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Sample records for donepezil reverses buprenorphine-induced

  1. Donepezil

    MedlinePlus

    Namzaric®(as a combination product containing Donepezil, Memantine) ... Donepezil is used to treat dementia (a brain disorder that affects the ability to remember, think clearly, communicate, and perform daily activities and may cause changes in mood and ...

  2. Phencyclidine withdrawal disrupts episodic-like memory in rats: reversal by donepezil but not clozapine.

    PubMed

    Le Cozannet, Romain; Fone, Kevin C F; Moran, Paula M

    2010-09-01

    Episodic memory is the capacity to recall an event in time and place (What? Where? When?). Impaired episodic memory is a debilitating cognitive symptom in schizophrenia but is poorly controlled by currently available antipsychotic drugs. Consistent with glutamatergic abnormality in schizophrenia, the NDMA receptor antagonist, phencyclidine (PCP), induces persistent 'schizophrenia-like' symptoms including memory deficits in humans and rodents and is widely used as an animal model of the disorder. However, in contrast to humans, PCP and PCP withdrawal-induced memory deficits in rodents are reversed by antipsychotic drugs such as clozapine. One possible explanation is that the memory tasks used in animal studies do not simultaneously test the What? Where? When? components that characterize episodic memory in human tasks. We investigated whether subchronic PCP withdrawal disrupts memory in rats in a task that requires simultaneous integration of memory for object, place and context. Rats learn to discriminate objects under specific spatial and contextual conditions analogous to the What? Where? When? components of human episodic memory. We found that PCP withdrawal impaired performance on this task and that the atypical antipsychotic drug clozapine did not reverse this impairment. However the acetylcholinesterase inhibitor (AChEI) donepezil, which has been shown to improve episodic memory in humans did reverse the effect of PCP. This suggests that PCP withdrawal disruption of object-place-context recognition in rats may prove to be a useful model to investigate episodic memory impairment in schizophrenia and supports the suggestion that AChEIs could prove to be a useful pharmacological strategy to specifically treat episodic memory problems in schizophrenia. PMID:20236574

  3. Reversible and persistent decreases in cocaine self-administration after cholinesterase inhibition: different effects of donepezil and rivastigmine.

    PubMed

    Grasing, Kenneth; Yang, Yungao; He, Shuangteng

    2011-02-01

    We recently observed that pretreatment with the cholinesterase inhibitor, tacrine can produce long-lasting reductions in cocaine-reinforced behavior, described as persistent attenuation. In addition to inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase, tacrine can potentiate actions of dopamine. This study was carried out to evaluate the effects of donepezil (which selectively inhibits AChE) and rivastigmine (which inhibits both AChE and butyrylcholinesterase) on cocaine self-administration. High self-administration rats self-administered different doses of cocaine under a fixed ratio-5 schedule. Over a 4-day period, vehicle, donepezil, or rivastigmine was infused as animals were maintained in home cages (21 h per day), with signs of cholinergic stimulation (fasciculation, vacuous jaw movements, yawning, and diarrhea) scored by a blinded observer. Both compounds dose-dependently decreased cocaine self-administration, but differed in the potency and temporal pattern of their effects. Self-administration of low-dose cocaine was decreased to a greater degree by rivastigmine than donepezil (50% effective doses of 2.33 and 6.21 mg/kg/day, respectively), but this early effect did not continue beyond sessions immediately after treatment with rivastigmine. Group means for cocaine self-administration were decreased at some time points occurring between 1 and 3 days after the treatment with 10 mg/kg/day of donepezil (late effects), with decreases of more than 80% observed in some individual rats that persisted for 1 week or longer. Early, but not late, effects were correlated with signs of cholinergic stimulation. In summary, pretreatment with donepezil, but not rivastigmine produced persistent reductions in cocaine-reinforced behavior, which were not associated with signs of cholinergic stimulation. PMID:22173266

  4. Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation.

    PubMed

    Zhang, Tao; Tian, Feng; Wang, Jing; Zhou, Shanshan; Dong, Xueqing; Guo, Kai; Jing, Jing; Zhou, Ying; Chen, Yundai

    2015-09-01

    Cellular senescence of endothelial cells is a damage and stress response which induces pro-inflammatory, pro-atherosclerotic, and pro-thrombotic phenotypes. Donepezil is a drug used for the treatment of mild to moderate dementia of the Alzheimer's disease (AD). The aim of the present study was to investigate the attenuation of endothelial cell senescence by donepezil and to explore the mechanisms underlying the anti-aging effects of donepezil. Our results indicated that high glucose (HG) markedly decreased cell viability of human umbilical vein endothelial cells (HUVECs), and this phenomenon was reversed by treatment with donepezil. Importantly, our results displayed that the frequency of senescent (SA-ß-gal-positive) cells and the expression level of senescence genes (PAI-1 and p21) were significantly higher in the HG group compared with the normal glucose (NG) group, and these changes were blocked by treatment with donepezil. Also, our results showed that donepezil inhibits the generation of reactive oxygen species (ROS), which promotes cellular senescence. Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with donepezil. Indeed, our results indicated that donepezil increased the SIRT1 enzyme activity. Therefore, these results show that donepezil delays cellular senescence that is promoted under HG condition via activation of SIRT1. PMID:26194321

  5. Morphology-based mammalian stem cell tests reveal potential developmental toxicity of donepezil.

    PubMed

    Lau, Caroline G Y; Marikawa, Yusuke

    2014-11-01

    Various compounds, including therapeutic drugs, can adversely impact the survival and development of embryos in the uterus. Identification of such development-interfering agents is a challenging task, although multi-angle approaches--including the use of in vitro toxicology studies involving embryonic stem cells--should alleviate some of the current difficulties. In the present study, we utilized the in vitro elongation of embryoid bodies (EBs) derived from mouse embryonal carcinoma stem cell line P19C5 as a model of early embryological events, specifically that of gastrulation and axial patterning. From our study, we identified donepezil, a medication indicated for the management of Alzheimer's disease, as a potential developmental toxicant. The extent of P19C5 EB axial elongation was diminished by donepezil in a dose-dependent manner. Although donepezil is a known inhibitor of acetylcholinesterase, interference of elongation was not mediated through this enzyme. Quantitative reverse-transcriptase PCR revealed that donepezil altered the expression pattern of a specific set of developmental regulator genes involved in patterning along the anterior-posterior body axis. When tested in mouse whole embryo culture, donepezil caused morphological abnormalities including impaired somitogenesis. Donepezil also diminished elongation morphogenesis of EBs generated from human embryonic stem cells. These results suggest that donepezil interferes with axial elongation morphogenesis of early embryos by altering the expression pattern of regulators of axial development. PMID:25269881

  6. Roles of μ-Opioid Receptors and Nociceptin/Orphanin FQ Peptide Receptors in Buprenorphine-Induced Physiological Responses in Primates

    PubMed Central

    Cremeans, Colette M.; Gruley, Erin; Kyle, Donald J.

    2012-01-01

    Buprenorphine is known as a μ-opioid peptide (MOP) receptor agonist, but its antinociception is compromised by the activation of nociceptin/orphanin FQ peptide (NOP) receptors in rodents. The aim of this study was to investigate the roles of MOP and NOP receptors in regulating buprenorphine-induced physiological responses in primates (rhesus monkeys). The effects of MOP antagonist (naltrexone), NOP antagonist [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)], and NOP agonists [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one (Ro 64-6198) and 3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)] on buprenorphine were studied in three functional assays for measuring analgesia, respiratory depression, and itch in primates. Over the dose range of 0.01 to 0.1 mg/kg, buprenorphine dose-dependently produced antinociception, respiratory depression, and itch/scratching responses, and there was a ceiling effect at higher doses (0.1–1 mg/kg). Naltrexone (0.03 mg/kg) produced similar degrees of rightward shifts of buprenorphine's dose-response curves for all three endpoints. Mean pKB values of naltrexone (8.1–8.3) confirmed that MOP receptors mediated mainly buprenorphine-induced antinociception, respiratory depression, and itch/scratching. In contrast, J-113397 (0.1 mg/kg) did not change buprenorphine-induced physiological responses, indicating that there were no functional NOP receptors in buprenorphine-induced effects. More importantly, both NOP agonists, Ro 64-6198 and SCH 221510, enhanced buprenorphine-induced antinociception without respiratory depression and itch/ scratching. The dose-addition analysis revealed that buprenorphine in combination with the NOP agonist synergistically produced antinociceptive effects. These findings provided functional evidence that the activation of NOP receptors did not

  7. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain.

    PubMed

    Creeley, Catherine E; Wozniak, David F; Nardi, Anthony; Farber, Nuri B; Olney, John W

    2008-02-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer's disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine's neurotoxic potential has not been investigated. In the present study, we determined that a dose of memantine (20mg/kg, i.p.), considered to be in the therapeutic (neuroprotective) range for rats, causes a mild neurotoxic reaction in the adult rat brain. Co-administration of memantine (20 or 30 mg/kg) with donepezil (2.5-10mg/kg) markedly potentiated this neurotoxic reaction, causing neuronal injury at lower doses of memantine, and causing the toxic reaction to become disseminated and lethal to neurons throughout many brain regions. These findings raise questions about using this drug combination in AD, especially in the absence of evidence that the combination is beneficial, or that either drug arrests or reverses the disease process. PMID:17112636

  8. Perspectives in the management of Alzheimer's disease: clinical profile of donepezil.

    PubMed

    Rogers, S L

    1998-01-01

    Donepezil HCI is a piperidine-based reversible acetylcholinesterase (AChE) inhibitor, chemically distinct from other cholinesterase (ChE) inhibitors and rationally designed to treat the symptoms of Alzheimer's disease (AD). It is highly selective for AChE in the central nervous system (CNS), with little or no affinity for butyrylcholinesterase (BuChE). In preclinical studies in animals, donepezil produced increased CNS acetylcholine. The resultant enhancement of cholinergic activity gave rise to improved performance by rats on tests of learning and memory, with no evidence of hepatic or renal toxicity. In subsequent phase I clinical evaluations in healthy volunteers, donepezil demonstrated favorable pharmacokinetic, pharmacodynamic and safety profiles. Its long terminal disposition half-life supported once-daily administration, with no requirement for dose modification in the elderly or in patients with renal or hepatic impairment. A 14-week, phase II dose-finding study in patients with mild to moderate AD (Clinical Dementia Rating [CDR], 1-2; Mini-Mental State Examination [MMSE], 10-26) showed that donepezil at a dose of 5 mg/day produced highly significant improvements in cognition (as measured by the Alzheimer's Disease Assessment Scale, cognitive subscale [ADAS-cog]). Subsequently, two pivotal parallel-group, placebo-controlled phase III trials (of 15 and 30 weeks' duration) showed highly statistically significant improvements in ADAS-cog, MMSE, Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus) and CDR-SB (Sum of the Boxes) scores, compared with placebo, in mild to moderate AD patients treated with either 5 or 10 mg/day donepezil. Adverse events in the phase II and III trials were mild and transient and resolved with continued donepezil administration. The donepezil clinical trials program has shown that this drug is a clinically effective and well-tolerated once-daily treatment for the symptoms of mild to moderate AD. PMID

  9. Donepezil is a strong antagonist of voltage-gated calcium and potassium channels in molluscan neurons.

    PubMed

    Solntseva, Elena I; Bukanova, Julia V; Marchenko, Evgeny; Skrebitsky, Vladimir G

    2007-01-01

    Donepezil is an acetylcholinesterase inhibitor used in Alzheimer's disease therapy. The neuroprotective effect of donepezil has been demonstrated in a number of different models of neurodegeneration including beta-amyloid toxicity. Since the mechanisms of neurodegeneration involve the activation of both Ca(2+)- and K(+)-channels, the study of donepezil action on voltage-gated ionic currents looked advisable. In the present study, the action of donepezil on voltage-gated Ca(2+)- and K(+)-channels was investigated on isolated neurons of the edible snail (Helix pomatia) using the two-microelectrodes voltage-clamp technique. Donepezil rapidly and reversibly inhibited voltage activated Ca(2+)-current (I(Ca)) (IC(50)=7.9 microM) and three types of high threshold K(+)-current: Ca(2+)-dependent K(+)-current (I(C)) (IC(50)=6.4 microM), delayed rectifier K(+)-current (I(DR)) (IC(50)=8.0 microM) and fast transient K(+)-current (I(Adepol)) (IC(50)=9.1 microM). The drug caused a dual effect on low-threshold fast transient K(+)-current (I(A)), potentiating it at low (5 microM) concentration, but inhibiting at higher (7 microM and above) concentration. Donepezil also caused a significant hyperpolarizing shift of the voltage-current relationship of I(Ca) (but not of any type of K(+)-current). Results suggest the possible contribution of the blocking effect of donepezil on the voltage-gated Ca(2+)- and K(+)-channels to the neuroprotective effect of the drug. PMID:17126610

  10. Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons chronically treated with donepezil.

    PubMed

    Takada-Takatori, Yuki; Kume, Toshiaki; Ohgi, Yuta; Izumi, Yasuhiko; Niidome, Tetsuhiro; Fujii, Takeshi; Sugimoto, Hachiro; Akaike, Akinori

    2008-12-01

    Previously, we showed that in rat cortical neurons, chronic donepezil treatment (10 microM, 4 days) up-regulates nicotinic receptors (nAChR) and makes neurons more sensitive to the neuroprotective effect of donepezil. Here we examined the mechanism of donepezil-induced neuroprotection in neurons chronically treated with donepezil. The mechanism of neuroprotection was examined under different conditions of exposure to glutamate, acute and moderate, that induce cell death associated with necrotic and apoptotic cell death, respectively. Concomitant treatment with antagonists of nAChRs but not muscarinic receptors inhibited donepezil pretreatment-induced neuroprotection against acute glutamate treatment-induced death. Donepezil pretreatment prevented acute glutamate- and ionomycin-induced neurotoxicity, but not S-nitrosocysteine-induced neurotoxicity, suggesting that donepezil protects neurons via nAChR at levels before nitric oxide synthase activation against acute glutamate neurotoxicity. Concomitant treatment with antagonists of nAChR or phosphatidylinositol 3-kinase (PI3K) signaling inhibitors significantly inhibited neuroprotection against moderate glutamate neurotoxicity and decreased the phosphorylation level of Akt. Neuroprotection was also inhibited by treatment with inhibitor of mitogen-activated protein kinase (MAPK) kinase. These results suggest that donepezil protects neurons against moderate glutamate neurotoxicity via nAChR-PI3K-Akt and MAPK signaling pathways. This study provides novel insight into the mechanism of donepezil-induced neuroprotection that involves nAChR up-regulation. PMID:18655200

  11. Donepezil

    MedlinePlus

    ... AD; a brain disease that slowly destroys the memory and the ability to think, learn, communicate and ... cholinesterase inhibitors. It improves mental function (such as memory, attention, the ability to interact with others, speak, ...

  12. Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics

    PubMed Central

    Cacabelos, Ramón

    2007-01-01

    Donepezil is the leading compound for the treatment of Alzheimer’s disease (AD) in more than 50 countries. As compared with other conventional acetylcholinesterase inhibitors (AChEIs), donepezil is a highly selective and reversible piperidine derivative with AChEI activity that exhibits the best pharmacological profile in terms of cognitive improvement, responders rate (40%–58%), dropout cases (5%–13%), and side-effects (6%–13%) in AD. Although donepezil represents a non cost-effective treatment, most studies convey that this drug can provide a modest benefit on cognition, behavior, and activities of the daily living in both moderate and severe AD, contributing to slow down disease progression and, to a lesser exetnt, to delay institutionalization. Patients with vascular dementia might also benefit from donepezil in a similar fashion to AD patients. Some potential effects of donepezil on the AD brain, leading to reduced cortico-hippocampal atrophy, include the following: AChE inhibition, enhancement of cholinergic neurotransmission and putative modulation of other neurotransmitter systems, protection against glutamate-induced excitotoxicity, activation of neurotrophic mechanisms, promotion of non-amyloidodgenic pathways for APP processing, and indirect effects on cerebrovascular function improving brain perfusion. Recent studies demonstrate that the therapeutic response in AD is genotype-specific. Donepezil is metabolized via CYP-related enzymes, especially CYP2D6, CYP3A4, and CYP1A2. Approximately, 15%–20% of the AD population may exhibit an abnormal metabolism of AChEIs; about 50% of this population cluster would show an ultrarapid metabolism, requiring higher doses of AChEIs to reach a therapeutic threshold, whereas the other 50% of the cluster would exhibit a poor metabolism, displaying potential adverse events at low doses. In AD patients treated with a multifactorial therapy, including donepezil, the best responders are the CYP2D6-related extensive

  13. Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells.

    PubMed

    Das, Jharna R; Tizabi, Yousef

    2009-10-01

    Although the etiology of Parkinson's disease (PD) remains elusive, a number of toxins including elevated salsolinol, an endogenous metabolite of dopamine may contribute to its pathology. It was reported recently that nicotine may have protective effects against salsolinol-induced toxicity in human neuroblastoma derived SH-SY5Y cells and that these effects of nicotine are mediated by nicotinic receptors. Donepezil (Aricept) is a reversible non-competitive acetylcholinesterase inhibitor that is approved for use in mild to moderate Alzheimer's disease. The increase in acetylcholine concentrations is believed to be the major contributory factor in donepezil's therapeutic efficacy. However, cholinesterase inhibitors may also directly interact with nicotinic receptors and possess neuroprotective properties. In this study, we sought to determine whether donepezil may have protective effects against salsolinol-induced toxicity in SH-SY5Y cells and whether the combination of donepezil and nicotine may result in additive protection. Moreover, it was of interest to elucidate the role of nicotinic receptors as well as cell cycle and apoptosis in mechanism of action of these compounds. SH-SY5Y cells were exposed to 0.6 mM salsolinol with and without various drug pretreatments for 48 h. Nicotine (50 muM) resulted in approximately 54% protection and donepezil (5 muM) resulted in approximately 40% protection, and the combination of the two resulted in an additive (approximately 93%) protection against salsolinol-induced toxicity. Salsolinol caused an arrest of the cells in G(1)-phase of cell cycle and an increase in apoptotic indices that were blocked by the combination of donepezil and nicotine. Mecamylamine, a non-selective nicotinic receptor antagonist completely blocked the effects of nicotine and partially attenuated the effects of donepezil. A combination of atropine, a muscarinic receptor antagonist and mecamylamine completely blocked the effects of donepezil, indicating

  14. The combination of donepezil and procyclidine protects against soman-induced seizures in rats

    SciTech Connect

    Haug, Kristin Huse . E-mail: k.h.haug@medisin.uio.no; Myhrer, Trond; Fonnum, Frode

    2007-04-15

    Current treatment of nerve agent poisoning consists of prophylactic administration of pyridostigmine and therapy using atropine, an oxime and a benzodiazepine. Pyridostigmine does however not readily penetrate the blood-brain barrier giving ineffective protection of Brain against centrally mediated seizure activity. In this study, we have evaluated donepezil hydrochloride, a partial reversible inhibitor of acetylcholinesterase (AChE) clinically used for treating Alzheimer's disease, in combination with procyclidine, used in treatment of Parkinson's disease and schizophrenia, as prophylaxis against intoxication by the nerve agent soman. The results demonstrated significant protective efficacy of donepezil (2.5 mg/kg) combined with procyclidine (3 or 6 mg/kg) when given prophylactically against a lethal dose of soman (1.6x LD{sub 50}) in Wistar rats. No neuropathological changes were found in rats treated with this combination 48 h after soman intoxication. Six hours after soman exposure cerebral AChE activity and acetylcholine (ACh) concentration was 5% and 188% of control, respectively. The ACh concentration had returned to basal levels 24 h after soman intoxication, while AChE activity had recovered to 20% of control. Loss of functioning muscarinic ACh receptors (17%) but not nicotinic receptors was evident at this time point. The recovery in brain AChE activity seen in our study may be due to the reversible binding of donepezil to the enzyme. Donepezil is well tolerated in humans, and a combination of donepezil and procyclidine may prove useful as an alternative to the currently used prophylaxis against nerve agent intoxication.

  15. Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil.

    PubMed

    Sharma, Bhupesh; Singh, Nirmal; Singh, Manjeet

    2008-03-01

    Present study was designed to investigate modulation of experimental dementia by Pitavastatin and donepezil. Learning and memory of the swiss albino mice were studied on Morris water-maze. Celecoxib orally (p.o.)/Streptozotocin (STZ) intracerebroventricular administrations were used to induce experimental dementia. Brain acetyl cholinesterase activity was measured by EllMann's method to assess cholinergic activity of the brain. Brain thio barbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively, to assess total oxidative stress in brain. Total serum cholesterol level was measured by Allain's method. Celecoxib/STZ treatments produced a significant loss of learning and memory. Pitavastatin/Donepezil successfully attenuated this Celecoxib/STZ induced dementia. Higher levels of brain acetyl-cholinesterase (AChE) activity, TBARS and lower level of GSH were observed in Celecoxib/STZ treated animals, which were significantly attenuated by Donepezil. Pitavastatin also attenuated the Celecoxib/STZ induced high levels of TBARS & low levels of GSH without effecting AChE activity and total serum cholesterol levels. Celecoxib induced dementia noted in the present study may be attributed to its stimulatory effect on amyloid beta-42, brain AChE activity, and oxidative stress. Sub-diabetogenic STZ induced memory deficits closely related to Alzheimer's disease. Reversal of Celecoxib/STZ induced memory deficits by Pitavastatin may be due to its antioxidative, anti beta amyloid aggregatory property, and by Donepezil, due to its anticholinesterase and neuroprotective actions. PMID:18208924

  16. Effects of Donepezil on Cognitive Functioning in Down Syndrome.

    ERIC Educational Resources Information Center

    Johnson, N.; Fahey, C.; Chicoine, B.; Chong, G.; Gitelman, D.

    2003-01-01

    Donepezil, an acetycholinesterase inhibitor, or a placebo were given to 29 subjects with Down syndrome and no dementia. Measures of cognitive functioning and caregiver ratings indicated no improvement in any cognitive subtests (with the exception of language), behavioral scores, or caregiver ratings. Results suggest donepezil may improve language…

  17. Anticholinesterase (DFP) toxicity antagonism by chronic donepezil: a potential nerve agent treatment.

    PubMed

    Janowsky, David S; Davis, John M; Overstreet, David H

    2005-08-01

    Animal studies exploring the antagonism of irreversible cholinesterase inhibitors (i.e. nerve agents) such as soman and sarin have shown that pretreatment with the reversible centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic drug, scopolamine, antagonizes the lethality and toxicity of these agents. This study evaluated the effects of pretreatment with the oral cholinesterase inhibitor and anti-Alzheimer's agent, donepezil (Aricept) on the hypokinetic, hypothermic and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor, diisopropylfluorophosphate (DFP) in adult Sprague-Dawley rats. Donepezil (2 mg/kg), given acutely (30 min pretreatment) or chronically (10 daily treatments), significantly antagonized the hypothermia, hypoactivity and diarrhea induced by DFP (1.25 mg/kg) administration. The effects were most prominent 4 and 6 h after the injection of DFP and some protection was observed even when the last treatment of the chronic donepezil protocol was given 24 h before the DFP injection. Although these phenomena are not the same as lethality, they may be parallel phenomena, and our results may have therapeutic implications for the treatment of nerve agent toxicity. PMID:16054679

  18. Study of neuroprotection of donepezil, a therapy for Alzheimer's disease.

    PubMed

    Akasofu, S; Kimura, M; Kosasa, T; Sawada, K; Ogura, H

    2008-09-25

    Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease. Although acetylcholinesterase inhibitors are thought to be symptomatic treatment of Alzheimer's disease, it is not clear whether they are effective against progressive degeneration of neuronal cells. In this study, we investigated the neuroprotective effects of donepezil against ischemic damage, N-methyl-d-aspartate (NMDA) excitotoxicity, and amyloid-beta (Abeta) toxicity using rat brain primary cultured neurons. Lactate dehydrogenase (LDH) released into the culture medium was measured as a marker of neuronal cell damage. As an ischemic damage model, we used oxygen-glucose deprivation in rat cerebral cortex primary cultured neurons. Pretreatment with donepezil (0.1, 1 and 10 microM) significantly decreased LDH release in a concentration-dependent manner. However, other acetylcholinesterase inhibitors (galantamine, tacrine and rivastigmine) did not significantly decrease LDH release. In a NMDA excitotoxicity model, pretreatment with donepezil (0.1, 1 and 10 microM) decreased the LDH release in a concentration-dependent manner. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. We further examined the effect of donepezil on Abeta (1-40)- and Abeta (1-42)-induced toxicity in primary cultures of rat septal neurons. Pretreatment with donepezil (0.1, 1 and 10 microM) significantly decreased LDH release induced by Abetas in a concentration-dependent manner. However, other acetylcholinesterase inhibitors (galantamine and tacrine) and NMDA receptor antagonists (memantine and dizocilpine (MK801)) did not significantly decrease LDH release. These results demonstrate that donepezil has protective effects against ischemic damage, glutamate excitotoxicity and Abeta toxicity to rat primary cultured neurons and these effects are not dependent on acetylcholinesterase inhibition

  19. Nicotinic acetylcholine receptors mediate donepezil-induced oligodendrocyte differentiation.

    PubMed

    Imamura, Osamu; Arai, Masaaki; Dateki, Minori; Ogata, Toru; Uchida, Ryuji; Tomoda, Hiroshi; Takishima, Kunio

    2015-12-01

    Oligodendrocytes are the myelin-forming cells of the central nervous system (CNS). Failure of myelin development and oligodendrocyte loss results in serious human disorders, including multiple sclerosis. Here, we show that donepezil, an acetlycholinesterase inhibitor developed for the treatment of Alzheimer's disease, can stimulate oligodendrocyte differentiation and maturation of neural stem cell-derived oligodendrocyte progenitor cells without affecting proliferation or cell viability. Transcripts for essential myelin-associated genes, such as PLP, MAG, MBP, CNPase, and MOG, in addition to transcription factors that regulate oligodendrocyte differentiation and myelination, were rapidly increased after treatment with donepezil. Furthermore, luciferase assays confirmed that both MAG and MBP promoters display increased activity upon donepezil-induced oligodendrocytes differentiation, suggesting that donepezil increases myelin gene expression mainly through enhanced transcription. We also found that the increase in the number of oligodendrocytes observed following donepezil treatment was significantly inhibited by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, but not by the muscarinic acetylcholine receptor antagonist scopolamine. Moreover, donepezil-induced myelin-related gene expression was suppressed by mecamylamine at both the mRNA and protein level. These results suggest that donepezil stimulates oligodendrocyte differentiation and myelin-related gene expression via nAChRs in neural stem cell-derived oligodendrocyte progenitor cells. We show that donepezil, a drug for the treatment of Alzheimer disease, can stimulate oligodendrocyte differentiation and maturation of oligodendrocyte progenitor cells. Transcripts for essential myelin-associated genes, such as PLP, MAG, MBP, CNPase and MOG in addition to transcripton factors that regulate oligodendrocyte differentiation and myelination were rapidly increased after treatment with donepezil

  20. Safety and efficacy of donepezil hydrochloride in patients with mild to moderate Alzheimer's disease: Findings of an observational study

    PubMed Central

    Mehta, Suyog; Chandersekhar, K.; Prasadrao, G.; Dutt, Lakshman; Patkar, S.; Nagpal, R. D.; Gupta, M.; Raju, G. S. P.; Praveen, K. K.; Prasad, B. S. V.; Roy, T.; Kushwaha, S.; Nag, Jyotindra; Langade, D.; Pawar, D.

    2012-01-01

    Background: Alzheimer's disease (AD), a progressive brain disorder, is the most common cause of dementia among the elderly. Donepezil hydrochloride is a potent, reversible, and highly selective inhibitor of acetylcholinesterase (AChE). It is chemically distinct from other cholinesterase (ChE) inhibitors which are effective in the treatment of AD. Objectives: To evaluate the safety and efficacy of donepezil hydrochloride therapy over a 12 weeks period in patients with mild to moderate AD in Indian population. Materials and Methods: In this post-marketing study, patients with mild to moderate AD received oral donepezil hydrochloride 5 mg/day for 4 weeks followed by 10 mg/day for 8 weeks. Patients were assessed 4 times weekly for cognition on ‘Mini Mental Status Examination (MMSE) scale’, and function on ‘Activities of Daily Living (ADL) index’. Clinicians and caregivers assessment of safety and efficacy was assessed on a 5-point rating scale. Results: One hundred and seventy two of one hundred and eighty two patients completed 12 weeks of study period. MMSE score significantly improved (P<0.0001) from 16.72 at baseline to 19.77 after 12 weeks, and there was significant improvement (P<0.05) in ADL index in 13 of 17 domains after 12 weeks. Caregivers and clinicians rated the therapy as very good to good in >80% and >90% patients, respectively. Adverse events were consistent with the known pharmacological and safety profile of donepezil. Conclusions: Donepezil is well tolerated in Indian patients with mild to moderate AD with significant improvement in cognition and function. PMID:23372236

  1. Unequal neuroprotection afforded by the acetylcholinesterase inhibitors galantamine, donepezil, and rivastigmine in SH-SY5Y neuroblastoma cells: role of nicotinic receptors.

    PubMed

    Arias, Esperanza; Gallego-Sandín, Sonia; Villarroya, Mercedes; García, Antonio G; López, Manuela G

    2005-12-01

    Donepezil, rivastigmine, and galantamine are three drugs with acetylcholinesterase (AChE)-inhibiting activity that are currently being used to treat patients suffering from Alzheimer's disease. We have studied the neuroprotective effects of these drugs, in comparison with nicotine, on cell death caused by beta-amyloid (Abeta) and okadaic acid, two models that are relevant to Alzheimer's pathology, in the human neuroblastoma cell line SH-SY5Y. Galantamine and donepezil showed a U-shaped neuroprotective curve against okadaic acid toxicity; maximum protection was achieved at 0.3 microM galantamine and at 1 microM donepezil; at higher concentrations, protection was diminished. Rivastigmine showed a concentration-dependent effect; maximum protection was achieved at 3 microM. When apoptosis was induced by Abeta25-35, galantamine, donepezil, and rivastigmine showed maximum protection at the same concentrations: 0.3, 1, and 3 microM, respectively. Nicotine also afforded protection against Abeta- and okadaic acid-induced toxicity. The neuroprotective effects of galantamine, donepezil, and nicotine were reversed by the alpha7 nicotinic antagonist methyllycaconitine but not by the alpha4beta2 nicotinic antagonist dihydro-beta-erythroidine. The phosphoinositide 3-kinase (PI3K)-Akt blocker 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) reversed the protective effects of galantamine, donepezil, and nicotine but not that of rivastigmine. In contrast, the bcl-2 antagonist ethyl[2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)]-4H-chromene-3-carboxylate (HA 14-1) reversed the protective effects of the three AChE inhibitors and that of nicotine. Our results show that galantamine, donepezil, and rivastigmine afford neuroprotection through a mechanism that is likely unrelated to AChE inhibition. Such neuroprotection seemed to be linked to alpha7 nicotinic receptors and the PI3K-Akt pathway in the case of galantamine and donepezil but not for rivastigmine

  2. Controlled release of donepezil intercalated in smectite clays.

    PubMed

    Park, Jin Kuen; Choy, Young Bin; Oh, Jae-Min; Kim, Ju Young; Hwang, Seong-Ju; Choy, Jin-Ho

    2008-07-01

    The inorganic-organic hybrid for a drug delivery system was successfully realized by intercalating donepezil molecules into smectite clays (laponite XLG, saponite, and montmorillonite). According to the powder XRD patterns, TG profiles, and FT-IR spectra, it was confirmed that donepezil molecules were well stabilized in the interlayer space of clay via mono or double layer stacking. The adsorption amount and molecular structure of donepezil appeared to depend on the cation exchange capacity of the clay, which in turn, tailored the drug release patterns. Especially in the presence of a bulky cationic polymer (Eudragit E-100) in the release media, the release rate was found to be improved due to its effective replacement with intercalated donepezil molecules. Therefore, to formulate a complete drug delivery system, the hybrids were coated with Eudragit E-100 using a spray dryer, which also showed great enhancement in the release rate during a short period of time (180min). PMID:18502063

  3. Neuroprotective effects of donepezil against Aβ42-induced neuronal toxicity are mediated through not only enhancing PP2A activity but also regulating GSK-3β and nAChRs activity.

    PubMed

    Noh, Min-Young; Koh, Seong H; Kim, Sung-Min; Maurice, Tangui; Ku, Sae-Kwang; Kim, Seung H

    2013-11-01

    The main purpose of this study was to evaluate whether donepezil, acetylcholinesterase inhibitor, shown to play a protective role through inhibiting glycogen synthesis kinase-3β (GSK-3β) activity, could also exert neuroprotective effects by stimulating protein phosphatase 2A (PP2A) activity in the amyloid-beta (Aβ)42-induced neuronal toxicity model of Alzheimer's disease. In Aβ42-induced toxic conditions, each PP2A and GSK-3β activity measured at different times showed time-dependent reverse pattern toward the direction of accelerating neuronal deaths with the passage of time. In addition, donepezil pre-treatment showed dose-dependent stepwise increase of neuronal viability and stimulation of PP2A activity. However, such effects on them were significantly reduced through the depletion of PP2A activity with either okadaic acid or PP2Ac siRNA. In spite of blocked PP2A activity in this Aβ42 insult, however, donepezil pretreatment showed additional significant recovering effect on neuronal viability when compared to the value without donepezil. Moreover, donepezil partially recovered its dephosphorylating effect on hyperphosphorylated tau induced by Aβ42. This observation led us to assume that additional mechanisms of donepezil, including its inhibitory effect on GSK-3β activity and/or the activation role of nicotinic acetylcholine receptors (nAChRs), might be involved. Taken together, our results suggest that the neuroprotective effects of donepezil against Aβ42-induced neurotoxicity are mediated through activation of PP2A, but its additional mechanisms including regulation of GSK-3β and nAChRs activity would partially contribute to its effects. We investigated neuroprotective mechanisms of donepezil against Aβ42 toxicity: Donepezil increased neuronal viability with reduced p-tau by enhancing PP2A activity. Despite of blocked PP2A activity, donepezil showed additional recovering effect on neuronal viability, which findings led us to assume that additional

  4. Donepezil Improved Cognitive Deficits in a Patient With Neurosyphilis.

    PubMed

    Wu, Yi-Shan; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2015-01-01

    A large number of patients with neurosyphilis present dementia with a progressive course and psychiatric symptoms such as depression, mania, and psychosis. Despite prompt and proper antibiotic treatment, the recovery is often incomplete, especially when tissue damage has occurred. We reported a patient with persisted cognitive decline associated with neurosyphilis that improved substantially after donepezil therapy. A 43-year-old man manifested significant psychiatric symptoms such as mania, psychosis, and cognitive impairment due to neurosyphilis. Subsequently, the patient was treated with antipsychotics and donepezil concurrent with an adequate antibiotic treatment for neurosyphilis. During the 1-year follow-up, his rapid plasma reagin titer approached from 1:256 to 1:64. His Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale scores improved from 12 to 25 and 42.3 to 6.3, respectively, after a 6-month donepezil treatment. Donepezil was discontinued. Three months later, worsening of cognitive impairment (MMSE score, 23) was noted. After donepezil was started again for 3 months, his MMSE score improved to 26. Persistent cognitive impairment is commonly associated with neurosyphilis despite adequate penicillin treatment. Treatment of the cognitive impairment is important but difficult. Cholinergic pathways are considered as involving in the cognitive deficit induced by neurosyphilis and donepezil, a cholinesterase inhibitor, which may be useful for the improvement of cognition. In this case report, we described for the first time the successful use of donepezil in treating cognitive impairment associated with neurosyphilis. The role of cholinesterase inhibitors in the treatment of cognitive impairments caused by neurosyphilis needs further studies. PMID:26166240

  5. Memantine ER/Donepezil: A Review in Alzheimer's Disease.

    PubMed

    Greig, Sarah L

    2015-11-01

    A once-daily, fixed-dose combination of memantine extended-release (ER)/donepezil 28/10 mg (Namzaric™) is available in the USA for patients with moderate to severe Alzheimer's disease (AD) on stable memantine and donepezil therapy. The fixed-dose formulation is bioequivalent to coadministration of the individual drugs. In a 24-week, phase III trial in patients with moderate to severe AD, addition of memantine ER 28 mg once daily to stable cholinesterase inhibitor (ChEI) therapy was more effective than add-on placebo on measures of cognition, global clinical status, dementia behaviour and semantic processing ability, although between-group differences on a measure of daily function did not significantly differ. In subgroup analyses in donepezil-treated patients, add-on memantine ER was more effective than add-on placebo on measures of cognition, dementia behaviour and semantic processing, although there were no significant between-group differences on measures of global clinical status and daily function. Memantine ER plus ChEI combination therapy was generally well tolerated in the phase III trial, with diarrhoea, dizziness and influenza occurring at least twice as often with add-on memantine ER as add-on placebo in donepezil-treated patients. Thus, memantine ER plus donepezil combination therapy is an effective and well tolerated treatment option for patients with moderate to severe AD. The fixed-dose combination is potentially more convenient than coadministration of the individual agents. PMID:26519339

  6. Dried blood spot analysis of donepezil in support of a GLP 3-month dose-range finding study in rats.

    PubMed

    Meier-Davis, Susan R; Meng, Min; Yuan, Weiwei; Diehl, Lisa; Arjmand, Fatima M; Lucke, Rebecca M; Huang, Betsy; Wen, Jianye; Shudo, Jutaro; Nagata, Tetsuto

    2012-01-01

    Donepezil hydrochloride is a reversible acetyl cholinesterase inhibitor approved for Alzheimer disease treatment. As an alternate therapy, a donepezil hydrochloride transdermal patch is in development. Recommended nonclinical safety studies include a 3-month Good Laboratory Practice (GLP) dose-range finding (DRF) study prior to conducting the 2-year dermal carcinogenicity study in rats. Demonstration of systemic exposure is necessary to interpret the in vivo data. Previous nonclinical reports supporting oral dosing have utilized liquid chromatography tandem mass spectrometry (LC/MS/MS) to quantify donepezil concentrations in plasma. Smaller species with limited blood volumes do not allow serial sampling to derive the full pharmacokinetic profile from a single animal. Therefore, the option of another analytical method requiring decreased sample volumes is desirable as it would decrease the required number of animals while obtaining the complete profile. The dried blood spot (DBS) technique allows drug level measurement from a few microliters; however, the method is still not widely utilized in GLP studies. Because donepezil plasma levels are known by the oral route, DBS was used to bridge the previous oral data and to support a 13-week GLP DRF study for repeated topical application in rats, comparing oral administration with 4 topical formulations. The DBS method was validated and demonstrated robustness and reproducibility for application to the DRF study. The assay results were comparable to a previously reported plasma LC/MS/MS assay-derived pharmacokinetic profile and provided justification for selection of the topical formulation and dose levels for the subsequent dermal carcinogenicity study. PMID:22705881

  7. A case of donepezil-related torsades de pointes.

    PubMed

    Kitt, Jamie; Irons, Robert; Al-Obaidi, Mohamed; Missouris, Constantinos

    2015-01-01

    An 80-year-old woman with Alzheimer's dementia presented with diarrhoea, vomiting and worsening confusion following an increase in donepezil dose from 5 to 10 mg. The ECG revealed prolongation of QTc interval. Soon after admission, she became unresponsive with polymorphic ventricular tachycardia (VT). Cardiopulmonary resuscitation with a 200 J shock was successful in establishing cardiac output. Following the discontinuation of donepezil, the QTc interval normalised and no further arrhythmias were recorded. Treatment with anticholinesterase inhibitors may result in life-threatening VT. Vigilance is required for the identification of this condition in patients presenting with presyncope, syncope or seizures. PMID:26438681

  8. Spectral studies of Donepezil release from streched PVA polymer films

    NASA Astrophysics Data System (ADS)

    Nechifor, Cristina-Delia; Zelinschi, Carmen-Beatrice; Stoica, Iuliana; Closca, Valentina; Dorohoi, Dana-Ortansa

    2013-07-01

    The focus of this research is to obtain poly vinyl alcohol (PVA) polymer foils containing Donepezil in different concentration, in order to be used in controlled drug release as a palliative treatment of mild to moderate Alzheimer's disease. The influence of polymeric foil stretching degree on drug release was analyzed using spectral measurements.

  9. Transdermal donepezil on the treatment of Alzheimer’s disease

    PubMed Central

    Sozio, Piera; Cerasa, Laura S; Marinelli, Lisa; Di Stefano, Antonio

    2012-01-01

    Alzheimer’s disease (AD) is the most common type of senile dementia, characterized by cognitive deficits related to degeneration of cholinergic neurons. The first anti-Alzheimer drugs approved by the Food and Drug Administration were the cholinesterase inhibitors (ChEIs), which are capable of improving cholinergic neurotransmission by inhibiting acetylcholinesterase. The most common ChEIs used to treat cognitive symptoms in mild to moderate AD are rivastigmine, galantamine, and donepezil. In particular, the lattermost drug has been widely used to treat AD patients worldwide because it is significantly less hepatotoxic and better tolerated than its predecessor, tetrahydroaminoacridine. It also demonstrates high selectivity towards acetylcholinesterase inhibition and has a long duration of action. The formulations available for donepezil are immediate release (5 or 10 mg), sustained release (23 mg), and orally disintegrating (5 or 10 mg) tablets, all of which are intended for oral-route administration. Since the oral donepezil therapy is associated with adverse events in the gastrointestinal system and in plasma fluctuations, an alternative route of administration, such as the transdermal one, has been recently attempted. The goal of this paper is to provide a critical overview of AD therapy with donepezil, focusing particularly on the advantages of the transdermal over the oral route of administration. PMID:22942647

  10. Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo.

