata (FCG) on the development of atopic dermatitis (AD) in mice. The mice were divided into five groups: untreated Balb/c mice; AD control (NC/Nga mice); FCGH (NC/Nga mice fed a dietary supplement of 300 mg/kg fermented C. gladiata water extract); FCG30 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 30% ethanol extract), and FCG80 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 80% ethanol extract). We found increases in the nonessential amino acids and essential amino acid in the FCG compared with the non-FCG. FCG attenuated macroscopic and histopathological changes in dorsal skin of mice when compared with the AD control group. The FCG30 and FCG80 groups, in particular, showed significant decreases in scratching episodes when compared with the AD control group. FCG improved immune responses, including increases in IgE and histamine for AD, through attenuation of Th1/Th2 cytokine imbalance and the production of proinflammatory cytokines and chemokines. We suggest that FCG may have benefits for improvement of AD function by improving the balance of Th1/Th2 cytokines and by producing anti-inflammatory effects. © 2015 S. Karger AG, Basel.

  5. Biodistribution and residence time of adenovector serotype 5 in normal and immunodeficient mice and rats detected with bioluminescent imaging.

    Science.gov (United States)

    Liu, Qiang; Zhou, Shuya; Fan, Changfa; Huang, Weijin; Li, Qianqian; Liu, Susu; Wu, Xi; Li, Baowen; Wang, Youchun

    2017-06-15

    As concerns increase about adenovirus type 5 (Ad5) being a safe gene transfer vector, it is important to evaluate its distribution, residence time, and possible toxicity in immunodeficient populations. To characterize the potential risk associated with different Ad5 vector delivery modes, we used immunocompetent and immunodeficient Rag2 -/- animals to establish mouse and rat models that could be monitored with bioluminescent imaging following intramuscular or intravascular infection with an engineered replication-incompetent Ad5 virus carrying the firefly luciferase gene (Ad5-Fluc). The Ad5 vector was less well-tolerated by Rag2 -/- animals than by wildtype ones, with delayed residence time, wider virus dissemination, less weight gain, and relatively severe pathological changes. In intravascularly Ad5-Fluc-infected Rag2 -/- mice, systemic virus dissemination extended from the abdomen to the limbs and head on day 9 post-infection. Additionally, significant increases in plasma TNF-α and IFN-γ, which may be important factors in the heightened immunopathology in the liver and brain, were detected in the Rag2 -/- mice 30 days after intravascular delivery. The Ad5 vector was better tolerated after intramuscular delivery than after intravascular delivery. Ad5-Fluc/Rag2 -/- mice and rats can be used as reliable models of an immunodeficient population in which to evaluate the safety of Ad5-vectored vaccines or gene therapy products.

  6. Effect of exercise and calorie restriction on biomarkers of aging in mice.

    Science.gov (United States)

    Huffman, Derek M; Moellering, Douglas R; Grizzle, William E; Stockard, Cecil R; Johnson, Maria S; Nagy, Tim R

    2008-05-01

    Unlike calorie restriction, exercise fails to extend maximum life span, but the mechanisms that explain this disparate effect are unknown. We used a 24-wk protocol of treadmill running, weight matching, and pair feeding to compare the effects of exercise and calorie restriction on biomarkers related to aging. This study consisted of young controls, an ad libitum-fed sedentary group, two groups that were weight matched by exercise or 9% calorie restriction, and two groups that were weight matched by 9% calorie restriction + exercise or 18% calorie restriction. After 24 wk, ad libitum-fed sedentary mice were the heaviest and fattest. When weight-matched groups were compared, mice that exercised were leaner than calorie-restricted mice. Ad libitum-fed exercise mice tended to have lower serum IGF-1 than fully-fed controls, but no difference in fasting insulin. Mice that underwent 9% calorie restriction or 9% calorie restriction + exercise, had lower insulin levels; the lowest concentrations of serum insulin and IGF-1 were observed in 18% calorie-restricted mice. Exercise resulted in elevated levels of tissue heat shock proteins, but did not accelerate the accumulation of oxidative damage. Thus, failure of exercise to slow aging in previous studies is not likely the result of increased accrual of oxidative damage and may instead be due to an inability to fully mimic the hormonal and/or metabolic response to calorie restriction.

  7. Local delivery of Granulocyte/Macrophage Colony Stimulating Factor protects mice from lethal pneumococcal pneumonia1

    Science.gov (United States)

    Steinwede, Kathrin; Tempelhof, Ole; Bolte, Kristine; Maus, Regina; Bohling, Jennifer; Ueberberg, Bianca; Länger, Florian; Christman, John W.; Paton, James C.; Ask, Kjetil; Maharaj, Shyam; Kolb, Martin; Gauldie, Jack; Welte, Tobias; Maus, Ulrich A.