    PubMed

    Kim, Hyo Geun; Moon, Minho; Choi, Jin Gyu; Park, Gunhyuk; Kim, Ae-Jung; Hur, Jinyoung; Lee, Kyung-Tae; Oh, Myung Sook

    2014-01-01

    Recent studies on Alzheimer's disease (AD) have focused on soluble oligomeric forms of amyloid-beta (Aβ oligomer, AβO) that are directly associated with AD-related pathologies, such as cognitive decline, neurodegeneration, and neuroinflammation. Donepezil is a well-known anti-dementia agent that increases acetylcholine levels through inhibition of acetylcholinesterase. However, a growing body of experimental and clinical studies indicates that donepezil may also provide neuroprotective and disease-modifying effects in AD. Additionally, donepezil has recently been demonstrated to have anti-inflammatory effects against lipopolysaccharides and tau pathology. However, it remains unknown whether donepezil has anti-inflammatory effects against AβO in cultured microglial cells and the brain in animals. Further, the effects of donepezil against AβO-mediated neuronal death, astrogliosis, and memory impairment have also not yet been investigated. Thus, in the present study, we examined the anti-inflammatory effect of donepezil against AβO and its neuroinflammatory mechanisms. Donepezil significantly attenuated the release of inflammatory mediators (prostaglandin E2, interleukin-1 beta, tumor necrosis factor-α, and nitric oxide) from microglia. Donepezil also decreased AβO-induced up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 protein and phosphorylation of p38 mitogen-activated protein kinase as well as translocation of nuclear factor-kappa B. We next showed that donepezil suppresses activated microglia-mediated toxicity in primary hippocampal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In intrahippocampal AβO-injected mice, donepezil significantly inhibited microgliosis and astrogliosis. Furthermore, behavioral tests revealed that donepezil (2 mg/kg/day, 5 days, p.o.) significantly ameliorated AβO-induced memory impairment. These results suggest that donepezil directly inhibits microglial activation

  11. Results, rhetoric, and randomized trials: the case of donepezil.

    PubMed

    Gilstad, John R; Finucane, Thomas E

    2008-08-01

    Whether donepezil provides meaningful benefit to patients with Alzheimer's disease (AD) is controversial, but drug sales annually total billions of dollars. A review of data from published randomized clinical trials (RCTs) found rhetorical patterns that may encourage use of this drug. To create a reproducible observation, the sentences occurring at five specific text sites in all 18 RCTs of donepezil for AD were tabulated, as were study design, sources of financial support, and outcomes that could be compared between trials. Rhetoric in the 13 vendor-supported trials (15 publications) was strongly positive. Three early trials used the motif "efficacious (or effective) ... treating ... symptoms" four times. "Well-tolerated and efficacious" or an equivalent motif appeared 11 times in five RCTs. Nine RCTs referred 15 times to previously proven effectiveness. Seven trials encourage off-label use, for "early" cognitive impairment, severe dementia in advance of the Food and Drug Administration labeling change, or behavioral symptoms. These rhetorical motifs and themes appeared only in the vendor-supported trials. Trials without vendor support described the drug's effects as "small" or absent; two emphasized the need for better treatments. RCT results were highly consistent in all trials; the small differences do not explain differences in rhetoric. At these text sites in the primary research literature on donepezil for AD, uniformly positive rhetoric is present in all vendor-supported RCTs. Reference to the limited benefit of donepezil is confined to RCTs without vendor support. Data in the trials are highly consistent. This observation generates the hypothesis that rhetoric in vendor-supported published RCTs may promote vendors' products. PMID:18662199

  12. PET Evidence of the Effect of Donepezil on Cognitive Performance in an Animal Model of Chemobrain.

    PubMed

    Lim, Ilhan; Joung, Hye-Young; Yu, A Ram; Shim, Insop; Kim, Jin Su

    2016-01-01

    A considerable number of patients with breast cancer complain of cognitive impairment after chemotherapy. In this study, we showed that donepezil enhanced memory function and increased brain glucose metabolism in a rat model of cognitive impairment after chemotherapy using behavioral analysis and positron emission tomography (PET). We found that chemotherapy affected spatial learning ability, reference memory, and working memory and that donepezil improved these cognitive impairments. According to PET analysis, chemotherapy reduced glucose metabolism in the medial prefrontal cortex and hippocampus, and donepezil increased glucose metabolism in the bilateral frontal lobe, parietal lobe, and hippocampus. Reduced glucose metabolism was more prominent after treatment with doxorubicin than cyclophosphamide. Our results demonstrated the neural mechanisms for cognitive impairment after chemotherapy and show that cognition was improved after donepezil intervention using both behavioral and imaging methods. Our results suggested that donepezil can be employed clinically for the treatment of cognitive deficits after chemotherapy. PMID:27556039

  13. PET Evidence of the Effect of Donepezil on Cognitive Performance in an Animal Model of Chemobrain

    PubMed Central

    Lim, Ilhan; Yu, A Ram

    2016-01-01

    A considerable number of patients with breast cancer complain of cognitive impairment after chemotherapy. In this study, we showed that donepezil enhanced memory function and increased brain glucose metabolism in a rat model of cognitive impairment after chemotherapy using behavioral analysis and positron emission tomography (PET). We found that chemotherapy affected spatial learning ability, reference memory, and working memory and that donepezil improved these cognitive impairments. According to PET analysis, chemotherapy reduced glucose metabolism in the medial prefrontal cortex and hippocampus, and donepezil increased glucose metabolism in the bilateral frontal lobe, parietal lobe, and hippocampus. Reduced glucose metabolism was more prominent after treatment with doxorubicin than cyclophosphamide. Our results demonstrated the neural mechanisms for cognitive impairment after chemotherapy and show that cognition was improved after donepezil intervention using both behavioral and imaging methods. Our results suggested that donepezil can be employed clinically for the treatment of cognitive deficits after chemotherapy. PMID:27556039

  14. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    PubMed Central

    Liu, Qiang; Wang, Xiu-juan; Zhang, Zhe-cheng; Xue, Rong; Li, Ping; Li, Bo

    2016-01-01

    Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days), or combined with acupuncture at Shenting (DU24), Tianzhu (BL10), Sishencong (Extra), Yintang (Extra), Renzhong (DU26), Neiguan (PC6), Shenmen (HT7), Fengchi (GB20), Wangu (GB12) and Baihui (DU20) (once a day for 56 days). Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia. PMID:27127486

  15. Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

    PubMed

    Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

    2014-07-15

    The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. PMID:24755308

  16. Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

    PubMed

    Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

    2016-07-01

    The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. PMID:27097732

  17. Donepezil Improves Episodic Memory in Young Individuals Vulnerable to the Effects of Sleep Deprivation

    PubMed Central

    Chuah, Lisa Y.M.; Chong, Delise L.; Chen, Annette K.; Rekshan, William R.; Tan, Jiat-Chow; Zheng, Hui; Chee, Michael W.L.

    2009-01-01

    Study Objectives: We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation. Design: Double-blind, placebo-controlled, crossover study involving 7 laboratory visits over 2 months. Participants underwent 4 functional MRI scans; 2 sessions (donepezil or placebo) followed a normal night's sleep, and 2 sessions followed a night of sleep deprivation. Setting: The study took place in a research laboratory. Participants: 26 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders. Interventions: 5 mg of donepezil was taken once daily for approximately 17 days. Measurements and Results: Subjects were scanned while performing a semantic judgment task and tested for word recognition outside the scanner 45 minutes later. Sleep deprivation increased the frequency of non-responses at encoding and impaired delayed recognition. No benefit of donepezil was evident when participants were well rested. When sleep deprived, individuals who showed greater performance decline improved with donepezil, whereas more resistant individuals did not benefit. Accompanying these behavioral effects, there was corresponding modulation of task-related activation in functionally relevant brain regions. Brain regions identified in relation to donepezil-induced alteration in non-response rates could be distinguished from regions relating to improved recognition memory. This suggests that donepezil can improve delayed recognition in sleep-deprived persons by improving attention as well as enhancing memory encoding. Conclusions: Donepezil reduced decline in recognition performance in individuals vulnerable to the effects of sleep deprivation. Additionally, our findings demonstrate the utility of combined fMRI–behavior evaluation in psychopharmacological studies. Citation: Chuah LYM; Chong DL; Chen AK; Rekshan WR; Tan JC; Zheng H; Chee MWL. Donepezil

  18. Donepezil attenuates excitotoxic damage induced by membrane depolarization of cortical neurons exposed to veratridine.

    PubMed

    Akasofu, Shigeru; Sawada, Kohei; Kosasa, Takashi; Hihara, Hiroe; Ogura, Hiroo; Akaike, Akinori

    2008-07-01

    Long-lasting membrane depolarization in cerebral ischemia causes neurotoxicity via increases of intracellular sodium concentration ([Na+]i) and calcium concentration ([Ca2+]i). Donepezil has been shown to exert neuroprotective effects in an oxygen-glucose deprivation model. In the present study, we examined the effect of donepezil on depolarization-induced neuronal cell injury resulting from prolonged opening of Na+ channels with veratridine in rat primary-cultured cortical neurons. Veratridine (10 microM)-induced neuronal cell damage was completely prevented by 0.1 microM tetrodotoxin. Pretreatment with donepezil (0.1-10 microM) for 1 day significantly decreased cell death in a concentration-dependent manner, and a potent NMDA receptor antagonist, dizocilpine (MK801), showed a neuroprotective effect at the concentration of 10 microM. The neuroprotective effect of donepezil was not affected by nicotinic or muscarinic acetylcholine receptor antagonists. We further characterized the neuroprotective properties of donepezil by measuring the effect on [Na+]i and [Ca2+]i in cells stimulated with veratridine. At 0.1-10 microM, donepezil significantly and concentration-dependently reduced the veratridine-induced increase of [Ca2+]i, whereas MK801 had no effect. At 10 microM, donepezil significantly decreased the veratridine-induced increase of [Na+]i. We also measured the effect on veratridine-induced release of the excitatory amino acids, glutamate and glycine. While donepezil decreased the release of glutamate and glycine, MK801 did not. In conclusion, our results indicate that donepezil has neuroprotective activity against depolarization-induced toxicity in rat cortical neurons via inhibition of the rapid influx of sodium and calcium ions, and via decrease of glutamate and glycine release, and also that this depolarization-induced toxicity is mediated by glutamate receptor activation. PMID:18508044

  19. Bioequivalence Study of Donepezil Hydrochloride Tablets in Healthy Male Volunteers

    PubMed Central

    Rojanasthien, Noppamas; Aunmuang, Siriluk; Hanprasertpong, Nutthiya; Roongapinun, Sukit; Teekachunhatean, Supanimit

    2012-01-01

    The objective of this study was to investigate the bioequivalence of two formulations of 5 mg donepezil HCL tablets: Tonizep as the test and Aricept as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 3-week washout period in 20 healthy Thai Male volunteers. After drug administration, serial blood samples were collected over a period of 216 hours. Plasma donepezil concentrations were measured by high performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0–∞ and Cmax were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0–∞ and Cmax values of the test product over those of the reference product were 1.08 (1.02–1.14) and 1.08 (0.99–1.17), respectively (within the bioequivalence range of 0.8–1.25). The median Tmax for the test product was similar to that of the reference product (2.0 hr), and the 90% CI for the Tmax difference between the two preparations was –0.19 to 0.29 hr and within the bioequivalence range of ± 20% of the Tmax of the reference formulation. Our study demonstrated the bioequivalence of the two preparations. PMID:23209934

  20. Alzheimer disease. Donepezil and nursing home placement--benefits and costs.

    PubMed

    Jelic, Vesna; Winblad, Bengt

    2016-01-01

    The recent DOMINO-AD trial suggests that continued treatment with donepezil delays nursing home placement for patients with severe Alzheimer disease, but more work is needed to support strong conclusions about whether the benefits outweigh the costs. PMID:26714658

  1. The safety and tolerability of donepezil in patients with Alzheimer's disease

    PubMed Central

    Jackson, Stephen; Ham, Richard J; Wilkinson, David

    2004-01-01

    Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug–drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug–drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia

  2. Donepezil Regulates 1-Methyl-4-phenylpyridinium-Induced Microglial Polarization in Parkinson's Disease.

    PubMed

    Chen, Teng; Hou, Ruihua; Xu, Shujun; Wu, Chengyuan

    2015-10-21

    1-Methyl-4-phenylpyridinium (MPP+) induces microglial activation and degeneration of dopaminergic (DAergic) neurons. Donepezil is a well-known acetylcholinesterase inhibitor used clinically to treat cognitive dysfunction in Alzheimer's disease (AD). In the present study, we tested the hypothesis that MPP+ promotes microglial M1 polarization and suppresses M2 polarization and that this can be restored by donepezil. Results indicate that MPP+ treatment in microglial BV2 cells promotes microglial polarization toward the M1 state. However, pretreatment with donepezil inhibited MPP+-induced M1 polarization in microglia by suppressing the release of interleukin (IL)-6, IL-1β, or tumor necrosis factor (TNF)-α. Importantly, we found that MPP+ inhibited microglial M2 polarization by suppressing expression of Arg-1, Fizz1, and Ym1, which was also rescued by pretreatment with donepezil. In addition, IL-4-mediated induction of anti-inflammatory marker genes IL-10, IL-13, and transforming growth factor-β2 (TGF-β2) were significantly attenuated by MPP+ in BV2 cells, which was restored by pretreatment with donepezil in a concentration-dependent manner. Mechanistically, we found that the addition of MPP+ reduced the intensity of phosphorylated signal transducer and activator of transcription 6 (STAT6) but not total STAT6 in IL-4-stimulated BV2 cells. Importantly, pretreatment of microglial BV2 cells with donepezil 3 h prior to administration of MPP+ rescued the reduction of STAT6 phosphorylation induced by MPP+. PMID:26114860

  3. Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception

    PubMed Central

    Ferrier, Jérémy; Bayet-Robert, Mathilde; Dalmann, Romain; El Guerrab, Abderrahim; Aissouni, Youssef; Graveron-Demilly, Danielle; Chalus, Maryse; Pinguet, Jérémy; Eschalier, Alain; Richard, Damien; Daulhac, Laurence; Balayssac, David

    2015-01-01

    Neuropathic pain is one of the most debilitating pain conditions, yet no therapeutic strategy has been really effective for its treatment. Hence, a better understanding of its pathophysiological mechanisms is necessary to identify new pharmacological targets. Here, we report important metabolic variations in brain areas involved in pain processing in a rat model of oxaliplatin-induced neuropathy using HRMAS 1H-NMR spectroscopy. An increased concentration of choline has been evidenced in the posterior insular cortex (pIC) of neuropathic animal, which was significantly correlated with animals' pain thresholds. The screening of 34 genes mRNA involved in the pIC cholinergic system showed an increased expression of the high-affinity choline transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analysis in oxaliplatin-treated rats and the spared nerve injury model (SNI). Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely reversed oxaliplatin-induced mechanical allodynia. Consistently, systemic treatment with donepezil, a centrally active acetylcholinesterase inhibitor, prevented and reversed oxaliplatin-induced cold and mechanical allodynia as well as social interaction impairment. Intracerebral microdialysis revealed a lower level of acetylcholine in the pIC of oxaliplatin-treated rats, which was significantly increased by donepezil. Finally, the analgesic effect of donepezil was markedly reduced by a microinjection of the M2 antagonist, methoctramine, within the pIC, in both oxaliplatin-treated rats and spared nerve injury rats. These findings highlight the crucial role of cortical cholinergic neurotransmission as a critical mechanism of neuropathic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used for neuropathic pain treatment. SIGNIFICANCE STATEMENT Our study describes a decrease in cholinergic neurotransmission in the posterior insular

  4. Randomized, Placebo-Controlled, Clinical Trial of Donepezil in Vascular Dementia

    PubMed Central

    Román, Gustavo C.; Salloway, Stephen; Black, Sandra E.; Royall, Donald R.; DeCarli, Charles; Weiner, Michael W.; Moline, Margaret; Kumar, Dinesh; Schindler, Rachel; Posner, Holly

    2010-01-01

    Background and Purpose We sought to assess the efficacy and safety of donepezil in patients with vascular dementia (VaD) fulfilling National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria. Methods This international, multicenter, 24-week trial was conducted from March 2003 to August 2005. Patients (N=974; mean age, 73.0 years) with probable or possible VaD were randomized 2:1 to receive donepezil 5 mg/d or placebo. Coprimary outcome measures were scores on the Vascular-Alzheimer Disease Assessment Scale–Cognitive Subscale and Clinician’s Interview–Based Impression of Change, plus carer interview. Analyses were performed for the intent-to-treat population with the last-observation-carried-forward method. Results Compared with placebo, donepezil-treated patients showed significant improvement from baseline to end point on the Vascular-Alzheimer Disease Assessment Scale–Cognitive Subscale (least-squares mean difference, −1.156; 95% CI, −1.98 to −0.33; P<0.01) but not on the Clinician’s Interview–Based Impression of Change, plus carer interview. Patients with hippocampal atrophy who were treated with donepezil demonstrated stable cognition versus a decline in the placebo-treated group; in those without atrophy, cognition improved with donepezil versus relative stability with placebo. Results on secondary efficacy measures were inconsistent. The incidence of adverse events was similar across groups. Eleven deaths occurred in the donepezil group (1.7%), similar to rates previously reported for donepezil trials in VaD, whereas no deaths occurred in the placebo group. Conclusions Patients treated with donepezil 5 mg/d demonstrated significant improvement in cognitive, but not global, function. Donepezil was relatively well tolerated; adverse events were consistent with current labeling. Mortality in the placebo group was unexpectedly low. The differential

  5. Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity.

    PubMed

    Akasofu, Shigeru; Kimura, Manami; Kosasa, Takashi; Ogura, Hiroo; Sawada, Kohei

    2006-01-20

    Donepezil has a neuroprotective effect against oxygen-glucose deprivation injury and glutamate toxicity in cultured cortical neurons. In this study, we further characterized the neuroprotective properties of donepezil in rat cortical cell cultures using glutamate receptor-specific agonists (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate). Pretreatment with donepezil (1 microM) for 12 h significantly decreased the lactate dehydrogenase (LDH) release in response to NMDA (100 microM) by 43.8%, and reduced the LDH release in response to kainate (100 microM) and AMPA (100 microM) by 11.9% and 7.5% (without statistical significance), respectively. Donepezil appeared to inhibit LDH release in a concentration-dependent manner at 0.1-10 microM. Cortical neurons exposed to NMDA retained a normal morphological appearance in the presence of 10 microM donepezil. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. On the other hand, 12 h pretreatment with donepezil at 10 and 100 microM significantly decreased the NMDA-induced increase of intracellular calcium concentration ([Ca2+]i). In conclusion, our results show that donepezil has protective activity against NMDA toxicity in cortical neurons, and this neuroprotection seems to be partially mediated by inhibition of the increase of [Ca2+]i. PMID:16406045

  6. Donepezil delays photoreceptor apoptosis induced by N-methyl-N-nitrosourea in mice

    PubMed Central

    WU, LONGYAN; XU, MAN; LIU, SHENGTAO; CHEN, GUO; ZHANG, FENGJUN; ZHAO, YAO; YI, JINGLIN

    2016-01-01

    Retinitis pigmentosa (RP) is a group of inherited retinal degeneration diseases characterized by photoreceptor cell death that causes visual disturbances and eventual blindness. Intraperitoneal injection of N-methyl-N-nitrosourea (MNU) causes photoreceptor loss, and is used to create an animal model for investigating the mechanisms that cause retinal degeneration diseases. Donepezil is an acetylcholinesterase inhibitor that has a protective effect on retinal ganglion cells in vitro and in vivo, and it is understood that donepezil increases the expression of a heat shock protein 70 (Hsp70), which serves to protect neurons. Hsp70 functions as a chaperone molecule that protects cells from protein aggregation and assists in the refolding of denatured proteins. In the present study, the effects of donepezil on photoreceptor survival in mice was investigated. It was observed that donepezil upregulates the expression of Hsp70, to increase resistance to MNU-induced photoreceptor cell apoptosis by using its anti-apoptotic properties. In addition, the present study observed that Hsp70 promotes photoreceptor cell survival by upregulating the expression levels of B-cell lymphoma 2 (Bcl-2). In conclusion, the results of the present study indicate that donepezil has the potential to be used as a treatment for retinal degenerative diseases. PMID:27284332

  7. Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer's disease.

    PubMed

    Kearney, Mary-Carmel; Caffarel-Salvador, Ester; Fallows, Steven J; McCarthy, Helen O; Donnelly, Ryan F

    2016-06-01

    Transdermal drug delivery is an attractive route of drug administration; however, there are relatively few marketed transdermal products. To increase delivery across the skin, strategies to enhance skin permeability are widely investigated, with microneedles demonstrating particular promise. Hydrogel-forming microneedles are inserted into the skin, and following dissolution of a drug loaded reservoir and movement of the drug through the created channels, the microneedle array is removed intact, and can then be readily and safely discarded. This study presents the formulation and evaluation of an integrated microneedle patch containing the Alzheimer's drug, donepezil hydrochloride. The integrated patch consisted of hydrogel-forming microneedles in combination with a donepezil hydrochloride containing film. Formulation and characterisation of plasticised films, prepared from poly(vinylpyrrolidone) or poly (methyl vinyl ether co-maleic anhydride/acid) (Gantrez®) polymers, is presented. Furthermore, in vitro permeation of donepezil hydrochloride across neonatal porcine skin from the patches was investigated, with 854.71μg±122.71μg donepezil hydrochloride delivered after 24h, using the optimum patch formulation. Following administration of the patch to an animal model, plasma concentrations of 51.8±17.6ng/mL were obtained, demonstrating the success of this delivery platform for donepezil hydrochloride. PMID:27018330

  8. Donepezil nanosuspension intended for nose to brain targeting: In vitro and in vivo safety evaluation.

    PubMed

    Bhavna; Md, Shadab; Ali, Mushir; Ali, Rashid; Bhatnagar, Aseem; Baboota, Sanjula; Ali, Javed

    2014-06-01

    The present study was to develop donepezil loaded nanosuspension for direct olfactory administration which reaches the brain and determining safety profile in Sprague-Dawley rats. Nanosuspension was prepared by ionic-crosslinking method. The developed nanosuspension was intranasally instilled into the nostrils of rats with the help of cannula (size 18/20) so that drug reached into the brain directly via nose to brain pathway. The nanosuspension had an average size of 150-200nm with a polydispersity index of 0.341. The donepezil concentration was estimated in the brain homogenate using HPLC method. The Cmax showed concentration of donepezil in brain and plasma as 7.2±0.86 and 82.8±5.42ng/ml, respectively, for drug suspension and concentration of donepezil in brain and plasma as 147.54±25.08 and 183.451±13.45ng/ml, respectively, for nanosuspension at same dose of 0.5mg/ml when administered intranasally (p<0.05). The in vivo safety evaluation studies showed that no mortality, hematological changes, body weight variations and toxicity in animals was observed, when nanosuspension was administered in different doses as compared to control group (normal saline). Donepezil loaded chitosan nanosuspension is a potential new delivery system for treatment of Alzheimer's disease, when transported via olfactory nasal pathway to the brain. PMID:24705169

  9. Antagonism of anticholinesterase (DFP) toxicity by donepezil plus scopolamine: a preliminary study.

    PubMed

    Janowsky, David S; Davis, John M; Overstreet, David H

    2004-02-01

    Studies in animals exploring the antagonism of the cholinesterase inhibitors soman and sarin have shown that pretreatment with low doses of the centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic agent, scopolamine, is effective against their lethality and toxicity. The current study evaluated the effects of pretreatment with the oral anticholinesterase agent, donepezil (Aricept, 2.0 mg/kg), used to treat Alzheimer's disease, with and without scopolamine in decreasing the hypothermic, hypokinetic, and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor diisopropyl fluorophosphate (DFP, 1.0 mg/kg) in adult Flinders sensitive line (FSL) male rats. Donepezil alone and donepezil plus scopolamine (0.1 mg/kg) to a greater extent antagonized the decrease in temperature, hypoactivity, and induction of diarrhea due to DFP observed at 4 h after its administration. However, donepezil alone induced hypothermia at 1 and 2 h after treatment. Therefore, these preliminary findings are encouraging, but many additional studies are needed to establish the effectiveness of donepezil as a prophylactic agent against irreversible cholinesterase inhibition by DFP. PMID:14751462

  10. [Nightmares in patients with Alzheimer's disease caused by donepezil. Therapeutic effect depends on the time of intake].

    PubMed

    Singer, M; Romero, B; Koenig, E; Förstl, H; Brunner, H

    2005-09-01

    Dementia of the Alzheimer type (DAT) has been linked to losses of cholinergic function in the brain. The acetylcholinesterase inhibitors donepezil, rivastigmine and galantamine improve cognitive performance in manifest dementia. These substances, however, also influence the quality of sleep, and particularly the quality and amount of dreams. We therefore investigated the influence of the time point of donepezil intake on the occurrence of nightmares. We observed a clear-cut relationship between the occurrence of nightmares and an evening dose of donepezil in eight patients with DAT. None of these patients reported nightmares when donepezil was taken in the morning. We suggest that the activation of the visual association cortex during REM sleep is enhanced by donepezil, a mechanism most likely facilitating the development of nightmares in patients with DAT. PMID:15630600

  11. Effects of selegiline alone or with donepezil on memory impairment in rats.

    PubMed

    Takahata, Kazue; Minami, Akiko; Kusumoto, Haruko; Shimazu, Seiichiro; Yoneda, Fumio

    2005-08-22

    Selegiline, a monoamine oxidase-B inhibitor, is reported to improve memory and learning in dementia of Alzheimer's type. However, only a few studies have reported its use in animal models. Here, we evaluated the effects of selegiline only or its combined use with donepezil, a selective acetylcholinesterase inhibitor on memory impairment, using a Morris water maze. Selegiline dose-dependently attenuated ethylcholine aziridinium ion-induced memory impairment. Co-administration of selegiline and donepezil, at doses that do not exert efficacy individually, significantly ameliorated scopolamine+p-chlorophenylalanine-induced memory deficits. These results suggest that selegiline improves memory impairment mediated by the cholinergic system, and provide evidence of the usefulness of co-treatment with selegiline and donepezil for treating spatial deficits in dementia. PMID:16061218

  12. Donepezil: an important prototype to the design of new drug candidates for Alzheimer's disease.

    PubMed

    Rodrigues Simões, Maria Cecilia; Dias Viegas, Flávia Pereira; Moreira, Marcella Soares; de Freitas Silva, Matheus; Riquiel, Mariana Máximo; da Rosa, Patrícia Mattos; Castelli, Maísa Rosa; dos Santos, Marcelo Henrique; Soares, Marisi Gomes; Viegas, Claudio

    2014-01-01

    Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder, with a dramatic socioeconomic impact. The progress of AD is characterized by a severe loss in memory and cognition, leading to behavioral changing, depression and death. During the last decades, only a few anticholinergic drugs were launched in the market, mainly acetylcholinesterase inhibitors (AChEIs), with indications for the treatment of initial and moderate stages of AD. The search for new AChEIs, capable to overcome the limitations observed for rivastigmine and tacrine, led Sugimoto and co-workers to the discovery of donepezil. Besides its high potency, donepezil also exhibited high selectivity for AChE and a very low toxicity. In this review, we discuss the main structural and pharmacological attributes that have made donepezil the first choice medicine for AD, and a versatile structural model for the design of novel AChEIs, in spite of multipotent and multitarget-directed ligands. Many recent data from literature transdue great efforts worldwide to produce modifications in the donepezil structure that could result in new bioactive chemical entities with innovative structural pattern. Furthermore, multi-potent ligands have also been designed by molecular hybridization, affording rivastigmine-, tacrine- and huperzine-donepezil potent and selective AChEIs. In a more recent strategy, structural features of donepezil have been used as a model to design multitarget-directed ligands, aiming at the discovery of new effective drug candidates that could exhibit concomitant pharmacological activities as dual or multi- enzymatic inhibitors as genuine innovative therapeutic alternatives for the treatment of AD. PMID:24251806

  13. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis

    PubMed Central

    Christodoulou, C.; Melville, P.; Scherl, W.F.; Pai, L.-Y.; Muenz, L.R.; He, D.; Benedict, R.H.B.; Goodman, A.; Rizvi, S.; Schwid, S.R.; Weinstock-Guttman, B.; Westervelt, H.J.; Wishart, H.

    2011-01-01

    Objectives: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). Methods: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18–59 years, clinically definite multiple sclerosis (MS), and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change. Results: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. Conclusions: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. Classification of evidence: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average. PMID:21519001

  14. Administration of donepezil does not rescue galanin-induced spatial learning deficits.

    PubMed

    Sabbagh, Jonathan J; Heaney, Chelcie F; Bolton, Monica M; Murtishaw, Andrew S; Ure, Jennifer A; Kinney, Jefferson W

    2012-12-01

    The neuropeptide galanin inhibits the evoked release of several neurotransmitters including acetylcholine and modulates adenylate cyclase (AC) activity. Galanin has also been established to impair various forms of learning and memory in rodents. However, whether galanin produces learning deficits by inhibiting cholinergic activity or decreasing AC function has not been clearly established. The current study investigated if donepezil, an acetylcholinesterase inhibitor utilized in Alzheimer's disease, could rescue galanin-induced Morris water task deficits in rats. The results demonstrated that donepezil did not alter the previously established deficits induced by galanin. These findings suggest that galanin-mediated spatial learning deficits may be unrelated to its modulation of the cholinergic system. PMID:22897394

  15. A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder.

    PubMed

    Hardan, Antonio Y; Handen, Benjamin L

    2002-01-01

    In light of the recently reported neuropathologic and neurochemical abnormalities of the cholinergic pathways in autism, donepezil, a cholinesterase inhibitor, is a potentially useful agent in the treatment of cognitive and behavioral symptoms observed in this disorder. A retrospective pilot study was conducted to determine whether donepezil is effective in the treatment of children and adolescents with autism. Eight patients (mean age = 11.0 +/- 4.1 years; range 7-19 years) who met Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria for autistic disorder were openly treated with donepezil. All patients were on concomitant psychoactive medications. Four of these patients (50%) demonstrated significant improvement as assessed by the Aberrant Behavior Checklist and the Clinical Global Impression Scale. Decreases in the Irritability and Hyperactivity subscales were observed, but no changes in the Inappropriate Speech, Lethargy, and Stereotypies subscales were noted. Limited and transient side effects were reported, with one patient experiencing gastrointestinal disturbances and another reporting mild irritability. Double-blind, placebo-controlled investigations are needed to provide further evidence of the potential benefits of donepezil to patients with autistic disorder. PMID:12427297

  16. Relevance of Donepezil in Enhancing Learning and Memory in Special Populations: A Review of the Literature

    ERIC Educational Resources Information Center

    Yoo, J. Helen; Valdovinos, Maria G.; Williams, Dean C.

    2007-01-01

    This review discusses the laboratory and clinical research supporting the rationale for the efficacy of donepezil (Aricept[R] USA) in enhancing cognition in autism, Alzheimer disease, Down syndrome, traumatic brain injury, Attention Deficit Hyperactivity Disorder (ADHD), and schizophrenia. While preliminary animal models have shown effective,…

  17. Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer's disease: preliminary report.

    PubMed

    Zaidel, Liam; Allen, Greg; Cullum, C Munro; Briggs, Richard W; Hynan, Linda S; Weiner, Myron F; McColl, Roderick; Gopinath, Kaundinya S; McDonald, Elizabeth; Rubin, Craig D

    2012-01-01

    We used functional connectivity magnetic resonance imaging (fcMRI) to investigate changes in interhemispheric brain connectivity in 11 patients with mild Alzheimer's disease (AD) following eight weeks of treatment with the cholinesterase inhibitor donepezil. We examined functional connectivity between four homologous temporal, frontal, and occipital regions. These regions were selected to represent sites of AD neuropathology, sites of donepezil-related brain activation change in prior studies, and sites that are minimally affected by the pathologic changes of AD. Based on previous findings of selective, localized frontal responses to donepezil, we predicted that frontal connectivity would be most strongly impacted by treatment. Of the areas examined, we found that treatment had a significant effect only on functional connectivity between right and left dorsolateral prefrontal cortices. Implications for understanding the impact of donepezil treatment on brain functioning and behavior in patients with AD are discussed. This preliminary report suggests that fcMRI may provide a useful index of treatment outcome in diseases affecting brain connectivity. Future research should investigate these treatment-related changes in larger samples of patients and age-matched controls. PMID:22886013

  18. High field (1)H MRS of the hippocampus after donepezil treatment in Alzheimer disease.

    PubMed

    Bartha, Robert; Smith, Matthew; Rupsingh, Raul; Rylett, Jane; Wells, Jennie L; Borrie, Michael J

    2008-04-01

    The purpose of this study was to measure metabolite level changes in patients with newly diagnosed Alzheimer Disease (AD) following four months of donepezil treatment. A small number of cognitively normal elderly subjects were also scanned longitudinally (twice within one year) to assess the reproducibility. Short echo-time (1)H magnetic resonance spectra were acquired at 4.0 T in the right hippocampus. Subjects were scanned at the time of first diagnosis (prior to receiving donepezil) and then following four months of donepezil treatment (5 mg/day for the first month, 10 mg/day thereafter). Changes in absolute metabolite levels and metabolite ratios were quantified and compared. There was no change in measured cognitive function following four months of donepezil treatment in the AD patients. Decreased levels of N-acetylaspartate, choline, N-acetylaspartate/creatine, choline/creatine, and myo-inositol/creatine were observed in AD patients after four months of treatment. Cognitively normal elderly subjects showed an increase in myo-inositol/choline ratio following one year. The reduced levels of N-acetylaspartate in AD patients indicates continued decline in neuronal function and/or integrity. However decreased levels of choline and myo-inositol/creatine ratio may indicate a positive treatment effect. PMID:18252268

  19. Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial

    PubMed Central

    Rapp, Stephen R.; Case, L. Doug; Peiffer, Ann; Naughton, Michelle M.; Chan, Michael D.; Stieber, Volker W.; Moore, Dennis F.; Falchuk, Steven C.; Piephoff, James V.; Edenfield, William J.; Giguere, Jeffrey K.; Loghin, Monica E.; Shaw, Edward G.

    2015-01-01

    Purpose Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. Patients and Methods A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Results Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Conclusion Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments. PMID:25897156

  20. Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects.

    PubMed

    Mumenthaler, Martin S; Yesavage, Jerome A; Taylor, Joy L; O'Hara, Ruth; Friedman, Leah; Lee, Hana; Kraemer, Helena C

    2003-07-01

    The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol. PMID:12784106

  1. Apolipoprotein E epsilon4 allele differentiates the clinical response to donepezil in Alzheimer's disease.

    PubMed

    Bizzarro, A; Marra, C; Acciarri, A; Valenza, A; Tiziano, F D; Brahe, C; Masullo, C

    2005-01-01

    The existence of an association between apolipoprotein E (APOE) and Alzheimer's disease (AD) has been reported in several studies. The possession of an ApoE epsilon4 allele is now considered a genetic risk factor for sporadic AD. There has been a growing agreement about the role exerted by the ApoE epsilon4 allele on the neuropsychological profile and the rate of cognitive decline in AD patients. However, a more controversial issue remains about a possible influence of the APOE genotype on acetylcholinesterase inhibitor therapy response in AD patients. In order to address this issue, 81 patients diagnosed as having probable AD were evaluated by a complete neuropsychological test battery at the time of diagnosis (baseline) and after 12-16 months (retest). Patients were divided into two subgroups: (1) treated with donepezil at a dose of 5 mg once a day (n = 41) and (2) untreated (n = 40). Donepezil therapy was started after baseline evaluation. The APOE genotype was determined according to standardized procedures. We evaluated the possible effect of the APOE genotype on the neuropsychological tasks in relation to donepezil therapy. The statistical analysis of the results showed a global worsening of cognitive performances for all AD patients at the retest. Differences in the clinical outcome were analysed in the four subgroups of AD patients for each neuropsychological task. ApoE epsilon4 carriers/treated patients had improved or unchanged scores at retest evaluation for the following tasks: visual and verbal memory, visual attention and inductive reasoning and Mini Mental State Examination. These results indicate an effect of donepezil on specific cognitive domains (attention and memory) in the ApoE epsilon4 carriers with AD. This might suggest an early identification of AD patients carrying at least one epsilon4 allele as responders to donepezil therapy. PMID:16103669

  2. Protective effects of NMDA receptor antagonist, memantine, against senescence of PC12 cells: A possible role of nNOS and combined effects with donepezil.

    PubMed

    Ota, Hidetaka; Ogawa, Sumito; Ouchi, Yasuyoshi; Akishita, Masahiro

    2015-12-01

    Alzheimer disease (AD) is a neurodegenerative disorder characterized by cognitive dysfunction. The pathology of AD is mainly related to amyloid ß (Aß)-peptides, but glutamate-mediated toxicity is also one of the main processes of memory impairment in AD. Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is particularly involved in synaptic plasticity, memory, and learning. Memantine is a low-affinity voltage-dependent noncompetitive antagonist at glutamatergic NMDA receptors. Here,we investigated whether memantine protects against glutamate-induced senescence. In PC12 cells, treatment with glutamate induced senescent phenotypes as judged by the cell appearance and senescence-associated ß-galactosidase (SA-ßgal) in parallel with decreased SIRT1 and increased p53 expression. However, treatment with memantine decreased glutamate-induced senescent PC12 cells and reversed the changes in SIRT1 and p53 expression. Glutamate is known to stimulate the production of NO and O2(-) and has the capacity to generate ONOO(-) in the CNS. Therefore, we investigated whether glutamate activates nNOS and memantine reverses it. Treatment with glutamate increased nNOS expression, activity, and production of NO,whereas memantine blocked them. Next, the in vivo effects of memantine on cognitive function in senescence-accelerated mouse prone 8 (SAMP8), as a model of AD, were investigated. In the Morris water maze test, SAMP8 showed a marked decline in performance, but memantine administration improved it. Moreover, neuronal senescence and the level of oxidative stress in the hippocampus were decreased by memantine. Finally, the effects of combination treatment with memantine and donepezil, a cholinesterase inhibitor, were investigated. We observed additive effects of memantine and donepezil on the senescent phenotype of PC12 cells and the hippocampus of SAMP8. These results indicate that inhibition of the NMDA receptor by memantine leads to a

  3. Spectroscopic studies of solid-state forms of donepezil free base and salt forms with various salicylic acids

    NASA Astrophysics Data System (ADS)

    Brittain, Harry G.

    2014-12-01

    The polymorphic forms of donepezil free base have been studied using X-ray powder diffraction, Fourier transform infrared absorption spectroscopy, and differential scanning calorimetry. None of the free base crystal forms was observed to exhibit detectable fluorescence in the solid state under ambient conditions. Crystalline salt products were obtained by the reaction of donepezil with salicylic and methyl-substituted salicylic acids, with the salicylate and 4-methylsalicylate salts being obtained as non-solvated products, and the 3-methylsalicylate and 5-methylsalicylate salts being obtained as methanol solvated products. The intensity of solid-state fluorescence from donepezil salicylate and donepezil 4-methylsalicylate was found to be reduced relative to the fluorescence intensity of the corresponding free acids, while the solid-state fluorescence intensity of donepezil 3-methylsalicylate methanolate and donepezil 5-methylsalicylate methanolate was greatly increased relative to the fluorescence intensity of the corresponding free acids. Desolvation of the solvated salt products led to formation of glassy solids that exhibited strong green fluorescence.

  4. Memantine and donepezil: a fixed drug combination for the treatment of moderate to severe Alzheimer's dementia.

    PubMed

    Owen, R T

    2016-04-01

    Donepezil (and other cholinesterase inhibitors [ChEIs]) and memantine are the mainstays of treatment in Alzheimer's dementia, addressing respectively, the cholinergic and glutamatergic dysregulation which underlies or results from its pathophysiology. To alleviate the pill burden and swallowing difficulties associated with the condition, a fixed drug combination of extended-release memantine and donepezil was developed. This combination was shown to be both bioequivalent to the components administered separately and could be administered sprinkled over soft food. The mode of action, pharmacokinetics, clinical efficacy and safety and tolerability of the combination are discussed together with the wider, often conflicting trial literature of combination versus monotherapy with memantine and ChEIs, their meta-analyses and treatment guidelines. PMID:27252988

  5. Donepezil Treatment of Older Adults with Cognitive Impairment and Depression (DOTCODE study): clinical rationale and design

    PubMed Central

    Pelton, Gregory H.; Andrews, Howard; Roose, Steven P.; Marcus, Sue M.; D’Antonio, Kristina; Husn, Hala; Petrella, Jeffrey R.; Zannas, Anthony S.; Doraiswamy, P. Murali; Devanand, D. P.

    2014-01-01

    Treatment strategies for patients with depression and cognitive impairment (DEP-CI), who are at high risk to develop a clinical diagnosis of dementia, are not established. This issue is addressed in the donepezil treatment of cognitive impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is the first long-term treatment trial that assesses differences in conversion to dementia and cognitive change in DEP-CI patients using a study design of open antidepressant medication plus add-on randomized, double-blind, placebo-controlled treatment with the acetylcholinesterase inhibitor donepezil. In Phase 1, DEP-CI patients receive optimized antidepressant treatment for 16 weeks. In Phase 2, antidepressant treatment is continued with the addition of randomized, double-blind treatment with donepezil or placebo. The total study duration for each patient is 78 weeks (18 months). Eighty DEP-CI outpatients (age 55 to 95 years) are recruited: 40 at New York State Psychiatric Institute/Columbia University and 40 at Duke University Medical Center. The primary outcome is conversion to a clinical diagnosis of dementia. The secondary outcomes are cognitive change scores in Selective Reminding Test (SRT) total recall and the modified Alzheimer’s Disease Assessment Scale (ADAS-cog). Other key assessments include the 24-item Hamilton Depression Rating Scale and antidepressant response; Clinical Global Impression (CGI) for depression, cognition, and global status; neuropsychological test battery for diagnosis; informant report of functional abilities (Pfeffer FAQ); Treatment Emergent Symptom Scale (TESS) for somatic side effects. Apolipoprotein E ε4 status, odor identification deficits, and MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects. PMID:24315979

  6. The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

    PubMed Central

    Yi, Yun-Min; Cai, Li; Shao, Yi; Xu, Man; Yi, Jing-Lin

    2015-01-01

    AIM To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE+/− mice (AChE knockout mice) of various ages. METHODS Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 µmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE+/− mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer. RESULTS Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE+/− mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE+/− mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05). CONCLUSION In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina. PMID:26558196

  7. Isoflurane-Induced Spatial Memory Impairment in Mice is Prevented by the Acetylcholinesterase Inhibitor Donepezil

    PubMed Central

    Wang, Beilei; Xu, Huan; Li, Wen; Chen, Jie; Wang, Xiangrui

    2011-01-01

    Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. PMID:22114680

  8. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.

    PubMed

    Su, Diansan; Zhao, Yanxing; Wang, Beilei; Xu, Huan; Li, Wen; Chen, Jie; Wang, Xiangrui

    2011-01-01

    Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. PMID:22114680

  9. In vitro toxicity of rivastigmine and donepezil in cells of epithelial origin.

    PubMed

    Goldblum, David; Gygax, Monika; Böhnke, Mattias; Garweg, Justus G

    2002-01-01

    Neurospecific acetylcholinesterase inhibitors have been shown to lower intraocular pressure (IOP) in normal rabbits and might have additional neuroprotective effects. This study was set out to explore and compare the toxicity of two selective acetylcholinesterase inhibitors, rivastigmine and donepezil, on two standardized cell lines of epithelial origin. Chang and Vero cells were incubated with various concentrations of rivastigmine or donepezil. Acute toxicity (4 h) was assessed by monitoring the permeability of cells to propidium iodide. Chronic toxicity (7 days) was determined by monitoring the effect of the two drugs on esterase activity and cell proliferation. The viability of cells was also assessed morphologically by microscopic inspection. Signs of acute toxicity became manifest at a rivastigmine concentration of 50 mg/ml in both Chang and Vero cells. Indications of chronic toxicity became obvious at concentrations of as low as 1 x 10(-5) mg/ml. In contrast, degenerative morphological changes became manifest only at a concentration of as high as 1 mg/ml. In donepezil-treated cells, acute toxicity was not observed in the concentration range tested, whereas chronic toxicity was detected at 1 x 10(-1) mg/ml in both Chang and Vero cells, a concentration at which degenerative morphological changes became evident as well. In contrast to rivastigmine, donepezil elicited no signs of acute or chronic toxicity in either Chang or Vero cells at the IOP-lowering concentration of 1 x 10(-4) mg/ml. At this dose, the drug is therefore unlikely to evoke deleterious effects on ocular surface tissues in the clinical setting. PMID:11914613

  10. Safety and efficacy of donepezil in African Americans with mild-to-moderate Alzheimer's disease.

    PubMed Central

    Griffith, Patrick; Lichtenberg, Peter; Goldman, Robert; Payne-Parrish, Jennifer

    2006-01-01

    BACKGROUND: African Americans have a higher incidence and prevalence of Alzheimer's disease (AD) than whites but have been underrepresented in clinical trials, including studies of cholinesterase inhibitors. PURPOSE: The purpose of this 12-week, open-label study was to evaluate the efficacy and safety of donepezil in African Americans with mild-to-moderate AD. METHODS: Efficacy was assessed via the Mini-Mental State Examination (MMSE), Clinician's Interview-Based Impression of Change-Plus interview with the patient and caregiver (CIBIC-Plus) and Fuld Object Memory Evaluation (FOME), a measure that has been validated for use with elderly African Americans. RESULTS: Significant improvements were observed in cognition (MMSE), global function (CIBIC-Plus) and memory (all four subscales of the FOME). Donepezil was well tolerated; 51% of patients experienced adverse events, most commonly diarrhea (5.6%), hypertension (5.6%) and urinary tract infection (4.8%). CONCLUSIONS: These results suggest that donepezil is effective and safe in treating African Americans with mild-to-moderate AD, and support the value of FOME in assessing efficacy in AD trials in diverse populations. PMID:17052048

  11. Antiamnesic and neuroprotective effects of donepezil against learning impairments induced in mice by exposure to carbon monoxide gas.

    PubMed

    Meunier, Johann; Ieni, John; Maurice, Tangui

    2006-06-01

    Donepezil is a potent acetylcholinesterase inhibitor that also interacts with the sigma1 receptor, an intracellular neuromodulatory protein. In the present study, we analyzed the antiamnesic and neuroprotective activities of donepezil in a mouse hypoxia model induced by repetitive CO exposure, comparing donepezil's pharmacological profile with other cholinesterase inhibitors tacrine, rivastigmine, and galanthamine, and the reference sigma1 agonist igmesine. CO exposure induced, after 7 days, hippocampal neurodegeneration, analyzed by Cresyl violet staining, and behavioral alterations, measured using spontaneous alternation and passive avoidance responses. When injected 20 min before the behavioral tests, i.e., 7 to 8 days after CO, all drugs showed antiamnesic properties. Preadministration of the sigma1 receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047) blocked only the igmesine and donepezil effects. The neuroprotective activity of the drugs was tested by injection 20 min before the first CO exposure (preinsult protection) or by injection 1 h after the last CO exposure (postinsult protection). All drugs alleviated the hypoxia-induced neurodegeneration and behavioral impairments when injected before CO exposure. Preadministration of BD1047 blocked both the igmesine and donepezil effects. However, when injected after CO exposure, only igmesine and donepezil induced effective neuroprotection, and the morphological and behavioral effects were BD1047-sensitive. These results showed that donepezil is a potent antiamnesic and neuroprotective compound against the neurodegeneration induced by excitotoxic insult, and its pharmacological actions as both an acetylcholinesterase inhibitor and sigma1 receptor agonist contribute to its marked efficacy. In particular, the drug is a more potent postinsult protecting agent compared with more selective cholinesterase inhibitors. PMID:16551835

  12. Donepezil delays progression to AD in MCI subjects with depressive symptoms

    PubMed Central

    Lu, P H.; Edland, S D.; Teng, E; Tingus, K; Petersen, R C.; Cummings, J L.

    2009-01-01

    Objective: To determine whether the presence of depression predicts higher rate of progression to Alzheimer disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and whether donepezil treatment beneficially affect this relationship. Methods: The study sample was composed of 756 participants with aMCI from the 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study drug trial of donepezil and vitamin E. Beck Depression Inventory (BDI) was used to assess depressive symptoms at baseline and participants were followed either to the end of study or to the primary endpoint of progression to probable or possible AD. Results: Cox proportional hazards regression, adjusted for age at baseline, gender, apolipoprotein genotype, and NYU paragraph delayed recall score, showed that higher BDI scores were associated with progression to AD (p = 0.03). The sample was stratified into depressed (BDI score ≥10; n = 208) and nondepressed (BDI <10; n = 548) groups. Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to AD was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years (p = 0.023), at 2.2 years (p = 0.025), and remained marginally lower at 2.7 years (p = 0.070). The survival curves among the three treatment groups did not differ within the nondepressed participants. Conclusions: Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms. GLOSSARY AD = Alzheimer disease; ADCS = Alzheimer's Disease Cooperative Study; aMCI = amnestic mild cognitive impairment; BDI = Beck Depression Inventory; CDR = Clinical Dementia Rating; ChEI = cholinesterase inhibitors; DSM-IV = Diagnostic and Statistical Manual

  13. The involvement of sigma1 receptors in donepezil-induced rescue of hippocampal LTP impaired by beta-amyloid peptide.

    PubMed

    Solntseva, E I; Kapai, N A; Popova, O V; Rogozin, P D; Skrebitsky, V G

    2014-07-01

    Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease (AD). Additional therapeutically relevant target for donepezil is sigma1 receptor (Sig1-R). Beta-amyloid peptide (Aβ) is believed to contribute to the pathogenesis of AD. In our previous work (Kapai et al., 2012), we have shown that donepezil antagonizes the suppressive action of Aβ(1-42) on long-term potentiation (LTP) in rat hippocampal slices. The purpose of the present study was to determine whether Sig1-R is involved into the mechanisms of donepezil action. For this purpose, we have tested whether agonist of Sig1-R PRE-084 mimics, and antagonist of Sig1-R haloperidol abolishes the effect of donepezil. Population spikes (PSs) were recorded from the pyramidal layer of the CA1 region of rat hippocampal slices. Drugs were applied by addition to the perfusate starting 15 min before and ending 5 min after the tetanus. In the control group, the amplitude of PS 30 min post-tetanus reached 153±10%. Aβ (200 nM) markedly suppressed the LTP magnitude or even caused the suppression of baseline PS (82±8%, P<0.001). This suppression of LTP could be markedly prevented when 1 μM donepezil was co-administered with Aβ (136±11%, P<0.05). Further, we co-administered three substances: Aβ, donepezil and 0.5 μM haloperidol and have found that haloperidol antagonized the stimulating effect of donepezil on LTP (92±6%, P<0.05). Agonist of Sig1-R PRE-084 (0.1-10 μM) enhanced control LTP and abolished the inhibitory effect of Aβ on LTP in a concentration-dependent manner. The amplitude of PS 30 min post-tetanus reached 183±7% (P<0.01) for 10 μM PRE-084. The results suggest that activation of Sig1-R is involved into the mechanisms of donepezil-induced rescue of hippocampal LTP impaired by Aβ. PMID:24956443

  14. Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease.

    PubMed

    Unzeta, Mercedes; Esteban, Gerard; Bolea, Irene; Fogel, Wieslawa A; Ramsay, Rona R; Youdim, Moussa B H; Tipton, Keith F; Marco-Contelles, José

    2016-01-01

    HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil-indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept®) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands

  15. Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease

    PubMed Central

    Unzeta, Mercedes; Esteban, Gerard; Bolea, Irene; Fogel, Wieslawa A.; Ramsay, Rona R.; Youdim, Moussa B. H.; Tipton, Keith F.; Marco-Contelles, José

    2016-01-01

    HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil-indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept®) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands

  16. Normal Hearing Ability but Impaired Auditory Selective Attention Associated with Prediction of Response to Donepezil in Patients with Alzheimer's Disease

    PubMed Central

    Ouchi, Yoshitaka; Meguro, Kenichi; Akanuma, Kyoko; Kato, Yuriko; Yamaguchi, Satoshi

    2015-01-01

    Background. Alzheimer's disease (AD) patients have a poor response to the voices of caregivers. After administration of donepezil, caregivers often find that patients respond more frequently, whereas they had previously pretended to be “deaf.” We investigated whether auditory selective attention is associated with response to donepezil. Methods. The subjects were40 AD patients, 20 elderly healthy controls (HCs), and 15 young HCs. Pure tone audiometry was conducted and an original Auditory Selective Attention (ASA) test was performed with a MoCA vigilance test. Reassessment of the AD group was performed after donepezil treatment for 3 months. Results. Hearing level of the AD group was the same as that of the elderly HC group. However, ASA test scores decreased in the AD group and were correlated with the vigilance test scores. Donepezil responders (MMSE 3+) also showed improvement on the ASA test. At baseline, the responders had higher vigilance and lower ASA test scores. Conclusion. Contrary to the common view, AD patients had a similar level of hearing ability to healthy elderly. Auditory attention was impaired in AD patients, which suggests that unnecessary sounds should be avoided in nursing homes. Auditory selective attention is associated with response to donepezil in AD. PMID:26161001

  17. Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses

    PubMed Central

    Nagy, Christa F; Kumar, Dinesh; Perdomo, Carlos A; Wason, Suman; Cullen, Edward I; Pratt, Raymond D

    2004-01-01

    Aim This study evaluated the safety and pharmacokinetics (PK) of donepezil HCl and sertraline HCl when administered separately and in combination. Methods This was a randomized, open-label, three-period crossover study. In consecutive dosing periods separated by washout periods of ≥3 weeks, healthy volunteers received either oral donepezil HCI 5 mg once daily for 15 days, oral sertraline HCl 50 mg once daily for 5 days followed by 10 days of once-daily sertraline HCl 100 mg, or the simultaneous administration of oral donepezil HCl and sertraline HCl. Plasma donepezil and sertraline concentrations were determined by high performance liquid chromatography/mass spectrometry. Safety was evaluated by physical and laboratory evaluations and the monitoring of adverse events (AEs). Results A total of 19 volunteers (16 male and three female) were enrolled. Three male subjects withdrew from the study prematurely due to AEs (one case of nausea/stomach cramps and one case of eosinophilia during combination treatment, and one upper respiratory tract infection during treatment with sertraline HCl alone). In subjects who completed all three treatment periods (n = 16), the concurrent administration of donepezil HCl and sertraline HCl did not alter the steady-state (day 15) PK parameters of donepezil HCl. A small (<12%) but statistically significant (P = 0.02) increase in donepezil Cmax was seen after single doses of sertraline HCl and donepezil HCl on day 1 but this was not thought to be clinically meaningful. No significant differences in the tmax or AUC0–24 h of donepezil were observed between the donepezil HCl only or donepezil HCl plus sertraline HCl groups on day 1. No significant changes in sertraline PK parameters were observed either on day 1 (single dose) or on day 15 (steady state) when sertraline HCl was co-administered with donepezil HCl. Generally, the concurrent administration of donepezil HCl and sertraline HCl was well tolerated, with no serious AEs reported

  18. Tacrine and donepezil attenuate the neurotoxic effect of A beta(25-35) in rat PC12 cells.

    PubMed

    Svensson, A L; Nordberg, A

    1998-05-11

    The effect of the cholinesterase inhibitors tacrine and donepezil on A beta(25-35)-induced toxicity was investigated in rat pheochromocytoma PC12 cells by measuring the mitochondrial activity. Tacrine and donepezil was found in clinical relevant concentrations (10(-7)-10(-6) M) to attenuate A beta(25-35)-induced toxicity in PC12 cells. The neuroprotective effect of tacrine was blocked in the presence of the nicotinic antagonists mecamylamine (10(-5) M) and tubocurarine (10(-5) M), suggesting an interaction via nicotinic receptors. This study demonstrates that tacrine and donepezil can exert neuroprotective properties which might be of importance and contribute to the clinical efficacy of cholinesterase inhibitors in the treatment of Alzheimer's disease. PMID:9631459

  19. Procognitive effect of AC-3933 in aged mice, and synergistic effect of combination with donepezil in scopolamine-treated mice.

    PubMed

    Hashimoto, Takashi; Hatayama, Yuki; Nakamichi, Keiko; Yoshida, Naoyuki

    2014-12-15

    We have previously reported that AC-3933, a newly developed benzodiazepine receptor partial inverse agonist, facilitates acetylcholine release in the hippocampus and ameliorates scopolamine-induced memory deficits in rats. To further confirm the procognitive effect of AC-3933, we assessed in this study the beneficial effects of this compound in aged mice using the Y-maze and object recognition tests. In addition, we investigated the synergistic effect of AC-3933 and donepezil, a cholinesterase inhibitor, on scopolamine-induced memory impairment in mice. In aged mice, oral administration of AC-3933 at doses of 0.05-0.1 mg/kg and 0.05 mg/kg significantly improved spatial working memory and episodic memory, respectively. In scopolamine-treated mice, both AC-3933 and donepezil significantly ameliorated memory deficits in the Y-maze test at doses of 0.3-3 mg/kg and 10-15 mg/kg, respectively. The beneficial effect of AC-3933, but not that of donepezil, on scopolamine-induced memory impairment was antagonized by flumazenil, a benzodiazepine receptor antagonist, indicating that the procognitive action of AC-3933 arises via a mechanism different from that of donepezil. Co-administration of donepezil at the suboptimal dose of 3 mg/kg with AC-3933 at doses of 0.1-1 mg/kg significantly ameliorated scopolamine-induced memory impairment, suggesting that AC-3933 potentiates the effect of donepezil on memory impairment induced by cholinergic hypofunction. These findings indicate that AC-3933 not only has good potential as a cognitive enhancer by itself, but also is useful as a concomitant drug for the treatment of Alzheimer׳s disease. PMID:25446931

  20. Comparison of donepezil and memantine for protective effect against amyloid-beta(1-42) toxicity in rat septal neurons.

    PubMed

    Kimura, Manami; Komatsu, Hiroko; Ogura, Hiroo; Sawada, Kohei

    2005-12-31

    Donepezil, a potent acetylcholinesterase (AChE) inhibitor and memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, have been used for the treatment of Alzheimer's disease (AD), and both of them have been shown to have neuroprotective action against glutamate excitotoxicity. However, it is not known whether donepezil and memantine similarly exert neuroprotective effects against amyloid-beta peptide(1-42) [Abeta(1-42)] toxicity in cholinergic neurons. Therefore, in the present study we compared the neuroprotective effects of donepezil and memantine against Abeta(1-42) toxicity in rat cultured septal cholinergic neurons, because deficit in cholinergic neurotransmission is a major feature in AD, and medial septal cholinergic neurons are known to degenerate in AD patients. Septal neuronal cells were cultured for 7 days and then 5 micromol/L of Abeta(1-42) was added to the medium for 48 h. Measurement of the efflux of lactate dehydrogenase (LDH) indicated that septal neuronal cells were highly susceptible to Abeta toxicity and relatively resistant to NMDA toxicity. Donepezil concentration-dependently reduced the LDH efflux induced by Abeta(1-42), and the effect was significant at 1 micromol/L and above. NMDA receptor antagonists, memantine and MK-801, did not show a significant neuroprotective effect against Abeta(1-42) toxicity. It is concluded that the neuroprotective effect of donepezil against Abeta(1-42) toxicity is not mediated by interference with the NMDA-mediated excitotoxic process, and that donepezil may be more effective than memantine against cholinergic neuronal damage induced by Abeta(1-42) exposure. PMID:16154269

  1. Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors.

    PubMed

    Costanzo, Paola; Cariati, Luca; Desiderio, Doriana; Sgammato, Roberta; Lamberti, Anna; Arcone, Rosaria; Salerno, Raffaele; Nardi, Monica; Masullo, Mariorosario; Oliverio, Manuela

    2016-05-12

    An ecofriendly synthetic pathway for the synthesis of donepezil precursors is described. Alternative energy sources were used for the total synthesis in order to improve yields, regioselectively, and rate of each synthetic step and to reduce the coproduction of waste at the same time. For all products, characterized by an improved structural rigidity respect to donepezil, the inhibitor activity on AChE, the selectivity vs BuChE, the side-activity on BACE-1, and the effect on SHSY-5Y neuroblastoma cells viability were tested. Two potential new lead compounds for a dual therapeutic strategy against Alzheimer's disease were envisaged. PMID:27190595

  2. Switching From Oral Donepezil to Rivastigmine Transdermal Patch in Alzheimer's Disease: 20-Week Extension Phase Results

    PubMed Central

    Dengiz, Alan; Meng, Xiangyi; Olin, Jason T.

    2010-01-01

    Objective: To evaluate the long-term safety, tolerability, and efficacy of 2 strategies for switching from donepezil to rivastigmine transdermal patches in patients with mild to moderate Alzheimer's disease. Method: This was a prospective, 25-week, randomized, open-label, parallel-group study to evaluate an immediate or delayed switch (7-day withdrawal) from donepezil (5 to 10 mg/d) to rivastigmine transdermal patches (4.6 mg/24 h). Participants included male and female patients, aged ≥ 50 years, with a DSM-IV-TR diagnosis of mild to moderate dementia of the Alzheimer's type, defined as a Mini-Mental State Examination score of 10–24, inclusive. Patients were enrolled between February 2007 and February 2008. The study was split into a 5-week core phase and a 20-week extension phase. Safety and efficacy results from the extension phase are presented. Results: Both switching strategies were well tolerated. Rates of discontinuation for any reason were similar between the groups. Discontinuations due to adverse events were also similar, and the incidence of gastrointestinal adverse events was low. Apart from Alzheimer's Disease Cooperative Study–Activities of Daily Living Scale scores, at the end of the study, there was no statistically significant change from baseline in cognitive, behavioral, or global outcomes. Over half of the patients preferred rivastigmine transdermal patches to a tablet. Conclusions: This study suggests that the majority of patients receiving donepezil tablets can be safely switched to rivastigmine transdermal patches without significant deterioration in cognition, behavior, and global functioning. Trial Registration: clinicaltrials.gov Identifier: NCT00305903 PMID:21274364

  3. Donepezil Impairs Memory in Healthy Older Subjects: Behavioural, EEG and Simultaneous EEG/fMRI Biomarkers

    PubMed Central

    Balsters, Joshua H.; O'Connell, Redmond G.; Martin, Mary P.; Galli, Alessandra; Cassidy, Sarah M.; Kilcullen, Sophia M.; Delmonte, Sonja; Brennan, Sabina; Meaney, Jim F.; Fagan, Andrew J.; Bokde, Arun L. W.; Upton, Neil; Lai, Robert; Laruelle, Marc; Lawlor, Brian; Robertson, Ian H.

    2011-01-01

    Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short- and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week follow-ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise

  4. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

    PubMed Central

    Hansen, Richard A; Gartlehner, Gerald; Webb, Aaron P; Morgan, Laura C; Moore, Charity G; Jonas, Daniel E

    2008-01-01

    Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine. PMID:18686744

  5. Donepezil provides greater benefits in mild compared to moderate Alzheimer's disease: implications for early diagnosis and treatment.

    PubMed

    Molinuevo, J L; Berthier, M L; Rami, L

    2011-01-01

    We assessed the cognitive and functional outcomes of donepezil treatment in mild versus moderate Alzheimer's disease (AD) patients. We performed a 6-month prospective, observational, multicenter study of the progression of cognitive and functionality abilities in a large sample patients with AD who initiated treatment with donepezil in monotherapy. According to baseline mini mental state examination (MMSE), patients were divided in two groups: mild AD (MMSE ≥ 21) and moderate AD (MMSE <21). Patients were evaluated with the memory alteration test (M@T) and the Alzheimer's disease functional assessment and change scale (ADFACS) at baseline and at 6 months. A total of 403 patients finished the study (mild AD=152; moderate AD=251). The MMSE total score and M@T score remained stable at 6 months in the whole sample, with MMSE memory domain and M@T free and cued recall domains improving significantly from baseline. Total ADFACS, instrumental (IADL) and basic activities of daily living (BADL) got significantly worse, with the worsening being significantly greater in the moderate AD group. Significant differences between the groups favoring mild AD were observed for MMSE memory, orientation and language domains, M@T temporal orientation and semantic memory domains, and for IADL. We concluded that in AD patients on donepezil, cognition remains stable at 6 months. The beneficial effect of donepezil treatment, in terms of cognition and functionality, is greater for mild than for moderate AD. PMID:19948364

  6. Donepezil in the Treatment of ADHD-Like Symptoms in Youths with Pervasive Developmental Disorder: A Case Series

    ERIC Educational Resources Information Center

    Doyle, Robert L.; Frazier, Jean; Spencer, Thomas J.; Geller, Daniel; Biederman, Joseph; Wilens, Timothy

    2006-01-01

    Background: Recent studies reported ADHD-like symptoms and cognitive deficits in pervasive developmental disorder (PDD). Because work in dementia documents improvement in executive function deficits with the acetylcholinesterase inhibitor donepezil, the authors reason that similar benefits could be obtained in PDD. Method: The authors describe…

  7. Switching From Donepezil to Rivastigmine Is Well Tolerated: Results of an Open-Label Safety and Tolerability Study.

    PubMed

    Sadowsky, Carl H; Farlow, Martin R; Atkinson, Leone; Steadman, Jennifer; Koumaras, Barbara; Chen, Michael; Mirski, Dario

    2005-01-01

    Background: Transitioning patients between cholinesterase inhibitors was thought to require a washout period to avoid cholinergic toxicity; however, evidence suggests that abrupt discontinuation of donepezil may lead to cognitive decline. We evaluated the safety and tolerability of an immediate switch from donepezil to rivastigmine.Method: This is an analysis of the safety and tolerability data from the first 28 days of an open-label, multicenter, prospective trial, conducted from August 2002 to August 2003, in which patients satisfying NINCDS-ADRDA criteria for probable Alzheimer's disease were administered rivastigmine 1.5 mg b.i.d. within 24 to 36 hours of donepezil discontinuation. Results are compared with adverse event rates from a retrospective analysis of a pivotal, placebo-controlled trial examining patients not previously treated with a cholinesterase inhibitor.Results: Fifty-eight of 61 patients completed the first 28 days, with no suspected drug-related discontinuations during this period. Incidence of overall gastrointestinal adverse events at day 7 was 8.2%, and at day 28 was 11.5%. The corresponding rate for rivastigmine-treated patients in the retrospective analysis of the pivotal trial for day 7 was 3.3%.Conclusion: These study results suggest that transitioning patients from donepezil to rivastigmine without a washout period is safe and well tolerated. PMID:15841194

  8. Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation.

    PubMed

    Wu, Ming-Yu; Esteban, Gerard; Brogi, Simone; Shionoya, Masahi; Wang, Li; Campiani, Giuseppe; Unzeta, Mercedes; Inokuchi, Tsutomu; Butini, Stefania; Marco-Contelles, Jose

    2016-10-01

    Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a new series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f exhibited moderate antioxidant properties as found by in vitro assessment. This compound represents a novel donepezil-hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD. PMID:26471320

  9. Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats.

    PubMed

    Sonkusare, Swapnil; Srinivasan, Krishnamoorthy; Kaul, Chamanlal; Ramarao, Poduri

    2005-05-20

    Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism in brain and synthesis of acetyl CoA. However, no reports are available regarding the cholinesterase inhibitors in this model. In aging brain, reduced energy metabolism increases glutamate release, which is blocked by L-type calcium channel blockers. These calcium channel blockers have shown beneficial effects on learning and memory in various models of cognitive impairment. The present study was designed to investigate the influence of chronic administration of donepezil (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ injected rats developed a severe deficit in learning and memory indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to control rats. Cholinesterase activity in brain was significantly increased in ICV STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity and improved performance in memory tests at both the doses. Lercanidipine (0.3 mg/kg) showed significant improvement in memory. When administered together, the effect of combination of these two drugs on memory and cholinesterase activity was higher than that obtained with either of the drugs when used alone. PMID:15848214

  10. Memory defect induced by β-amyloid plus glutamate receptor agonist is alleviated by catalpol and donepezil through different mechanisms.

    PubMed

    Xia, Zhiming; Zhang, Rui; Wu, Pingping; Xia, Zongqin; Hu, Yaer

    2012-03-01

    Our previous studies demonstrate that a non-cholinesterase inhibitor (AChEI) compound catalpol, purified from a traditional Chinese medicinal herb Rehmannia glutinosa, could improve the symptoms and pathological changes in animal and cellular models of memory related neurodegenerative diseases. In this study, we compared catalpol with the most commonly used AChEI donepezil in respect to their mechanism of action on the neurodegenerative changes in an animal model induced by beta-amyloid (Aβ) plus glutamate receptor agonist. It was found that the model mice showed significant deficit in the learning ability and memory in Y maze avoidance test, and meanwhile both donepezil and catalpol greatly improve the learning ability and memory after 2 to 3 months' administration. At the selected doses, donepezil only partially raised the declined brain muscarinic acetylcholine receptor (M receptor) density and choline acetyltransferase (ChAT) activity resulting in these levels still lower than normal control, while catalpol completely retrieved these two parameters. ELISA revealed that catalpol, instead of donepezil, possessed the capability of elevating the declined brain BDNF level of the animal model. The ELISA results on the BDNF protein level was confirmed by quantitative RT-PCR measurement of BDNF mRNA in Aβ₂₅₋₃₅-treated primary culture of forebrain neurons. In combination with our previous work, we think the neuroprotective effects of donepezil and catalpol are mediated through different mechanisms. Since BDNF has been proved to be an important intrinsic factor in protecting neurodegenerative diseases, catalpol may be a hopefully effective compound against neurodegenerative changes induced by Aβ and glutamate receptor agonist. PMID:22305339

  11. Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses

    PubMed Central

    Okereke, Chukwuemeka S; Kirby, Louis; Kumar, Dinesh; Cullen, Edward I; Pratt, Raymond D; Hahne, William A

    2004-01-01

    Aim The use of acetylcholinesterase inhibitors for the treatment of comorbid Alzheimer's disease in Parkinson's disease (PD) patients stabilized on a levodopa regimen may potentially disrupt cholinergic balance. This randomized, double-blind, crossover study investigated the safety of, and possible drug–drug interaction between, donepezil HCl and levodopa/carbidopa. Methods Twenty-five patients with PD who were taking physician-optimized doses of levodopa/carbidopa (with daytime dosing intervals of 4–8 h) were administered once-daily doses of either donepezil HCl (5 mg) or placebo for 15 days, in two treatment periods, separated by a washout of at least 2 weeks. Some patients took a second dose of levodopa/carbidopa after 4 h, therefore subanalysis of the levodopa/carbidopa data was conducted up to 4 h and 8 h after dosing. Twenty-six healthy matched controls received open-label donepezil HCl only, for a single 15-day period. Blood samples were collected before, during and after the 15 doses of donepezil HCl for pharmacokinetic (PK) assessments. Pharmacokinetic parameters included maximum attained plasma drug concentration (Cmax), time at which Cmax is attained (tmax), plasma drug concentration at steady state (Css), and area under the drug concentration–time curve over the dosing interval. Safety assessments included monitoring adverse events, and the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. Results The mean age of all subjects was 72.6 ± 1.3 years. Donepezil PK assessments of PD patients receiving levodopa/carbidopa were similar to the PK results from healthy controls who received donepezil HCl only (mean AUC0–12 h = 281.6 ± 17.6 and 268.6 ± 19.9 ng·h ml−1, respectively). Carbidopa PK were not significantly altered by the concomitant administration of multiple doses of donepezil HCl, compared with when PD patients received placebo (mean AUC0–8 h = 921.8 ± 160 and 821.8 ± 113 ng·h ml−1, respectively). Four hours

  12. Acetylcholinesterase inhibitors for the treatment of Wernicke-Korsakoff syndrome--three further cases show response to donepezil.

    PubMed

    Cochrane, Murray; Cochrane, Ashley; Jauhar, Pramod; Ashton, Elizabeth

    2005-01-01

    Three patients diagnosed with Wernicke-Korsakoff syndrome were treated with the acetylcholinesterase inhibitor, donepezil, for periods of 6 to 8 months. Cognitive testing [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), Mini-mental state examination (MMSE), Clock drawing test and six item 2 min recall] and carer questionnaires [Informant Questionnaire (IQ Code), Neuropsychiatric inventory scale (NPI)] were performed at baseline, mid- and endpoint of the treatment period and post-discontinuation. Progressive partial improvement occurred in cognitive measurements through the treatment period, some of which was sustained after discontinuing donepezil. Carer questionnaires also indicated improvement. Confounding factors necessitate caution when attributing improvements to the medication, but these cases suggest that this option merits further investigation. PMID:15596427

  13. Safety and Efficacy of Rivastigmine in Patients With Alzheimer's Disease Not Responding Adequately to Donepezil: An Open-Label Study

    PubMed Central

    Figiel, Gary S.; Sadowsky, Carl H.; Strigas, John; Koumaras, Barbara; Meng, Xiangyi; Gunay, Ibrahim

    2008-01-01

    Objective: Switching patients with Alzheimer's disease from one cholinesterase inhibitor to another represents a viable option for patients not responding to current therapy. The objective of this large U.S.-based study was to evaluate the safety and efficacy of a treatment switch to rivastigmine in patients not responding adequately to or declining on treatment with donepezil. Method: In this 26-week, prospective, open-label, single-arm, multicenter study conducted from April 24, 2003, to June 25, 2004, patients with mild-to-moderate Alzheimer's disease (DSM-IV-TR criteria) who were not responding to donepezil were treated with rivastigmine 3–12 mg/day. Safety and tolerability were measured by the occurrence of adverse events and patient disposition. Treatment effects on global functioning were assessed using the Clinical Global Impression of Change (CGIC) scale. Results: Two hundred seventy patients with a mean age of 78.5 (SD = 7.56) years and a mean duration of dementia of 3.5 (SD = 2.06) years were included in the study. Sixty-nine percent of patients completed the study with 17.8% discontinuing due to adverse events. Eighty-three percent of patients reported at least 1 adverse event, with the most frequently occurring adverse events affecting the gastrointestinal system (54%). The majority of patients were reported to have either improvement or no decline on the CGIC. A limitation of the study is that the interpretation of the results is based on an overall completion rate of 69%. Conclusion: Immediately switching patients from donepezil to rivastigmine without a washout period was safe and well tolerated in the current study. Additionally, these results suggest that patients not responding adequately to or declining while taking donepezil may improve or stabilize after switching to rivastigmine. PMID:18787673

  14. Cognitive Results of CANTAB Tests and Their Change Due to the First Dose of Donepezil May Predict Treatment Efficacy in Alzheimer Disease

    PubMed Central

    Kuzmickienė, Jurgita; Kaubrys, Gintaras

    2015-01-01

    Background Ability to predict the efficacy of treatment in Alzheimer disease (AD) may be very useful in clinical practice. Cognitive predictors should be investigated alongside with the demographic, genetic, and other predictors of treatment efficacy. The aim of this study was to establish whether the baseline measures of CANTAB tests and their changes due to the first donepezil dose are able to predict the efficacy of treatment after 4 months of therapy. We also compared the predictive value of cognitive, clinical, and demographic predictors of treatment efficacy in AD. Material/Methods Seventy-two AD patients (62 treatment-naïve and 10 donepezil-treated) and 30 controls were enrolled in this prospective, randomized, rater-blinded, follow-up study. Treatment-naïve AD patients were randomized to 2 groups to take the first donepezil dose after the first or second CANTAB testing, separated by 4 hours. Follow-up Test 3 was performed 4 months after the initial assessment. Results The groups were similar in age, education, gender, Hachinski index, and depression. General Regression Models (GRM) have shown that cognitive changes after the first dose of donepezil in PAL (t-values for regression coefficients from 3.43 to 6.44), PRMd (t=4.33), SWM (t=5.85) test scores, and baseline results of PAL (t=2.57–2.86), PRM (t=3.08), and CRT (t=3.42) tests were significant predictors of long-term donepezil efficacy in AD (p<0.05). Conclusions The cognitive changes produced by the first donepezil dose in CANTAB PAL, PRM, and SWM test measures are able to predict the long-term efficacy of donepezil in AD. Baseline PAL, PRM, and CRT test results were significant predictors. PMID:26656642

  15. Effects of memantine and donepezil on amyloid beta-induced memory impairment in a delayed-matching to position task in rats.

    PubMed

    Yamada, Kiyofumi; Takayanagi, Masanori; Kamei, Hiroyuki; Nagai, Taku; Dohniwa, Misato; Kobayashi, Kana; Yoshida, Shigeru; Ohhara, Tatsuo; Takuma, Kazuhiro; Nabeshima, Toshitaka

    2005-07-30

    We investigated the effects of memantine and donepezil on amyloid beta (Abeta)-induced memory impairment in rats, which was assessed by a delayed-matching to position (DMPT) paradigm in three-lever operant chambers. Aggregated Abeta1-40 was microinjected bilaterally (1 nmol/side) into both CA1 and CA3 subfields of the hippocampus in rats that had previously performed the DMTP task. Memantine (20 mg/(kg day), s.c.) was continuously infused by an osmotic minipump for 4 weeks from 3 days before the microinjection of Abeta. Donepezil (2.5 mg/kg, p.o.) was administered 60 min before the DMTP test session. Bilateral microinjections of Abeta1-40 into the hippocampus resulted in a delayed, but persistent impairment of DMTP performance, which appeared more than 50 days after the injection. Memantine prevented the development of Abeta-induced memory impairment, while donepezil symptomatically alleviated the deficits. Because of a ceiling effect, the combination of donepezil with memantine failed to produce any additive or synergic effects. These results support the clinical data showing that memantine and donepezil are effective for the treatment of Alzheimer's disease. Moreover, it is suggested that memantine is effective for preventing Abeta-induced short-term memory impairment. PMID:15904984

  16. Effects of donepezil and serotonin reuptake inhibitor on acute regression during adolescence in Down syndrome.

    PubMed

    Tamasaki, Akiko; Saito, Yoshiaki; Ueda, Riyo; Ohno, Koyo; Yokoyama, Katsutoshi; Satake, Takahiro; Sakuma, Hiroshi; Takahashi, Yukitoshi; Kondoh, Tatsuro; Maegaki, Yoshihiro

    2016-01-01

    A 14-year-old boy with Down syndrome (DS) showed a gradual decline in his daily activities and feeding capacities, and a marked deterioration triggered by a streptococcal infection was observed at the age of 15 years. He became bedridden, accompanied by sleep disturbance, sustained upward gaze, and generalized rigidity. Magnetic resonance imaging showed unremarkable findings, but antiglutamate receptor autoantibodies were positive in his cerebrospinal fluid. Treatment with thiamine infusion and steroid pulse therapy showed little effect, but gross motor dysfunction and appetite loss were ameliorated by the administration of l-DOPA and serotonin reuptake inhibitors. Thereafter, autistic behaviors predominated, including loss of social interaction, oral tendency, water phobia, and aggressiveness. Initiation of donepezil, an acetylcholinesterase inhibitor, resulted in the disappearance of these symptoms and total recovery of the patient to his previous psychosocial levels. We hypothesize that the acute regression in adolescence represents a process closely related to the defects of serotonergic and cholinergic systems that are innate to DS brains and not just a nonspecific comorbidity of depression or limbic encephalitis. PMID:26143664

  17. Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina.

    PubMed

    Bezerra da Silva, Cristiane; Pott, Arnildo; Elifio-Esposito, Selene; Dalarmi, Luciane; Fialho do Nascimento, Kátia; Moura Burci, Ligia; de Oliveira, Maislian; de Fátima Gaspari Dias, Josiane; Warumby Zanin, Sandra Maria; Gomes Miguel, Obdulio; Dallarmi Miguel, Marilis

    2016-01-01

    Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity of the enzyme acetylcholinesterase. Trials were performed with four drugs commercialized in Brazil: donepezil, tacrine, galantamine and rivastigmine, utilized in the control of Alzheimer's disease, to inhibit the activity of acetylcholinesterase. We tested five concentrations of the drugs, with an exposure of 24 h, and the mortality and the inhibition of acetylcholinesterase planarian seizure-like activity (pSLA) and planarian locomotor velocity (pLMV) were measured. Galantamine showed high anticholinesterasic activity when compared to the other drugs, with a reduction of 0.05 μmol·min(-1) and 63% of convulsant activity, presenting screw-like movement and hypokinesia, with pLMV of 65 crossed lines during 5 min. Our results showed for the first time the anticholinesterasic and convulsant effect, in addition to the decrease in locomotion induced by those drugs in a model of invertebrates. The experimental model proposed is simple and low cost and could be utilized in the screening of substances with anticholinesterasic action. PMID:26760993

  18. Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil.

    PubMed

    Al Asmari, Abdulrahman K; Ullah, Zabih; Tariq, Mohammad; Fatani, Amal

    2016-01-01

    The adequate amount of drug delivery to the brain in neurological patients is a major problem faced by the physicians. Recent studies suggested that intranasal administration of liposomal formulation may improve the drug delivery to the brain. In the present study, an attempt was made to study the brain bioavailability of commonly used anti-Alzheimer drug donepezil (DNP) liposomal formulation by intranasal route in rats. We adopted the thin layer hydration technique for the preparation of liposomes by using cholesterol, polyethylene glycol, and 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC). The prepared liposomes were characterized by determining particle size, shape, surface morphology, zeta potential, encapsulation efficiency, and in vitro release of DNP. The pharmacokinetic parameters of liposomal DNP in plasma and brain of rats were determined following oral and nasal administration. The results of this study showed that the DNP liposomal formulation was stable with a consistent size (102 ± 3.3 nm) and shape. The prepared liposomes showed high encapsulation efficiency (84.91% ±3 .31%) and sustained-release behavior. The bioavailability of DNP in plasma and brain increased significantly (P<0.05) after administration of liposomal formulation by the intranasal route. Histopathological examination showed that the formulation was safe and free from toxicity. It can be concluded that the nasal administration of liposomal preparation may provide an efficient and reliable mode of drug delivery to the central nervous system. PMID:26834457

  19. Long-term safety and tolerability of donepezil 23 mg in patients with moderate to severe Alzheimer’s disease

    PubMed Central

    2012-01-01

    Background Donepezil (23 mg/day) is approved by the US Food and Drug Administration for the treatment of patients with moderate to severe Alzheimer’s disease (AD). Approval was based on results from a 24-week, randomized, double-blind study of patients who were stable on donepezil 10 mg/day and randomized 2:1 to either increase their donepezil dose to 23 mg/day or continue taking 10 mg/day. The objective of this study was to assess the long-term safety and tolerability of donepezil 23 mg/day in patients with moderate to severe AD. Methods Patients who completed the double-blind study and were eligible could enroll into a 12-month extension study of open-label donepezil 23 mg/day. Clinic visits took place at open-label baseline and at months 3, 6, 9, and 12. Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs); changes in weight, electrocardiogram, vital signs, and laboratory parameters; and discontinuation due to AEs. Results 915 double-blind study completers were enrolled in the open-label extension study and 902 comprised the safety population. Mean treatment duration in this study was 10.3 ± 3.5 months. In total, 674 patients (74.7%) reported at least one AE; in 320 of these patients (47.5%) at least one AE was considered to be possibly or probably study drug related. The majority of patients reporting AEs (81.9%) had AEs of mild or moderate severity. There were 268 patients (29.7%) who discontinued early, of which 123 (13.6%) were due to AEs. Patients increasing donepezil dose from 10 mg/day in the double-blind study to 23 mg/day in the extension study had slightly higher rates of AEs and SAEs than patients who were already receiving 23 mg (78.0% and 16.9% vs 72.8% and 14.0%, respectively). The incidence of new AEs declined rapidly after the first 2 weeks and remained low throughout the duration of the study. Conclusion This study shows that long-term treatment with

  20. Effects of donepezil on brain morphometric and metabolic changes in patients with Alzheimer's disease: A DARTEL-based VBM and (1)H-MRS.