    2013-01-01

    The growth factor granulocyte/macrophage-colony stimulating factor (GM-CSF) has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities of lung sentinel cells. However, the potential of intra-alveolar GM-CSF to augment lung protective immunity against inhaled bacterial pathogens has not been defined in preclinical infection models. We hypothesized that transient overexpression of GM-CSF in the lungs of mice by adenoviral gene transfer (Ad-GM-CSF) would protect mice from subsequent lethal pneumococcal pneumonia. Our data show that intra-alveolar delivery of Ad-GM-CSF led to sustained increased pSTAT5 expression and PU.1 protein expression in alveolar macrophages during a 28 day observation period. Pulmonary Ad-GM-CSF delivery two or four weeks prior to infection of mice with S. pneumoniae significantly reduced mortality rates relative to control vector treated mice. This increased survival was accompanied by increased iNOS expression, antibacterial activity and a significant reduction in caspase 3 dependent apoptosis and secondary necrosis of lung sentinel cells. Importantly, therapeutic treatment of mice with recombinant GM-CSF improved lung protective immunity and accelerated bacterial clearance after pneumococcal challenge. We conclude that prophylactic delivery of GM-CSF triggers long-lasting immunostimulatory effects in the lung in vivo and rescues mice from lethal pneumococcal pneumonia by improving antibacterial immunity. These data support use of novel antibiotic-independent immunostimulatory therapies to protect patients against bacterial pneumonias. PMID:22003204

  8. Mice Drawer System

    Science.gov (United States)

    Cancedda, Ranieri

    2008-01-01

    The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and

  9. New Penrose limits and AdS/CFT

    DEFF Research Database (Denmark)

    Grignani, Gianluca; Harmark, Troels; Marini, Andrea

    2010-01-01

    We find a new Penrose limit of AdS 5 × S 5 giving the maximally supersymmetric pp-wave background with two explicit space-like isometries. This is an important missing piece in studying the AdS/CFT correspondence in certain subsectors. In particular whereas the Penrose limit giving one space......-like isometry is useful for the SU(2) sector of N = 4 SYM, this new Penrose limit is instead useful for studying the SU(2|3) and SU(1, 2|3) sectors. In addition to the new Penrose limit of AdS 5 × S 5 we also find a new Penrose limit of AdS4 × ℂP 3....

  10. Partial Return Yoke for MICE

    Energy Technology Data Exchange (ETDEWEB)

    Witte H.; Plate, S

    2013-05-03

    The international Muon Ionization Cooling Experiment (MICE) is a large scale experiment which is presently assembled at the Rutherford Appleton Laboratory in Didcot, UK. The purpose of MICE is to demonstrate the concept of ionization cooling experimentally. Ionization cooling is an important accelerator concept which will be essential for future HEP experiments such as a potential Muon Collider or a Neutrino Factory. The MICE experiment will house up to 18 superconducting solenoids, all of which produce a substantial amount of magnetic flux. Recently it was realized that this magnetic flux leads to a considerable stray magnetic field in the MICE hall. This is a concern as technical equipment in the MICE hall may may be compromised by this. In July 2012 a concept called partial return yoke was presented to the MICE community, which reduces the stray field in the MICE hall to a safe level. This report summarizes the general concept, engineering considerations and the expected shielding performance.

  11. A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging.

    Science.gov (United States)

    Tanifum, Eric A; Ghaghada, Ketan; Vollert, Craig; Head, Elizabeth; Eriksen, Jason L; Annapragada, Ananth

    2016-01-01

    Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.

  12. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    thoroughly validated antibodies and oligos, we give a detailed brain anatomical characterization of transgenic mice over expressing Neuroglobin. Moreover, using permanent middle artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage was studied. Lastly, the impact of mouse strain...... genetic background on ischemic damage was investigated. PRINCIPAL FINDINGS: A four to five fold increase in Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice. A β-actin promoter was used to drive Neuroglobin over expression, but immunohistochemistry and in situ hybridization...... showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction...

  13. The Status of MICE

    Science.gov (United States)

    Dobbs, A. J.; MICE Collaboration

    2017-09-01

    Muon beams of low emittance provide the basis for the intense, well characterised neutrino beams for a Neutrino Factory and for lepton-antilepton collisions at energies of up to several TeV at a Muon Collider. The international Muon Ionization Cooling Experiment (MICE) will demonstrate ionization cooling, the technique by which it is proposed to reduce the phase-space volume occupied by the muon beam. MICE is being constructed in a series of Steps. The configuration currently in operation at the Rutherford Appleton Laboratory is optimised for the study of the properties of liquid hydrogen and lithium hydride that affect cooling. The plans for data taking in the present configuration will be described together with some preliminary results. A description of the next experimental configuration, used for the final cooling demonstration, is also presented.

  14. GM-CSF upregulated in rheumatoid arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice.

    Science.gov (United States)

    Boyd, Tim D; Bennett, Steven P; Mori, Takashi; Governatori, Nicholas; Runfeldt, Melissa; Norden, Michelle; Padmanabhan, Jaya; Neame, Peter; Wefes, Inge; Sanchez-Ramos, Juan; Arendash, Gary W; Potter, Huntington