    PubMed

    Moon, Chung-Man; Kim, Byeong-Chae; Jeong, Gwang-Woo

    2016-09-01

    A few studies have performed on the brain morphometric changes over the whole brain structure following donepezil treatment in patients with Alzheimer's disease (AD). We evaluated the gray matter (GM) and white matter (WM) volume alterations and cellular metabolic changes in patients with AD before and after donepezil treatment, and further to reveal the correlations of the scores of various neuropsychological scales with the volumetric and metabolic changes. Twenty-one subjects comprising of 11 patients with AD and 10 age-matched healthy controls participated in this study. All of the patients participated in the follow-up study 24weeks following donepezil treatment. In this study, a combination of voxel-based morphometry (VBM) and proton magnetic resonance spectroscopy ((1)H-MRS) was used to assess the brain morphometric and metabolic alterations in AD. In the GM volumetric analysis, both of the untreated and treated patients with donepezil showed significantly reduced volumes in the hippocampus (Hip), parahippocampal gyrus (PHG), precuneus (PCu) and middle frontal gyrus compared with healthy controls. However, donepezil-treated patients showed significantly increased volumes in the Hip, PCu, fusiform gyrus and caudate nucleus compared to untreated patients. In the WM volumetric analysis, untreated and treated patients showed significant volume reductions in the posterior limb of internal capsule (PLIC), cerebral peduncle of the midbrain and PHG compared to healthy controls. However, there was no significant WM morphological change after donepezil treatment in patients with AD. In MRS study, untreated patients with AD showed decreased N-acetylaspartate/creatine (NAA/Cr) and increased myo-inositol (mI)/Cr compared to healthy controls, while treated patients showed only decreased NAA/Cr in the same comparison. However, the treated patients showed simultaneously increased NAA/Cr and decreased mI/Cr and choline (Cho)/Cr ratios compared to untreated patients. This

  1. Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

    PubMed

    Aracava, Yasco; Pereira, Edna F R; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X

    2009-12-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. PMID:19741148

  2. Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.

    PubMed

    Kim, Ji-Woon; Seung, Hana; Kwon, Kyung Ja; Ko, Mee Jung; Lee, Eun Joo; Oh, Hyun Ah; Choi, Chang Soon; Kim, Ki Chan; Gonzales, Edson Luck; You, Jueng Soo; Choi, Dong-Hee; Lee, Jongmin; Han, Seol-Heui; Yang, Sung Min; Cheong, Jae Hoon; Shin, Chan Young; Bahn, Geon Ho

    2014-01-01

    Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance. PMID:25133713

  3. Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine.

    PubMed

    Nagakura, Akira; Shitaka, Yoshitsugu; Yarimizu, Junko; Matsuoka, Nobuya

    2013-03-01

    Alzheimer's disease is characterized by a progressive decline in cognitive function and involves β-amyloid (Aβ) in its pathogenesis. To characterize cognitive deficits associated with Aβ accumulation, we analyzed PS1/APP mice overexpressing mutant presenilin-1 (PS1, M146L; line 6.2) and amyloid precursor protein (APP, K670N/M671L; line Tg2576), a mouse model of Alzheimer's disease with accelerated Aβ production. Age-dependent changes in working and spatial memory behaviors were investigated using Y-maze and Morris water maze tasks, respectively, in female PS1/APP mice at ages of 2, 4, 6, and 12 months. Significant deficits in working and spatial memory were observed from 4 and 6 months of age, respectively. Acute single-dose administrations of memantine, a low-to-moderate-affinity N-methyl-d-aspartate (NMDA) antagonist, showed improvements in working memory deficits at 4 months of age, whereas donepezil, an acetylcholinesterase (AChE) inhibitor, did not. However, both drugs improved spatial memory dysfunction at 6 months of age at therapeutically relevant doses. No age-related dramatic changes were observed in expression levels of several proteins relating to memory dysfunction and also the mechanisms of donepezil and memantine in the cerebral cortex of PS1/APP mice until 6 months of age. Taken together, these results suggest dysfunctions in cholinergic and/or glutamatergic transmissions may be involved in the cognitive deficits associated with Aβ toxicity. Since donepezil and memantine have been widely used for treating patients of Alzheimer's disease, these results also suggest that cognitive deficits in PS1/APP mice assessed in the Y-maze and Morris water maze tasks are a useful animal model for evaluating novel Alzheimer's disease therapeutics. PMID:23276665

  4. Combined administration of cerebrolysin and donepezil induces plastic changes in prefrontal cortex in aged mice.

    PubMed

    Alcántara-González, Faviola; Mendoza-Perez, Claudia Rebeca; Zaragoza, Néstor; Juarez, Ismael; Arroyo-García, Luis Enrique; Gamboa, Citlalli; De La Cruz, Fidel; Zamudio, Sergio; Garcia-Dolores, Fernando; Flores, Gonzalo

    2012-11-01

    Cerebrolysin (Cbl) shows neurotrophic and neuroprotective properties while donepezil (Dnp) is a potent acetylcholinesterase (AChE) inhibitor, both drugs are prescribed for Alzheimer's disease (AD) treatment. Previous studies have shown that the Dnp and Cbl administered separately, modify dendritic morphology of neurons in the prefrontal cortex and hippocampus in senile rodents. Since the deficit of neurotrophic factor activity is implicated in the degeneration of cholinergic neurons of basal forebrain, a combination therapy of Dnp and Cbl has been tested recently in Alzheimer's patients. However, the plastic changes that may underlie this combined treatment have not yet been explored. We present here the effect of the combined administration of Cbl and Dnp on dendritic morphology in brain regions related to learning and memory in aged mice. The Golgi-Cox staining protocol and Sholl analysis were used for studying dendritic changes. Cbl and Dnp were administrated daily for 2 months to 9-months-old mice. Locomotor activity was assessed, as well as the dendritic morphology of neurons in several limbic regions was analyzed. Results showed that Cbl and Dnp induced an increase in locomotor activity without synergistic effect. The Cbl or Dnp treatment modified the dendritic morphology of neurons from prefrontal cortex (PFC), dorsal hippocampus (DH), dentate gyrus (DG), and the shell of nucleus accumbens (NAcc). These changes show an increase in the total dendritic length and spine density, resulting in an improvement of dendritic arborization. Prominently, a synergistic effect of Cbl and Dnp was observed on branching order and total dendritic length of pyramidal neurons from PFC. These results suggest that Dnp and Cbl may induce plastic changes in a manner independent of each other, but could enhance their effect in target cells from PFC. PMID:22826038

  5. Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer's disease.

    PubMed

    Kim, Ji-Yeon; Han, Mee-Ree; Kim, Yong-Han; Shin, Seung-Woo; Nam, Su-Youn; Park, Jung-Hwan

    2016-08-01

    Donepezil hydrochloride (DPH) is often used in the treatment of Alzheimer's disease. A new treatment method was developed by encapsulating high DPH content in the tips of dissolving microneedles for rapid, transdermal delivery of a predetermined dose of DPH. The microneedles were prepared by a micromolding method using a hydroxy-propyl-methyl-cellulose (HPMC)-ethanol/water mixture (80:20, v/v) for the tips and carboxy-methyl cellulose (CMC)-water for the base of the needles. The micromolding method involved centrifuging a DPH-HPMC-ethanol/water mixture at 10°C to obtain tips with sufficient mechanical strength. To test their mechanical strength, microneedles with different DPH content were inserted into porcine skin. Then the amount of DPH encapsulated in the microneedles was measured using high-performance liquid chromatography. The efficiency of administering DPH tip-loaded microneedles was investigated using four administrations of a pharmacokinetic test: (1) two oral administration groups (283μg/kg and 692μg/kg) and (2) two microneedle administration groups (283μg/kg and 692μg/kg). High DPH content (up to 78%, w/w) was encapsulated in the microneedle tips without serious loss of mechanical strength by using a mixture of hydroxy-propyl-methyl-cellulose (HPMC) and ethanol/water mixture (80:20, v/v). Because of the distribution of DPH in the tips, 95% of the DPH was delivered into porcine skin after 5min of insertion. As measured by Cmax and AUC, transdermal delivery of DPH tip-loaded microneedles was more effective compared to oral administration of the same dose of DPH. Transdermal delivery could replace oral administration of DPH. PMID:27288938

  6. Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases

    PubMed Central

    Alvarez, Irene; Iglesias, Olalla; Crespo, Ignacio; Figueroa, Jesus; Aleixandre, Manuel; Linares, Carlos; Granizo, Elias; Garcia-Fantini, Manuel; Marey, Jose; Masliah, Eliezer; Winter, Stefan; Muresanu, Dafin; Moessler, Herbert

    2016-01-01

    Background: Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer’s disease. Methods: We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer’s disease patients. Results: Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy. Conclusion: Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer’s disease cases with apolipoprotein E epsilon-4 allele. PMID:27207906

  7. Drug induced parkinsonism caused by the concurrent use of donepezil and risperidone in a patient with traumatic brain injuries.

    PubMed

    Kang, Si Hyun; Kim, Don-Kyu

    2013-02-01

    A 69-year-old male patient with previous history of traumatic brain injury 5 months ago was admitted to the Department of Neuropsychiatry because of aggressive behavior and delusional features. After starting on 2 mg of risperidone per day, his delusion, anxiety, and aggressive behavior gradually improved. Two weeks later, he was given 10 mg of donepezil per day for his mild cognitive impairment. After 6 weeks of admission in the Department of Neuropsychiatry, he showed parkinsonian features including difficulty in walking, decreased arm swing during walking, narrowed step width, scooped posture, bradykinesia, tremor, and sleep disorder. To rule out the primary Parkinsonism, dopamine transporter imaging technique [18F]fluoropropyl-carbomethoxy-iodopropyl-nor-β-tropane positron emission tomography-computed tomography (18F]FP(IT PET-CT)) was performed, and dopamine transporter activity was not decreased. We considered that his parkinsonian features were associated with the combination of risperidone and donepezil. Both drugs were stopped and symptoms rapidly disappeared in several days. PMID:23526695

  8. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients.

    PubMed

    Talib, L L; Hototian, S R; Joaquim, H P G; Forlenza, O V; Gattaz, W F

    2015-12-01

    Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein. PMID:25920742

  9. Donepezil Treatment Restores the Ability of Estradiol to Enhance Cognitive Performance in Aged Rats: Evidence for the Cholinergic Basis of the Critical Period Hypothesis

    PubMed Central

    Gibbs, R.B.; Mauk, R.; Nelson, D.; Johnson, D.A.

    2009-01-01

    Recent studies suggest that the ability of estradiol to enhance cognitive performance diminishes with age and/or time following loss of ovarian function. We hypothesize that this is due, in part, to a decrease in basal forebrain cholinergic function. This study tested whether donepezil, a cholinesterase inhibitor, could restore estradiol effects on cognitive performance in aged rats that had been ovariectomized as young adults. Rats were ovariectomized at 3 months of age, and then trained on a delayed matching to position (DMP) T-maze task, followed by a configural association (CA) operant condition task, beginning at 12–17 or 22–27 months of age. Three weeks prior to testing, rats started to receive either donepezil or vehicle. After one week, half of each group also began receiving estradiol. Acclimation and testing began seven days later and treatment continued throughout testing. Estradiol alone significantly enhanced DMP acquisition in middle-aged rats, but not in aged rats. Donepezil alone had no effect on DMP acquisition in either age group; however, donepezil treatment restored the ability of estradiol to enhance DMP acquisition in aged rats. This effect was due largely to a reduction in the predisposition to adopt a persistent turn strategy during acquisition. These same treatments did not affect acquisition of the CA task in middle-aged rats, but did have small but significant effects on response time in aged rats. The data are consistent with the idea that estrogen effects on cognitive performance are task specific, and that deficits in basal forebrain cholinergic function are responsible for the loss of estradiol effect on DMP acquisition in aged ovariectomized rats. In addition, the data suggest that enhancing cholinergic function pharmacologically can restore the ability of estradiol to enhance acquisition of the DMP task in very old rats following long periods of hormone deprivation. Whether donepezil has similar restorative effects on other

  10. Role of Donepezil in the Management of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia with Lewy Bodies.

    PubMed

    Cummings, Jeffrey; Lai, Te-Jen; Hemrungrojn, Solaphat; Mohandas, E; Yun Kim, Sang; Nair, Girish; Dash, Amitabh

    2016-03-01

    Alzheimer's disease (AD) is a progressive condition that affects cognition, function, and behavior. Approximately 60-90% of patients with AD develop neuropsychiatric symptoms (NPS) such as hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep disturbances, appetite and eating changes, or altered sexual behavior. These noncognitive behavior changes are thought to result from anatomical and biochemical changes within the brain, and have been linked, in part, to cholinergic deficiency. Cholinesterase inhibitors may reduce the emergence of NPS and have a role in their treatment. These agents may delay initiation of, or reduce the need for, other drugs such as antipsychotics. This article summarizes the effects of donepezil, a cholinesterase inhibitor, on the NPS of dementia with emphasis on AD and dementia with Lewy bodies. PMID:26778658

  11. Efficacy of Galantamine on Cognition in Mild-to-Moderate Alzheimer's Dementia after Failure to Respond to Donepezil

    PubMed Central

    Hwang, Tae-Young; Ahn, Inn-Sook; Kim, Seonwoo

    2016-01-01

    Objective This study compares the efficacy of the cholinesterase inhibitor (ChEI) galantamine on cognition in patients with mild-to-moderate Alzheimer's dementia (AD) who were either naïve to ChEI drugs or who had failed a trial of the ChEI donepezil. Methods Outpatients with AD were sequentially referred for screening and enrollment. Current outpatients who had taken donepezil for at least 6 months without demonstrated efficacy on cognition were switched to galantamine (switched group). New outpatients with no ChEI prescription history were classified as the naïve group and were given galantamine. The primary outcome measures for the between-group comparison were response rate on cognition at 26 and 52 weeks (categorical) and change on the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (dimensional). Secondary cognitive outcomes were measured using the subset of frontal executive function and the Korean Mini-Mental State Examination. Results Seventy outpatients were enrolled and 66 were analyzed by Intent-to-treat (ITT). There were 42 cases in the naïve group and 24 in the switched group. Response rates did not differ at 26 weeks (71.4% naïve vs. 58.3% switched; p=0.277) or at 52 weeks (59.5% naïve vs. 41.6% switched; p=0.162). No significant differences were observed in the pattern of change over the 52 weeks on the primary and secondary cognitive scales. Conclusion As the efficacy of galantamine on cognition was not inferior in the switched group compared to that in the naïve group, switching ChEI drugs is clinically feasible for non-responding patients with mild-to-moderate AD. PMID:27247602

  12. The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer’s Disease

    PubMed Central

    Lee, Kang Uk; Lee, Jung Hie; Lee, Dong Young; Youn, Jong Chul; Kim, Jeong Lan; Moon, Seok Woo; Kim, Bong-Jo; Ryu, Seung-Ho; Kim, Moon Doo; Lee, Chang-Uk; Lee, Nam-Jin; Chang, Sung Man; Kim, Young Hoon; Kim, Do Hoon; Lee, Hae-Kook; Woo, Jong Inn; Kim, Ki Woong; Jhoo, Jin Hyeong

    2015-01-01

    Objective We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans. Methods Patients who met the criteria for probable Alzheimer’s disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student’s t-test. Results At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively). Conclusion Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans. PMID:26243844

  13. Selective Ability of Some CANTAB Battery Test Measures to Detect Cognitive Response to a Single Dose of Donepezil in Alzheimer Disease

    PubMed Central

    Kuzmickienė, Jurgita; Kaubrys, Gintaras

    2015-01-01

    Background The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to explore which tests and their measures are able to detect cognitive change after a single dose of donepezil in Alzheimer disease (AD) patients. The aim of this study was to establish the ability of CANTAB tests and their measures to detect cognitive change after a single 5-mg dose of donepezil in treatment-naïve AD patients. Material/Methods We enrolled 62 treatment-naïve AD patients and 30 healthy controls in this prospective, randomized, rater-blinded study. AD patients were randomized to 2 groups: the AD+ group received donepezil after the first CANTAB testing and the AD− group remained treatment-naïve at second testing. The time period between repeated testing was 4 hours. Parallel versions of CRT, SOC, PAL, SWM, and PRM tests were used. Results All groups did not differ according to age, education, gender, or depression (p>0.05). AD+ and AD− groups did not differ according to MMSE. SOC, PAL, PRM, and SWM tests distinguished AD from controls. Eight measures of PAL and PRM had a strong correlation with MMSE (r>0.7). Repeated-measures ANOVA with Bonferroni post-hoc test showed the difference of change in AD+ and AD− groups between first and second CANTAB testing in 7 PAL measures. AD+ and AD− groups differed in the second testing by 7 PAL measures. Four PAL measures differed in first and second testing within the AD+ group. Conclusions The CANTAB PAL test measures, able to detect cognitive change after a single dose of donepezil in AD patients, are: PAL mean trials to success, total errors (adjusted), total errors (6 shapes, adjusted), and total trials (adjusted). PMID:26336931

  14. A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy

    PubMed Central

    Griffin, L.; Balcueva, E. P.; Groteluschen, D. L.; Samuel, T. A.; Lesser, G. J.; Naughton, M. J.; Case, L. D.; Shaw, E. G.; Rapp, S. R.

    2016-01-01

    Purpose Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Methods Women who received adjuvant chemotherapy 1–5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Results Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory—the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p=0.033) and HVLT-R Discrimination (p=0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Conclusion Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Implications for Cancer Survivors Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results. PMID:26130292

  15. A Randomized, Crossover, Single-Dose Bioequivalence Study of Two Extended-Release Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed States

    PubMed Central

    Gadiko, Chaitanya; Tippabhotla, Sudhakar Koundinya; Thota, Satyanarayana; Battula, Ramakrishna; Khan, Sohel Md.; Vobalaboina, Venkateswarlu

    2013-01-01

    To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period crossover studies under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers were conducted. Subjects were randomized to either of the two treatment arms (test or reference) separated by a washout period of 28 days. Blood samples were collected up to 72 h post-dose and plasma samples were analyzed for donepezil using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using a non-compartmental approach. Bioequivalence was evaluated in 69 subjects in the fasting study, and 71 subjects in the fed study. In the fasting study, the 90% CI of Cmax and AUC0-72 were 82.50–90.10 and 92.38–98.60, respectively. Corresponding values in the fed study were 91.82–98.05 and 97.27–100.27. Based on the results, the test product (donepezil) met the US regulatory criteria of bioequivalence relative to the reference product (Aricept®) under both fasting and fed conditions. PMID:24106673

  16. Synthesis and evaluation of multi-target-directed ligands against Alzheimer's disease based on the fusion of donepezil and ebselen.

    PubMed

    Luo, Zonghua; Sheng, Jianfei; Sun, Yang; Lu, Chuanjun; Yan, Jun; Liu, Anqiu; Luo, Hai-Bin; Huang, Ling; Li, Xingshu

    2013-11-27

    A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 μM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν0 = 123.5 μM min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system. PMID:24160297

  17. Ventricular enlargement and its clinical correlates in the imaging cohort from the ADCS MCI donepezil/vitamin E study.

    PubMed

    Apostolova, Liana G; Babakchanian, Sona; Hwang, Kristy S; Green, Amity E; Zlatev, Dimitar; Chou, Yi-Yu; DeCarli, Charlie; Jack, Clifford R; Petersen, Ronald C; Aisen, Paul S; Cummings, Jeffrey L; Toga, Arthur W; Thompson, Paul M

    2013-01-01

    We analyzed the baseline and 3-year T1-weighted magnetic resonance imaging data of 110 amnestic mild cognitive impairment (MCI) participants with minimal hippocampal atrophy at baseline from the Alzheimer's Disease Cooperative Study group MCI Donepezil/Vitamin E trial. Forty-six subjects converted to Alzheimer disease (AD) (MCIc), whereas 64 remained stable (MCInc). We used the radial distance technique to examine the differences in lateral ventricle shape and size between MCIc and MCInc and the associations between ventricular enlargement and cognitive decline. MCIc group had significantly larger frontal and right body/occipital horns relative to MCInc at baseline and significantly larger bilateral frontal, body/occipital, and left temporal horns at follow-up. Global cognitive decline measured with AD Assessment scale cognitive subscale and Mini-Mental State Examination and decline in activities of daily living (ADL) were associated with posterior lateral ventricle enlargement. Decline in AD Assessment scale cognitive subscale and ADL were associated with left temporal and decline in Mini-Mental State Examination with right temporal horn enlargement. After correction for baseline hippocampal volume, decline in ADL showed a significant association with right frontal horn enlargement. Executive decline was associated with right frontal and left temporal horn enlargement. PMID:23694947

  18. Donepezil, an acetylcholine esterase inhibitor, and ABT-239, a histamine H3 receptor antagonist/inverse agonist, require the integrity of brain histamine system to exert biochemical and procognitive effects in the mouse.

    PubMed

    Provensi, Gustavo; Costa, Alessia; Passani, M Beatrice; Blandina, Patrizio

    2016-10-01

    Histaminergic H3 receptors (H3R) antagonists enhance cognition in preclinical models and modulate neurotransmission, in particular acetylcholine (ACh) release in the cortex and hippocampus, two brain areas involved in memory processing. The cognitive deficits seen in aging and Alzheimer's disease have been associated with brain cholinergic deficits. Donepezil is one of the acetylcholinesterase (AChE) inhibitor approved for use across the full spectrum of these cognitive disorders. We addressed the question if H3R antagonists and donepezil require an intact histamine neuronal system to exert their procognitive effects. The effect of the H3R antagonist ABT-239 and donepezil were evaluated in the object recognition test (ORT), and on the level of glycogen synthase kinase 3 beta (GSK-3β) phosphorylation in normal and histamine-depleted mice. Systemic administration of ABT-239 or donepezil ameliorated the cognitive performance in the ORT. However, these compounds were ineffective in either genetically (histidine decarboxylase knock-out, HDC-KO) or pharmacologically, by means of intracerebroventricular (i.c.v.) injections of the HDC irreversible inhibitor a-fluoromethylhistidine (a-FMHis), histamine-deficient mice. Western blot analysis revealed that ABT-239 or donepezil systemic treatments increased GSK-3β phosphorylation in cortical and hippocampal homogenates of normal, but not of histamine-depleted mice. Furthermore, administration of the PI3K inhibitor LY294002 that blocks GSK-3β phosphorylation, prevented the procognitive effects of both drugs in normal mice. Our results indicate that both donepezil and ABT-239 require the integrity of the brain histaminergic system to exert their procognitive effects and strongly suggest that impairments of PI3K/AKT/GSK-3β intracellular pathway activation is responsible for the inefficacy of both drugs in histamine-deficient animals. PMID:27291828

  19. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  20. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  1. Effectiveness of Donepezil, Rivastigmine, and (±)Huperzine A in Counteracting the Acute Toxicity of Organophosphorus Nerve Agents: Comparison with Galantamine

    PubMed Central

    Aracava, Yasco; Pereira, Edna F. R.; Akkerman, Miriam; Adler, Michael

    2009-01-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (±)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 × LD50 soman (42 μg/kg s.c.). All animals that were pretreated with galantamine (6–8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 × LD50 soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 × LD50 soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 × LD50 soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. PMID:19741148

  2. Effect and mechanism of fuzhisan and donepezil on the sirtuin 1 pathway and amyloid precursor protein metabolism in PC12 cells.

    PubMed

    Guo, Peng; Wang, Desheng; Wang, Xiaomin; Feng, Honglin; Tang, Ying; Sun, Ruihong; Zheng, Yan; Dong, Lin; Zhao, Jiaying; Zhang, Xin; Wang, Shuyu; Sun, Hongxu

    2016-04-01

    The present study aimed to determine the effect and mechanism of fuzhisan (FZS) and donepezil on the SIRT1 signaling pathway and the metabolism of the amyloid precursor protein (APP) in PC12 cells. An experimental cell model of PC12 cells with Aβ25‑35‑induced neurotoxicity was established and cell proliferation was determined by the MTT assay following treatment with donepezil and FZS. In addition, cell apoptosis was determined using DAPI staining and light microscopy. Furthermore, western blot analysis and ELISA were utilized to evaluate the expression levels of associated APP, Aβ40, Aβ42, sAPPα, sAPPβ, ADAM10, sirtuin 1 (SIRT1) and forkhead box O (FoxO) protein. The results indicated that the cell model was successfully established and FZS protected the PC12 cells from the neurotoxic effects of Aβ25‑35, in a similar effect to donepezil, in a dose‑dependent manner. The expression of APP remained at the same level during the experimental period. The levels of Aβ40, Aβ42 and sAPPβ were downregulated, where as sAPPα, ADAM10, SIRT1 and FoxO expression levels were upregulated. In conclusion, FZS treatment attenuated the Aβ25‑35‑induced neurotoxicity in vitro. The neuroprotective mechanism of FZS was determined, including the induction of ADAM10 and SIRT1‑FoxO pathway, which participated in the process of neuroprotection. The present study identified the neuroprotective function of FZS, which may protect against Aβ‑induced toxicity. Therefore, FZS may be used clinically as a beneficial therapeutic drug for the development or progression of Alzheimer's disease. PMID:26936536

  3. Effectiveness and Tolerability of High-Dose (23 mg/d) Versus Standard-Dose (10 mg/d) Donepezil in Moderate to Severe Alzheimer’s Disease: A 24-Week, Randomized, Double-Blind Study

    PubMed Central

    Farlow, Martin R.; Salloway, Stephen; Tariot, Pierre N.; Yardley, Jane; Moline, Margaret L.; Wang, Qin; Brand-Schieber, Elimor; Zou, Heng; Hsu, Timothy; Satlin, Andrew

    2010-01-01

    Background Currently approved Alzheimer’s disease (AD) treatments have been reported to provide symptomatic benefit, without proven impact on clinical progression. We hypothesized that the loss of initial therapeutic benefit over time may be mitigated by higher doses of a cholinesterase inhibitor. Objective The aim of this study was to determine the effectiveness and tolerability of increasing donepezil from 10 to 23 mg/d in patients with moderate to severe AD. Methods This randomized, double-blind study was conducted at 219 sites in Asia, Europe, Australia, North America, South Africa, and South America from June 6, 2007, to March 27, 2009. Patients aged 45 to 90 years with probable AD, Mini-Mental State Examination score 0 to 20 (moderate to severe impairment), and who were receiving donepezil 10 mg once daily for ≥12 weeks before the start of the study were eligible. Patients (n = 1467) were randomly assigned to receive high-dose donepezil (23 mg once daily) or standard-dose donepezil (10 mg once daily) for 24 weeks. Coprimary effectiveness measures were changes in cognition and global functioning, as assessed using least squares mean changes from baseline (LSM [SE] Δ) scores (last observation carried forward) on the Severe Impairment Battery (SIB; cognition) and the Clinician’s Interview-Based Impression of Change Plus Caregiver Input scale (CIBIC+; global function rating) overall change score (mean [SD]) at week 24. Treatment-emergent adverse events (TEAEs) were assessed using spontaneous patient/caregiver reporting and open-ended questioning; clinical laboratory testing (hematology, biochemistry, and urinalysis panels analyzed by a central laboratory); 12-lead ECG; and physical and neurologic examinations, including vital sign measurements. Results The effectiveness analyses included 1371 patients (mean age, 73.8 years; 62.8% female; 73.5% white; weight range, 34.0–138.7 kg). A total of 296 of 981 patients (30.2%) withdrew from the donepezil 23-mg

  4. Vasectomy reversal.

    PubMed

    Belker, A M

    1987-02-01

    A vasovasostomy may be performed on an outpatient basis with local anesthesia, but also may be performed on an outpatient basis with epidural or general anesthesia. Local anesthesia is preferred by most of my patients, the majority of whom choose this technique. With proper preoperative and intraoperative sedation, patients sleep lightly through most of the procedure. Because of the length of time often required for bilateral microsurgical vasoepididymostomy, epidural or general anesthesia and overnight hospitalization are usually necessary. Factors influencing the preoperative choice for vasovasostomy or vasoepididymostomy in patients undergoing vasectomy reversal are considered. The preoperative planned choice of vasovasostomy or vasoepididymostomy for patients having vasectomy reversal described herein does not have the support of all urologists who regularly perform these procedures. My present approach has evolved as the data reported in Tables 1 and 2 have become available, but it may change as new information is evaluated. However, it offers a logical method for planning choices of anesthesia and inpatient or outpatient status for patients undergoing vasectomy reversal procedures. PMID:3811050

  5. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer's disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids.

    PubMed

    Bautista-Aguilera, Oscar M; Esteban, Gerard; Chioua, Mourad; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Soriano, Elena; Samadi, Abdelouahid; Unzeta, Mercedes; Marco-Contelles, José

    2014-01-01

    The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs) as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM) was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE) inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE). Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for hBuChE. Concerning human monoamine oxidase (hMAO) A inhibition, only DPH9 and 5 proved active, compound DPH9 being the most potent (IC50 [MAO A] =5,700±2,100 nM). For hMAO B, only DPHs 13 and 14 were moderate inhibitors, and compound DPH14 was the most potent (IC50 [MAO B] =3,950±940 nM). Molecular modeling of inhibitor DPH14 within EeAChE showed a binding mode with an extended conformation, interacting simultaneously with both catalytic and peripheral sites of EeAChE thanks to a linker of appropriate length. Absortion, distribution, metabolism, excretion and toxicity analysis showed that structures lacking phenyl-substituent show better druglikeness profiles; in particular, DPHs13-15 showed the most suitable absortion, distribution, metabolism, excretion and toxicity properties. Novel donepezil-pyridyl hybrid DPH14 is a potent, moderately selective h

  6. Use of a novel radiometric method to assess the inhibitory effect of donepezil on acetylcholinesterase activity in minimally diluted tissue samples

    PubMed Central

    Kikuchi, Tatsuya; Okamura, Toshimitsu; Arai, Takuya; Obata, Takayuki; Fukushi, Kiyoshi; Irie, Toshiaki; Shiraishi, Tetsuya

    2010-01-01

    Background and purpose: Cholinesterase inhibitors have been widely used for the treatment of patients with dementia. Monitoring of the cholinesterase activity in the blood is used as an indicator of the effect of the cholinesterase inhibitors in the brain. The selective measurement of cholinesterase with low tissue dilution is preferred for accurate monitoring; however, the methods have not been established. Here, we investigated the effect of tissue dilution on the action of cholinesterase inhibitors using a novel radiometric method with selective substrates, N-[14C]methylpiperidin-4-yl acetate ([14C]MP4A) and (R)-N-[14C]methylpiperidin-3-yl butyrate ([14C]MP3B_R), for AChE and butyrylcholinesterase (BChE) respectively. Experimental approach: We investigated the kinetics of hydrolysis of [14C]-MP4A and [14C]-MP3B_R by cholinesterases, and evaluated the selectivity of [14C]MP4A and [14C]MP3B_R for human AChE and BChE, respectively, compared with traditional substrates. Then, IC50 values of cholinesterase inhibitors in minimally diluted and highly diluted tissues were measured with [14C]MP4A and [14C]MP3B_R. Key results: AChE and BChE activities were selectively measured as the first-order hydrolysis rates of [14C]-MP4A and [14C]MP3B_R respectively. The AChE selectivity of [14C]MP4A was an order of magnitude higher than traditional substrates used for the AChE assay. The IC50 values of specific AChE and BChE inhibitors, donepezil and ethopropazine, in 1.2-fold diluted human whole blood were much higher than those in 120-fold diluted blood. In addition, the IC50 values of donepezil in monkey brain were dramatically decreased as the tissue was diluted. Conclusions and implications: This method would effectively monitor the activity of cholinesterase inhibitors used for therapeutics, pesticides and chemical warfare agents. PMID:20401964

  7. Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease.

    PubMed

    Xie, Sai-Sai; Lan, Jin-Shuai; Wang, Xiaobing; Wang, Zhi-Min; Jiang, Neng; Li, Fan; Wu, Jia-Jia; Wang, Jin; Kong, Ling-Yi

    2016-04-01

    Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87μM and 0.93μM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37μM for hAChE; 1.98μM for hBuChE; 2.62μM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. PMID:26917219

  8. Inhibitory effect of ebselen on cerebral acetylcholinesterase activity in vitro: kinetics and reversibility of inhibition.

    PubMed

    Martini, Franciele; Bruning, César Augusto; Soares, Suelen Mendonca; Nogueira, Cristina Wayne; Zeni, Gilson

    2015-01-01

    Ebselen is a synthetic organoselenium compound that has been considered a potential pharmacological agent with low toxicity, showing antioxidant, anti-inflammatory and neuroprotective effects. It is bioavailable, blood-brain barrier permeant and safe based on cellular toxicity and Phase I-III clinical trials. There is evidence that ebselen inhibits acetylcholinesterase (AChE) activity, an enzyme that plays a key role in the cholinergic system by hydrolyzing acetylcholine (ACh), in vitro and ex vivo. This system has a well-known relationship with cognitive process, and AChE inhibitors, such as donepezil and galantamine, have been used to treat cognitive deficits, mainly in the Alzheimer's Disease (AD). However, these drugs have poor bioavailability and a number of side effects, including gastrointestinal upsets and hepatotoxicity. In this way, this study aimed to evaluate the effect of ebselen on cerebral AChE activity in vitro and to determine the kinetic profile and the reversibility of inhibition by dialysis. Ebselen inhibited the cerebral AChE activity with an IC50 of 29 µM, similar to IC50 found with pure AChE from electric eel, demonstrating a mixed and reversible inhibition of AChE, since it increased Km and decreased Vmax. The AChE activity was recovered within 60 min of dialysis. Therefore, the use of ebselen as a therapeutic agent for treatment of AD should be considered, although memory behavior tasks are needed to support such hypothesis. PMID:25312723

  9. Reversible Thermoset Adhesives

    NASA Technical Reports Server (NTRS)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  10. Reverse Correlation in Neurophysiology

    ERIC Educational Resources Information Center

    Ringach, Dario; Shapley, Robert

    2004-01-01

    This article presents a review of reverse correlation in neurophysiology. We discuss the basis of reverse correlation in linear transducers and in spiking neurons. The application of reverse correlation to measure the receptive fields of visual neurons using white noise and m-sequences, and classical findings about spatial and color processing in…

  11. Impacts of thyroxine combined with donepezil on hippocampal ultrastructures and expressions of synaptotagmin-1 and SNAP-25 in adult rats with hypothyroidism

    PubMed Central

    Yang, Hao; Zha, Xiaoxue; Cai, Yaojun; Wang, Fen; Wu, Zhangbi; Wu, Bo; Jia, Xuemei; Zhu, Defa

    2015-01-01

    The study aims to observe the impacts of thyroxine (T4) combined with donepezil (DON) on hippocampal ultrastructures and expressions of synaptotagmin-1 and SNAP-25 in adult rats with hypothyroidism. All rats were randomly divided into five groups: the normal control group (CON), the hypothyroidism group (Hypo), the T4 treatment group (T4), the DON treatment group (DON) and the T4+DON combined treatment group (T4+DON). Technique of Electron Microscope (TEM) was used to observe the hippocampal ultrastructures of each group, Western blot and real-time RT-PCR were performed to analyze the protein and mRNA expressions of syt-1 and SNAP-25 in the hippocampus of each group. TEM revealed that the Hypo group exhibited the significant vacuolar degeneration of mitochondria in the hippocampal neurons, the free ribosomes were sparse, the synaptic structures were damaged, and the number of synaptic vesicles was reduced, the above injuries in the T4 or DON group were improved, and the performance of the T4+DON group was the most close to the CON group. From the protein and mRNA levels, the dorsal hippocampal syt-1 expression of the Hypo group was significantly reduced, while SNAP-25 was significantly increased, the expressions were partially recovered after the T4 treatment, and the T4+DON combined treatment made the expression return to normal. The adult hypothyroid rats exhibited pathological damages in the hippocampal ultrastructures, the expression of syt-1 was downregulated, while that of SNAP-25 was upregulated, the T4+DON combined therapy could repair the above injuries, and the roles were better than the single drug treatment. PMID:26770386

  12. Synthesis and evaluation of multi-target-directed ligands for the treatment of Alzheimer's disease based on the fusion of donepezil and melatonin.

    PubMed

    Wang, Jin; Wang, Zhi-Min; Li, Xue-Mei; Li, Fan; Wu, Jia-Jia; Kong, Ling-Yi; Wang, Xiao-Bing

    2016-09-15

    A novel series of compounds obtained by fusing the acetylcholinesterase (AChE) inhibitor donepezil and the antioxidant melatonin were designed as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (eqBuChE and hBuChE), and β-amyloid (Aβ) aggregation, and to act as potential antioxidants and biometal chelators. Especially, 4u displayed a good inhibition of AChE (IC50 value of 193nM for eeAChE and 273nM for hAChE), strong inhibition of BuChE (IC50 value of 73nM for eqBuChE and 56nM for hBuChE), moderate inhibition of Aβ aggregation (56.3% at 20μM) and good antioxidant activity (3.28trolox equivalent by ORAC assay). Molecular modeling studies in combination with kinetic analysis revealed that 4u was a mixed-type inhibitor, binding simultaneously to catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4u could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results strongly indicated the hybridization approach is an efficient strategy to identify novel scaffolds with desired bioactivities, and further optimization of 4u may be helpful to develop more potent lead compound for AD treatment. PMID:27460699

  13. Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats.

    PubMed

    Wang, Fen; Zeng, Xianzhong; Zhu, Yangbo; Ning, Dan; Liu, Junxia; Liu, Chunlei; Jia, Xuemei; Zhu, Defa

    2015-02-01

    A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a significant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism. PMID:25371181

  14. Quantum Operation Time Reversal

    SciTech Connect

    Crooks, Gavin E.

    2008-03-25

    The dynamics of an open quantum system can be described by a quantum operation: A linear, complete positive map of operators. Here, I exhibit a compact expression for the time reversal of a quantum operation, which is closely analogous to the time reversal of a classical Markov transition matrix. Since open quantum dynamics are stochastic, and not, in general, deterministic, the time reversal is not, in general, an inversion of the dynamics. Rather, the system relaxes toward equilibrium in both the forward and reverse time directions. The probability of a quantum trajectory and the conjugate, time reversed trajectory are related by the heat exchanged with the environment.

  15. Effects of thyroxin and donepezil on hippocampal acetylcholine content and syntaxin-1 and munc-18 expression in adult rats with hypothyroidism

    PubMed Central

    WANG, NAN; CAI, YAOJUN; WANG, FEN; ZENG, XIANZHONG; JIA, XUEMEI; TAO, FANGBIAO; ZHU, DEFA

    2014-01-01

    Adult-onset hypothyroidism induces various impairments in hippocampus-dependent cognitive function, in which numerous synaptic proteins and neurotransmitters are involved. Donepezil (DON), an acetylcholinesterase inhibitor, has been shown to be efficient in improving cognitive function. The aim of the present study was to investigate the effects of adult-onset hypothyroidism on the expression levels of the synaptic proteins syntaxin-1 and munc-18, as well as the content of the neurotransmitter acetylcholine (ACh) in the hippocampus. In addition, the study explored the effects of thyroxin (T4) and DON treatment on the altered parameters. The study involved 55 Sprague-Dawley rats that were randomly divided into five groups: Control, hypothyroid (0.05% 6-n-propyl-2-thiouracil; added to the drinking water), hypothyroid treated with T4 (6 μg/100 g body weight once daily; intraperitoneal injection), hypothyroid treated with DON (0.005%; added to the drinking water) and hypothyroid treated with a combination of the two drugs (6 μg/100 g T4 and 0.005% DON). The concentration of ACh was determined in the homogenized hippocampus of each animal by alkaline hydroxylamine colorimetry. The protein levels of syntaxin-1 and munc-18 were determined by immunohistochemistry. The results showed that the content of ACh in the hippocampi of the hypothyroid rats was significantly decreased compared with that in the controls and that T4 monotherapy and DON administration restored the ACh content to normal values. In the hippocampi of the hypothyroid group, munc-18 was expressed at significantly lower levels, while the expression levels of syntaxin-1 were increased compared with the levels in the control group. Treatment with T4 alone restored the expression of syntaxin-1 but failed to normalize munc-18 expression levels. The co-administration of T4 and DON returned the munc-18 levels to normal values. These observations indicate that adult-onset hypothyroidism induces alterations in the

  16. The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice

    PubMed Central

    2013-01-01

    Introduction Despite years of research, there are no disease-modifying drugs for Alzheimer's disease (AD), a fatal, age-related neurodegenerative disorder. Screening for potential therapeutics in rodent models of AD has generally relied on testing compounds before pathology is present, thereby modeling disease prevention rather than disease modification. Furthermore, this approach to screening does not reflect the clinical presentation of AD patients which could explain the failure to translate compounds identified as beneficial in animal models to disease modifying compounds in clinical trials. Clearly a better approach to pre-clinical drug screening for AD is required. Methods To more accurately reflect the clinical setting, we used an alternative screening strategy involving the treatment of AD mice at a stage in the disease when pathology is already advanced. Aged (20-month-old) transgenic AD mice (APP/swePS1ΔE9) were fed an exceptionally potent, orally active, memory enhancing and neurotrophic molecule called J147. Cognitive behavioral assays, histology, ELISA and Western blotting were used to assay the effect of J147 on memory, amyloid metabolism and neuroprotective pathways. J147 was also investigated in a scopolamine-induced model of memory impairment in C57Bl/6J mice and compared to donepezil. Details on the pharmacology and safety of J147 are also included. Results Data presented here demonstrate that J147 has the ability to rescue cognitive deficits when administered at a late stage in the disease. The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory. The comparison between J147 and donepezil in the scopolamine model showed that while both compounds were comparable at rescuing short term memory, J147 was superior at rescuing spatial

  17. Reverse Transfer in Australia

    ERIC Educational Resources Information Center

    Moodie, Gavin

    2004-01-01

    This article considers national Australian data on reverse transfer--the transfer of students from bachelor programs or higher to sub baccalaureate programs, institutions and sectors. It finds that previous studies have overstated the prevalence and perhaps also the significance of reverse transfer. The data are not good, but the best conclusion…

  18. Quantum reverse hypercontractivity

    SciTech Connect

    Cubitt, Toby; Kastoryano, Michael; Montanaro, Ashley; Temme, Kristan

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  19. Justice and Reverse Discrimination.

    ERIC Educational Resources Information Center

    Goldman, Alan H.

    Defining reverse discrimination as hiring or admissions decisions based on normally irrelevant criteria, this book develops principles of rights, compensation, and equal opportunity applicable to the reverse discrimination issue. The introduction defines the issue and discusses deductive and inductive methodology as applied to reverse…

  20. Reverse Discrimination: Recent Cases.

    ERIC Educational Resources Information Center

    Steinhilber, August W.

    This paper discusses reverse discrimination cases with particular emphasis on Bakke v. Regents of University of California and those cases which preceded it. A brief history is given of court cases used by opponents and proponents in the discussion of reverse discrimination. Legal theory and a discussion of court cases that preceded Bakke follow.…

  1. Ultrasonic Time Reversal Mirrors

    NASA Astrophysics Data System (ADS)

    Fink, Mathias; Montaldo, Gabriel; Tanter, Mickael

    2004-11-01

    For more than ten years, time reversal techniques have been developed in many different fields of applications including detection of defects in solids, underwater acoustics, room acoustics and also ultrasound medical imaging and therapy. The essential property that makes time reversed acoustics possible is that the underlying physical process of wave propagation would be unchanged if time were reversed. In a non dissipative medium, the equations governing the waves guarantee that for every burst of sound that diverges from a source there exists in theory a set of waves that would precisely retrace the path of the sound back to the source. If the source is pointlike, this allows focusing back on the source whatever the medium complexity. For this reason, time reversal represents a very powerful adaptive focusing technique for complex media. The generation of this reconverging wave can be achieved by using Time Reversal Mirrors (TRM). It is made of arrays of ultrasonic reversible piezoelectric transducers that can record the wavefield coming from the sources and send back its time-reversed version in the medium. It relies on the use of fully programmable multi-channel electronics. In this paper we present some applications of iterative time reversal mirrors to target detection in medical applications.

  2. Reversible Shape Memory

    NASA Astrophysics Data System (ADS)

    Zhou, Jing; Li, Qiaoxi; Turner, Sara; Brosnan, Sarah; Tippets, Cary; Carrillo, Jan-Michael; Nykypnachuk, Dmytro; Gang, Oleg; Dobrynin, Andrey; Lopez, Rene; Ashby, Valerie; Sheiko, Sergei

    2014-03-01

    Reversible shape memory has been achieved on various shapes, e.g. hairpin, origami, coil, robotic gripper and flow rate control device, allowing for multiple switching between encoded shapes without applying any external force. Also, the reversible photonic structure molded in dielectric elastomers has been designed. Maximum reversibility can be achieved by tuning the crosslinking density and the degree of crystallinity of semi-crystalline elastomers. Different crystallization protocols including isothermal and cooling crystallization have been applied to develop a universal picture integrating different shape memory (SM) behaviors: conventional one-way SM, two-way reversible SM, and one-way reversible SM. Acknowledge financial support from the NSF DMR-1122483, DMR- 1004576, and DMR-1206957.

  3. Novel ionically crosslinked acrylamide-grafted poly(vinyl alcohol)/sodium alginate/sodium carboxymethyl cellulose pH-sensitive microspheres for delivery of Alzheimer's drug donepezil hydrochloride: Preparation and optimization of release conditions.

    PubMed

    Bulut, Emine; Şanlı, Oya

    2016-01-01

    In this work, the graft copolymer, poly(vinyl alcohol)-grafted polyacrylamide (PVA-g-PAAm), was synthesized and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and elemental analysis. Microspheres of PVA-g-PAAm/sodium alginate (NaAlg)/sodium carboxymethyl cellulose (NaCMC) were prepared by the emulsion-crosslinking method and used for the delivery of an Alzheimer's drug, donepezil hydrochloride (DP). The release of DP increased with the increase in drug/polymer ratio (d/p) and PVA-g-PAAm/NaAlg/NaCMC ratio, while it decreased with the increase in the extent of crosslinking. The optimum DP release was obtained as 92.9% for a PVA-g-PAAm/NaAlg/NaCMC ratio of 1/2/1, d/p ratio of 1/8, and FeCl3 concentration of 7% (w/v). PMID:25301684

  4. Reversible shape memory

    NASA Astrophysics Data System (ADS)

    Sheiko, Sergei; Zhou, Jing; White, Sarah; Ashby, Valerie

    2012-02-01

    An ``Achilles' heel'' of shape memory materials is that shape transformations triggered by an external stimulus are usually irreversible. Here we present a new concept of reversible transitions between two well-defined shapes by controlling hierarchic crystallization of a dual-network elastomer. The reversibility was demonstrated for different types of shape transformations including rod bending, winding of a helical coil, and widening an aperture. The distinct feature of the reversible shape alterations is that both counter-shapes are infinitely stable at a temperature of exploitation. Shape reversibility is highly desirable property in many practical applications such as non-surgical removal of a previously inserted catheter and handfree wrapping up of an earlier unraveled solar sail on a space shuttle.

  5. Tubal ligation reversal

    MedlinePlus

    ... Fernandez H, Gervaise A. Tubal anastomosis after tubal sterilization: a review. Arch Gynecol Obstet . 2011 May;283( ... Berger GS, Zerden ML. Pregnancy success after hysteroscopic sterilization reversal. Obstet Gynecol . 2014 Dec;124(6):1183- ...

  6. Giant rodlike reversed micelles

    SciTech Connect

    Yu, Z.J.; Neuman, R.D. )

    1994-05-04

    Herein we report that sodium bis(2-ethylhexyl)phosphate, which is similar in structure to the classical surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOT), forms very large rodlike reversed micelles and that their size can be even much larger if water is removed from the apolar solution. We further suggest that long-range electrostatic interactions are the primary driving force for the formation of giant reversed micelles. 19 refs., 3 figs.

  7. On thermodynamic and microscopic reversibility

    SciTech Connect

    Crooks, Gavin E.

    2011-07-12

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa.

  8. Reversible collisionless magnetic reconnection

    SciTech Connect

    Ishizawa, A.; Watanabe, T.-H.

    2013-10-15

    Reversible magnetic reconnection is demonstrated for the first time by means of gyrokinetic numerical simulations of a collisionless magnetized plasma. Growth of a current-driven instability in a sheared magnetic field is accompanied by magnetic reconnection due to electron inertia effects. Following the instability growth, the collisionless reconnection is accelerated with development of a cross-shaped structure of current density, and then all field lines are reconnected. The fully reconnected state is followed by the secondary reconnection resulting in a weakly turbulent state. A time-reversed simulation starting from the turbulent state manifests that the collisionless reconnection process proceeds inversely leading to the initial state. During the reversed reconnection, the kinetic energy is reconverted into the original magnetic field energy. In order to understand the stability of reversed process, an external perturbation is added to the fully reconnected state, and it is found that the accelerated reconnection is reversible when the deviation of the E × B streamlines due to the perturbation is comparable with or smaller than a current layer width.

  9. Sequential Polarity-Reversing Circuit

    NASA Technical Reports Server (NTRS)

    Labaw, Clayton C.

    1994-01-01

    Proposed circuit reverses polarity of electric power supplied to bidirectional dc motor, reversible electro-mechanical actuator, or other device operating in direction depending on polarity. Circuit reverses polarity each time power turned on, without need for additional polarity-reversing or direction signals and circuitry to process them.

  10. Time reversal communication system

    DOEpatents

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  11. Justice and Reverse Discrimination

    ERIC Educational Resources Information Center

    Strike, Kenneth A.

    1976-01-01

    Although this article does not necessarily recommend policies of reverse discrimination, arguments indicating that such policies are not contradictory to accepted concepts of justice are presented. The necessity of dispersing any consequent injury to society as a whole rather than to individuals is stressed. (RW)

  12. Reversing Discrimination: A Perspective

    ERIC Educational Resources Information Center

    Pati, Gopal; Reilly, Charles W.

    1977-01-01

    Examines the debate over affirmative action and reverse discrimination, and discusses how and why the present dilemma has developed. Suggests that organizations can best address the problem through an honest, in-depth analysis of their organizational structure and management practices. (JG)

  13. Andexanet: Effectively Reversing Anticoagulation.

    PubMed

    Lippi, Giuseppe; Sanchis-Gomar, Fabian; Favaloro, Emmanuel J

    2016-06-01

    Despite direct oral anticoagulants becoming a mainstay of anticoagulant therapy, the effective, timely, and safe reversal of their anticoagulant effect remains challenging. Emerging evidence attests that andexanet, a recombinant and inactive variant of native factor X (FXa), competitively inhibits and counteracts the anticoagulant effect of many inhibitors of native activated FXa. PMID:27048885

  14. Reversible Ising dynamics

    SciTech Connect

    Creutz, M.

    1985-01-01

    The author discusses a reversible deterministic dynamics for Ising spins. The algorithm is a variation of microcanonical Monte Carlo techniques and is easily implemented with simple bit manipulation. This provides fast programs to study non-equilibrium phenomena such as heat flow.

  15. Reverse Coherent Information

    NASA Astrophysics Data System (ADS)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-05-01

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  16. Reverse Coherent Information

    NASA Astrophysics Data System (ADS)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-04-01

    We define a family of entanglement distribution protocols assisted by classical feedback communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This protocol family leads to the definition of a new entanglement distribution capacity that exceeds the unassisted entanglement distribution capacity for some interesting channels.

  17. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants shall be maintained in a safe and suitable condition for service. Reverse lever latch shall be...

  18. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants shall be maintained in a safe and suitable condition for service. Reverse lever latch shall be...

  19. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants shall be maintained in a safe and suitable condition for service. Reverse lever latch shall be...

  20. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants shall be maintained in a safe and suitable condition for service. Reverse lever latch shall be...

  1. Reverse genetics of mononegavirales.

    PubMed

    Conzelmann, K K

    2004-01-01

    "Reverse genetics" or de novo synthesis of nonsegmented negative-sense RNA viruses (Mononegavirales) from cloned cDNA has become a reliable technique to study this group of medically important viruses. Since the first generation of a negative-sense RNA virus entirely from cDNA in 1994, reverse genetics systems have been established for members of most genera of the Rhabdo-, Paramyxo-, and Filoviridae families. These systems are based on intracellular transcription of viral full-length RNAs and simultaneous expression of viral proteins required to form the typical viral ribonucleoprotein complex (RNP). These systems are powerful tools to study all aspects of the virus life cycle as well as the roles of virus proteins in virus-host interplay and pathogenicity. In addition, recombinant viruses can be designed to have specific properties that make them attractive as biotechnological tools and live vaccines. PMID:15298166

  2. Gridded electron reversal ionizer

    NASA Technical Reports Server (NTRS)

    Chutjian, Ara (Inventor)

    1993-01-01

    A gridded electron reversal ionizer forms a three dimensional cloud of zero or near-zero energy electrons in a cavity within a filament structure surrounding a central electrode having holes through which the sample gas, at reduced pressure, enters an elongated reversal volume. The resultant negative ion stream is applied to a mass analyzer. The reduced electron and ion space-charge limitations of this configuration enhances detection sensitivity for material to be detected by electron attachment, such as narcotic and explosive vapors. Positive ions may be generated by generating electrons having a higher energy, sufficient to ionize the target gas and pulsing the grid negative to stop the electron flow and pulsing the extraction aperture positive to draw out the positive ions.

  3. Field reversed ion rings

    SciTech Connect

    Sudan, R.N.; Omelchenko, Y.A.

    1995-09-01

    In typical field-reversed ion ring experiments, an intense annular ion beam is injected across a plasma-filled magnetic cusp region into a neutral gas immersed in a ramped solenoidal magnetic field. Assuming the characteristic ionization time is much shorter than the long ({ital t}{approx_gt}2{pi}/{Omega}{sub {ital i}}) beam evolution time scale, we investigate the formation of an ion ring in the background plasma followed by field reversal, using a 21/2-D hybrid, PIC code FIRE, in which the beam and background ions are treated as particles and the electrons as a massless fluid. We show that beam bunching and trapping occurs downstream in a ramped magnetic field for an appropriate set of experimental parameters. We find that a compact ion ring is formed and a large field reversal {zeta}={delta}{ital B}/{ital B}{approx_gt}1 on axis develops. We also observe significant deceleration of the ring on reflection due to the transfer of its axial momentum to the background ions, which creates favorable trapping conditions. {copyright} {ital 1995 American Institute of Physics.}

  4. Tevatron reverse injection

    SciTech Connect

    Saritepe, S.; Annala, G.

    1993-06-25

    In the new injection scenario antiprotons are injected onto a helical orbit in the Tevatron in order to avoid the detrimental effects of the beam-beam interaction at 150 GeV. The new scenario required changes in the tuning procedure. Antiprotons are too precious to be used for tuning, therefore the antiproton injection line has to be tuned with protons by reverse injecting them from the Tevatron into the Main Pang (MR). Previously, the reverse injection was performed in one supercycle. One batch of uncoalesced bunches was injected into the Tevatron and ejected after 40 seconds. Then the orbit closure was performed in the MR. In the new scheme the lambertson magnets have to be moved and separator polarities have to be switched, activities that cannot be completed in one supercycle. Therefore, the reverse injection sequence was changed. This involved the redefinition of TVBS dock event $D8 as MRBS $D8 thus marking it possible to inject 6 proton batches and eject them one at a time on command, performing orbit closure each time in the MR.

  5. Reversible DNA compaction.

    PubMed

    González-Pérez, Alfredo

    2014-01-01

    In this review we summarize and discuss the different methods we can use to achieve reversible DNA compaction in vitro. Reversible DNA compaction is a natural process that occurs in living cells and viruses. As a result these process long sequences of DNA can be concentrated in a small volume (compacted) to be decompacted only when the information carried by the DNA is needed. In the current work we review the main artificial compacting agents looking at their suitability for decompaction. The different approaches used for decompaction are strongly influenced by the nature of the compacting agent that determines the mechanism of compaction. We focus our discussion on two main artificial compacting agents: multivalent cations and cationic surfactants that are the best known compacting agents. The reversibility of the process can be achieved by adding chemicals like divalent cations, alcohols, anionic surfactants, cyclodextrins or by changing the chemical nature of the compacting agents via pH modifications, light induced conformation changes or by redox-reactions. We stress the relevance of electrostatic interactions and self-assembly as a main approach in order to tune up the DNA conformation in order to create an on-off switch allowing a transition between coil and compact states. The recent advances to control DNA conformation in vitro, by means of molecular self-assembly, result in a better understanding of the fundamental aspects involved in the DNA behavior in vivo and serve of invaluable inspiration for the development of potential biomedical applications. PMID:24444152

  6. [Reverse Chaddock sign].

    PubMed

    Tashiro, Kunio

    2011-08-01

    It is widely accepted that the Babinski reflex is the most well-known and important pathological reflex in clinical neurology. Among many other pathological reflexes that elicit an upgoing great toe, such as Chaddock, Oppenheim, Gordon, Schaefer, and Stransky, only the Chaddock reflex is said to be as sensitive as the Babinski reflex. The optimal receptive fields of the Babinski and Chaddock reflexes are the lateral plantar surface and the external inframalleolar area of the dorsum, respectively. It has been said that the Babinski reflex, obtained by stroking the sole, is by far the best and most reliable method of eliciting an upgoing great toe. However, the Chaddock reflex, the external malleolar sign, is also considered sensitive and reliable according to the literature and everyday neurological practice. The major problems in eliciting the Babinski reflex by stroking the lateral part of the sole are false positive or negative responses due to foot withdrawal, tonic foot response, or some equivocal movements. On the other hand, according to my clinical experience, the external inframalleolar area, which is the receptive field of the Chaddock reflex, is definitely suitable for eliciting the upgoing great toe. In fact, the newly proposed method to stimulate the dorsum of the foot from the medial to the lateral side, which I term the "reversed Chaddock method," is equally sensitive to demonstrate pyramidal tract involvement. With the "reversed Chaddock method", the receptive field of the Chaddock reflex may be postulated to be in the territory of the sural nerve, which could be supported by the better response obtained on stimulation of the postero-lateral calf than the anterior shin. With regard to the receptive fields of the Babinski and Chaddock reflexes, the first sacral dermatome (S1) is also considered a reflexogenous zone, but since the dermatome shows marked overlapping, the zones vary among individuals. As upgoing toe responses are consistently observed in

  7. Affirmative Action, or Reverse Discrimination?

    ERIC Educational Resources Information Center

    Dansby, Ike

    1996-01-01

    Determines the impact of affirmative action programs in response to charges that they are policies of reverse discrimination. Reviewing affirmative action programs submitted by Michigan State departments, researchers determined no reverse discrimination was apparent based on low numbers of reverse discrimination complaints filed by whites. (GR)

  8. Reversible brazing process

    DOEpatents

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  9. Reversal bending fatigue testing

    SciTech Connect

    Wang, Jy-An John; Wang, Hong; Tan, Ting

    2014-10-21

    Embodiments for apparatuses for testing reversal bending fatigue in an elongated beam are disclosed. Embodiments are configured to be coupled to first and second end portions of the beam and to apply a bending moment to the beam and create a pure bending condition in an intermediate portion of the beam. Embodiments are further configured to cyclically alternate the direction of the bending moment applied to the beam such that the intermediate portion of the beam cyclically bends in opposite directions in a pure bending condition.

  10. Reverse Quantum Waves

    NASA Astrophysics Data System (ADS)

    Boyd, Jeffrey

    2010-02-01

    As preposterous as it might sound, if quantum waves travel in the reverse direction from subatomic particles, then most of quantum physics can be explained without quantum weirdness or Schr"odinger's cat. Quantum mathematics is unchanged. The diffraction pattern on the screen of the double slit experiment is the same. This proposal is not refuted by the Innsbruck experiments; this is NOT a hidden local variable theory. Research evidence will be presented that is consistent with the idea waves travel in the opposite direction as neutrons. If one's thinking shifts from forwards to backwards quantum waves, the world changes so drastically it is almost unimaginable. Quantum waves move from the mathematical to the real world, multiply in number, and reverse in direction. Wave-particle duality is undone. In the double slit experiment every part of the target screen is emitting such quantum waves in all directions. Some pass through the two slits. Interference occurs on the opposite side of the barrier than is usually imagined. They impinge on ``S'' and an electron is released at random. Because of the interference it is more likely to follow some waves than others. It follows one and only one wave backward; hitting the screen where it's wave originated. )

  11. Reversed-polarity regions

    NASA Technical Reports Server (NTRS)

    Tang, F.

    1982-01-01

    It is found by a statistical study of 58 reversed-polarity regions (RPRs) covering the 11-year period 1969-1979 that RPRs (1) have a lifespan comparable to normal active regions, (2) do not show a tendency to rotate toward a more normal alignment, and (3) have stable configurations that do not suggest stress due to their anomalous magnetic alignment. As in normal regions, RPR magnetic complexity is found to be the primary factor in flare productivity. Weak-field RPRs produce no flares, and regions with complex spots produce more flares than regions with non-complex spots by a factor of five. The main difference between RPRs and normal regions lies in complex spot frequency, with less that 17% of normal active regions having such spots and fewer than 1.8% having long-lived complex ones, while 41% of RPRs have complex spots and 24% have long-lived complex spots.

  12. A reversible molecular valve

    PubMed Central

    Nguyen, Thoi D.; Tseng, Hsian-Rong; Celestre, Paul C.; Flood, Amar H.; Liu, Yi; Stoddart, J. Fraser; Zink, Jeffrey I.

    2005-01-01

    In everyday life, a macroscopic valve is a device with a movable control element that regulates the flow of gases or liquids by blocking and opening passageways. Construction of such a device on the nanoscale level requires (i) suitably proportioned movable control elements, (ii) a method for operating them on demand, and (iii) appropriately sized passageways. These three conditions can be fulfilled by attaching organic, mechanically interlocked, linear motor molecules that can be operated under chemical, electrical, or optical stimuli to stable inorganic porous frameworks (i.e., by self-assembling organic machinery on top of an inorganic chassis). In this article, we demonstrate a reversibly operating nanovalve that can be turned on and off by redox chemistry. It traps and releases molecules from a maze of nanoscopic passageways in silica by controlling the operation of redox-activated bistable [2]rotaxane molecules tethered to the openings of nanopores leading out of a nanoscale reservoir. PMID:16006520

  13. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2003-12-09

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  14. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2006-04-25

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  15. Reverse photoacoustic standoff spectroscopy

    DOEpatents

    Van Neste, Charles W.; Senesac, Lawrence R.; Thundat, Thomas G.

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  16. Reverse slapper detonator

    DOEpatents

    Weingart, Richard C.

    1990-01-01

    A reverse slapper detonator (70), and methodology related thereto, are provided. The detonator (70) is adapted to be driven by a pulse of electric power from an external source (80). A conductor (20) is disposed along the top (14), side (18), and bottom (16) surfaces of a sheetlike insulator (12). Part of the conductor (20) comprises a bridge (28), and an aperture (30) is positioned within the conductor (20), with the bridge (28) and the aperture (30) located on opposite sides of the insulator (12). A barrel (40) and related explosive charge (50) are positioned adjacent to and in alignment with the aperture (30), and the bridge (28) is buttressed with a backing layer (60). When the electric power pulse vaporizes the bridge (28), a portion of the insulator (12) is propelled through the aperture (30) and barrel (40), and against the explosive charge (50), thereby detonating it.

  17. Reverse Osmosis Optimization

    SciTech Connect

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  18. Reverse Osmosis Optimization

    SciTech Connect

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  19. Reversibility of skeletal fluorosis.

    PubMed Central

    Grandjean, P; Thomsen, G

    1983-01-01

    At two x ray examinations in 1957 and 1967, 17 cases of skeletal fluorosis were identified among long term cryolite workers in Copenhagen. In 1982 four of these patients were alive, eight to 15 years after exposure had ended. Radiographs were obtained, and the urinary fluoride excretion was measured. A similar picture emerged in all four cases: extensive fading of the sclerosis of trabecular bone in ribs, vertebral bodies, and pelvis, whereas cortical bone thickening and calcification of muscle insertions and ligaments remained virtually unchanged. The fluoride excretion was increased in three cases (with the shortest exposure free period). These findings indicate that with continuous remodelling of bone tissue trabecular sclerosis is slowly reversible and the excess fluoride is excreted in the urine. Images PMID:6626475

  20. Reversibility of skeletal fluorosis.

    PubMed

    Grandjean, P; Thomsen, G

    1983-11-01

    At two x ray examinations in 1957 and 1967, 17 cases of skeletal fluorosis were identified among long term cryolite workers in Copenhagen. In 1982 four of these patients were alive, eight to 15 years after exposure had ended. Radiographs were obtained, and the urinary fluoride excretion was measured. A similar picture emerged in all four cases: extensive fading of the sclerosis of trabecular bone in ribs, vertebral bodies, and pelvis, whereas cortical bone thickening and calcification of muscle insertions and ligaments remained virtually unchanged. The fluoride excretion was increased in three cases (with the shortest exposure free period). These findings indicate that with continuous remodelling of bone tissue trabecular sclerosis is slowly reversible and the excess fluoride is excreted in the urine. PMID:6626475

  1. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

  2. Reducing Reversals in Reading and Writing.

    ERIC Educational Resources Information Center

    Heydorn, Bernard L.

    1984-01-01

    Reversals can be remediated in a variety of ways that focus on single symbol reversals (e.g., by tracing overlarge letters or numerals) or whole word reversals (e.g., by using flash cards for identified reverse words). (CL)

  3. On time reversal mirrors

    NASA Astrophysics Data System (ADS)

    Fannjiang, Albert C.

    2009-09-01

    The concept of time reversal (TR) of a scalar wave is reexamined from basic principles. Five different time-reversal mirrors (TRMs) are introduced and their relations are analyzed. For the boundary behavior, it is shown that for a paraxial wave only the monopole TR scheme satisfies the exact boundary condition while for the spherical wave only the MD-mode TR scheme satisfies the exact boundary condition. The asymptotic analysis of the near-field focusing property is presented for two dimensions and three dimensions. It is shown that to have a subwavelength focal spot, the TRM should consist of dipole transducers. The transverse resolution of the dipole TRM is linearly proportional to the distance between the point source and the TRM. The mixed mode TRM has the similar (linear) behavior in three dimensions, but in two dimensions the transverse resolution behaves as the square root of the distance between the point source and the TRM. The monopole TRM is ineffective in focusing below the wavelength. Contrary to the matched field processing and the phase processor, both of which resemble TR, TR in a weak- or non-scattering medium is usually biased in the longitudinal direction, especially when TR is carried out on a single plane with a finite aperture. This is true for all five TR schemes. On the other hand, the TR focal spot has been shown repeatedly in the literature, both theoretically and experimentally, to be centered at the source point when the medium is multiple scattering. A reconciliation of the two seemingly conflicting results is found in the random fluctuations in the intensity of the Green function for a multiple scattering medium and the notion of scattering-enlarged effective aperture.

  4. Reverse Engineering Podkletnov's Experiments

    NASA Astrophysics Data System (ADS)

    Solomon, B. T.

    Experiments reported by Podkletnov et al. suggest that gravity modification is within reach in our lifetimes. Solomon used process models to introduced the concept of non-inertia Ni fields and derived the massless gravitational acceleration formula g = τc2 that is consistent with Hooft's finding that absence of matter no longer guarantees local flatness. Solomon had also shown that many photon experimental results could be modeled without the use of quantum theory. This would imply that neither a quantum nor a relativistic type theory would be indispensible to formulating a theory on gravity modification. This paper, therefore, explores the use of Ni fields and process models to reverse engineer Podkletnov's experiments from first principles to determine a possible theoretical or at least an engineering basis for the observed gravity shielding effects. This paper scrutinizes and documents Podkletnov's papers for detailed experimental clues and applies them to new process models. The paper shows that it is possible to infer gravity modifying effects using non-inertia Ni fields, without taking into consideration the quantum mechanical properties of the ceramic superconducting disc. That is without considering how or why these fields are produced. The modeling suggests that there are two similar but different phenomena present, the stationary disc and spinning disc effects. The observed weight loss with the stationary disc is due to the asymmetric magnetic field and the observed weight loss with the spinning disc is due to the electromagnetic Ni field. There are several keys to reproducing Podkletnov's experimental results, asymmetric fields, dual layer disc, and the presence of both electric and magnetic fields. Finally the paper shows that if the magnetic field was not superconducting, but a regular magnetic field, that the observed weight change should be reversed, and therefore, a non-superconducting disc would lend itself to simpler and easier experimental

  5. Magnetic reversals and mass extinctions

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1985-01-01

    The results of a study of reversals of the earth's magnetic field over the past 165 Myr are presented. A stationary periodicity of 30 Myr emerges which predicts pulses of increased reversal activity centered at 10, 40, 70, . . . Myr before the present. The correlation between the reversal intensity and biological extinctions is examined, and a nontrivial discrepancy is found between the magnetic and extinction periodicity.

  6. Geomagnetic Reversals during the Phanerozoic.

    PubMed

    McElhinny, M W

    1971-04-01

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency. PMID:17735224

  7. ASYMMETRIC SOLAR POLAR FIELD REVERSALS

    SciTech Connect

    Svalgaard, Leif; Kamide, Yohsuke

    2013-01-20

    The solar polar fields reverse because magnetic flux from decaying sunspots moves toward the poles, with a preponderance of flux from the trailing spots. If there is a strong asymmetry, in the sense that most activity is in the northern hemisphere, then that excess flux will move toward the north pole and reverse that pole first. If there is more activity in the south later on, then that flux will help to reverse the south pole. In this way, two humps in the solar activity and a corresponding difference in the time of reversals develop (in the ideal case). Such a difference was originally noted in the very first observation of polar field reversal just after the maximum of the strongly asymmetric solar cycle 19, when the southern hemisphere was most active before sunspot maximum and the south pole duly reversed first, followed by the northern hemisphere more than a year later, when that hemisphere became most active. Solar cycles since then have had the opposite asymmetry, with the northern hemisphere being most active before solar maximum. We show that polar field reversals for these cycles have all happened in the north first, as expected. This is especially noteworthy for the present solar cycle 24. We suggest that the association of two or more peaks of solar activity when separated by hemispheres with correspondingly different times of polar field reversals is a general feature of the cycle, and that asymmetric polar field reversals are simply a consequence of the asymmetry of solar activity.

  8. [Posterior reversible encephalopathy syndrome].

    PubMed

    Fischer, M; Schmutzhard, E

    2016-06-01

    Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely. PMID:27272329

  9. Time Reversal Violation

    SciTech Connect

    Quinn, H; /SLAC

    2009-01-27

    This talk briefly reviews three types of time-asymmetry in physics, which I classify as universal, macroscopic and microscopic. Most of the talk is focused on the latter, namely the violation of T-reversal invariance in particle physics theories. In sum tests of microscopic T-invariance, or observations of its violation, are limited by the fact that, while we can measure many processes, only in very few cases can we construct a matched pair of process and inverse process and observe it with sufficient sensitivity to make a test. In both the cases discussed here we can achieve an observable T violation making use of flavor tagging, and in the second case also using the quantum properties of an antisymmetric coherent state of two B mesons to construct a CP-tag. Both these tagging properties depend only on very general properties of the flavor and/or CP quantum numbers and so provide model independent tests for T-invariance violations. The microscopic laws of physics are very close to T-symmetric. There are small effects that give CP- and T-violating processes in three-generation-probing weak decays. Where a T-violating observable can be constructed we see the relationships between T-violation and CP-violation expected in a CPT conserving theory. These microscopic effects are unrelated to the 'arrow of time' that is defined by increasing entropy, or in the time direction defined by the expansion of our Universe.

  10. Reversible micromachining locator

    DOEpatents

    Salzer, Leander J.; Foreman, Larry R.

    1999-01-01

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved.

  11. Reversible micromachining locator

    DOEpatents

    Salzer, L.J.; Foreman, L.R.

    1999-08-31

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved. 7 figs.

  12. Reverse genetics of avian metapneumoviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An overview of avian metapneumovirus (aMPV) infection in turkeys and development of a reverse genetics system for aMPV subgroup C (aMPV-C) virus will be presented. By using reverse genetics technology, we generated recombinant aMPV-C viruses containing a different length of glycoprotein (G) gene or...

  13. Preference Reversal in Multiattribute Choice

    ERIC Educational Resources Information Center

    Tsetsos, Konstantinos; Usher, Marius; Chater, Nick

    2010-01-01

    A central puzzle for theories of choice is that people's preferences between options can be reversed by the presence of decoy options (that are not chosen) or by the presence of other irrelevant options added to the choice set. Three types of reversal effect reported in the decision-making literature, the attraction, compromise, and similarity…

  14. Reverse Transfer Project, Summer 1986.

    ERIC Educational Resources Information Center

    Reis, Elizabeth

    In 1986, a Reverse Transfer Project was initiated at Moraine Valley Community College (MVCC) in order to promote the summer school attendance at MVCC of "reverse transfer" students (i.e., students who attended another institution during the regular academic year). A mailing, containing a cover letter, informational brochure, summer catalog, and…

  15. Reversal of novel oral anticoagulants.

    PubMed

    Abo-Salem, Elsayed; Becker, Richard C

    2016-04-01

    The development of a new generation of non-vitamin K oral anticoagulants represents a potential breakthrough in the management of patients with thrombotic diseases, disorders and conditions. While a large and growing body of evidence from large-scale clinical trials and registries supports a favorable safety profile, having a means to rapidly reverse their anticoagulant effects represents an unmet need among practicing clinicians. Several targeted reversal agents are currently in development and the early results are promising. Idarucizumab is a monoclonal antibody that can immediately and specifically reverse dabigatran. Andexanet alfa is a recombinant modified factor Xa that can bind and reverse oral and parenteral factor Xa inhibitors, including rivaroxaban, apixaban and edoxaban, and low molecular weight heparin. Aripazine is a small molecule that can reverse the action of factor Xa inhibitors and possibly dabigatran as well through non-covalent binding and charge-charge interactions. PMID:26939028

  16. Classical Analog to Entanglement Reversibility

    NASA Astrophysics Data System (ADS)

    Chitambar, Eric; Fortescue, Ben; Hsieh, Min-Hsiu

    2015-08-01

    In this Letter we study the problem of secrecy reversibility. This asks when two honest parties can distill secret bits from some tripartite distribution pX Y Z and transform secret bits back into pX Y Z at equal rates using local operation and public communication. This is the classical analog to the well-studied problem of reversibly concentrating and diluting entanglement in a quantum state. We identify the structure of distributions possessing reversible secrecy when one of the honest parties holds a binary distribution, and it is possible that all reversible distributions have this form. These distributions are more general than what is obtained by simply constructing a classical analog to the family of quantum states known to have reversible entanglement. An indispensable tool used in our analysis is a conditional form of the Gács-Körner common information.

  17. Parkinson's disease managing reversible neurodegeneration.

    PubMed

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson's disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient's PD symptoms. PMID:27103805

  18. The Geomagnetic Field During a Reversal

    NASA Technical Reports Server (NTRS)

    Heirtzler, James R.

    2003-01-01

    By modifying the IGRF it is possible to learn what may happen to the geomagnetic field during a geomagnetic reversal. If the entire IGRF reverses then the declination and inclination only reverse when the field strength is zero. If only the dipole component of the IGRF reverses a large geomagnetic field remains when the dipole component is zero and he direction of the field at the end of the reversal is not exactly reversed from the directions at the beginning of the reversal.

  19. Reverse osmosis reverses conventional wisdom with Superfund cleanup success

    SciTech Connect

    Collins, M. ); Miller, K. )

    1994-09-01

    Although widely recognized as the most efficient means of water purification, reverse osmosis has not been considered effective for remediating hazardous wastewater. Scaling and fouling, which can cause overruns and downtime, and require membrane replacement, have inhibited success in high-volume wastewater applications. Despite this background, a reverse osmosis technology developed in Europe recently was used successfully to treat large volumes of contaminated water at a major Superfund site in Texas. The technology's success there may increase the chances for reverse osmosis to find wider use in future cleanups and other waste treatment applications.

  20. How decision reversibility affects motivation.

    PubMed

    Bullens, Lottie; van Harreveld, Frenk; Förster, Jens; Higgins, Tory E

    2014-04-01

    The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed. PMID:23815456

  1. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  2. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  3. Molecularly Regulated Reversible DNA Polymerization.

    PubMed

    Chen, Niancao; Shi, Xuechen; Wang, Yong

    2016-06-01

    Natural polymers are synthesized and decomposed under physiological conditions. However, it is challenging to develop synthetic polymers whose formation and reversibility can be both controlled under physiological conditions. Here we show that both linear and branched DNA polymers can be synthesized via molecular hybridization in aqueous solutions, on the particle surface, and in the extracellular matrix (ECM) without the involvement of any harsh conditions. More importantly, these polymers can be effectively reversed to dissociate under the control of molecular triggers. Since nucleic acids can be conjugated with various molecules or materials, we anticipate that molecularly regulated reversible DNA polymerization holds potential for broad biological and biomedical applications. PMID:27100911

  4. Ferroelectric polarization reversal in single crystals

    NASA Technical Reports Server (NTRS)

    Stadler, Henry L.

    1992-01-01

    Research on the reversal of polarization in ferroelectric crystals is reviewed. Particular attention is given to observation methods for polarization reversal, BaTiO3 polarization reversal, crystal thickness dependence of polarization reversal, and domain wall movement during polarization reversal in TGS.

  5. Improving reversal median computation using commuting reversals and cycle information.

    PubMed

    Arndt, William; Tang, Jijun

    2008-10-01

    In the past decade, genome rearrangements have attracted increasing attention from both biologists and computer scientists as a new type of data for phylogenetic analysis. Methods for reconstructing phylogeny from genome rearrangements include distance-based methods, MCMC methods, and direct optimization methods. The latter, pioneered by Sankoff and extended with the software suites GRAPPA and MGR, is the most accurate approach, but is very limited due to the difficulty of its scoring procedure--it must solve multiple instances of the reversal median problem to compute the score of a given tree. The reversal median problem is known to be NP-hard and all existing solvers are extremely slow when the genomes are distant. In this paper, we present a new reversal median heuristic for unichromosomal genomes. The new method works by applying sets of reversals in a batch where all such reversals both commute and do not break the cycle of any other. Our testing using simulated datasets shows that this method is much faster than the leading solver for difficult datasets with only a slight accuracy penalty, yet retains better accuracy than other heuristics with comparable speed, and provides the additional option of searching for multiple medians. This method dramatically increases the speed of current direct optimization methods and enables us to extend the range of their applicability to organellar and small nuclear genomes with more than 50 reversals along each edge. PMID:18774904

  6. Reverse Discrimination and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Johnson, Stephen D.

    1980-01-01

    White subjects were aggressive toward Black opponents when contest results appeared to reflect elements of reverse discrimination; but they showed less aggressive behavior toward Black opponents when they thought their loss was due to their opponents' superior ability. (RL)

  7. The evolution of vasectomy reversal.

    PubMed

    Dickey, Ryan M; Pastuszak, Alexander W; Hakky, Tariq S; Chandrashekar, Aravind; Ramasamy, Ranjith; Lipshultz, Larry I

    2015-06-01

    In the USA, about 500,000 vasectomies are performed each year, with up to 6% of men requesting reversal. The technique of vasectomy reversal has evolved from macrosurgical to the implementation of both microscopic and robotic technologies. The very earliest attempts at vasectomy reversal, the vasoepididymostomy and vasovasostomy, have remained central in the treatment of male infertility and will continue to be so for years to come. As seen throughout its history, urological microsurgery has consistently implemented advanced techniques and state-of-the art technology in its craft, and its continued refinement will allow for even more favorable outcomes in the lives of patients seeking restoration of fertility following vasectomy. Here, we review the evolution of vasectomy reversal and its current techniques. PMID:25980804

  8. Deciphering records of geomagnetic reversals

    NASA Astrophysics Data System (ADS)

    Valet, Jean-Pierre; Fournier, Alexandre

    2016-06-01

    Polarity reversals of the geomagnetic field are a major feature of the Earth's dynamo. Questions remain regarding the dynamical processes that give rise to reversals and the properties of the geomagnetic field during a polarity transition. A large number of paleomagnetic reversal records have been acquired during the past 50 years in order to better constrain the structure and geometry of the transitional field. In addition, over the past two decades, numerical dynamo simulations have also provided insights into the reversal mechanism. Yet despite the large paleomagnetic database, controversial interpretations of records of the transitional field persist; they result from two characteristics inherent to all reversals, both of which are detrimental to an ambiguous analysis. On the one hand, the reversal process is rapid and requires adequate temporal resolution. On the other hand, weak field intensities during a reversal can affect the fidelity of magnetic recording in sedimentary records. This paper is aimed at reviewing critically the main reversal features derived from paleomagnetic records and at analyzing some of these features in light of numerical simulations. We discuss in detail the fidelity of the signal extracted from paleomagnetic records and pay special attention to their resolution with respect to the timing and mechanisms involved in the magnetization process. Records from marine sediments dominate the database. They give rise to transitional field models that often lead to overinterpret the data. Consequently, we attempt to separate robust results (and their subsequent interpretations) from those that do not stand on a strong observational footing. Finally, we discuss new avenues that should favor progress to better characterize and understand transitional field behavior.

  9. Reversible Shape Memory Optical Gratings

    NASA Astrophysics Data System (ADS)

    Li, Qiaoxi; Tippets, Cary; Fu, Yulan; Donev, Eugene; Turner, Sara; Ashby, Valerie; Lopez, Rene; Sheiko, Sergei

    2015-03-01

    Recent advancements in the understanding of the mechanisms that control shape memory in semi-crystalline polymers, has led to the development of protocols that allow for reversibility in complex shape transformations. The shifting between two programmable shapes is reversible without applying any external force. This is made possible by thermodynamically driven relaxation of extended polymer chains on heating is then inverted by kinetically preferred pathways of polymer crystallization on cooling. Reversible shapeshifting was applied to modulation of photonic gratings to create hands-free reversibly tunable optical elements. We have fabricated a sub-micron ratio optical square grating that presents reversible magnitude changes of its diffraction intensity (up to about 38% modulation) when subject to changes in temperature. This result is attributed to programmable changes in the grating height due to reversible shape memory and is repeatable over multiple cycles. Besides, roughness-induced variations in scattering signal observed upon heating-cooling cycles may offer another way to monitor kinetics of polymer melting and crystallization. Grants: NSF DMR-1407645,

  10. Reversal Transition Records from Intrusions: Implications for the Reversal Process.

    NASA Astrophysics Data System (ADS)

    Fuller, M. D.; Williams, I. S.