    2010-01-01

    Rheumatoid arthritis (RA) is a negative risk factor for the development of Alzheimer's disease (AD). While it has been commonly assumed that RA patients' usage of non-steroidal anti-inflammatory drugs (NSAIDs) helped prevent onset and progression of AD, NSAID clinical trials have proven unsuccessful in AD patients. To determine whether intrinsic factors within RA pathogenesis itself may underlie RA's protective effect, we investigated the activity of colony-stimulating factors, upregulated in RA, on the pathology and behavior of transgenic AD mice. 5 microg bolus injections of macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factors (M-CSF, G-CSF, or GM-CSF) were administered unilaterally into the hippocampus of aged cognitively-impaired AD mice and the resulting amyloid load reductions determined one week later, using the artificial cerebrospinal fluid-injected contralateral sides as controls. G-CSF and more significantly, GM-CSF reduced amyloidosis throughout the treated brain hemisphere one week following bolus administration to AD mice. 20 daily subcutaneous injections of 5 microg of GM-CSF (the most amyloid-reducing CSF in the bolus experiment) were administered to balanced cohorts of AD mice after assessment in a battery of cognitive tests. Reductions in amyloid load and improvements in cognitive function were assessed. Subcutaneous GM-CSF administration significantly reduced brain amyloidosis and completely reversed the cognitive impairment, while increasing hippocampal synaptic area and microglial density. These findings, along with two decades of accrued safety data using Leukine, recombinant human GMCSF, in elderly leukopenic patients, suggest that Leukine should be tested as a treatment to reverse cerebral amyloid pathology and cognitive impairment in AD.

  15. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice

    Directory of Open Access Journals (Sweden)

    Krstic Dimitrije

    2012-07-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is the most prevalent form of age-related dementia, and its effect on society increases exponentially as the population ages. Accumulating evidence suggests that neuroinflammation, mediated by the brain’s innate immune system, contributes to AD neuropathology and exacerbates the course of the disease. However, there is no experimental evidence for a causal link between systemic inflammation or neuroinflammation and the onset of the disease. Methods The viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C was used to stimulate the immune system of experimental animals. Wild-type (WT and transgenic mice were exposed to this cytokine inducer prenatally (gestation day (GD17 and/or in adulthood. Behavioral, immunological, immunohistochemical, and biochemical analyses of AD-associated neuropathologic changes were performed during aging. Results We found that a systemic immune challenge during late gestation predisposes WT mice to develop AD-like neuropathology during the course of aging. They display chronic elevation of inflammatory cytokines, an increase in the levels of hippocampal amyloid precursor protein (APP and its proteolytic fragments, altered Tau phosphorylation, and mis-sorting to somatodendritic compartments, and significant impairments in working memory in old age. If this prenatal infection is followed by a second immune challenge in adulthood, the phenotype is strongly exacerbated, and mimics AD-like neuropathologic changes. These include deposition of APP and its proteolytic fragments, along with Tau aggregation, microglia activation and reactive gliosis. Whereas Aβ peptides were not significantly enriched in extracellular deposits of double immune-challenged WT mice at 15 months, they dramatically increased in age-matched immune-challenged transgenic AD mice, precisely around the inflammation-induced accumulations of APP and its proteolytic fragments, in striking similarity to

  16. Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation.

    Directory of Open Access Journals (Sweden)

    Dag Sehlin

    Full Text Available Soluble amyloid-β (Aβ aggregates of various sizes, ranging from dimers to large protofibrils, have been associated with neurotoxicity and synaptic dysfunction in Alzheimer's Disease (AD. To investigate the properties of biologically relevant Aβ species, brain extracts from amyloid β protein precursor (AβPP transgenic mice and AD patients as well as synthetic Aβ preparations were separated by size under native conditions with density gradient ultracentrifugation. The fractionated samples were then analyzed with atomic force microscopy (AFM, ELISA, and MTT cell viability assay. Based on AFM appearance and immunoreactivity to our protofibril selective antibody mAb158, synthetic Aβ42 was divided in four fractions, with large aggregates in fraction 1 and the smallest species in fraction 4. Synthetic Aβ aggregates from fractions 2 and 3 proved to be most toxic in an MTT assay. In AβPP transgenic mouse brain, the most abundant soluble Aβ species were found in fraction 2 and consisted mainly of Aβ40. Also in AD brains, Aβ was mainly found in fraction 2 but primarily as Aβ42. All biologically derived Aβ from fraction 2 was immunologically discriminated from smaller species with mAb158. Thus, the predominant species of biologically derived soluble Aβ, natively separated by density gradient ultracentrifugation, were found to match the size of the neurotoxic, 80-500 kDa synthetic Aβ protofibrils and were equally detected with mAb158.

  17. Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease

    Science.gov (United States)

    Lee, Linda; Dale, Elena; Staniszewski, Agnes; Zhang, Hong; Saeed, Faisal; Sakurai, Mikako; Fa', Mauro; Orozco, Ian; Michelassi, Francesco; Akpan, Nsikan; Lehrer, Helena; Arancio, Ottavio

    2014-01-01

    Learning and memory and the underlying cellular correlate, long-term synaptic plasticity, involve regulation by posttranslational modifications (PTMs). Here we demonstrate that conjugation with the small ubiquitin-like modifier (SUMO) is a novel PTM required for normal synaptic and cognitive functioning. Acute inhibition of SUMOylation impairs long-term potentiation (LTP) and hippocampal-dependent learning. Since Alzheimer's disease (AD) prominently features both synaptic and PTM dysregulation, we investigated SUMOylation under pathology induced by amyloid-β (Aβ), a primary neurotoxic molecule implicated in AD. We observed that SUMOylation is dysregulated in both human AD brain tissue and the Tg2576 transgenic AD mouse model. While neuronal activation normally induced upregulation of SUMOylation, this effect was impaired by Aβ42 oligomers. However, supplementing SUMOylation via transduction of its conjugating enzyme, Ubc9, rescued Aβ-induced deficits in LTP and hippocampal-dependent learning and memory. Our data establish SUMO as a novel regulator of LTP and hippocampal-dependent cognition and additionally implicate SUMOylation impairments in AD pathogenesis. PMID:25448527

  18. [Effects of ketamine and alcohol on learning and memory impairment in mice].