    2014-12-01

    The nature of reversals of the geomagnetic field and the details of the transition fields remain controversial. However, reversal records from the Agno batholith and Tatoosh intrusion confirm the suggestion of Valet et al., (2012) from studies of lava records, that there is a threefold division in reversal transition directions. In the Agno, the first phase, or precursor, consists of a CCW loop of the VGP moving from high southerly latitude reverse poles to reach North America. The second phase takes the VGP along a half CCW loop from the tip of South America to northern latitudes at the intensity minimum. The third phase, or rebound is a smaller CCW loop and the main intensity recovery begins. The first and third phases appear to be paleosecular variation loops analogous to present London-Paris secular variation loops. The Tatoosh intrusion gives a similar, but less complete record with the VGPs again confined to the East Pacific and the Americas. Away from the reversal region, secular variation loops in the Tatoosh were shown to be comparable in duration to the precursor in the transition record, consistent with the first phase being a paleosecular variation loop in the Agno. Using westward drift estimates from the present field, this should last about1800 years. This gives ~3300 for phase 2, in an intensity low of >16,000 years. A feature of R to N reversal field models is a low latitude magnetic field flux concentration of the same sign as the polar vortex of the south geographic pole. This is followed by northward flux flow, e.g. Shao et al., (1999). The reversal is achieved by northward motion of this flux feature. The feature is locked in longitudinal mantle coordinates and similarly the VGPs in the Agno and Tatoosh records are confined to the longitudes of the eastern Pacific and the Americas. Whether we are approaching a reversal remains to be seen, although judging by these intrusion records the field intensity would need to decrease much further before

  11. Vasectomy reversal: a clinical update.

    PubMed

    Patel, Abhishek P; Smith, Ryan P

    2016-01-01

    Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery. PMID:26975488

  12. Vasectomy reversal: a clinical update

    PubMed Central

    Patel, Abhishek P; Smith, Ryan P

    2016-01-01

    Vasectomy is a safe and effective method of contraception used by 42–60 million men worldwide. Approximately 3%–6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery. PMID:26975488

  13. Ice ages and geomagnetic reversals

    NASA Technical Reports Server (NTRS)

    Wu, Patrick

    1992-01-01

    There have been speculations on the relationship between climatic cooling and polarity reversals of the earth's magnetic field during the Pleistocene. Two of the common criticisms on this relationship have been the reality of these short duration geomagnetic events and the accuracy of their dates. Champion et al. (1988) have reviewed recent progress in this area. They identified a total of 10 short-duration polarity events in the last 1 Ma and 6 of these events have been found in volcanic rocks, which also have K-Ar dates. Supposing that the speculated relationship between climatic cooling and geomagnetic reversals actually exist, two mechanisms that assume climatic cooling causes short period magnetic reversals will be investigated. These two methods are core-mantle boundary topography and transfer of the rotational energy to the core.

  14. Time-reversed, flow-reversed ballistics simulations

    SciTech Connect

    Zernow, L.; Chapyak, E. J.; Scheffler, D. R.

    2001-01-01

    Two-dimensional simulations of planar sheet jet formation are studied to examine the hydrodynamic issues involved when simulations are carried out in the inverse direction, that is, with reversed time and flow. Both a realistic copper equation of state and a shockless equation of state were used. These studies are an initial step in evaluating this technique as a ballistics design tool.

  15. Marburg Virus Reverse Genetics Systems

    PubMed Central

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-01-01

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

  16. Marburg Virus Reverse Genetics Systems.

    PubMed

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-01-01

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

  17. Stagnation point reverse flow combustor

    NASA Technical Reports Server (NTRS)

    Zinn, Ben T. (Inventor); Neumeier, Yedidia (Inventor); Seitzman, Jerry M. (Inventor); Jagoda, Jechiel (Inventor); Weksler, Yoav (Inventor)

    2008-01-01

    A method for combusting a combustible fuel includes providing a vessel having an opening near a proximate end and a closed distal end defining a combustion chamber. A combustible reactants mixture is presented into the combustion chamber. The combustible reactants mixture is ignited creating a flame and combustion products. The closed end of the combustion chamber is utilized for directing combustion products toward the opening of the combustion chamber creating a reverse flow of combustion products within the combustion chamber. The reverse flow of combustion products is intermixed with combustible reactants mixture to maintain the flame.

  18. Nickel-hydrogen cell reversal characteristics

    NASA Technical Reports Server (NTRS)

    Lurie, Charles

    1994-01-01

    Nickel-hydrogen cell reversal characteristics are being studied as part of a TRW program directed towards development of a high current battery cell bypass switch. The following are discussed: cell bypass switch; nickel-hydrogen cell reversal characteristics; and nickel-hydrogen cell chemistry: discharge/reversal and overdischarge (reversal) with nickel and hydrogen precharge.

  19. Reversing: A Fundamental Idea in Computer Science

    ERIC Educational Resources Information Center

    Armoni, Michal; Ginat, David

    2008-01-01

    Reversing is the notion of thinking or working in reverse. Computer science textbooks and tutors recognize it primarily in the form of recursion. However, recursion is only one form of reversing. Reversing appears in the computer science curriculum in many other forms, at various intellectual levels, in a variety of fundamental courses. As such,…

  20. Reversible logic gate using adiabatic superconducting devices

    PubMed Central

    Takeuchi, N.; Yamanashi, Y.; Yoshikawa, N.

    2014-01-01

    Reversible computing has been studied since Rolf Landauer advanced the argument that has come to be known as Landauer's principle. This principle states that there is no minimum energy dissipation for logic operations in reversible computing, because it is not accompanied by reductions in information entropy. However, until now, no practical reversible logic gates have been demonstrated. One of the problems is that reversible logic gates must be built by using extremely energy-efficient logic devices. Another difficulty is that reversible logic gates must be both logically and physically reversible. Here we propose the first practical reversible logic gate using adiabatic superconducting devices and experimentally demonstrate the logical and physical reversibility of the gate. Additionally, we estimate the energy dissipation of the gate, and discuss the minimum energy dissipation required for reversible logic operations. It is expected that the results of this study will enable reversible computing to move from the theoretical stage into practical usage. PMID:25220698

  1. Reversible colour change in Arthropoda.

    PubMed

    Umbers, Kate D L; Fabricant, Scott A; Gawryszewski, Felipe M; Seago, Ainsley E; Herberstein, Marie E

    2014-11-01

    The mechanisms and functions of reversible colour change in arthropods are highly diverse despite, or perhaps due to, the presence of an exoskeleton. Physiological colour changes, which have been recorded in 90 arthropod species, are rapid and are the result of changes in the positioning of microstructures or pigments, or in the refractive index of layers in the integument. By contrast, morphological colour changes, documented in 31 species, involve the anabolism or catabolism of components (e.g. pigments) directly related to the observable colour. In this review we highlight the diversity of mechanisms by which reversible colour change occurs and the evolutionary context and diversity of arthropod taxa in which it has been observed. Further, we discuss the functions of reversible colour change so far proposed, review the limited behavioural and ecological data, and argue that the field requires phylogenetically controlled approaches to understanding the evolution of reversible colour change. Finally, we encourage biologists to explore new model systems for colour change and to engage scientists from other disciplines; continued cross-disciplinary collaboration is the most promising approach to this nexus of biology, physics, and chemistry. PMID:24495279

  2. Law: Reverse Discrimination, Legal Briefs

    ERIC Educational Resources Information Center

    Nation's Schools and Colleges, 1974

    1974-01-01

    Just as schools and colleges are starting to hire more black and female faculty members through affirmative action programs, there is a new battle cry on the civil rights front: "reverse discrimination." Qualified whites claim they are being shoved aside in the scramble for less-qualified blacks, Chicanos, American Indians, and members of other…

  3. Quotas Are Not Reverse Discrimination

    ERIC Educational Resources Information Center

    McDonald, Gabrielle K.

    1975-01-01

    The findings of the Morrow v. Crisler and NAACP v. Allen civil rights cases are discussed. It is concluded from these employment discrimination cases that quotas are not reverse discrimination because no one has the right to continue to receive the benefits of racial discrimination at the expense of others. (LBH)

  4. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    EPA Science Inventory

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  5. Reversal agents in anaesthesia and critical care

    PubMed Central

    Pani, Nibedita; Dongare, Pradeep A; Mishra, Rajeeb Kumar

    2015-01-01

    Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice. PMID:26644615

  6. [Reverse genetics system for flaviviruses].

    PubMed

    Suzuki, Ryosuke; Konishi, Eiji

    2013-01-01

    Flaviviruses such as Japanese encephalitis virus, West Nile virus, yellow fever virus, dengue virus, and tick-borne encephalitis virus belong to a family Flaviviridae. These viruses are transmitted to vertebrates by infected mosquitoes or ticks, producing diseases, which have a serious impact on global public health. Reverse genetics is a powerful tool for studying the viruses. Although infectious full-length clones have been obtained for multiple flaviviruses, their early-stage development had the difficulty because of the instability problem of the viral cDNA in E. coli. Several strategies have been developed to circumvent the problem of infectious clone instability. The current knowledge accumulated on reverse genetics system of flaviviruses and its application are summarized in this review. PMID:24769573

  7. Reverse osmosis water purification system

    NASA Technical Reports Server (NTRS)

    Ahlstrom, H. G.; Hames, P. S.; Menninger, F. J.

    1986-01-01

    A reverse osmosis water purification system, which uses a programmable controller (PC) as the control system, was designed and built to maintain the cleanliness and level of water for various systems of a 64-m antenna. The installation operates with other equipment of the antenna at the Goldstone Deep Space Communication Complex. The reverse osmosis system was designed to be fully automatic; with the PC, many complex sequential and timed logic networks were easily implemented and are modified. The PC monitors water levels, pressures, flows, control panel requests, and set points on analog meters; with this information various processes are initiated, monitored, modified, halted, or eliminated as required by the equipment being supplied pure water.

  8. Reversing the Brazil Nut Effect

    NASA Astrophysics Data System (ADS)

    Ludewig, F.; Vandewalle, N.

    2005-12-01

    We propose a lattice model for studying the Brazil Nut Effect (BNE), i.e. the phase segregation occuring when a granular material is vertically shaked. The model considers the tap intensity and the mobility μ of the grains as the main physical parameters. Different mobilities for different grain species lead to segregation (BNE) patterns, reverse segregation (RBNE) patterns, “sandwhich" layered structures or vertical domains. A phase diagram (decompaction χ, mobility difference between both species Δ μ) is obtained in which the different phases are emphasized. In a narrow region of the diagram, different phases coexist. It is shown that the BNE segregation could be reversed by increasing the tap intensity or the characteristics of the grains. Numerical results are compared with earlier experimental works.

  9. Scaling in reversible submonolayer deposition

    NASA Astrophysics Data System (ADS)

    Oliveira, T. J.; Aarão Reis, F. D. A.

    2013-06-01

    The scaling of island and monomer density, capture zone distributions (CZDs), and island size distributions (ISDs) in reversible submonolayer growth was studied using the Clarke-Vvedensky model. An approach based on rate-equation results for irreversible aggregation (IA) models is extended to predict several scaling regimes in square and triangular lattices, in agreement with simulation results. Consistently with previous works, a regime I with fractal islands is observed at low temperatures, corresponding to IA with critical island size i=1, and a crossover to a second regime appears as the temperature is increased to ɛR2/3˜1, where ɛ is the single bond detachment probability and R is the diffusion-to-deposition ratio. In the square (triangular) lattice, a regime with scaling similar to IA with i=3 (i=2) is observed after that crossover. In the triangular lattice, a subsequent crossover to an IA regime with i=3 is observed, which is explained by the recurrence properties of random walks in two-dimensional lattices, which is beyond the mean-field approaches. At high temperatures, a crossover to a fully reversible regime is observed, characterized by a large density of small islands, a small density of very large islands, and total island and monomer densities increasing with temperature, in contrast to IA models. CZDs and ISDs with Gaussian right tails appear in all regimes for R˜107 or larger, including the fully reversible regime, where the CZDs are bimodal. This shows that the Pimpinelli-Einstein approach for IA explains the main mechanisms for the large islands to compete for free adatom aggregation in the reversible model, and may be the reason for its successful application to a variety of materials and growth conditions.

  10. Reverse engineering of integrated circuits

    DOEpatents

    Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

    2003-01-01

    Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

  11. Reversing Neurodevelopmental Disorders in Adults

    PubMed Central

    Ehninger, Dan; Li, Weidong; Fox, Kevin; Stryker, Michael P.; Silva, Alcino J.

    2009-01-01

    Abnormalities in brain development, thought to be irreversible in adults, have long been assumed to underlie the neurological and psychiatric symptoms associated with neurodevelopmental disorders. Surprisingly, a number of recent animal model studies of neurodevelopmental disorders demonstrate that reversing the underlying molecular deficits can result in substantial improvements in function even if treatments are started in adulthood. These findings mark a paradigmatic change in the way we understand and envision treating neurodevelopmental disorders. PMID:19109903

  12. Reversible Seeding in Storage Rings

    SciTech Connect

    Ratner, Daniel; Chao, Alex; /SLAC

    2011-12-14

    We propose to generate steady-state microbunching in a storage ring with a reversible seeding scheme. High gain harmonic generation (HGHG) and echo-enabled harmonic generation (EEHG) are two promising methods for microbunching linac electron beams. Because both schemes increase the energy spread of the seeded beam, they cannot drive a coherent radiator turn-by-turn in a storage ring. However, reversing the seeding process following the radiator minimizes the impact on the electron beam and may allow coherent radiation at or near the storage ring repetition rate. In this paper we describe the general idea and outline a proof-of-principle experiment. Electron storage rings can drive high average power light sources, and free-electron lasers (FELs) are now producing coherent light sources of unprecedented peak brightness While there is active research towards high repetition rate FELs (for example, using energy recovery linacs), at present there are still no convenient accelerator-based sources of high repetition rate, coherent radiation. As an alternative avenue, we recently proposed to establish steady-state microbunching (SSMB) in a storage ring. By maintaining steady-state coherent microbunching at one point in the storage ring, the beam generates coherent radiation at or close to the repetition rate of the storage ring. In this paper, we propose a method of generating a microbunched beam in a storage ring by using reversible versions of linac seeding schemes.

  13. Reversible fluorescence photoswitching in DNA.

    PubMed

    Smith, Darren A; Holliger, Philipp; Flors, Cristina

    2012-08-30

    We describe the engineering of reversible fluorescence photoswitching in DNA with high-density substitution, and its applications in advanced fluorescence microscopy methods. High-density labeling of DNA with cyanine dyes can be achieved by polymerase chain reaction using a modified DNA polymerase that has been evolved to efficiently incorporate Cy3- and Cy5-labeled cytosine base analogues into double-stranded DNA. The resulting biopolymer, "CyDNA", displays hundreds of fluorophores per DNA strand and is strongly colored and highly fluorescent, although previous observations suggest that fluorescence quenching at such high density might be a concern, especially for Cy5. Herein, we first investigate the mechanisms of fluorescence quenching in CyDNA and we suggest that two different mechanisms, aggregate formation and resonance energy transfer, are responsible for fluorescence quenching at high labeling densities. Moreover, we have been able to re-engineer CyDNA into a reversible fluorescence photoswitchable biopolymer by using the properties of the Cy3-Cy5 pair. This novel biopolymer constitutes a new class of photoactive DNA-based nanomaterial and is of great interest for advanced microscopy applications. We show that reversible fluorescence photoswitching in CyDNA can be exploited in optical lock-in detection imaging. It also lays the foundations for improved and sequence-specific super-resolution fluorescence microscopy of DNA. PMID:22861666

  14. Three distinct reversing modes in the geodynamo

    NASA Astrophysics Data System (ADS)

    Gallet, Y.; Pavlov, V. E.

    2016-03-01

    The data that describe the long-term reversing behavior of the geodynamo show strong and sudden changes in magnetic reversal frequency. This concerns both the onset and the end of superchrons and most probably the occurrence of episodes characterized by extreme geomagnetic reversal frequency (>10-15 rev./Myr). To account for the complexity observed in geomagnetic reversal frequency evolution, we propose a simple scenario in which the geodynamo operates in three distinct reversing modes: i—a "normal" reversing mode generating geomagnetic polarity reversals according to a stationary random process, with on average a reversal rate of ˜3 rev./Myr; ii—a non-reversing "superchron" mode characterizing long time intervals without reversal; iii—a hyper-active reversing mode characterized by an extreme geomagnetic reversal frequency. The transitions between the different reversing modes would be sudden, i.e., on the Myr time scale. Following previous studies, we suggest that in the past, the occurrence of these transitions has been modulated by thermal conditions at the core-mantle boundary governed by mantle dynamics. It might also be possible that they were more frequent during the Precambrian, before the nucleation of the inner core, because of a stronger influence on geodynamo activity of the thermal conditions at the core-mantle boundary.

  15. Rapid evaluation of reverse-osmosis membranes

    NASA Technical Reports Server (NTRS)

    Hollahan, J. R.; Wydeven, T.

    1972-01-01

    Simultaneous reverse-osmosis tests conducted with centrifuges having multiple compartment heads are discussed. Equipment for retaining reverse-osmosis membrane is illustrated. Method of conducting tests is described.

  16. Ancient Magnetic Reversals: Clues to the Geodynamo.

    ERIC Educational Resources Information Center

    Hoffman, Kenneth A.

    1988-01-01

    Discusses the question posed by some that the earth's magnetic field may reverse. States that rocks magnetized by ancient fields may offer clues to the underlying reversal mechanism in the earth's core. (TW)

  17. Statistical Learning, Letter Reversals, and Reading

    ERIC Educational Resources Information Center

    Treiman, Rebecca; Gordon, Jessica; Boada, Richard; Peterson, Robin L.; Pennington, Bruce F.

    2014-01-01

    Reversal errors play a prominent role in theories of reading disability. We examined reversal errors in the writing of letters by 5- to 6-year-old children. Of the 130 children, 92 had a history of difficulty in producing speech sounds, a risk factor for reading problems. Children were more likely to reverse letter forms that face left, such as…

  18. Cleaning Our World through Reverse Graffiti

    ERIC Educational Resources Information Center

    Randazzo, Gabe; LaJevic, Lisa

    2013-01-01

    Over the last decade artists have begun to experiment with "reverse pollution" techniques, such as reverse graffiti, which focuses on cleaning environmental surfaces. Having recently been introduced to the works of Moose, the artist known for inventing the reverse graffiti technique, the authors decided to design a curriculum to increase…

  19. 14 CFR 23.933 - Reversing systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Reversing systems. 23.933 Section 23.933... systems. (a) For turbojet and turbofan reversing systems. (1) Each system intended for ground operation... flight and landing under any possible position of the thrust reverser. (2) Each system intended for...

  20. 14 CFR 25.933 - Reversing systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Reversing systems. 25.933 Section 25.933... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.933 Reversing systems. (a) For turbojet reversing systems— (1) Each system intended for ground operation only must be designed so that during...

  1. Reverse genetics for mammalian reovirus.

    PubMed

    Boehme, Karl W; Ikizler, Miné; Kobayashi, Takeshi; Dermody, Terence S

    2011-10-01

    Mammalian orthoreoviruses (reoviruses) are highly tractable models for studies of viral replication and pathogenesis. The versatility of reovirus as an experimental model has been enhanced by development of a plasmid-based reverse genetics system. Infectious reovirus can be recovered from cells transfected with plasmids encoding cDNAs of each reovirus gene segment using a strategy that does not require helper virus and is independent of selection. In this system, transcription of each gene segment is driven by bacteriophage T7 RNA polymerase, which can be supplied transiently by recombinant vaccinia virus (rDIs-T7pol) or by cells that constitutively express the enzyme. Reverse genetics systems have been developed for two prototype reovirus strains, type 1 Lang (T1L) and type 3 Dearing (T3D). Each reovirus cDNA was encoded on an independent plasmid for the first-generation rescue system. The efficiency of virus recovery was enhanced in a second-generation system by combining the cDNAs for multiple reovirus gene segments onto single plasmids to reduce the number of plasmids from 10 to 4. The reduction in plasmid number and the use of baby hamster kidney cells that express T7 RNA polymerase increased the efficiency of viral rescue, reduced the incubation time required to recover infectious virus, and eliminated potential biosafety concerns associated with the use of recombinant vaccinia virus. Reovirus reverse genetics has been used to introduce mutations into viral capsid and nonstructural components to study viral protein-structure activity relationships and can be exploited to engineer recombinant reoviruses for vaccine and oncolytic applications. PMID:21798351

  2. Remote Whispering Applying Time Reversal

    SciTech Connect

    Anderson, Brian Eric

    2015-07-16

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wires and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.

  3. Kondorski reversal in magnetic nanowires

    NASA Astrophysics Data System (ADS)

    Skomski, Ralph; Schubert, Eva; Enders, Axel; Sellmyer, D. J.

    2014-05-01

    Magnetization reversal in nanowire systems, such as alnico-type permanent magnets, slanted columns produced by glancing-angle deposition, and nanowires embedded in alumina templates, is investigated by model calculations. The angular dependence of the domain-wall propagation is Kondorski-like, reminiscent of Kondorski pinning in bulk materials but with a somewhat different physics and consistent with Kerr hysteresis-loop measurements. Criss-cross patterning of alnicos improves the coercivity but reduces the remanence, with virtually zero net effect on energy product. Finally, we briefly discuss the wire-radius dependence of the coercivity in the context of "shape anisotropy" and the occurrence of interaction domains in alnico.

  4. Corrosion protected reversing heat exchanger

    SciTech Connect

    Zawierucha, R.

    1984-09-25

    A reversing heat exchanger of the plate and fin type having multiple aluminum parting sheets in a stacked arrangement with corrugated fins separating the sheets to form multiple flow paths, means for closing the ends of the sheets, an input manifold arrangement of headers for the warm end of of the exchanger and an output manifold arrangement for the cold end of the exchanger with the input air feed stream header and the waste gas exhaust header having an alloy of zinc and aluminum coated on the inside surface for providing corrosion protection to the stack.

  5. Reversible Photoswitching of Carbon Dots

    PubMed Central

    Khan, Syamantak; Verma, Navneet Chandra; Gupta, Abhishek; Nandi, Chayan Kanti

    2015-01-01

    We present a method of reversible photoswitching in carbon nanodots with red emission. A mechanism of electron transfer is proposed. The cationic dark state, formed by the exposure of red light, is revived back to the bright state with the very short exposure of blue light. Additionally, the natural on-off state of carbon dot fluorescence was tuned using an electron acceptor molecule. Our observation can make the carbon dots as an excellent candidate for the super-resolution imaging of nanoscale biomolecules within the cell. PMID:26078266

  6. Steganography using reversible texture synthesis.

    PubMed

    Wu, Kuo-Chen; Wang, Chung-Ming

    2015-01-01

    We propose a novel approach for steganography using a reversible texture synthesis. A texture synthesis process resamples a smaller texture image, which synthesizes a new texture image with a similar local appearance and an arbitrary size. We weave the texture synthesis process into steganography to conceal secret messages. In contrast to using an existing cover image to hide messages, our algorithm conceals the source texture image and embeds secret messages through the process of texture synthesis. This allows us to extract the secret messages and source texture from a stego synthetic texture. Our approach offers three distinct advantages. First, our scheme offers the embedding capacity that is proportional to the size of the stego texture image. Second, a steganalytic algorithm is not likely to defeat our steganographic approach. Third, the reversible capability inherited from our scheme provides functionality, which allows recovery of the source texture. Experimental results have verified that our proposed algorithm can provide various numbers of embedding capacities, produce a visually plausible texture images, and recover the source texture. PMID:25415988

  7. Multiwire Thermocouples in Reversing Flow

    NASA Technical Reports Server (NTRS)

    Forney, L. J.; Fralick, G. C.

    1995-01-01

    Measurements are recorded for multiwire thermocouples consisting of either two or three wires of unequal diameters. Signals from the multiwire probe are recorded for a reversing gas flow with both a periodic temperature and time constant fluctuation. It is demonstrated that the reconstructed signal from the multiwire thermocouple requires no compensation provided omega/omega(sub 1) less than 2.3 for two wires or omega/omega(sub 1) less than 3.6 for three wires where omega(sub 1) (= 2(pi)f) is the natural frequency of the smaller wire based on the maximum gas velocity. The latter results were possible provided Fourier transformed data from the wires were used and knowledge of the gas velocity phase angle was available.

  8. Investigations of reversible thermochromic mixtures

    NASA Astrophysics Data System (ADS)

    MacLaren, Douglas C.

    Three-component organic thermochromic systems have potential applications in reversible, rewritable thermal printing. In principle, such mixtures could maintain a coloured or non-coloured state at ambient temperature depending on their thermal treatment. These systems generally consist of a functional dye (1--3 mol%), a weakly acidic colour developer (5--25 mol%), and a high-melting organic solvent (75--90 mol%). Colour development occurs at the fusion temperature of the mixture, which triggers the interaction of the dye and developer. Slow cooling of the melt results in an equilibrium state with low colour density, whereas rapid cooling of the melt results in a metastable state with high colour density. The metastable state can be decoloured by heating to an intermediate decolourisation temperature at which the coloured state becomes unstable. Barriers to the widespread use of reversible, rewritable thermochromic materials include problems with colour contrast, colour stability, and decolourisation rates. Development is hindered by a lack of detailed knowledge of the interactions between components in these systems. In this study the developer-dye and developer-solvent interactions were examined for an archetypal dye/developer/solvent thermochromic system. Vibrational spectroscopy, NMR, and thermal analysis were used to examine compounds formed in developer/dye and developer/solvent binary mixtures. Rewritable thermochromic properties such as metastable colour density, equilibrium colour density, and decolourisation rates were examined and discussed in terms of the thermodynamics of the developer/dye and developer/solvent interactions. Observed thermochromic properties are shown to be strongly correlated to a competition between the dye and the solvent for interaction with the developer. Increasing the attractive interaction between the solvent and developer results in enhanced rewritable thermochromic properties.

  9. Process of forming compounds using reverse micelle or reverse microemulsion systems

    DOEpatents

    Linehan, John C.; Fulton, John L.; Bean, Roger M.

    1998-01-01

    The present invention is directed to a process for producing a nanometer-sized metal compound. The process comprises forming a reverse micelle or reverse microemulsion system comprising a polar fluid in a non-polar or low-polarity fluid. A first reactant comprising a multi-component, water-soluble metal compound is introduced into the polar fluid in a non-polar or low-polarity fluid. This first reactant can be introduced into the reverse micelle or reverse microemulsion system during formation thereof or subsequent to the formation of the reverse micelle or microemulsion system. The water-soluble metal compound is then reacted in the reverse micelle or reverse microemulsion system to form the nanometer-sized metal compound. The nanometer-sized metal compound is then precipitated from the reverse micelle or reverse microemulsion system.

  10. Periodicity of the earth's magnetic reversals

    NASA Technical Reports Server (NTRS)

    Stothers, R. B.

    1986-01-01

    Results are presented from an attempt to perform a relatively comprehensive analysis of the evidence for a periodicity, with harmonics, of the observed regular reversals of the earth's magnetic field. The database considered covers 296 reversals over the past 165 Myr. Histograms with bins 1 Myr apart reveal only 30 Myr reversal patterns. The reversal dates are fitted to a linear periodic function and a spectrum is computed for the residuals at the adopted dates. The possible presence of multiple periodicities is evaluated and over various time intervals. The analysis shows that a recently observed 15 Myr periodicity is probably a harmonic of the 29.5-30.5 Myr period. The calculations do not confirm an inherent magnetic reversal property of the earth. The reversals may arise from tectonic events or from impacts from extraterrestrial objects.

  11. Gravity controlled anti-reverse rotation device

    DOEpatents

    Dickinson, Robert J.; Wetherill, Todd M.

    1983-01-01

    A gravity assisted anti-reverse rotation device for preventing reverse rotation of pumps and the like. A horizontally mounted pawl is disposed to mesh with a fixed ratchet preventing reverse rotation when the pawl is advanced into intercourse with the ratchet by a vertically mounted lever having a lumped mass. Gravitation action on the lumped mass urges the pawl into mesh with the ratchet, while centrifugal force on the lumped mass during forward, allowed rotation retracts the pawl away from the ratchet.

  12. On the regimes of charge reversal.

    PubMed

    Jiménez-Angeles, Felipe; Lozada-Cassou, Marcelo

    2008-05-01

    Charge reversal of the planar electrical double layer is studied by means of a well known integral equation theory. By a numerical analysis, a diagram is constructed with the onset points of charge reversal in the space of the fundamental variables of the system. Within this diagram, two regimes of charge reversal are identified, which are referred to as oscillatory and nonoscillatory. We found that these two regimes can be distinguished through a simple formula. Furthermore, a symmetry between electrostatic and size correlations in charge reversal is exhibited. Agreement of our results with other theories and molecular simulations data is discussed. PMID:18465930

  13. Sickle cell disease and posterior reversible leukoencephalopathy.

    PubMed

    Geevasinga, Nimeshan; Cole, Catherine; Herkes, Geoffrey K; Barnett, Yael; Lin, Jamie; Needham, Merrilee

    2014-08-01

    Sickle cell disease can present with neurological manifestations. One such presentation is with posterior reversible leukoencephalopathy also known as reversible posterior leukoencephalopathy. The condition is classically described as reversible over time; it commonly presents with oedematous changes involving the white matter of the occipital and parietal regions. Only a few patients with the association between sickle cell disease and posterior reversible leukoencephalopathy have been described in the adult literature. We present two patients from our institutions to emphasise the association between the two conditions and summarise the published cases in the literature. PMID:24656986

  14. Reversing expectations during discourse comprehension

    PubMed Central

    Xiang, Ming; Kuperberg, Gina

    2014-01-01

    In two ERP experiments, we asked whether comprehenders used the concessive connective, even so, to predict upcoming events. Participants read coherent and incoherent scenarios, with and without even so, e.g. “Elizabeth had a history exam on Monday. She took the test and aced/failed it. (Even so), she went home and celebrated wildly.”, as they rated coherence (Experiment 1) or simply answered intermittent comprehension questions (Experiment 2). The semantic function of even so was used to reverse real-world knowledge predictions, leading to an attenuated N400 to coherent versus incoherent target words (“celebrated”). Moreover, its pragmatic communicative function enhanced predictive processing, leading to more N400 attenuation to coherent targets in scenarios with than without even so. This benefit however, did not come for free: the detection of failed event predictions triggered a later posterior positivity and/or an anterior negativity effect, and costs of maintaining alternative likelihood relations manifest as a sustained negativity effect on sentence-final words. PMID:25914891

  15. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  16. High Performance Field Reversed Configurations

    NASA Astrophysics Data System (ADS)

    Binderbauer, Michl

    2014-10-01

    The field-reversed configuration (FRC) is a prolate compact toroid with poloidal magnetic fields. FRCs could lead to economic fusion reactors with high power density, simple geometry, natural divertor, ease of translation, and possibly capable of burning aneutronic fuels. However, as in other high-beta plasmas, there are stability and confinement concerns. These concerns can be addressed by introducing and maintaining a significant fast ion population in the system. This is the approach adopted by TAE and implemented for the first time in the C-2 device. Studying the physics of FRCs driven by Neutral Beam (NB) injection, significant improvements were made in confinement and stability. Early C-2 discharges had relatively good confinement, but global power losses exceeded the available NB input power. The addition of axially streaming plasma guns, magnetic end plugs as well as advanced surface conditioning leads to dramatic reductions in turbulence driven losses and greatly improved stability. As a result, fast ion confinement significantly improved and allowed for build-up of a dominant fast particle population. Under such appropriate conditions we achieved highly reproducible, long-lived, macroscopically stable FRCs with record lifetimes. This demonstrated many beneficial effects of large orbit particles and their performance impact on FRCs Together these achievements point to the prospect of beam-driven FRCs as a path toward fusion reactors. This presentation will review and expand on key results and present context for their interpretation.

  17. Entropic uncertainty and measurement reversibility

    NASA Astrophysics Data System (ADS)

    Berta, Mario; Wehner, Stephanie; Wilde, Mark M.

    2016-07-01

    The entropic uncertainty relation with quantum side information (EUR-QSI) from (Berta et al 2010 Nat. Phys. 6 659) is a unifying principle relating two distinctive features of quantum mechanics: quantum uncertainty due to measurement incompatibility, and entanglement. In these relations, quantum uncertainty takes the form of preparation uncertainty where one of two incompatible measurements is applied. In particular, the ‘uncertainty witness’ lower bound in the EUR-QSI is not a function of a post-measurement state. An insightful proof of the EUR-QSI from (Coles et al 2012 Phys. Rev. Lett. 108 210405) makes use of a fundamental mathematical consequence of the postulates of quantum mechanics known as the non-increase of quantum relative entropy under quantum channels. Here, we exploit this perspective to establish a tightening of the EUR-QSI which adds a new state-dependent term in the lower bound, related to how well one can reverse the action of a quantum measurement. As such, this new term is a direct function of the post-measurement state and can be thought of as quantifying how much disturbance a given measurement causes. Our result thus quantitatively unifies this feature of quantum mechanics with the others mentioned above. We have experimentally tested our theoretical predictions on the IBM quantum experience and find reasonable agreement between our predictions and experimental outcomes.

  18. Reverse transcriptase inhibitors as microbicides.

    PubMed

    Lewi, Paul; Heeres, Jan; Ariën, Kevin; Venkatraj, Muthusamy; Joossens, Jurgen; Van der Veken, Pieter; Augustyns, Koen; Vanham, Guido

    2012-01-01

    The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies. PMID:22264043

  19. Reverse Genetics in Ecological Research

    PubMed Central

    Schwachtje, Jens; Kutschbach, Susan; Baldwin, Ian T.

    2008-01-01

    By precisely manipulating the expression of individual genetic elements thought to be important for ecological performance, reverse genetics has the potential to revolutionize plant ecology. However, untested concerns about possible side-effects of the transformation technique, caused by Agrobacterium infection and tissue culture, on plant performance have stymied research by requiring onerous sample sizes. We compare 5 independently transformed Nicotiana attenuata lines harboring empty vector control (EVC) T-DNA lacking silencing information with isogenic wild types (WT), and measured a battery of ecologically relevant traits, known to be important in plant-herbivore interactions: phytohormones, secondary metabolites, growth and fitness parameters under stringent competitive conditions, and transcriptional regulation with microarrays. As a positive control, we included a line silenced in trypsin proteinase inhibitor gene (TPI) expression, a potent anti-herbivore defense known to exact fitness costs in its expression, in the analysis. The experiment was conducted twice, with 10 and 20 biological replicates per genotype. For all parameters, we detected no difference between any EVC and WT lines, but could readily detect a fitness benefit of silencing TPI production. A statistical power analyses revealed that the minimum sample sizes required for detecting significant fitness differences between EVC and WT was 2–3 orders of magnitude larger than the 10 replicates required to detect a fitness effect of TPI silencing. We conclude that possible side-effects of transformation are far too low to obfuscate the study of ecologically relevant phenotypes. PMID:18253491

  20. Reversing Africa's Decline. Worldwatch Paper 65.

    ERIC Educational Resources Information Center

    Brown, Lester R.; Wolf, Edward C.

    This paper highlights some of the themes that any successful strategy to reverse the decline of Africa must embrace. Africa is a continent experiencing a breakdown in the relationship between people and their natural support systems. Famine and the threat of famine are among the manifestations of this breakdown. This decline can be reversed. To do…

  1. Sotalol-induced bradycardia reversed by glucagon.

    PubMed Central

    Fernandes, C. M.; Daya, M. R.

    1995-01-01

    Glucagon is considered the drug of choice for treating bradycardia and hypotension encountered during beta-blocker poisoning. Its potential usefulness in reversing adverse effects encountered during therapeutic dosing with beta-blockers has not been well characterized. We present a case of sotalol-induced bradycardia reversed by glucagon. PMID:7787496

  2. 32 CFR 701.37 - Reverse FOIA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Reverse FOIA. 701.37 Section 701.37 National... DOCUMENTS AFFECTING THE PUBLIC FOIA Definitions and Terms § 701.37 Reverse FOIA. When the “submitter” of... revealing the data to a third party in response to the latter's FOIA request....

  3. 32 CFR 701.37 - Reverse FOIA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Reverse FOIA. 701.37 Section 701.37 National... DOCUMENTS AFFECTING THE PUBLIC FOIA Definitions and Terms § 701.37 Reverse FOIA. When the “submitter” of... revealing the data to a third party in response to the latter's FOIA request....

  4. 32 CFR 701.37 - Reverse FOIA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Reverse FOIA. 701.37 Section 701.37 National... DOCUMENTS AFFECTING THE PUBLIC FOIA Definitions and Terms § 701.37 Reverse FOIA. When the “submitter” of... revealing the data to a third party in response to the latter's FOIA request....

  5. 32 CFR 701.37 - Reverse FOIA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Reverse FOIA. 701.37 Section 701.37 National... DOCUMENTS AFFECTING THE PUBLIC FOIA Definitions and Terms § 701.37 Reverse FOIA. When the “submitter” of... revealing the data to a third party in response to the latter's FOIA request....

  6. 32 CFR 701.37 - Reverse FOIA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Reverse FOIA. 701.37 Section 701.37 National... DOCUMENTS AFFECTING THE PUBLIC FOIA Definitions and Terms § 701.37 Reverse FOIA. When the “submitter” of... revealing the data to a third party in response to the latter's FOIA request....

  7. The Rate Laws for Reversible Reactions.

    ERIC Educational Resources Information Center

    King, Edward L.

    1986-01-01

    Provides background information for teachers on the rate laws for reversible reactions. Indicates that although prediction of the form of the rate law for a reverse reaction given the rate law for the forward reaction is not certain, the number of possibilities is limited because of relationships described. (JN)

  8. Reverse Transfer Students: Characteristics, Motivations, and Implications

    ERIC Educational Resources Information Center

    Lowrey, Kathryn Elizabeth

    2010-01-01

    The reverse transfer literature contains studies investigating the demographic characteristics of postsecondary students that attended a community college after attending a four-year institution, and their proportion in the community college student population. A few researchers have investigated reverse transfer student motives for enrolling in…

  9. Reversible logic gates on Physarum Polycephalum

    SciTech Connect

    Schumann, Andrew

    2015-03-10

    In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum.

  10. Neuronal Activation for Semantically Reversible Sentences

    ERIC Educational Resources Information Center

    Richardson, Fiona M.; Thomas, Michael S. C.; Price, Cathy J.

    2010-01-01

    Semantically reversible sentences are prone to misinterpretation and take longer for typically developing children and adults to comprehend; they are also particularly problematic for those with language difficulties such as aphasia or Specific Language Impairment. In our study, we used fMRI to compare the processing of semantically reversible and…

  11. 14 CFR 25.507 - Reversed braking.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Reversed braking. 25.507 Section 25.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Ground Loads § 25.507 Reversed braking. (a) The airplane must be in a three point static...

  12. 14 CFR 25.507 - Reversed braking.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Reversed braking. 25.507 Section 25.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Ground Loads § 25.507 Reversed braking. (a) The airplane must be in a three point static...

  13. 14 CFR 25.507 - Reversed braking.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Reversed braking. 25.507 Section 25.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Ground Loads § 25.507 Reversed braking. (a) The airplane must be in a three point static...

  14. 14 CFR 25.507 - Reversed braking.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Reversed braking. 25.507 Section 25.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Ground Loads § 25.507 Reversed braking. (a) The airplane must be in a three point static...

  15. 14 CFR 25.507 - Reversed braking.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Reversed braking. 25.507 Section 25.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Ground Loads § 25.507 Reversed braking. (a) The airplane must be in a three point static...

  16. 14 CFR 33.97 - Thrust reversers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Thrust reversers. 33.97 Section 33.97 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If...

  17. 14 CFR 33.97 - Thrust reversers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Thrust reversers. 33.97 Section 33.97 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If...

  18. 14 CFR 33.97 - Thrust reversers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Thrust reversers. 33.97 Section 33.97 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If...

  19. 43 CFR 2641.5 - Reversion.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Reversion. 2641.5 Section 2641.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) FAA AIRPORT GRANTS Procedures § 2641.5 Reversion....

  20. 43 CFR 2641.5 - Reversion.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Reversion. 2641.5 Section 2641.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) FAA AIRPORT GRANTS Procedures § 2641.5 Reversion. A conveyance shall be made only on the...

  1. Three component vibrational time reversal communication

    DOE PAGESBeta

    Anderson, Brian E.; Ulrich, Timothy J.; Ten Cate, James A.

    2015-01-01

    Time reversal provides an optimal prefilter matched signal to apply to a communication signal before signal transmission. Time reversal allows compensation for wave speed dispersion and can function well in reverberant environments. Time reversal can be used to focus elastic energy to each of the three components of motion independently. A pipe encased in concrete was used to demonstrate the ability to conduct communications of information using three component time reversal. Furthermore, the ability of time reversal to compensate for multi-path distortion (overcoming reverberation) will be demonstrated and the rate of signal communication will be presented. [The U.S. Department ofmore » Energy, through the LANL/LDRD Program, is gratefully acknowledged for supporting this work.]« less

  2. Three component vibrational time reversal communication

    SciTech Connect

    Anderson, Brian E.; Ulrich, Timothy J.; Ten Cate, James A.

    2015-01-01

    Time reversal provides an optimal prefilter matched signal to apply to a communication signal before signal transmission. Time reversal allows compensation for wave speed dispersion and can function well in reverberant environments. Time reversal can be used to focus elastic energy to each of the three components of motion independently. A pipe encased in concrete was used to demonstrate the ability to conduct communications of information using three component time reversal. Furthermore, the ability of time reversal to compensate for multi-path distortion (overcoming reverberation) will be demonstrated and the rate of signal communication will be presented. [The U.S. Department of Energy, through the LANL/LDRD Program, is gratefully acknowledged for supporting this work.

  3. Parkinson’s disease managing reversible neurodegeneration

    PubMed Central

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

  4. Estimation and uncertainty of reversible Markov models

    NASA Astrophysics Data System (ADS)

    Trendelkamp-Schroer, Benjamin; Wu, Hao; Paul, Fabian; Noé, Frank

    2015-11-01

    Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta-stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software — http://pyemma.org — as of version 2.0.

  5. Improving the Convergence of Reversible Samplers

    NASA Astrophysics Data System (ADS)

    Rey-Bellet, Luc; Spiliopoulos, Konstantinos

    2016-06-01

    In Monte-Carlo methods the Markov processes used to sample a given target distribution usually satisfy detailed balance, i.e. they are time-reversible. However, relatively recent results have demonstrated that appropriate reversible and irreversible perturbations can accelerate convergence to equilibrium. In this paper we present some general design principles which apply to general Markov processes. Working with the generator of Markov processes, we prove that for some of the most commonly used performance criteria, i.e., spectral gap, asymptotic variance and large deviation functionals, sampling is improved for appropriate reversible and irreversible perturbations of some initially given reversible sampler. Moreover we provide specific constructions for such reversible and irreversible perturbations for various commonly used Markov processes, such as Markov chains and diffusions. In the case of diffusions, we make the discussion more specific using the large deviations rate function as a measure of performance.

  6. Improving the Convergence of Reversible Samplers

    NASA Astrophysics Data System (ADS)

    Rey-Bellet, Luc; Spiliopoulos, Konstantinos

    2016-08-01

    In Monte-Carlo methods the Markov processes used to sample a given target distribution usually satisfy detailed balance, i.e. they are time-reversible. However, relatively recent results have demonstrated that appropriate reversible and irreversible perturbations can accelerate convergence to equilibrium. In this paper we present some general design principles which apply to general Markov processes. Working with the generator of Markov processes, we prove that for some of the most commonly used performance criteria, i.e., spectral gap, asymptotic variance and large deviation functionals, sampling is improved for appropriate reversible and irreversible perturbations of some initially given reversible sampler. Moreover we provide specific constructions for such reversible and irreversible perturbations for various commonly used Markov processes, such as Markov chains and diffusions. In the case of diffusions, we make the discussion more specific using the large deviations rate function as a measure of performance.

  7. MANAGEMENT OF ENDOCRINE DISEASE: Reversible hypogonadotropic hypogonadism.

    PubMed

    Dwyer, Andrew A; Raivio, Taneli; Pitteloud, Nelly

    2016-06-01

    Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of puberty and infertility. Traditionally, it has been considered a life-long condition yet cases of reversibility have been described wherein patients spontaneously recover function of the reproductive axis following treatment. Reversibility occurs in both male and female CHH cases and appears to be more common (~10-15%) than previously thought. These reversal patients span a range of GnRH deficiency from mild to severe and many reversal patients harbor mutations in genes underlying CHH. However, to date there are no clear factors for predicting reversible CHH. Importantly, recovery of reproductive axis function may not be permanent. Thus, CHH is not always life-long and the incidence of reversal warrants periodic treatment withdrawal with close monitoring and follow-up. Reversible CHH highlights the importance of environmental (epigenetic) factors such as sex steroid treatment on the reproductive axis in modifying the phenotype. This review provides an overview and an update on what is known about this phenomenon. PMID:26792935

  8. Partial spin reversal in magnetic deflagration

    NASA Astrophysics Data System (ADS)

    Vélez, S.; Subedi, P.; Macià, F.; Li, S.; Sarachik, M. P.; Tejada, J.; Mukherjee, S.; Christou, G.; Kent, A. D.

    2014-04-01

    The reversal of spins in a magnetic material as they relax toward equilibrium is accompanied by the release of Zeeman energy, which can lead to accelerated spin relaxation and the formation of a well-defined self-sustained propagating spin-reversal front known as magnetic deflagration. To date, studies of Mn12-acetate single crystals have focused mainly on deflagration in large longitudinal magnetic fields, and they found a fully spin-reversed final state. We report a systematic study of the effect of a transverse magnetic field on magnetic deflagration, and we demonstrate that in small longitudinal fields the final state consists of only partially reversed spins. Further, we measured the front speed as a function of applied magnetic field. The theory of magnetic deflagration, together with a modification that takes into account partial spin reversal, fits the transverse field dependence of the front speed but not its dependence on the longitudinal field. The most significant result of this study is the finding of a partially spin-reversed final state, which is evidence that the spins at the deflagration front are also only partially reversed.

  9. Chemical reactions in reverse micelle systems

    DOEpatents

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.

    1993-08-24

    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.

  10. Why Contextual Preference Reversals Maximize Expected Value

    PubMed Central

    2016-01-01

    Contextual preference reversals occur when a preference for one option over another is reversed by the addition of further options. It has been argued that the occurrence of preference reversals in human behavior shows that people violate the axioms of rational choice and that people are not, therefore, expected value maximizers. In contrast, we demonstrate that if a person is only able to make noisy calculations of expected value and noisy observations of the ordinal relations among option features, then the expected value maximizing choice is influenced by the addition of new options and does give rise to apparent preference reversals. We explore the implications of expected value maximizing choice, conditioned on noisy observations, for a range of contextual preference reversal types—including attraction, compromise, similarity, and phantom effects. These preference reversal types have played a key role in the development of models of human choice. We conclude that experiments demonstrating contextual preference reversals are not evidence for irrationality. They are, however, a consequence of expected value maximization given noisy observations. PMID:27337391

  11. Reversibility and efficiency in coding protein information.

    PubMed

    Tamir, Boaz; Priel, Avner

    2010-12-21

    Why the genetic code has a fixed length? Protein information is transferred by coding each amino acid using codons whose length equals 3 for all amino acids. Hence the most probable and the least probable amino acid get a codeword with an equal length. Moreover, the distributions of amino acids found in nature are not uniform and therefore the efficiency of such codes is sub-optimal. The origins of these apparently non-efficient codes are yet unclear. In this paper we propose an a priori argument for the energy efficiency of such codes resulting from their reversibility, in contrast to their time inefficiency. Such codes are reversible in the sense that a primitive processor, reading three letters in each step, can always reverse its operation, undoing its process. We examine the codes for the distributions of amino acids that exist in nature and show that they could not be both time efficient and reversible. We investigate a family of Zipf-type distributions and present their efficient (non-fixed length) prefix code, their graphs, and the condition for their reversibility. We prove that for a large family of such distributions, if the code is time efficient, it could not be reversible. In other words, if pre-biotic processes demand reversibility, the protein code could not be time efficient. The benefits of reversibility are clear: reversible processes are adiabatic, namely, they dissipate a very small amount of energy. Such processes must be done slowly enough; therefore time efficiency is non-important. It is reasonable to assume that early biochemical complexes were more prone towards energy efficiency, where forward and backward processes were almost symmetrical. PMID:20868696

  12. Time reversibility in the quantum frame

    SciTech Connect

    Masot-Conde, Fátima

    2014-12-04

    Classic Mechanics and Electromagnetism, conventionally taken as time-reversible, share the same concept of motion (either of mass or charge) as the basis of the time reversibility in their own fields. This paper focuses on the relationship between mobile geometry and motion reversibility. The goal is to extrapolate the conclusions to the quantum frame, where matter and radiation behave just as elementary mobiles. The possibility that the asymmetry of Time (Time’s arrow) is an effect of a fundamental quantum asymmetry of elementary particles, turns out to be a consequence of the discussion.

  13. Biomechanics of reverse total shoulder arthroplasty.

    PubMed

    Berliner, Jonathan L; Regalado-Magdos, Ashton; Ma, C Benjamin; Feeley, Brian T

    2015-01-01

    Reverse total shoulder arthroplasty is an effective procedure for treatment of glenohumeral joint disease among patients with severe rotator cuff deficiency. Improvements in prosthetic design are the result of an evolved understanding of both shoulder and joint replacement biomechanics. Although modern generations of the reverse shoulder prosthesis vary in specific design details, they continue to adhere to Grammont's core principles demonstrated by his original Delta III prosthesis. This review article discusses the biomechanics of reverse total shoulder arthroplasty with a focus on elements of implant design and surgical technique that may affect stability, postoperative complications, and functional outcomes. PMID:25441574

  14. Cheaper Adjoints by Reversing Address Computations

    DOE PAGESBeta

    Hascoët, L.; Utke, J.; Naumann, U.

    2008-01-01

    The reverse mode of automatic differentiation is widely used in science and engineering. A severe bottleneck for the performance of the reverse mode, however, is the necessity to recover certain intermediate values of the program in reverse order. Among these values are computed addresses, which traditionally are recovered through forward recomputation and storage in memory. We propose an alternative approach for recovery that uses inverse computation based on dependency information. Address storage constitutes a significant portion of the overall storage requirements. An example illustrates substantial gains that the proposed approach yields, and we show use cases in practical applications.

  15. Constraining the reversing and non-reversing modes of the geodynamo. New insights from magnetostratigraphy.

    NASA Astrophysics Data System (ADS)

    Gallet, Y.; Pavlov, V.; Shatsillo, A.; Hulot, G.

    2015-12-01

    Constraining the evolution in the geomagnetic reversal frequency over hundreds of million years is not a trivial matter. Beyond the fact that there are long periods without reversals, known as superchrons, and periods with many reversals, the way the reversal frequency changes through time during reversing periods is still debated. A smooth evolution or a succession of stationary segments have both been suggested to account for the geomagnetic polarity time scale since the Middle-Late Jurassic. Sudden changes from a reversing mode to a non-reversing mode of the geodynamo may also well have happened, the switch between the two modes having then possibly been controlled by the thermal conditions at the core-mantle boundary. There is, nevertheless, a growing set of magnetostratigraphic data, which could help decipher a proper interpretation of the reversal history, in particular in the early Paleozoic and even during the Precambrian. Although yielding a fragmentary record, these data reveal the occurrence of both additional superchrons and periods characterized by extremely high, not to say extraordinary, magnetic reversal frequencies. In this talk, we will present a synthesis of these data, mainly obtained from Siberia, and discuss their implication for the magnetic reversal behavior over the past billion years.

  16. Reverse Engineering Adverse Outcome Pathways in Ecotoxicology

    EPA Science Inventory

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, meabolic, signaling) t...

  17. Pressure reversal study through tensile tests

    SciTech Connect

    Swinson, W.F.; Battiste, R.L.; Wright, A.L.; Yahr, G.T.; Robertson, J.P.

    1997-12-31

    This paper is a summary of the results from a study of the variables related to pressure reversal and was sponsored by the US Department of Transportation, Office of Pipeline Safety. The circumferential pipe stress, which is the most significant variable in pressure reversal, was examined by using tensile specimens and then relating the results to pressurized pipe. A model is proposed that gives some insight into how pressure reversal can be minimized when a section of pipe is being hydrotested. Twenty tensile specimens from X-42 electric resistance welded (ERW) pipe and twenty specimens from X-52 ERW pipe were tested. Each specimen had a machined flaw. The flaw regions were monitored using strain gages and photoelasticity. These tensile tests represent the first phase of a research effort to examine and understand the variables related to pressure reversal. The second phase of this effort will be with pipe specimens and presently is in progress.

  18. Posterior Reversible Encephalopathy Syndrome in ALL.

    PubMed

    Millichap, J Gordon

    2015-07-01

    Investigators from Soochow University, Suzhou, China, studied the possible pathogenetic mechanisms and treatment of posterior reversible encephalopathy syndrome (PRES) observed in 11 cases of pediatric acute lymphoblastic leukemia (ALL) after induction chemotherapy. PMID:26933594

  19. Chain friction system gives positive, reversible drive

    NASA Technical Reports Server (NTRS)

    Davidsen, J. S.

    1964-01-01

    By cementing a strip of an elastomer to the smooth metal rim of the pulley and neoprene covered idlers providing suitable tension to the chain around the pulley, a positive reversible drive is accomplished more quietly and with less vibration.

  20. Reverse-osmosis membranes by plasma polymerization

    NASA Technical Reports Server (NTRS)

    Hollahan, J. R.; Wydeven, T.

    1972-01-01

    Thin allyl amine polymer films were developed using plasma polymerization. Resulting dry composite membranes effectively reject sodium chloride during reverse osmosis. Films are 98% sodium chloride rejective, and 46% urea rejective.

  1. Local heating realization by reverse thermal cloak

    PubMed Central

    Hu, Run; Wei, Xuli; Hu, Jinyan; Luo, Xiaobing

    2014-01-01

    Transformation thermodynamics, as one of the important branches among the extensions of transformation optics, has attracted plentiful attentions and interests recently. The result of transformation thermodynamics, or called as “thermal cloak”, can realize isothermal region and hide objects from heat. In this paper, we presented the concept of “reverse thermal cloak” to correspond to the thermal cloak and made a simple engineering definition to identify them. By full-wave simulations, we verified that the reverse thermal cloak can concentrate heat and realize local heating. The performance of local heating depends on the anisotropic dispersion of the cloaking layer's thermal conductivity. Three-dimensional finite element simulations demonstrated that the reverse thermal cloak can be used to heat up objects. Besides pre-engineered metamaterials, such reverse thermal cloak can even be realized with homogenous materials by alternating spoke-like structure or Hashin coated-sphere structure. PMID:24398592

  2. Flow reversal power limit for the HFBR

    SciTech Connect

    Cheng, Lap Y.; Tichler, P.R.

    1995-10-01

    The High Flux Beam Reactor (HFBR) undergoes a buoyancy-driven reversal of flow in the reactor core following certain postulated accidents. Uncertainties about the afterheat removal capability during the flow reversal has limited the reactor operating power to 30 MW. An experimental and analytical program to address these uncertainties is described in this report. The experiments were single channel flow reversal tests under a range of conditions. The analytical phase involved simulations of the tests to benchmark the physical models and development of a criterion for dryout. The criterion is then used in simulations of reactor accidents to determine a safe operating power level. It is concluded that the limit on the HFBR operating power with respect to the issue of flow reversal is in excess of 60 MW.

  3. Local heating realization by reverse thermal cloak.

    PubMed

    Hu, Run; Wei, Xuli; Hu, Jinyan; Luo, Xiaobing

    2014-01-01

    Transformation thermodynamics, as one of the important branches among the extensions of transformation optics, has attracted plentiful attentions and interests recently. The result of transformation thermodynamics, or called as "thermal cloak", can realize isothermal region and hide objects from heat. In this paper, we presented the concept of "reverse thermal cloak" to correspond to the thermal cloak and made a simple engineering definition to identify them. By full-wave simulations, we verified that the reverse thermal cloak can concentrate heat and realize local heating. The performance of local heating depends on the anisotropic dispersion of the cloaking layer's thermal conductivity. Three-dimensional finite element simulations demonstrated that the reverse thermal cloak can be used to heat up objects. Besides pre-engineered metamaterials, such reverse thermal cloak can even be realized with homogenous materials by alternating spoke-like structure or Hashin coated-sphere structure. PMID:24398592

  4. RNA Virus Reverse Genetics and Vaccine Design

    PubMed Central

    Stobart, Christopher C.; Moore, Martin L.

    2014-01-01

    RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. PMID:24967693

  5. Ciprofloxacin-associated posterior reversible encephalopathy

    PubMed Central

    Al Bu Ali, Waleed Hammad

    2013-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterised by numerous symptoms and of no specific aetiology. Headache, confusion, seizures, cortical visual disturbances or blindness are the key symptoms. As this syndrome is reversible and readily treated by interrupting or discontinuing the aetiology, it should sharply be acknowledged. Ciprofloxacin was associated with PRES in an adolescent male treated from chest infection. It was managed in a hospital intensive care unit and was observed until disappearance. PMID:23585504

  6. Fertility following reversal of female sterilization.

    PubMed

    Rachagan, S P; Jaafar, Y

    1993-06-01

    This retrospective study presents data from 26 women who underwent a reversal of female sterilization. The intrauterine pregnancy rate and ectopic pregnancy rate were 38.5% and 7.7% respectively. The most successful site of tubal anastomosis was isthmic-isthmic anastomosis. The importance of proper patient selection and factors that affect the success rate in attempted reversals are emphasised. The importance of microsurgical approach is highlighted. PMID:8350801

  7. Another look at children's symbol reversals.

    PubMed

    Patton, J E; Yarbrough, D B; Thursby, D

    2000-04-01

    In a previously reported longitudinal study of reversal errors for static and kinetic written symbols we found no compelling support for their academic importance in kindergarten (n = 201), Grade 1 (n = 156), or Grade 2 (n = 129); however, for Grade 3 (n = 105), kinetic reversals became a significant predictor of tested reading achievement. If reliable, this finding might have implications for the identification of children with long-term reading impairment. PMID:10833756

  8. Vasectomy and vasectomy reversal: An update

    PubMed Central

    Ramasamy, Ranjith; Schlegel, Peter N.

    2011-01-01

    Vasectomy is an elective surgical sterilization procedure for men that is intended to obstruct or remove a portion of both vas deferens, thereby preventing sperm from moving from the testes to the ejaculatory ducts. Although intended for permanent sterilization, vasectomy can be reversed in most men seeking to restore their fertility due to a change in marital status or reproductive goals. The purpose of this document is to provided a synopsis of the latest techniques used in vasectomy and reversal. PMID:21716894

  9. Streamwise Oscillation of Airfoils into Reverse Flow

    NASA Astrophysics Data System (ADS)

    Granlund, Kenneth; Jones, Anya; Ol, Michael

    2015-11-01

    An airfoil in freestream is oscillated in streamwise direction to cyclically enter reverse flow. Measured lift is compared to analytical blade element theories. Advance ratio, reduced frequency and angle of attack is varied within those typical for helicopters. Experimental results reveal that lift does not become negative in the flow reversal part, contradicting one theory and supported by another. Flow visualization reveal the leading edge vortex advecting against the freestream to a point in front of the leading edge.

  10. How the geomagnetic field vector reverses polarity

    USGS Publications Warehouse

    Prevot, M.; Mankinen, E.A.; Gromme, C.S.; Coe, R.S.

    1985-01-01

    A highly detailed record of both the direction and intensity of the Earth's magnetic field as it reverses has been obtained from a Miocene volcanic sequence. The transitional field is low in intensity and is typically non-axisymmetric. Geomagnetic impulses corresponding to astonishingly high rates of change of the field sometimes occur, suggesting that liquid velocity within the Earth's core increases during geomagnetic reversals. ?? 1985 Nature Publishing Group.

  11. Miniature Reversal Electron-Attachment Detector

    NASA Technical Reports Server (NTRS)

    Chutjian, Ara

    1994-01-01

    Miniature reversal electron-attachment detector (miniREAD) enables direct injection of air or vapor at atmospheric pressure from monitored area into mass-spectrometric instrument to detect explosives, narcotics, or other substances, vapors of which suspected of being present in low concentrations. In comparison with older reversal electron-attachment detector, miniREAD simpler in design; more rugged; and easier to build, repair, and maintain. In addition, probably more sensitive.

  12. Geomagnetic reversal in brunhes normal polarity epoch.

    PubMed

    Smith, J D; Foster, J H

    1969-02-01

    The magnetic stratigraphly of seven cores of deep-sea sediment established the existence of a short interval of reversed polarity in the upper part of the Brunches epoch of normal polarity. The reversed zone in the cores correlates well with paleontological boundaries and is named the Blake event. Its boundaries are estimated to be 108,000 and 114,000 years ago +/- 10 percent. PMID:17750890

  13. Emerging Indications for Reverse Shoulder Arthroplasty.

    PubMed

    Urch, Ekaterina; Dines, Joshua S; Dines, David M

    2016-01-01

    Historically, reverse shoulder arthroplasty was reserved for older, low-demand patients in whom rotator cuff arthropathy was diagnosed. Other common indications included sequelae of previously treated proximal humerus fractures, failed anatomic total shoulder arthroplasty, tumor resection, and rheumatoid arthritis in the elderly population. Unpredictable implant durability and high complication rates have limited the use of reverse shoulder arthroplasty to a narrow group of patients. Over the past decade, however, research has led to an improved understanding of the biomechanics behind reverse shoulder prostheses, which has improved implant design and surgical techniques. Consequently, orthopaedic surgeons have slowly begun to expand the indications for reverse shoulder arthroplasty to include a wider spectrum of shoulder pathologies. Recent studies have shown promising results for patients who undergo reverse shoulder arthroplasty for the treatment of acute proximal humerus fractures, massive rotator cuff tears without arthropathy, primary osteoarthritis, and chronic anterior dislocation, as well as for younger patients who have rheumatoid arthritis. These data suggest that, with judicious patient selection, reverse shoulder arthroplasty can be an excellent treatment option for a growing patient cohort. PMID:27049188

  14. Rotating Reverse-Osmosis for Water Purification

    NASA Technical Reports Server (NTRS)

    Lueptow, RIchard M.

    2004-01-01

    A new design for a water-filtering device combines rotating filtration with reverse osmosis to create a rotating reverse- osmosis system. Rotating filtration has been used for separating plasma from whole blood, while reverse osmosis has been used in purification of water and in some chemical processes. Reverse- osmosis membranes are vulnerable to concentration polarization a type of fouling in which the chemicals meant not to pass through the reverse-osmosis membranes accumulate very near the surfaces of the membranes. The combination of rotating filtration and reverse osmosis is intended to prevent concentration polarization and thereby increase the desired flux of filtered water while decreasing the likelihood of passage of undesired chemical species through the filter. Devices based on this concept could be useful in a variety of commercial applications, including purification and desalination of drinking water, purification of pharmaceutical process water, treatment of household and industrial wastewater, and treatment of industrial process water. A rotating filter consists of a cylindrical porous microfilter rotating within a stationary concentric cylindrical outer shell (see figure). The aqueous suspension enters one end of the annulus between the inner and outer cylinders. Filtrate passes through the rotating cylindrical microfilter and is removed via a hollow shaft. The concentrated suspension is removed at the end of the annulus opposite the end where the suspension entered.

  15. Neuronal Activation for Semantically Reversible Sentences

    PubMed Central

    Richardson, Fiona M.; Thomas, Michael S. C.; Price, Cathy J.

    2010-01-01

    Semantically reversible sentences are prone to misinterpretation and take longer for typically developing children and adults to comprehend; they are also particularly problematic for those with language difficulties such as aphasia or Specific Language Impairment. In our study we used fMRI to compare the processing of semantically reversible and nonreversible sentences in 41 healthy participants to identify how semantic reversibility influences neuronal activation. By including several linguistic and nonlinguistic conditions within our paradigm, we were also able to test whether the processing of semantically reversible sentences places additional load on sentence-specific processing, such as syntactic processing and syntactic-semantic integration, or on phonological working memory. Our results identified increased activation for reversible sentences in a region on the left temporal–parietal boundary, which was also activated when the same group of participants carried out an articulation task which involved saying “one, three” repeatedly. We conclude that the processing of semantically reversible sentences places additional demands on the subarticulation component of phonological working memory. PMID:19445603

  16. Time reversals of irreversible quantum maps

    NASA Astrophysics Data System (ADS)

    Aurell, Erik; Zakrzewski, Jakub; Życzkowski, Karol

    2015-09-01

    We propose an alternative notion of time reversal in open quantum systems as represented by linear quantum operations, and a related generalization of classical entropy production in the environment. This functional is the ratio of the probability to observe a transition between two states under the forward and the time reversed dynamics, and leads, as in the classical case, to fluctuation relations as tautological identities. As in classical dynamics in contact with a heat bath, time reversal is not unique, and we discuss several possibilities. For any bistochastic map its dual map preserves the trace and describes a legitimate dynamics reversed in time, in that case the entropy production in the environment vanishes. For a generic stochastic map we construct a simple quantum operation which can be interpreted as a time reversal. For instance, the decaying channel, which sends the excited state into the ground state with a certain probability, can be reversed into the channel transforming the ground state into the excited state with the same probability.

  17. Reversible formation of Ag44 from selenolates

    NASA Astrophysics Data System (ADS)

    Chakraborty, Indranath; Pradeep, T.

    2014-11-01

    The cluster Ag44SePh30, originally prepared from silver selenolate, upon oxidative decomposition by H2O2 gives the same cluster back, in an apparently reversible synthesis. Such an unusual phenomenon was not seen for the corresponding thiolate analogues. From several characterization studies such as mass spectrometry, Raman spectroscopy, etc., it has been confirmed that the degraded and as-synthesized selenolates are the same in nature, which leads to the reversible process. The possibility of making clusters from the degraded material makes cluster synthesis economical. This observation makes one to consider cluster synthesis to be a reversible chemical process, at least for selenolates.The cluster Ag44SePh30, originally prepared from silver selenolate, upon oxidative decomposition by H2O2 gives the same cluster back, in an apparently reversible synthesis. Such an unusual phenomenon was not seen for the corresponding thiolate analogues. From several characterization studies such as mass spectrometry, Raman spectroscopy, etc., it has been confirmed that the degraded and as-synthesized selenolates are the same in nature, which leads to the reversible process. The possibility of making clusters from the degraded material makes cluster synthesis economical. This observation makes one to consider cluster synthesis to be a reversible chemical process, at least for selenolates. Electronic supplementary information (ESI) available: Details of experimental procedures; instrumentation; reversible cycles, UV/Vis spectra of thiophenol, 4-FTP, 3-FTP protected Ag44, and Ag152 cluster; UV/Vis, SEM images and Raman spectra of as-synthesized and degraded thiolates & selenolates; SEM/EDAX of degraded selenolates, UV/Vis of the Ag44(SePh)30 cluster under different selenol concentrations and temperatures. See DOI: 10.1039/c4nr03267e

  18. Reverse logistics in the construction industry.

    PubMed

    Hosseini, M Reza; Rameezdeen, Raufdeen; Chileshe, Nicholas; Lehmann, Steffen

    2015-06-01

    Reverse logistics in construction refers to the movement of products and materials from salvaged buildings to a new construction site. While there is a plethora of studies looking at various aspects of the reverse logistics chain, there is no systematic review of literature on this important subject as applied to the construction industry. Therefore, the objective of this study is to integrate the fragmented body of knowledge on reverse logistics in construction, with the aim of promoting the concept among industry stakeholders and the wider construction community. Through a qualitative meta-analysis, the study synthesises the findings of previous studies and presents some actions needed by industry stakeholders to promote this concept within the real-life context. First, the trend of research and terminology related with reverse logistics is introduced. Second, it unearths the main advantages and barriers of reverse logistics in construction while providing some suggestions to harness the advantages and mitigate these barriers. Finally, it provides a future research direction based on the review. PMID:26018543

  19. How common are ALS plateaus and reversals?

    PubMed Central

    Vaughan, Timothy; Wicks, Paul; Heywood, Jamie; Sinani, Ervin; Selsov, Roger; Macklin, Eric A.; Schoenfeld, David; Cudkowicz, Merit; Sherman, Alex

    2016-01-01

    Objective: To determine the frequency of amyotrophic lateral sclerosis (ALS) plateaus and reversals in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. Methods: We analyzed Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS–revised (ALSFRS-R) data from PRO-ACT participants. The frequencies of participants experiencing plateaus (periods where scores did not change) were calculated over 6-, 12-, and 18-month epochs. The percentage of participants ever experiencing reversals (periods where scores improved) of different lengths were also calculated and plotted. Results: Over 6 months, 25% of 3,132 participants did not decline. Over 12 months, 16% of 2,105 participants did not decline. Over 18 months, 7% of 1,218 participants did not decline. Small ALS reversals were also common, especially over shorter follow-up intervals; 14% of 1,343 participants had a 180-day interval where their ALSFRS-R slope was greater than zero. Fewer than 1% of participants ever experienced improvements of 4 or more ALSFRS-R points lasting at least 12 months. Conclusion: ALS plateaus and small reversals are common, especially over brief intervals. In light of these data, stable disease, especially for a short period of time, should not be interpreted as an ALS treatment effect. Large sustained ALS reversals, on the other hand, are rare, potentially important, and warrant further study. PMID:26658909

  20. Rapidly reversible visual loss in posterior reversible encephalopathy syndrome: An ophthalmologist's enigma.

    PubMed

    Sachdeva, Virender; Garg, Ravi; Pathengay, Avinash; Chandrasekharan, Anjali; Kekunnaya, Ramesh

    2015-01-01

    Posterior reversible encephalopathy Syndrome (PRES) may present with a sudden onset reversible visual loss under special visual conditions. Such patients' may initially be misdiagnosed as Malingering. Ophthalmologists may be the first physicians to be confronted by such patients. Hence, a knowledge of this condition is vital to diagnosis and management of such conditions. PMID:26903736

  1. Conditional reversibility in nonequilibrium stochastic systems.

    PubMed

    Bonança, Marcus V S; Jarzynski, Christopher

    2016-02-01

    For discrete-state stochastic systems obeying Markovian dynamics, we establish the counterpart of the conditional reversibility theorem obtained by Gallavotti for deterministic systems [Ann. de l'Institut Henri Poincaré (A) 70, 429 (1999)]. Our result states that stochastic trajectories conditioned on opposite values of entropy production are related by time reversal, in the long-time limit. In other words, the probability of observing a particular sequence of events, given a long trajectory with a specified entropy production rate σ, is the same as the probability of observing the time-reversed sequence of events, given a trajectory conditioned on the opposite entropy production, -σ, where both trajectories are sampled from the same underlying Markov process. To obtain our result, we use an equivalence between conditioned ("microcanonical") and biased ("canonical") ensembles of nonequilibrium trajectories. We provide an example to illustrate our findings. PMID:26986282

  2. Conditional reversibility in nonequilibrium stochastic systems

    NASA Astrophysics Data System (ADS)

    Bonança, Marcus V. S.; Jarzynski, Christopher

    2016-02-01

    For discrete-state stochastic systems obeying Markovian dynamics, we establish the counterpart of the conditional reversibility theorem obtained by Gallavotti for deterministic systems [Ann. de l'Institut Henri Poincaré (A) 70, 429 (1999)]. Our result states that stochastic trajectories conditioned on opposite values of entropy production are related by time reversal, in the long-time limit. In other words, the probability of observing a particular sequence of events, given a long trajectory with a specified entropy production rate σ , is the same as the probability of observing the time-reversed sequence of events, given a trajectory conditioned on the opposite entropy production, -σ , where both trajectories are sampled from the same underlying Markov process. To obtain our result, we use an equivalence between conditioned ("microcanonical") and biased ("canonical") ensembles of nonequilibrium trajectories. We provide an example to illustrate our findings.

  3. Investigation into reversion of polyurethane encapsulants

    NASA Technical Reports Server (NTRS)

    Lynch, C. R.

    1973-01-01

    The effect of high humidity (95% RH) at 60 C, 70 C, 85 C and 100 C on the solid-to-liquid reversion of polyurethane elastomers (used for potting electrical connectors and conformal coating printed circuit boards) was investigated. Hardness measurements were conducted on eleven elastomers to track reversion for a 101-day period. The primary purpose of the tests was to provide data to predict service life for the polyurethane elastomers. This was not accomplished as the hardness did not deteriorate rapidly enough at the lower test temperatures. The tests did determine that the potting and coating materials most widely used on the S-1C Program are susceptible to reversion but appear adequate for service in the S-1C environment.

  4. The thermodynamics of reversible thermoelectric nanomaterials

    NASA Astrophysics Data System (ADS)

    Humphrey, Tammy; Linke, Heiner

    2005-03-01

    Irreversible effects in thermoelectric materials limit their efficiency and economy for applications in power generation and refrigeration. While electron transport is unavoidably irreversible in bulk materials, here we derive conditions under which reversible diffusive electron transport can be achieved in nanostructured thermoelectric materials via the same physical mechanism utilized in the three-level amplifier (thermally pumped laser) and idealized thermophotovoltaic and thermionic devices. From a broader physical perspective, the most interesting aspect of this work is that it suggests that all of the above-mentioned solid-state devices may be unified as a single `type' of heat engine which achieves reversibility when heat transfer via particle exchange between reservoirs is isentropic (but non-isothermal), in contrast to heat engines such as Carnot, Otto or Brayton cycles, which achieve reversibility when heat transfer between the working gas and heat reservoirs is isothermal.

  5. Optimal design of reverse osmosis module networks

    SciTech Connect

    Maskan, F.; Wiley, D.E.; Johnston, L.P.M.; Clements, D.J.

    2000-05-01

    The structure of individual reverse osmosis modules, the configuration of the module network, and the operating conditions were optimized for seawater and brackish water desalination. The system model included simple mathematical equations to predict the performance of the reverse osmosis modules. The optimization problem was formulated as a constrained multivariable nonlinear optimization. The objective function was the annual profit for the system, consisting of the profit obtained from the permeate, capital cost for the process units, and operating costs associated with energy consumption and maintenance. Optimization of several dual-stage reverse osmosis systems were investigated and compared. It was found that optimal network designs are the ones that produce the most permeate. It may be possible to achieve economic improvements by refining current membrane module designs and their operating pressures.

  6. Importance of Reversibility in the Quantum Formalism

    NASA Astrophysics Data System (ADS)

    David, François

    2011-10-01

    In this Letter I stress the role of causal reversibility (time symmetry), together with causality and locality, in the justification of the quantum formalism. First, in the algebraic quantum formalism, I show that the assumption of reversibility implies that the observables of a quantum theory form an abstract real C⋆ algebra, and can be represented as an algebra of operators on a real Hilbert space. Second, in the quantum logic formalism, I emphasize which axioms for the lattice of propositions (the existence of an orthocomplementation and the covering property) derive from reversibility. A new argument based on locality and Soler’s theorem is used to derive the representation as projectors on a regular Hilbert space from the general quantum logic formalism. In both cases it is recalled that the restriction to complex algebras and Hilbert spaces comes from the constraints of locality and separability.

  7. Influenza reverse genetics: dissecting immunity and pathogenesis.

    PubMed

    Ye, Siying; Evans, Justin G; Stambas, John

    2014-01-01

    Reverse genetics systems allow artificial generation of non-segmented and segmented negative-sense RNA viruses, like influenza viruses, entirely from cloned cDNA. Since the introduction of reverse genetics systems over a decade ago, the ability to generate 'designer' influenza viruses in the laboratory has advanced both basic and applied research, providing a powerful tool to investigate and characterise host-pathogen interactions and advance the development of novel therapeutic strategies. The list of applications for reverse genetics has expanded vastly in recent years. In this review, we discuss the development and implications of this technique, including the recent controversy surrounding the generation of a transmissible H5N1 influenza virus. We will focus on research involving the identification of viral protein function, development of live-attenuated influenza virus vaccines, host-pathogen interactions, immunity and the generation of recombinant influenza virus vaccine vectors for the prevention and treatment of infectious diseases and cancer. PMID:24528628

  8. Magnetization reversal in single ferromagnetic rectangular nanowires

    NASA Astrophysics Data System (ADS)

    de Oliveira, Alexandre B.; da Silva, Gilvânia L.; Rezende, Sergio M.; Azevedo, Antonio

    2010-01-01

    We report on the magnetoresistance (MR) investigation of the magnetization reversal processes in single rectangular nanowire of Permalloy. A set of nanowires with lengths ranging from 6 to 20 μm, thicknesses fixed in 10 nm, and widths between 250 nm and 1.2 μm, was fabricated by means of AFM local anodic oxidation lithography. Magnetoresistive hysteresis loops show an abrupt jump corresponding to the magnetization reversal that depends on the angle between the wire axis and the applied magnetic field direction. The field value corresponding to the abrupt jump of the MR was associated to the nucleation field deduced from the Brown equations. By the angular dependence of this magnetization reversal field we were able to identify the nucleation mode as the magnetization buckling. We have investigated the temperature dependence of the switching field as well as its stochastic nature as a function of the in-plane angle.

  9. Time reversal signal processing for communication.

    SciTech Connect

    Young, Derek P.; Jacklin, Neil; Punnoose, Ratish J.; Counsil, David T.

    2011-09-01

    Time-reversal is a wave focusing technique that makes use of the reciprocity of wireless propagation channels. It works particularly well in a cluttered environment with associated multipath reflection. This technique uses the multipath in the environment to increase focusing ability. Time-reversal can also be used to null signals, either to reduce unintentional interference or to prevent eavesdropping. It does not require controlled geometric placement of the transmit antennas. Unlike existing techniques it can work without line-of-sight. We have explored the performance of time-reversal focusing in a variety of simulated environments. We have also developed new algorithms to simultaneously focus at a location while nulling at an eavesdropper location. We have experimentally verified these techniques in a realistic cluttered environment.

  10. A Reverse Shock in GRB 130427A

    NASA Astrophysics Data System (ADS)

    Laskar, Tanmoy; Berger, Edo; Zauderer, B. Ashley; Margutti, Raffaella; Soderberg, Alicia Margarita; Lunnan, Ragnhild; Chornock, Ryan

    2014-06-01

    We present extensive radio and millimeter observations of the unusually bright GRB 130427A at z=0.340, spanning 0.67 to 12 days after the burst. Taken in conjunction with detailed multi-band UV, optical, NIR, and X-ray observations we find that the broad-band afterglow emission is composed of distinct reverse shock and forward shock contributions. The reverse shock emission dominates in the radio/millimeter and at <0.1 days in the UV/optical/NIR, while the forward shock emission dominates in the X-rays and at >0.1 days in the UV/optical/NIR. We further find that the optical and X-ray data require a Wind circumburst environment, pointing to a massive star progenitor. Using the combined forward and reverse shock emission we find that the parameters of the burst are an isotropic kinetic energy of E_Kis 2e53 erg, a mass loss rate of Mdo 3e-8 Msun/yr (for a wind velocity of 1,000 km/s), and a Lorentz factor at the deceleration time of Gamma(200s 130. Due to the low density and large isotropic energy, the absence of a jet break to ~15 days places only a weak constraint on the opening angle of theta_j>2.5 deg, and therefore a total energy of E_gamma+E_K>1.2e51 erg, similar to other GRBs. The reverse shock emission is detectable in this burst due to the low circumburst density, which leads to a slow cooling shock. We speculate that this is a required property for the detectability of reverse shocks in the radio and millimeter bands. Following on GRB 130427A as a benchmark event, observations of future GRBs with the exquisite sensitivity of VLA and ALMA, coupled with detailed modeling of the reverse and forward shock contributions will test this hypothesis.

  11. Reverse mutations in fragile X syndrome

    SciTech Connect

    Brown, W.T.; Nolin, S.; Houck, G.E.

    1994-09-01

    The fragile X syndrome is the most common inherited form of mental retardation. Yet new mutations have not been described and no affected child has been born to a carrier mother having less than 60 FMR-1 CGG triplet repeats. Reverse mutations also appear to be very rare. We have previously identified the daughter of a premutation mother (95 CGGs) who inherited a normal repeat size of 35 as a reverse mutation. In the process of carrier testing by PCR, we have now identified two additional females with reverse mutations. All three of these reverse mutation women were previously tested by linkage as part of known fragile X families (subsequently confirmed by direct analysis), and assigned a > 99% risk as a carrier. In the second family, the mother carries a premutation allele of 95 repeats and the daughter inherited a 43 repeat allele. Prior to direct DNA testing, she had a positive prenatal diagnosis by linkage (> 99% risk) and cytogenetics with 3/450 cells apparently positive. Subsequent retesting of the products of conception by PCR now reveals a 43 repeat allele from her carrier mother with an 82 repeat allele. Testing with close CA markers (FRAXAC1 and DXS548) confirmed that these women inherited the same chromosome and their full mutation brothers. Further analysis is pending. These examples of reverse mutations are the only ones we have identified in our study of offspring of more than 200 carriers (400+ meioses) examined to date. Therefore, we conclude the frequency of fragile X back mutations is likely to be less than 1%. Retesting of linkage positive carriers is recommended to detect reverse mutations and assure accurate genetic counseling.

  12. Noise of Reverse Biased Solar Cells

    NASA Astrophysics Data System (ADS)

    Skarvada, P.; Macku, R.; Koktavy, P.; Raska, M.

    2009-04-01

    The non-destructive testing and analysis of single crystal silicon solar cell is the focal point of our research. The noise spectroscopy and I-V curve measurement of reverse biased pn junction provide information that is connected with solar cell reliability and that provide for not only local defect characterization. We propose a new electric solar cell model, as a base for an enhanced noise model, which is in accordance with the experimentally obtained I-V curves. We suggest the physical nature of an unconventional behavior in reverse I-V characteristics, which is typical for solar cells without apparent local avalanche breakdowns.

  13. Reversible intraframe compression of medical images.

    PubMed

    Roos, P; Viergever, M A; van Dijke, M A; Peters, J H

    1988-01-01

    The performance of several reversible, intraframe compression methods is compared by applying them to angiographic and magnetic resonance (MR) images. Reversible data compression involves two consecutive steps: decorrelation and coding. The result of the decorrelation step is presented in terms of entropy. Because Huffman coding generally approximates these entropy measures within a few percent, coding has not been investigated separately. It appears that a hierarchical decorrelation method based on interpolation (HINT) outperforms all other methods considered. The compression ratio is around 3 for angiographic images of 8-9 b/pixel, but is considerably less for MR images whose noise level is substantially higher. PMID:18230486

  14. STOL landing thrust: Reverser jet flowfields

    NASA Technical Reports Server (NTRS)

    Kotansky, D. R.; Glaze, L. W.

    1987-01-01

    Analysis tools and modeling concepts for jet flow fields encountered upon use of thrust reversers for high performance military aircraft are described. A semi-empirical model of the reverser ground wall jet interaction with the uniform cross flow due to aircraft forward velocity is described. This ground interaction model is used to demonstrate exhaust gas ingestion conditions. The effects of control of exhaust jet vector angle, lateral splay, and moving versus fixed ground simulation are discussed. The Adler/Baron jet-in-cross flow model is used in conjunction with three dimensional panel methods to investigate the upper surface jet induced flow field.

  15. Tokamak Equilibria with Reversed Current Density

    NASA Astrophysics Data System (ADS)

    Martynov, A. A.; Medvedev, S. Yu.; Villard, L.