    Science.gov (United States)

    Yang, Mei-Yu; Ding, Fei; Jiang, Xiao-Gang; Wu, Xie-Xing; Gu, Zhen-Lun; Guo, Ci-Yi; Bian, Shi-Zhong

    2012-04-01

    To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism. Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism. (1) Step-down: The treatment groups lessened the latency and added wrong times (P effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.

  19. Aspects of AdS, CFT. Black solutions in gauged supergravity and holographic conductivities

    Energy Technology Data Exchange (ETDEWEB)

    Barisch-Dick, Susanne

    2013-04-26

    We have met some interesting results within the wide subject of the AdS/CFT correspondence. We have seen how to apply AdS/CFT techniques to calculate the frequency dependent conductivity tensor for field theories dual to a black hole in Einstein-Yang-Mills theory with SU(2) gauge group. Further, we have constructed several new black solutions in N=2 U(1) gauged supergravity in four and five dimensions. The larger part of these solutions behave asymptotically like AdS which makes them interesting within the AdS/CFT context. In addition we found extremal black branes with zero entropy density - the Nernst branes. Nonetheless we are left with some yet unsolved problems. It is very interesting to see what causes the negative entropy production rate we found in chapter 4 for the normal state of the field theory. The next task is to see whether we can find an instability on the gravity side looking at the full Einstein-Yang-Mills equations. Also our work on supergravity solutions in four and five dimension exhibits some ''loose ends''. Since all our four-dimensional Nernst solutions were axion-free it would be nice to find one with axions excited. Moreover, it would be interesting to see whether the singular solutions with flowing γ could be cured by taking into account higher derivative corrections or whether there exist non-singular solutions with non-constant γ. In five dimensions we met problems when adding electric charge. At present we could not find a dyonic solution and we had the impression that having electric charges and having magnetic fields seemed to be somehow complementary to each other. We saw these difficulties even at the beginning when we performed the first-order rewriting since the first-order rewriting in chapter 6 leads to flow equations for the scalars X{sup A} which only contain magnetic fields and fluxes but no electric charges. The latter only influence the equations of motion for the X{sup A} in an indirect way. However

  20. Dietary Protective Effects Against Hepatocellular Carcinoma Development in Mdr2-/- Knockout Mice.

    Science.gov (United States)

    Gentileschi, Maria Pia; Lattanzio, Claudia; Menicagli, Francesco; Vincenzi, Bruno; Cigliana, Giovanni; Baldi, Alfonso; Blandino, Giovanni; Muti, Paola; Fanciulli, Maurizio; Spugnini, Enrico P

    2016-01-01

    The Mdr2(-/-) mouse develops early chronic cholestatic hepatitis and hepatocellularcarcinoma (HCC) when adult. We tested the effects of a restricted-calorie diet on HCC development in Mdr2(-/-) mice. Mdr2(-/-) mice (n=40, divided into two groups of 20 mice each) were randomized to receive ad libitum diet or restricted-calorie diet. Two mice from each group were sacrificed at 3 and 6 months, and liver tissue samples were removed for analysis. The remaining mice were fed their respective diets until the age of 30 months, at which time they were euthanized and livers were collected for analysis. The restricted-calorie diet had partial chemopreventive effect on the development of HCC in Mdr2(-/-) mice. Moreover, mice with ad libitum diet had a median survival of 361 days, while the restricted-calorie group had a median survival of 500 days (p=0.0001). A restricted diet might reduce the chance of developing HCC in patients at risk and could increase the protective action of anti-inflammatory agents. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Evaluation of antidiabetic potential of oyster mushroom (Pleurotus ostreatus) in alloxan-induced diabetic mice.

    Science.gov (United States)

    Ravi, Bindhu; Renitta, R Emilin; Prabha, M Lakshmi; Issac, Reya; Naidu, Shanti

    2013-02-01

    To study the antidiabetic activity of Pleurotus ostreatus in normal and alloxan-induced diabetic mice. Ethanolic extract of fruiting bodies of P. ostreatus was tested for their antidiabetic activity. BALB/C mice (25-30 g) were divided into four groups of six animals each normal control mice, diabetic control mice, diabetic mice posttreated with standard drug glibenclamide and diabetic mice treated with P. ostreatus ethanolic extract. Blood glucose level, biochemical parameters such as serum total cholesterol, LDL, HDL, VLDL, triglyceride creatinine, urea, and Serum glutamate oxaloacetate transaminase and Serum glutamate pyruvate transaminase were studied in alloxan-induced diabetic mice after 15 days of treatment. Animals treated with the ethanolic extract of P. ostreatus showed a significant decrease in serum glucose level (p ostreatus extract reduced serum cholesterol, triglyceride and LDL-cholesterol. The serum HDL cholesterol was significantly increased in posttreated groups. The serum creatinine, urea levels were significantly reduced in posttreated group, whereas the decrease in the body weight was arrested by administration of P. ostreatus extract to the animals. The consumption of P. ostreatus produced a significant hypoglycemic effect in diabetic mice and it is capable of improving hyperlipidemia and the impaired kidney functions in alloxan-induced diabetic mice. Thus, indicating that the ethanolic extract of P. ostreatus could be added in the list of medicinal preparations beneficial in diabetes mellitus.

  2. A local insult of okadaic acid in wild-type mice induces tau phosphorylation and protein aggregation in anatomically distinct brain regions

    OpenAIRE

    Baker, Si?n; G?tz, J?rgen

    2016-01-01

    In Alzheimer?s disease (AD), the distribution and density of neurofibrillary tangles, a histological hallmark comprised predominately of phosphorylated tau protein, follows a distinct pattern through anatomically connected brain regions. Studies in transgenic mice engineered to regionally confine tau expression have suggested spreading of tau within neural networks. Furthermore, injection of protein lysates isolated from brains of transgenic mice or patients with tauopathies, including AD, we...

  3. Nonvacuum AdS cosmology and comments on gauge theory correlator

    Science.gov (United States)

    Chatterjee, Soumyabrata; Chowdhury, Sudipto Paul; Mukherji, Sudipta; Srivastava, Yogesh K.

    2017-02-01

    Several time dependent backgrounds, with perfect fluid matter, can be used to construct solutions of Einstein equations in the presence of a negative cosmological constant along with some matter sources. In this work we focus on the non-vacuum Kasner-AdS geometry and its solitonic generalization. To characterize these space-times, we provide ways to embed them in higher dimensional flat space-times. General space-like geodesics are then studied and used to compute the two point boundary correlators within the geodesic approximation.

  4. Geometric polarization of plasmas and Love numbers of AdS black branes

    Science.gov (United States)

    Emparan, Roberto; Fernández-Piqué, Alejandro; Luna, Raimon

    2017-09-01

    We use AdS/CFT holography to study how a strongly-coupled plasma polarizes when the geometry where it resides is not flat. We compute the linear-response polarization coefficients, which are directly related to the static two-point correlation function of the stress-energy tensor. In the gravitational dual description, these parameters correspond to the tidal deformation coefficients — the Love numbers — of a black brane. We also compute the coefficients of static electric polarization of the plasma.

  5. The UK Virtual Observatory - Adding Planetary Data

    Science.gov (United States)

    Allan, Peter

    The UK has built a virtual observatory called AstroGrid. Using this facility, scientists can already get access to a wide range of data on traditional astronomy, the Sun and solar-terrestrial physics (STP). This paper describes the AstroGrid system and what would be involved in adding access to planetary data to those already on offer. In recent years, there have been activities in several countries to create what are known as virtual observatories. The idea is that you should be able to easily get to all of the astronomical data that exist from your desktop computer. You do not need to know that specific data exist and you do not need to know where these data reside. In order to make this possible, it is essential that data archives and software that accesses those archives is built around a set of internationally agreed standards. These standards have been developed by the International Virtual Observatory Alliance (IVOA). A data archive that adheres to these standards can publish data on the internet to registries of resources that client software can search. The AstroGrid software developed in the UK adheres to these standards and provides a comprehensive set of services for data archives to provide dataset access, registries of data holdings, virtual file stores, communities of users, workflow for execution of complex grid applications and an environment into which pre-existing data processing applications can be plugged. There is also client software for searching registries and remote data archives, accessing the remote data, and a basic set of tools for displaying and analysing those data. AstroGrid is unique amongst virtual observatories in that it includes major data sources on the Sun and solar-terrestrial physics as well as more traditional astronomy. The need to support these very different types of data has led to the development of tools that can handle very different coordinate systems and display data in a variety of ways. For example, we have a

  6. Topics On Ads/cft Duality And Holography

    CERN Document Server

    Lin, F

    2000-01-01

    This dissertation presents our study on various aspects of Maldacena's AdS/CFT duality and on a generalization of it from the point of view of holography. The AdS/CFT duality states that supergravity on anti-de Sitter (AdS) background is equivalent to a local conformal field theory (CFT) on the boundary at infinity of AdS space. One way to generalize the AdS/CFT duality is to turn on more background fields of supergravity such as the r-form fields. The bulk geometry is no longer AdS, and one finds that in the spirit of AdS/CFT duality, it corresponds to a nonconformal field theory with the radial position of the boundary as the energy scale and with the boundary at infinity as the ultraviolet fixed point. Moreover, one can derive the holographic renormalization group (RG) flows of the field theory from its gravity dual. A specific case of interest is the Neveu-Schwarz 2-form potential on the world volume of a D-brane, the resulting open-string low energy effective field theory has been shown to be a Yang-Mill...

  7. Ginsenoside Rd Improves Learning and Memory Ability in APP Transgenic Mice.

    Science.gov (United States)

    Liu, Juanfang; Yan, Xiaodong; Li, Ling; Li, Yuan; Zhou, Linfu; Zhang, Xiaohui; Hu, Xinghua; Zhao, Gang

    2015-12-01

    Alzheimer's disease (AD) is a complicated neurodegenerative disease which causes memory loss and dementia. Many researchers have revealed the vital roles of β-amyloid proteins (Aβ) in the proceeds of AD. Aβ deposition in AD patients' brains might function as immune stimulus, and inflammation is believed to play an important role in AD pathologically. We experimentally used amyloid β-protein precursor (APP) transgenic (Tg) mice in this study to further clarify the neuroprotective effects of ginsenoside Rd on AD and its possible mechanisms. It was found that Rd could improve learning and memory ability in APP Tg mice, probably through inhibiting the transcription activity of NFκB. With the activation of the NFκB pathway being suppressed, the reduction of pro-inflammatory cytokines and the generation of protective factors had been increased ultimately. In conclusion, Rd had a neuroprotective effect on APP Tg mice, and it can be used as an alternative drug therapy in AD patients for their memory dysfunction.

  8. Geniposide attenuates mitochondrial dysfunction and memory deficits in APP/PS1 transgenic mice.

    Science.gov (United States)

    Lv, Cui; Liu, Xiaoli; Liu, Hongjuan; Chen, Tong; Zhang, Wensheng

    2014-01-01

    Oxidative stress and mitochondrial dysfunction appear early and contribute to the disease progression in Alzheimer's disease (AD), which can be detected extensively in AD patients brains as well as in transgenic AD mice brains. Thus, treatments that result in attenuation of oxidative stress and mitochondrial dysfunction may hold potential for AD treatment. Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits anti-oxidative, antiinflammatory and other important therapeutic properties. However, whether geniposide has any protective effect on oxidative stress and mitochondrial dysfunction in AD transgenic mouse model has not yet been reported. Here, we demonstrate that intragastric administration of geniposide significantly reduces oxidative stress and mitochondrial dysfunction in addition to improving learning and memory in APP/PS1 mice. Geniposide exerts protective effects on mitochondrial dysfunction in APP/PS1 mice through suppressing the mitochondrial oxidative damage and increasing the mitochondrial membrane potential and activity of cytochrome c oxidase. These studies indicate that geniposide may attenuate memory deficits through the suppression of mitochondrial oxidative stress. Thus, geniposide may be a potential therapeutic reagent for halting and preventing AD progress.

  9. Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - a novel immunotherapeutic strategy.

    Directory of Open Access Journals (Sweden)

    Nina Movsesyan

    2008-05-01

    Full Text Available The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42 (Abeta(1-11 , a non-self T helper cell epitope (PADRE, and macrophage-derived chemokine (MDC/CCL22 as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype.We generated pMDC-3Abeta(1-11-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages.Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials.

  10. Properdin Regulation of Complement Activation Affects Colitis in Interleukin 10 Gene-Deficient Mice.

    Science.gov (United States)

    Jain, Umang; Midgen, Craig A; Schwaeble, Wilhelm J; Stover, Cordula M; Stadnyk, Andrew W

    2015-07-01

    Interleukin 10-deficient mice (IL-10(-/-)) are a popular model used to dissect the mechanisms underlying inflammatory bowel diseases. The role of complement, a host defense mechanism that bridges the innate and adaptive immune systems, has not been described in this model. We therefore studied the effect of deficiency of properdin, a positive regulator of complement, on colitis in mice with the IL-10(-/-) background. For acute colitis, IL-10(-/-) and IL-10/properdin double knockout (DKO) or radiation bone marrow-reconstituted chimeric mice, had piroxicam added to their powdered chow for 14 days. For chronic colitis, 2.5% dextran sodium sulfate was added to the animals' water for 4 days then the mice were killed 8 weeks later. Colons were assessed for inflammation, cell infiltration, and cytokine and complement measurements. Bacterial translocation was measured by cultivating bacteria from organs on Luria broth agar plates. C3a and C5a levels and C9 deposition were all increased in piroxicam-fed IL-10(-/-) mice compared with mice not fed piroxicam. Piroxicam-fed DKO mice lacked increased C5a and C9 deposition combined with exacerbated colitis, reduced numbers of infiltrating neutrophils, and markedly higher local and systemic bacterial numbers compared with IL-10(-/-) mice. Bone marrow cells from IL-10(-/-) mice were sufficient to restore protection against the heightened colitis in piroxicam-fed DKO mice. Complement is activated in the IL-10(-/-) mouse mucosa in a properdin-dependent manner. In the absence of terminal complement activation, the inflammation is heightened, likely due to a lack of neutrophil control over microbes escaping from the intestines.

  11. Region-Specific Vulnerability to Oxidative Stress, Neuroinflammation, and Tau Hyperphosphorylation in Experimental Diabetes Mellitus Mice.

    Science.gov (United States)

    Elahi, Montasir; Hasan, Zafrul; Motoi, Yumiko; Matsumoto, Shin-Ei; Ishiguro, Koichi; Hattori, Nobutaka

    2016-01-01

    Recent epidemiological evidence suggests that diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD). One of the pathological hallmarks of AD is hyperphosphorylated tau protein, which forms neurofibrillary tangles. Oxidative stress and the activation of inflammatory pathways are features that are associated with both DM and AD. However, the brain region specificity of AD-related neurodegeneration, which mainly occurs in the hippocampus while the cerebellum is relatively unaffected, has not yet been clarified. Therefore, we used experimental DM mice (caused by an intraperitoneal injection of streptozotocin [STZ]) to determine whether these neurodegeneration-associated mechanisms were associated with region-specific selective vulnerability or tau phosphorylation. The hippocampus, midbrain, and cerebellum of aged (14 to 18 months old) non-transgenic (NTg) and transgenic mice overexpressing wild-type human tau (Tg601 mice) were evaluated after a treatment with STZ. The STZ injection increased reactive oxygen species, lipid peroxidation markers such as 4-hydroxynonenal and malondialdehyde in the hippocampus, but not in the midbrain or cerebellum. The STZ treatment also increased the number of Iba-1-positive and CD68-positive microglial cells, astrocytes, and IL-1β, IL-6, IL-10, and IL-18 levels in the hippocampus, but not in the midbrain or cerebellum. Tau hyperphosphorylation was also enhanced in the hippocampus, but not in the midbrain or cerebellum. When the effects of STZ were compared between Tg601 and NTg mice, microglial proliferation and elevations in IL-6 and phosphorylated tau were higher in Tg601 mice. These results suggest that neuroinflammation and oxidative stress in STZ-treated mice are associated with tau hyperphosphorylation, which may contribute to selective neurodegeneration in human AD.

  12. Estrous Cyclicity in Mice During Simulated Weightlessness

    Science.gov (United States)

    Moyer, E. L.; Talyansky, Y.; Scott, R. T.; Tash, J. S.; Christenson, L. K.; Alwood, J. S.; Ronca, A. E.

    2017-01-01

    Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n=22), normally loaded HU Cage Pair-Fed controls (CPF; n=22), and Vivarium controls fed ad libitum (VIV; n=10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8+/- 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, and/or due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5% vs 3.0%, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU

  13. Estrous Cyclicity of Mice During Simulated Weightlessness

    Science.gov (United States)

    Moyer, Eric; Talyansky, Yuli; Scott, Ryan; Tash, Joseph; Christenson, Lane; Alwood, Joshua; Ronca, April

    2017-01-01

    Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n22), normally loaded HU Cage Pair-Fed controls (CPF; n22), and Vivarium controls fed ad libitum (VIV; n10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, andor due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5 vs 3.0, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future

  14. Aerodigitalni senzori - LH Systems ADS 40 / Airborne digital sensors: LH Systems ADS 40

    Directory of Open Access Journals (Sweden)

    Marko Pejić

    2004-01-01

    Full Text Available U radu su prezentovane osnove prikupljanja prostornih podataka metodom daljinske detekcije i klasičnim fotogrametrijskim metodom. Ukazano je na kompromis između dva metoda koji nudi digitalna aerokamera. Kompanija LH Systems proizvela je digitalnu aerokameru ADS 40 koja nudi sasvim nov koncept prikupljanja prostornih podataka. Sistem kamere obezbeđuje panhromatske i trodimenzionalne informacije koristeći tri CCD linije i opciono još pet linija iz multispektralnog opsega. Kamera skenira teren sa prostornom rezolucijom od 25 cm, površine od 300 kvadratnih kilometara, uz vreme trajanja leta koje je nešto kraće od jednog sata. / This paper presents basics of collecting spatial data with remote sensing and the classical photogrammetric method. A compromise between two methods, offered by a digital aero camera, is also suggested. The LH Systems has produced a new camera concept called Airborne Digital Sensor (ADS 40 which uses a new way of collecting spatial data. The camera system provides panchromatic and stereo information using three CCD lines and up to five more lines for multispectral imagery. The performance of the camera allows a three dimensional and multispectral image with a ground sample distance of 25 cm for an area of 300 square miles within a flight time shorter than one hour.

  15. Higher spin theories in AdS3 and a gravitational exclusion principle

    Science.gov (United States)

    Castro, Alejandra; Lepage-Jutier, Arnaud; Maloney, Alexander

    2011-01-01

    We consider theories of three dimensional quantum gravity in Anti-de Sitter space which possess massless higher-spin gauge symmetry. The perturbative spectrum of the theory includes higher spin excitations which can be organized into vacuum representations of the {mathcal{W}_N} algebra; these are higher spin versions of the boundary gravitons. We describe a fundamental bound which relates the value of the cosmological constant to the amount of gauge symmetry present. In the dual CFT language, this is the statement that modular invariance implies that the theory can not be quantized unless the central charge is sufficiently large, i.e. if c ≥ N - 1. This bound relies on the assumption that all of the perturbative excitations exist as full states in the quantum theory, and can be circumvented if the theory possesses a linearization instability. The {mathcal{W}_N} minimal models — recently conjectured to be dual to certain higher spin AdS theories by Gaberdiel and Gopakumar — provide an example of this phenomenon. This result can be regarded as an example of a "gravitational exclusion principle" in Anti-de Sitter space, where a non-perturbative quantum gravity mechanism involving black holes places a limit on the number of light degrees of freedom present.

  16. Exceptional $N=6$ and $N=2 AdS_4$ Supergravity, and Zero-Center Modules

    CERN Document Server

    Andrianopoli, L; Ferrara, Sergio; Grassi, P A; Trigiante, M

    2009-01-01

    We study the gauging of the orthosymplectic algebras OSp(6|4)xSO(2) and its "dual" OSp(2|4)x SO(6), both based on supergravities with the same exceptional coset SO*(12)/U(6), and gauge group SO(6)xSO(2). The two dual theories are obtained by two different truncations of gauged N=8 AdS_4 supergravity. We explicitly study the gauge sector of the two dual theories with the most general group allowed by supersymmetry. In the ungauged (super-Poincar\\'e) case they exhibit the same (large) black-hole attractor solutions with dual relations between the 1/N-BPS and non-BPS configurations. The N=6 gravity multiplet has also the exceptional property to be a {\\em zero-center module} of OSp(6|4), as it is the case for superconformal Yang--Mills theory in four dimensions based on SU(2,2|n) (PSU(2,2|4) for n=4) or OSp(n|4).

  17. Analytic self-gravitating Skyrmions, cosmological bounces and AdS wormholes

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    Eloy Ayón-Beato

    2016-01-01

    Full Text Available We present a self-gravitating, analytic and globally regular Skyrmion solution of the Einstein–Skyrme system with winding number w=±1, in presence of a cosmological constant. The static spacetime metric is the direct product R×S3 and the Skyrmion is the self-gravitating generalization of the static hedgehog solution of Manton and Ruback with unit topological charge. This solution can be promoted to a dynamical one in which the spacetime is a cosmology of the Bianchi type-IX with time-dependent scale and squashing coefficients. Remarkably, the Skyrme equations are still identically satisfied for all values of these parameters. Thus, the complete set of field equations for the Einstein–Skyrme–Λ system in the topological sector reduces to a pair of coupled, autonomous, nonlinear differential equations for the scale factor and a squashing coefficient. These equations admit analytic bouncing cosmological solutions in which the universe contracts to a minimum non-vanishing size, and then expands. A non-trivial byproduct of this solution is that a minor modification of the construction gives rise to a family of stationary, regular configurations in General Relativity with negative cosmological constant supported by an SU(2 nonlinear sigma model. These solutions represent traversable AdS wormholes with NUT parameter in which the only “exotic matter” required for their construction is a negative cosmological constant.

  18. Covariant charges in Chern-Simons AdS sub 3 gravity

    CERN Document Server

    Allemandi, G; Raiteri, M

    2003-01-01

    We try to give hereafter an answer to some open questions about the definition of conserved quantities in Chern-Simons theory, with particular reference to Chern-Simons AdS sub 3 gravity. Our attention is focused on the problem of global covariance and gauge invariance of the variation of Noether charges. A theory which satisfies the principle of covariance on each step of its construction is developed, starting from a gauge invariant Chern-Simons Lagrangian and using a recipe developed by Allemandi et al (2002 Class. Quantum Grav. 19 2633-55, 237-58) to calculate the variation of conserved quantities. The problem of giving a mathematical well-defined expression for the infinitesimal generators of symmetries is pointed out and it is shown that the generalized Kosmann lift of spacetime vector fields leads to the expected numerical values for the conserved quantities when the solution corresponds to the BTZ black hole. The fist law of black-hole mechanics for the BTZ solution is then proved and the transition b...

  19. Static structures of the BCS-like holographic superfluid in AdS4 spacetime

    Science.gov (United States)

    Lan, Shanquan; Liu, Wenbiao; Tian, Yu

    2017-03-01

    We investigate in detail the m2=0 Abelian Higgs model in AdS4 , which is considered as the holographic dual of the most BCS-like superfluid. In homogeneous and isotropic superfluid solutions, we calculate the fourth-sound speeds, the square of which approaches 1 /2 with increasing chemical potential (lowering temperature). Then we present the single dark soliton solutions, which becomes thinner with increasing chemical potential. For the first time, we also find the interesting double and triple dark soliton solutions, which is unexpected and shows the possibility of more complicated static configurations. Finally, we investigate vortex solutions. For winding number n =1 , the vortex becomes thinner with increasing chemical potential. At a given chemical potential, with increasing winding number, first the vortex becomes bigger and the charge density depletion becomes larger, and then the charge density depletion settles down at a certain value and the growth of the vortex size is found to obey a scaling symmetry.

  20. Quantization of the AdS3 superparticle on OSP(1|22/SL(2,R

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    Martin Heinze

    2017-02-01

    Full Text Available We analyze AdS3 superparticle dynamics on the coset OSP(1|2×OSP(1|2/SL(2,R. The system is quantized in canonical coordinates obtained by gauge invariant Hamiltonian reduction. The left and right Noether charges of a massive particle are parametrized by coadjoint orbits of a timelike element of osp(1|2. Each chiral sector is described by two bosonic and two fermionic canonical coordinates corresponding to a superparticle with superpotential W=q−m/q, where m is the particle mass. Canonical quantization then provides a quantum realization of osp(1|2⊕osp(1|2. For the massless particle the chiral charges lie on the coadjoint orbit of a nilpotent element of osp(1|2 and each of them depends only on one real fermion, which demonstrates the underlying κ-symmetry. These remaining left and right fermionic variables form a canonical pair and the system is described by four bosonic and two fermionic canonical coordinates. Due to conformal invariance of the massless particle, the osp(1|2⊕osp(1|2 extends to the corresponding superconformal algebra osp(2|4. Its 19 charges are given by all real quadratic combinations of the canonical coordinates, which trivializes their quantization.