    2003-08-01

    Observations of nearly zero toroidal current in the central region of tokamaks (the “current hole”) raises the question of the existence of toroidal equilibria with very low or reversed current in the core. The solutions of the Grad-Shafranov equilibrium equation with hollow toroidal current density profile including negative current density in the plasma center are investigated. Solutions of the corresponding eigenvalue problem provide simple examples of such equilibrium configurations. More realistic equilibria with toroidal current density reversal are computed using a new equilibrium problem formu­lation and computational algorithm which do not assume nested magnetic surfaces.

  16. Reversible Chemisorption Gas-Gap Thermal Switch

    NASA Technical Reports Server (NTRS)

    Jones, Jack A.; Bard, Steven; Blue, Gary

    1991-01-01

    Gas/sorbent combinations provide means to turn heat-conduction paths on and off. Single-stage gas-gap thermal switch based on reversible chemisorption of hydrogen gas by ZrNiH. Two-stage gas-gap thermal switch based on reversible desorption of O2 from MnO2 in first stage, followed by absorption in Cu on zeolite in second stage. Requires relatively low power. Used in sorption refrigeration systems designed to operate for long times without maintenance.

  17. Thermally activated helicity reversals of skyrmions

    NASA Astrophysics Data System (ADS)

    Yu, X. Z.; Shibata, K.; Koshibae, W.; Tokunaga, Y.; Kaneko, Y.; Nagai, T.; Kimoto, K.; Taguchi, Y.; Nagaosa, N.; Tokura, Y.

    2016-04-01

    Magnetic bubbles with winding number S =1 are topologically equivalent to skyrmions. Here we report the discovery of helicity (in-plane magnetization-swirling direction) reversal of skyrmions, while keeping their hexagonal lattice form, at above room temperature in a thin hexaferrite magnet. We have observed that the frequency of helicity reversals dramatically increases with temperature in a thermally activated manner, revealing that the generation energy of a kink-soliton pair for switching helicity on a skyrmion rapidly decreases towards the magnetic transition temperature.

  18. Reversed-field pinch and screw pinch

    SciTech Connect

    Kito, M.; Yoshimura, H.

    1983-12-01

    The Electrotechnical Laboratory and the College of Science and Technology at Nihon University discuss the results, device parameters, and objectives of reversed-field pinch TPE-1R(M). This device is illustrated and tables are given of machine parameters, as well as plasma parameters and temperature and density scalings. Other reversed-field pinch (RFP) machines are discussed, and tables show the RFP devices of Japan and design parameters of TPE-2, a screw-pinch device with a noncircular cross section. The STP-3 screw-pinch device is also discussed.

  19. Electrodynamic treatment of reversed-type emulsions

    SciTech Connect

    Skachkov, A.E.; Lavrov, I.S.; Timonov, S.M.

    1985-11-01

    The authors have produced an inhomogeneous electric field in processing reversed emulsions by using the oscillations of conducting spheres in an electric field; this is known as the electrical pendulum effect. The apparatus for the electrodynamic treatment of reversed-type emulsion is shown and the physical characteristics (density, kinematic viscosity, dielectric constant) are shown for the hydrocarbons used: hexane, octane, hexadecane and diesel fuel. It is shown that there is a minimum in the dependence of the residual water content after electrodynamic treatment on the external field strength; the minimum shifts to larger external field strength as the viscosity increases.

  20. Reverse preferential spread in complex networks

    NASA Astrophysics Data System (ADS)

    Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

    2012-08-01

    Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

  1. (PCG) Protein Crystal Growth HIV Reverse Transcriptase

    NASA Technical Reports Server (NTRS)

    1992-01-01

    HIV Reverse Transcriptase crystals grown during the USML-1 (STS-50) mission using Commercial Refrigerator/Incubator Module (CR/IM) at 4 degrees C and the Vapor Diffusion Apparatus (VDA). Reverse transcriptase is an enzyme responsible for copying the nucleic acid genome of the AIDS virus from RNA to DNA. Studies indicated that the space-grown crystals were larger and better ordered (beyond 4 angstroms) than were comparable Earth-grown crystals. Principal Investigators were Charles Bugg and Larry DeLucas.

  2. A simple statistical model for geomagnetic reversals

    NASA Technical Reports Server (NTRS)

    Constable, Catherine

    1990-01-01

    The diversity of paleomagnetic records of geomagnetic reversals now available indicate that the field configuration during transitions cannot be adequately described by simple zonal or standing field models. A new model described here is based on statistical properties inferred from the present field and is capable of simulating field transitions like those observed. Some insight is obtained into what one can hope to learn from paleomagnetic records. In particular, it is crucial that the effects of smoothing in the remanence acquisition process be separated from true geomagnetic field behavior. This might enable us to determine the time constants associated with the dominant field configuration during a reversal.

  3. Time reversal communication with a mobile source.

    PubMed

    Song, H C

    2013-10-01

    Broadband underwater acoustic communication signals undergo either a compression or dilation in the presence of relative motion between a source and a receiver. Consequently, underwater acoustic communications with a mobile source/receiver require Doppler compensation through resampling. However, resampling may not be necessary when a channel-estimate-based time reversal approach is applied with frequent channel updates. Using experimental data (20-30 kHz), it is demonstrated that the performance of time reversal communication without resampling is similar to the case with resampling, along with the benefit of a modest computational saving. PMID:24116398

  4. 12 CFR 7.2023 - Reverse stock splits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Reverse stock splits. 7.2023 Section 7.2023... Corporate Practices § 7.2023 Reverse stock splits. (a) Authority to engage in reverse stock splits. A national bank may engage in a reverse stock split if the transaction serves a legitimate corporate...

  5. 12 CFR 7.2023 - Reverse stock splits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Reverse stock splits. 7.2023 Section 7.2023 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Corporate Practices § 7.2023 Reverse stock splits. (a) Authority to engage in reverse stock splits. A national bank may engage in a reverse...

  6. Design of a novel quantum reversible ternary up-counter

    NASA Astrophysics Data System (ADS)

    Houshmand, Pouran; Haghparast, Majid

    2015-08-01

    Reversible logic has been recently considered as an interesting and important issue in designing combinational and sequential circuits. The combination of reversible logic and multi-valued logic can improve power dissipation, time and space utilization rate of designed circuits. Only few works have been reported about sequential reversible circuits and almost there are no paper exhibited about quantum ternary reversible counter. In this paper, first we designed 2-qutrit and 3-qutrit quantum reversible ternary up-counters using quantum ternary reversible T-flip-flop and quantum reversible ternary gates. Then we proposed generalized quantum reversible ternary n-qutrit up-counter. We also introduced a new approach for designing any type of n-qutrit ternary and reversible counter. According to the results, we can conclude that applying second approach quantum reversible ternary up-counter is better than the others.

  7. The effect of left-right reversal on film: Watching Kurosawa reversed

    PubMed Central

    Bertamini, Marco; Bode, Carole; Bruno, Nicola

    2011-01-01

    The mirror reversal of an image is subtly different from the original. Often such change goes unnoticed in pictures, although it can affect preference. For the first time we studied the effect of mirror reversal of feature films. People watched Yojimbo or Sanjuro in a cinema, both classic films by Akira Kurosawa. They knew that this was a study and filled out a questionnaire. On one day Yojimbo was shown in its original orientation, and on another day the film was mirror reversed. Sanjuro was shown reversed on one day and non-reversed on another day. Viewers did not notice the reversal, even when they had seen the film before and considered themselves fans of Kurosawa. We compared this with estimates from a survey. In addition, the question about the use of space (scenography) revealed that although people who had seen the film before gave higher ratings compared with those who had not, this was only true when the film was not reversed. PMID:23145243

  8. [Breast cancer and Axillary Reverse Mapping].

    PubMed

    Baron, M; Forestier-Lebreton, F; Muller, M; Teig, B; Laberge-Le Couteulx, S

    2008-01-01

    We report a case of T1N0 left breast cancer in a 47-year-old woman. Histopathological examination of a non sentinel axillary lymph node showed a pigmentation due to a decorative tattoo of the arm. The authors discuss a new concept: Axillary Reverse Mapping. PMID:18653372

  9. The Constitutionality of Reverse Racial Discrimination

    ERIC Educational Resources Information Center

    Ely, John Hart

    1974-01-01

    In discussing the Defunis v. Odegaard case and the busing issue in reference to reverse race discrimination, the author concludes that measures that favor racial minorities pose a difficult moral question that should be left to the states. (Author/PG)

  10. Psychophysical Reverse Correlation with Multiple Response Alternatives

    ERIC Educational Resources Information Center

    Dai, Huanping; Micheyl, Christophe

    2010-01-01

    Psychophysical reverse-correlation methods such as the "classification image" technique provide a unique tool to uncover the internal representations and decision strategies of individual participants in perceptual tasks. Over the past 30 years, these techniques have gained increasing popularity among both visual and auditory psychophysicists.…

  11. The Expertise Reversal Effect Concerning Instructional Explanations

    ERIC Educational Resources Information Center

    Rey, Gunter Daniel; Fischer, Andreas

    2013-01-01

    The expertise reversal effect occurs when learner's expertise moderates design principles derived from cognitive load theory. Although this effect is supported by numerous empirical studies, indicating an overall large effect size, the effect was never tested by inducing expertise experimentally and using instructional explanations in a…

  12. The reverse control of irreversible biological processes.

    PubMed

    Cho, Kwang-Hyun; Joo, Jae Il; Shin, Dongkwan; Kim, Dongsan; Park, Sang-Min

    2016-09-01

    Most biological processes have been considered to be irreversible for a long time, but some recent studies have shown the possibility of their reversion at a cellular level. How can we then understand the reversion of such biological processes? We introduce a unified conceptual framework based on the attractor landscape, a molecular phase portrait describing the dynamics of a molecular regulatory network, and the phenotype landscape, a map of phenotypes determined by the steady states of particular output molecules in the attractor landscape. In this framework, irreversible processes involve reshaping of the phenotype landscape, and the landscape reshaping causes the irreversibility of processes. We suggest reverse control by network rewiring which changes network dynamics with constant perturbation, resulting in the restoration of the original phenotype landscape. The proposed framework provides a conceptual basis for the reverse control of irreversible biological processes through network rewiring. WIREs Syst Biol Med 2016, 8:366-377. doi: 10.1002/wsbm.1346 For further resources related to this article, please visit the WIREs website. PMID:27327189

  13. Postscript: Contrasting Predictions for Preference Reversal

    ERIC Educational Resources Information Center

    Usher, Marius; Tsetsos, Konstantinos; Chater, Nick

    2010-01-01

    In this post scrit, the authors discuss an article by Hotaling, Busemeyer, and Li which provided a valuable reply to the challenges the current authors raised for the decision field theory (DFT) account of preference reversal in multiattribute choice. They agree with Hotaling, Busemeyer, and Li's observation that with the addition of an internal…

  14. Detection of Machining Chips by Pressure Reversal

    NASA Technical Reports Server (NTRS)

    Wyett, L. M.

    1986-01-01

    Inaccessible interior spaces inspected acoustically. In acoustic inspection, inlet and outlet ports of component connected to pneumatic hoses of apparatus that rapidly reverses induced pressure differential. If loose particles inside this component, they will generate noise detected by series of contact microphones attached to component. Noise indicates general location of contaminants, and its characteristic helps in identifying particles from their acoustic signatures.

  15. 14 CFR 23.933 - Reversing systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... systems. (a) For turbojet and turbofan reversing systems. (1) Each system intended for ground operation... testing, or both, for propeller systems that allow the propeller blades to move from the flight...

  16. 14 CFR 25.933 - Reversing systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.933 Reversing systems. (a) For turbojet... analysis or testing, or both, for propeller systems that allow propeller blades to move from the flight...

  17. Galen: Developer of the Reversal Design?

    ERIC Educational Resources Information Center

    Brown, Robert T.

    2007-01-01

    In this article, the author talks about Galen, a Greek physician who is known to psychologists largely for his personality theory of the four temperaments, and his method of diagnosing the basis of one of his patients' symptoms using a form of single-subject reversal design long before its formal description. Galen's method to diagnose the cause…

  18. Students' Reasoning with Reversible Multiplicative Relationships

    ERIC Educational Resources Information Center

    Hackenberg, Amy J.

    2010-01-01

    In an 8-month teaching experiment, I investigated how 4 sixth-grade students reasoned with reversible multiplicative relationships. One type of problem involved a known quantity that was a whole number multiple of an unknown quantity, and students were asked to determine the value of the unknown quantity. To solve these problems, students needed…

  19. TREATMENT OF ELECTROPLATING WASTES BY REVERSE OSMOSIS

    EPA Science Inventory

    Reverse osmosis treatment of plating bath rinsewaters has been examined. Emphasis has been placed on closed-loop operation with recycle of purified water for rinsing, and return of plating chemical concentrate to the bath. Three commercially available membrane configurations have...

  20. Compound nucleus studies withy reverse kinematics

    SciTech Connect

    Moretto, L.G.

    1985-06-01

    Reverse kinematics reactions are used to demonstrate the compound nucleus origin of intermediate mass particles at low energies and the extension of the same mechanism at higher energies. No evidence has appeared in our energy range for liquid-vapor equilibrium or cold fragmentation mechanisms. 11 refs., 12 figs.

  1. Preparation of nanoparticles in reverse microemulsions

    NASA Astrophysics Data System (ADS)

    Tovstun, Sergey A.; Razumov, Vladimir F.

    2011-10-01

    Experimental data and results of theoretical studies dealing with the synthesis of nanoparticles by the condensation of products of chemical reactions in reverse microemulsions are generalized. Attention is focused on the analysis of mechanisms of nanoparticle nucleation and growth. The bibliography includes 252 references.

  2. Reversing the Effects of Fragile X Syndrome

    ERIC Educational Resources Information Center

    Ogren, Marilee P.; Lombroso, Paul J.

    2008-01-01

    A research on how synaptic plasticity is abnormally regulated in fragile X syndrome and how this abnormality can be reversed by therapeutic interventions is presented. Fragile X syndrome is a disorder of synaptic plasticity that contributes to abnormal development and interferes with normal learning and memory.

  3. Reversible leukopenia related to ciprofloxacin therapy.

    PubMed

    Choo, P W; Gantz, N M

    1990-05-01

    In general, ciprofloxacin is well tolerated. The most common adverse effects are nausea, vomiting, diarrhea, dizziness, nervousness, and rash. Reversible leukopenia can be associated with the use of oral ciprofloxacin, as shown by our case. Leukopenia should be watched for as the use of this drug increases. PMID:2188377

  4. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Throttles and.... Steam locomotives that are equipped with air operated power reverse gear shall be equipped with a connection whereby such gear may be operated by steam or by an auxiliary supply of air in case of failure...

  5. Time reversal technique for gas leakage detection.

    PubMed

    Maksimov, A O; Polovinka, Yu A

    2015-04-01

    The acoustic remote sensing of subsea gas leakage traditionally uses sonars as active acoustic sensors and hydrophones picking up the sound generated by a leak as passive sensors. When gas leaks occur underwater, bubbles are produced and emit sound at frequencies intimately related to their sizes. The experimental implementation of an acoustic time-reversal mirror (TRM) is now well established in underwater acoustics. In the basic TRM experiment, a probe source emits a pulse that is received on an array of sensors, time reversed, and re-emitted. After time reversal, the resulting field focuses back at the probe position. In this study, a method for enhancing operation of the passive receiving system has been proposed by using it in the regime of TRM. Two factors, the local character of the acoustic emission signal caused by the leakage and a resonant nature of the bubble radiation at their birth, make particularly effective scattering with the conjugate wave (CW). Analytical calculations are performed for the scattering of CW wave on a single bubble when CW is formed by bubble birthing wail received on an array, time reversed, and re-emitted. The quality of leakage detection depends on the spatio-temporal distribution of ambient noise. PMID:25920866

  6. New Oral Anticoagulants and Their Reversal.

    PubMed

    Pinto, Ian; Giri, Anshu; Arshad, Umbreen; Gajra, Ajeet

    2015-01-01

    The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation. PMID:25877809

  7. Reversibility of continuous-variable quantum cloning

    SciTech Connect

    Filip, Radim; Marek, Petr; Fiurasek, Jaromir

    2004-01-01

    We analyze a reversibility of optimal Gaussian 1{yields}2 quantum cloning of a coherent state using only local operations on the clones and classical communication between them and propose a feasible experimental test of this feature. Performing Bell-type homodyne measurement on one clone and anticlone, an arbitrary unknown input state (not only a coherent state) can be restored in the other clone by applying appropriate local unitary displacement operation. We generalize this concept to a partial reversal of the cloning using only local operations and classical communication (LOCC) and we show that this procedure converts the symmetric cloner to an asymmetric cloner. Further, we discuss a distributed LOCC reversal in optimal 1{yields}M Gaussian cloning of coherent states which transforms it to optimal 1{yields}M{sup '} cloning for M{sup '}reversibility can be utilized to improve the security of the link even after the attack.

  8. Reverse Stroop Effects with Untranslated Responses

    ERIC Educational Resources Information Center

    Blais, Chris; Besner, Derek

    2006-01-01

    Translation accounts have argued that the presence of a Stroop effect in the context of a nonvocal untranslated response is caused by verbal mediation. In its simplest form, color-labeled buttons are translated into a verbal code that interferes with color responses. On this logic, in the reverse Stroop task (identify the word; ignore the color),…

  9. Can biological complexity be reverse engineered?

    PubMed

    Green, Sara

    2015-10-01

    Concerns with the use of engineering approaches in biology have recently been raised. I examine two related challenges to biological research that I call the synchronic and diachronic underdetermination problem. The former refers to challenges associated with the inference of design principles underlying system capacities when the synchronic relations between lower-level processes and higher-level systems capacities are degenerate (many-to-many). The diachronic underdetermination problem regards the problem of reverse engineering a system where the non-linear relations between system capacities and lower-level mechanisms are changing over time. Braun and Marom argue that recent insights to biological complexity leave the aim of reverse engineering hopeless - in principle as well as in practice. While I support their call for systemic approaches to capture the dynamic nature of living systems, I take issue with the conflation of reverse engineering with naïve reductionism. I clarify how the notion of design principles can be more broadly conceived and argue that reverse engineering is compatible with a dynamic view of organisms. It may even help to facilitate an integrated account that bridges the gap between mechanistic and systems approaches. PMID:25903121

  10. Thrust reverser for high bypass turbofan engine

    SciTech Connect

    Matta, R.K.; Bhutiani, P.K.

    1990-05-08

    This patent describes a thrust reverser for a gas turbine engine of the type which includes an outer wall spaced from the center body of a core engine to define a bypass duct therebetween. The thrust reverser comprising: circumferentially displaced blocker doors, each of the doors being movable between a normal position generally aligned with the outer wall and a thrust reversing position extending transversely of the bypass duct for blocking the exhaust of air through the bypass duct and directing the air through an opening in the outer wall for thrust reversal; each of the blocker doors being of lightweight construction and including a pit in the inner surface thereof in the normal position; means for covering the pit during normal flow of air through the bypass duct to reduce the pressure drop in the bypass duct and to reduce noise. The covering means including a pit cover hingedly mounted at one end thereof on the blocker door and means of biasing the pit cover away from the blocker door to a position providing smooth flow of air through the bypass duct during normal operation.

  11. Reverse Transfer Students in Illinois Community Colleges.

    ERIC Educational Resources Information Center

    Kajstura, Alex; Keim, Marybelle C.

    1992-01-01

    Describes a study of 525 students attending an Illinois community college having previously attended a 4-year college. Reports findings on reverse transfers' demographic and academic background, reasons for leaving the four-year institution and enrolling in a two-year college, primary educational goal, and evaluation of their educational…

  12. Modified borohydrides for reversible hydrogen storage

    SciTech Connect

    Au, Ming

    2005-08-29

    In attempt to develop lithium borohydrides as the reversible hydrogen storage materials with the high capacity, the feasibility to reduce dehydrogenation temperature of the lithium borohydride and moderate rehydrogenation condition has been explored. The commercial available lithium borohydride has been modified by ball milling with metal oxides and metal chlorides as the additives. The modified lithium borohydrides release 9 wt% hydrogen starting from 473K. The dehydrided modified lithium borohydrides absorb 7-9 wt% hydrogen at 873K and 7 MPa. The additive modification reduces dehydriding temperature from 673K to 473K and moderates rehydrogenation conditions to 923K and 15 MPa. XRD and SEM analysis discovered the formation of the intermediate compound TiB{sub 2} that may plays the key role in change the reaction path resulting the lower dehydriding temperature and reversibility. The reversible hydrogen storage capacity of the oxide modified lithium borohydrides decreases gradually during hydriding-dehydriding cycling due to the lost of the boron during dehydrogenation. But, it can be prevented by selecting the suitable additive, forming intermediate boron compounds and changing the reaction path. The additives reduce dehydriding temperature and improve the reversibility, it also reduces the hydrogen storage capacity. The best compromise can be reached by optimization of the additive loading and introducing new process other than ball milling.

  13. On the composition fluctuations of reverse micelles.

    PubMed

    Tovstun, Sergey A; Razumov, Vladimir F

    2010-11-15

    The polydispersity of the reverse micelles is determined mainly by the fluctuations of their composition. The composition of the reverse micelle is a two-dimensional random variable whose components are the numbers of water (i) and surfactant (j) molecules. In this study the fluctuations of the composition of the reverse micelles are considered in the Gaussian approximation. It is shown that the standard deviation of the quantity w=i/j may be calculated from the dependence of the water vapor pressure above the microemulsion on the molar ratio W=[water]/[surfactant]. The estimation based on the literature data for microemulsion system sodium bis(2-ethylhexyl)sulfosuccinate/water/isooctane at 37°C in the range W=0-18 has shown that the relative standard deviation of the quantity w is about 10%. It is shown that the value of the composition fluctuations is related to the dependence of average composition on the concentration of reverse micelles at constant parameter W. PMID:20800237

  14. Reverse ray tracing for transformation optics.

    PubMed

    Hu, Chia-Yu; Lin, Chun-Hung

    2015-06-29

    Ray tracing is an important technique for predicting optical system performance. In the field of transformation optics, the Hamiltonian equations of motion for ray tracing are well known. The numerical solutions to the Hamiltonian equations of motion are affected by the complexities of the inhomogeneous and anisotropic indices of the optical device. Based on our knowledge, no previous work has been conducted on ray tracing for transformation optics with extreme inhomogeneity and anisotropicity. In this study, we present the use of 3D reverse ray tracing in transformation optics. The reverse ray tracing is derived from Fermat's principle based on a sweeping method instead of finding the full solution to ordinary differential equations. The sweeping method is employed to obtain the eikonal function. The wave vectors are then obtained from the gradient of that eikonal function map in the transformed space to acquire the illuminance. Because only the rays in the points of interest have to be traced, the reverse ray tracing provides an efficient approach to investigate the illuminance of a system. This approach is useful in any form of transformation optics where the material property tensor is a symmetric positive definite matrix. The performance and analysis of three transformation optics with inhomogeneous and anisotropic indices are explored. The ray trajectories and illuminances in these demonstration cases are successfully solved by the proposed reverse ray tracing method. PMID:26191770

  15. Listing all sorting reversals in quadratic time

    PubMed Central

    2011-01-01

    We describe an average-case O(n2) algorithm to list all reversals on a signed permutation π that, when applied to π, produce a permutation that is closer to the identity. This algorithm is optimal in the sense that, the time it takes to write the list is Ω(n2) in the worst case. PMID:21504604

  16. Modified lithium borohydrides for reversible hydrogen storage.

    PubMed

    Au, Ming; Jurgensen, Arthur

    2006-04-01

    In an attempt to develop lithium borohydrides as reversible hydrogen storage materials with high hydrogen storage capacities, the feasibility of reducing the dehydrogenation temperature of the lithium borohydride and moderating rehydrogenation conditions was explored. The lithium borohydride was modified by ball milling with metal oxides and metal chlorides as additives. The modified lithium borohydrides released 9 wt % hydrogen starting from 473 K. The dehydrided modified lithium borohydrides absorbed 7-9 wt % hydrogen at 873 K and 7 MPa. The modification with additives reduced the dehydriding starting temperature from 673 to 473 K and moderated the rehydrogenation conditions from 923 K/15 MPa to 873 K/7 MPa. XRD and SEM analysis revealed the formation of an intermediate compound that might play a key role in changing the reaction path, resulting in the lower dehydriding temperature and reversibility. The reversible hydrogen storage capacity of the oxide-modified lithium borohydrides decreased gradually during hydriding/dehydriding cycling. One of the possible reasons for this effect might be the loss of boron during dehydrogenation, but this can be prevented by changing the dehydriding path using appropriate additives. The additives reduced the dehydriding temperature and improved the reversibility, but they also reduced the hydrogen storage capacity. The best compromise can be reached by selecting appropriate additives, optimizing the additive loading, and using new synthesis processes other than ball milling. PMID:16571023

  17. Dynamical similarity of geomagnetic field reversals.

    PubMed

    Valet, Jean-Pierre; Fournier, Alexandre; Courtillot, Vincent; Herrero-Bervera, Emilio

    2012-10-01

    No consensus has been reached so far on the properties of the geomagnetic field during reversals or on the main features that might reveal its dynamics. A main characteristic of the reversing field is a large decrease in the axial dipole and the dominant role of non-dipole components. Other features strongly depend on whether they are derived from sedimentary or volcanic records. Only thermal remanent magnetization of lava flows can capture faithful records of a rapidly varying non-dipole field, but, because of episodic volcanic activity, sequences of overlying flows yield incomplete records. Here we show that the ten most detailed volcanic records of reversals can be matched in a very satisfactory way, under the assumption of a common duration, revealing common dynamical characteristics. We infer that the reversal process has remained unchanged, with the same time constants and durations, at least since 180 million years ago. We propose that the reversing field is characterized by three successive phases: a precursory event, a 180° polarity switch and a rebound. The first and third phases reflect the emergence of the non-dipole field with large-amplitude secular variation. They are rarely both recorded at the same site owing to the rapidly changing field geometry and last for less than 2,500 years. The actual transit between the two polarities does not last longer than 1,000 years and might therefore result from mechanisms other than those governing normal secular variation. Such changes are too brief to be accurately recorded by most sediments. PMID:23038471

  18. A REVERSE SHOCK IN GRB 130427A

    SciTech Connect

    Laskar, T.; Berger, E.; Zauderer, B. A.; Margutti, R.; Soderberg, A. M.; Chakraborti, S.; Lunnan, R.; Chornock, R.; Chandra, P.; Ray, A.

    2013-10-20

    We present extensive radio and millimeter observations of the unusually bright GRB 130427A at z = 0.340, spanning 0.67-12 days after the burst. We combine these data with detailed multi-band UV, optical, NIR, and Swift X-ray observations and find that the broadband afterglow emission is composed of distinct reverse shock and forward shock contributions. The reverse shock emission dominates in the radio/millimeter and at ∼< 0.1 days in the UV/optical/NIR, while the forward shock emission dominates in the X-rays and at ∼> 0.1 days in the UV/optical/NIR. We further find that the optical and X-ray data require a wind circumburst environment, pointing to a massive star progenitor. Using the combined forward and reverse shock emission, we find that the parameters of the burst include an isotropic kinetic energy of E{sub K,{sub iso}} ≈ 2 × 10{sup 53} erg, a mass loss rate of M-dot ∼3×10{sup -8} M{sub ☉} yr{sup –1} (for a wind velocity of 1000 km s{sup –1}), and a Lorentz factor at the deceleration time of Γ(200 s) ≈ 130. Due to the low density and large isotropic energy, the absence of a jet break to ≈15 days places only a weak constraint on the opening angle, θ{sub j} ∼> 2.°5, and therefore a total energy of E{sub γ} + E{sub K} ∼> 1.2 × 10{sup 51} erg, similar to other gamma-ray bursts (GRBs). The reverse shock emission is detectable in this burst due to the low circumburst density, which leads to a slow cooling shock. We speculate that this property is required for the detectability of reverse shocks in radio and millimeter bands. Following on GRB 130427A as a benchmark event, observations of future GRBs with the exquisite sensitivity of the Very Large Array and ALMA, coupled with detailed modeling of the reverse and forward shock contributions, will test this hypothesis.

  19. Transport Barrier inside the Reversal Surface in the Chaotic Regime of the Reversed-Field Pinch

    SciTech Connect

    Spizzo, G.; Cappello, S.; Cravotta, A.; Predebon, I.; Marrelli, L.; Martin, P.; Escande, D.F.; White, R.B.

    2006-01-20

    Magnetic field lines and the corresponding particle orbits are computed for a typical chaotic magnetic field provided by a magnetohydrodynamics numerical simulation of the reversed-field pinch. The m=1 modes are phase locked and produce a toroidally localized bulging of the plasma which increases particle transport. The m=0 and m=1 modes produce magnetic chaos implying poor confinement. However, they also allow for the formation of magnetic islands which induce transport barriers inside the reversal surface.

  20. Reverse thrust performance of the QCSEE variable pitch turbofan engine

    NASA Technical Reports Server (NTRS)

    Samanich, N. E.; Reemsnyder, D. C.; Blodmer, H. E.

    1980-01-01

    Results of steady state reverse and forward to reverse thrust transient performance tests are presented. The original quiet, clean, short haul, experimental engine four segment variable fan nozzle was retested in reverse and compared with a continuous, 30 deg half angle conical exlet. Data indicated that the significantly more stable, higher pressure recovery flow with the fixed 30 deg exlet resulted in lower engine vibrations, lower fan blade stress, and approximately a 20 percent improvement in reverse thrust. Objective reverse thrust of 35 percent of takeoff thrust was reached. Thrust response of less than 1.5 sec was achieved for the approach and the takeoff to reverse thrust transients.

  1. FTIR study of horseradish peroxidase in reverse micelles.

    PubMed

    Chen, J; Xia, C; Niu, J; Li, S

    2001-04-20

    Fourier transform infrared (FTIR) method was used to study the secondary structures of horseradish peroxidase (HRP) in aqueous solution and in reverse micelles for the first time. Results indicated that the structure of HRP in sodium bis(2-ethylhexy)sulfosuccinate (AOT) reverse micelles was close to that in aqueous solution. In cetyltrimethylammonium bromide (CTAB) and sodium dodecylfate (SDS) reverse micelles the position of some bands changed. Results indicated that the secondary structure had a close relationship with the surfactant species of the reverse micelles. Among the three types of reverse micelles, the system of AOT reverse micelles was probably the most beneficial reaction media to HRP. PMID:11302746

  2. Reverse thrust performance of the QCSEE variable pitch turbofan engine

    NASA Technical Reports Server (NTRS)

    Samanich, N. E.; Reemsnyder, D. C.; Bloomer, H. E.

    1980-01-01

    Results of steady-state reverse and forward-to-reverse thrust transient performance tests are presented. The original QCSEE 4-segment variable fan nozzle was retested in reverse and compared with a continuous, 30-deg half-angle conical exlet. Data indicated that the significantly more stable, higher pressure recovery flow with the fixed 30-deg exlet resulted in lower engine vibrations, lower fan blade stress and approximately a 20% improvement in reverse thrust. Objective reverse thrust of 35% of takeoff thrust was reached. Thrust response of less than 1.5 sec was achieved for the approach and the takeoff-to-reverse thrust transients.

  3. Mechanism of reverse-offset printing

    NASA Astrophysics Data System (ADS)

    Choi, Young-Man; Lee, Eonseok; Lee, Taik-Min

    2015-07-01

    We propose a mechanism for reverse-offset printing based on a mathematical model. In reverse-offset printing, high resolution is achieved by patterning a coated, thin ink film with an intaglio-patterned cliché. By using the relationships among the ink blanket adhesion strength, the ink cliché adhesion strength, and the ink cohesion strength, a criterion for successful patterning is derived. We found that there is a printing window in the ink blanket adhesion strength that depends on the shear strength of the ink film and the dimensions of the pattern. The printing window diminishes as the line width decreases, resulting in a minimum printable line width. The proposed mechanism was verified by printing patterns with various shapes and dimensions.

  4. Reverse surface-polariton cherenkov radiation.

    PubMed

    Tao, Jin; Wang, Qi Jie; Zhang, Jingjing; Luo, Yu

    2016-01-01

    The existence of reverse Cherenkov radiation for surface plasmons is demonstrated analytically. It is shown that in a metal-insulator-metal (MIM) waveguide, surface plasmon polaritons (SPPs) excited by an electron moving at a speed higher than the phase velocity of SPPs can generate Cherenkov radiation, which can be switched from forward to reverse direction by tuning the core thickness of the waveguide. Calculations are performed in both frequency and time domains, demonstrating that a radiation pattern with a backward-pointing radiation cone can be achieved at small waveguide core widths, with energy flow opposite to the wave vector of SPPs. Our study suggests the feasibility of generating and steering electron radiation in simple plasmonic systems, opening the gate for various applications such as velocity-selective particle detections. PMID:27477061

  5. Time-reversal generation of rogue waves.

    PubMed

    Chabchoub, Amin; Fink, Mathias

    2014-03-28

    The formation of extreme localizations in nonlinear dispersive media can be explained and described within the framework of nonlinear evolution equations, such as the nonlinear Schrödinger equation (NLS). Within the class of exact NLS breather solutions on a finite background, which describe the modulational instability of monochromatic wave trains, the hierarchy of rational solutions localized in both time and space is considered to provide appropriate prototypes to model rogue wave dynamics. Here, we use the time-reversal invariance of the NLS to propose and experimentally demonstrate a new approach to constructing strongly nonlinear localized waves focused in both time and space. The potential applications of this time-reversal approach include remote sensing and motivated analogous experimental analysis in other nonlinear dispersive media, such as optics, Bose-Einstein condensates, and plasma, where the wave motion dynamics is governed by the NLS. PMID:24724652

  6. The initiation of orogenic margin reverse faulting

    NASA Astrophysics Data System (ADS)

    Bailey, R. C.

    2002-04-01

    Laboratory values of rock friction coefficients suggest that reverse faulting should be very difficult to initiate by simple horizontal compression of the crust. Values of stresses required by Andersonian faulting may be an order of magnitude higher than those actually present in orogenic margins. A simple stress balance calculation shows that the effect of the excess lithostatic pressure under an elevated orogen, if transmitted laterally through a crustal ductile layer to the orogenic margin, is to provide sufficient hydraulic lift under the orogen flanks to initiate reverse faulting by direct lift, even with rock friction coefficients of order 0.8. The required orogenic elevation above surrounding ``normal'' lithosphere is about one fifth of the thickness of the brittle crust of the orogen. This elevation may be as small as 2 km in tectonically active regions. The mechanism works even in the absence of regional lithospheric compressive stresses.

  7. Arthroscopic Reverse Remplissage for Posterior Instability.

    PubMed

    Lavender, Chad D; Hanzlik, Shane R; Pearson, Sara E; Caldwell, Paul E

    2016-02-01

    Posterior shoulder dislocation is an unusual injury often associated with electrical shock or seizure. As with anterior instability, patients frequently present with an impaction injury to the anterior aspect of the humeral head known as a "reverse Hill-Sachs lesion." The treatment of this bony defect is controversial, and multiple surgical procedures to fill the defect in an effort to decrease recurrence have been described. Most of the reports have focused on an open approach using variations of lesser tuberosity and subscapularis transfers, bone allograft, and even arthroplasty to assist with persistent instability. We advocate an arthroscopic technique that involves a suture anchor-based distal tenodesis of the subscapularis tendon or a reverse remplissage procedure. PMID:27073776

  8. Reversible Conjunctival Pigmentation Associated With Prostaglandin Use.

    PubMed

    Choi, Daniel Y; Chang, Robert T; Yegnashankaran, Krishnan; Friedman, Neil J

    2016-01-01

    A 54-year-old Indian male with a diagnosis of ocular hypertension was started on a prostaglandin analog (PGA) in both eyes to lower intraocular pressure. Six years later, he developed progressively increasing bilateral limbal conjunctival hyperpigmentation. Travoprost was discontinued and replaced with brinzolamide and over the next year, the patient's conjunctival pigmentation improved significantly in both the eyes. This case report documents with slit-lamp photography the first case of conjunctival pigmentation associated with PGA use that has been shown to have reversal with discontinuation of the PGA. Because of the widespread use of PGAs, and the evolving nature of the conjunctival pigmentation, clinicians should be aware of this reversible condition when considering biopsy or removal of conjunctival melanocytic lesions. PMID:25967530

  9. Forward and reverse transfer function model synthesis

    NASA Technical Reports Server (NTRS)

    Houghton, J. R.

    1985-01-01

    A process for synthesizing a mathematical model for a linear mechanical system using the forward and reverse Fourier transform functions is described. The differential equation for a system model is given. The Bode conversion of the differential equation, and the frequency and time-domain optimization matching of the model to the forward and reverse transform functions using the geometric simplex method of Nelder and Mead (1965) are examined. The effect of the window function on the linear mechanical system is analyzed. The model is applied to two examples; in one the signal damps down before the end of the time window and in the second the signal has significant energy at the end of the time window.

  10. Optical Image Contrast Reversal Using Bacteriorhodopsin Films

    NASA Astrophysics Data System (ADS)

    Wang, Ying-Li; Yao, Bao-Li; Menke, Neimule; Zheng, Yuan; Lei, Ming; Chen, Guo-Fu

    2005-05-01

    The implementation of image contrast reversal by using a photochromic material of Bacteriorhodopsin (BR) films is demonstrated with two methods based on the optical properties of BR. One is based on the absorption difference between the B and M states. Images recorded by green light can be contrast reversed readout by violet light. The other is based on the photoinduced anisotropy of BR when it is excited by linear polarization light. By placing the BR film between two crossed polarizers (i.e. a polarizer and an analyser), the difference of polarization states of the recorded area and the unrecorded area can be detected, and thus different contrast images can be obtained by rotating the polarization axis of the analyser.

  11. Reversible watermarking using edge based difference modification

    NASA Astrophysics Data System (ADS)

    Qu, Xiaochao; Kim, Suah; Kim, Hyoungjoong

    2014-01-01

    Reversible watermarking can embed data into the cover image and extract data from stego image, where the original cover image can be recovered perfectly after the extraction of data. Difference expansion (DE) and prediction error expansion (PEE) are two popular reversible watermarking methods. DE has the advantage of small distortion while PEE has the advantage of large embedding capacity and smaller prediction error compared with pixel difference. In this paper, we proposed a novel method that combines the advantages of DE and PEE, where the difference calculated between two pixels is combined with the edge information near this pixel pair. The proposed difference calculation can produce smaller pixel difference compared with the original simple pixel difference calculation. Overlapping embedding is then used to increase the embedding capacity. Our proposed method gives excellent results which is shown by several experiments.

  12. Reversibility of red blood cell deformation

    NASA Astrophysics Data System (ADS)

    Zeitz, Maria; Sens, P.

    2012-05-01

    The ability of cells to undergo reversible shape changes is often crucial to their survival. For red blood cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of μm dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar “pearling instability.”

  13. Reversing entanglement change by a weak measurement

    SciTech Connect

    Sun Qingqing; Zubairy, M. Suhail; Al-Amri, M.; Davidovich, Luiz

    2010-11-15

    Entanglement of a system changes due to interactions with the environment. A typical type of interaction is amplitude damping. If we add a detector to monitor the environment and only select the no-damping outcome, this amplitude damping is modified into a weak measurement. Here we show that the entanglement change of a two-qubit state due to amplitude damping or weak measurement can be probabilistically reversed. For the amplitude-damping case, the entanglement partially recovers under most conditions. For the weak-measurement case, the recovery of the initial entangled state is exact. The reversal procedure involves another weak measurement, preceded and followed by bit flips applied to both qubits. We propose a linear optics scheme for the experimental demonstration of these procedures.

  14. Reverse surface-polariton cherenkov radiation

    NASA Astrophysics Data System (ADS)

    Tao, Jin; Wang, Qi Jie; Zhang, Jingjing; Luo, Yu

    2016-08-01

    The existence of reverse Cherenkov radiation for surface plasmons is demonstrated analytically. It is shown that in a metal-insulator-metal (MIM) waveguide, surface plasmon polaritons (SPPs) excited by an electron moving at a speed higher than the phase velocity of SPPs can generate Cherenkov radiation, which can be switched from forward to reverse direction by tuning the core thickness of the waveguide. Calculations are performed in both frequency and time domains, demonstrating that a radiation pattern with a backward-pointing radiation cone can be achieved at small waveguide core widths, with energy flow opposite to the wave vector of SPPs. Our study suggests the feasibility of generating and steering electron radiation in simple plasmonic systems, opening the gate for various applications such as velocity-selective particle detections.

  15. Nanosecond magnetization reversal in nanocrystalline magnetic films

    NASA Astrophysics Data System (ADS)

    Rahman, I. Z.; Gandhi, A. A.; Khaddem-Mousavi, M. V.; Lynch, T. F.; Rahman, M. A.

    2007-03-01

    This paper reports on the investigation of dynamic magnetization reversal process in electrodeposited nanocrystalline Ni and Ni80Fe20 films by employing nanosecond magnetic pulse technique. The surface morphology has been investigated using SEM, EDAX, XRD and AFM analyses and static magnetic properties of the films are characterized by vibrating sample magnetometer (VSM). Two different techniques are designed and employed to study the nanosecond magnetization reversal process in nanocrystalline thin films: Magneto-Optical Kerr Effect (MOKE) and nanosecond pulsed field magnetometer. Results of dynamical behavior as a function of several variables such as magnitude of applied bias magnetic field, amplitude and width of the pulsed magnetic field are analyzed in detail using both techniques. A computer simulation package called Object Oriented Micro-Magnetic Framework (OOMMF) has been used to simulate the magnetic domain patterns of the samples.

  16. Generic area-preserving reversible diffeomorphisms

    NASA Astrophysics Data System (ADS)

    Bessa, Mário; Carvalho, Maria; Rodrigues, Alexandre

    2015-06-01

    Let M be a surface and R : M → M an area-preserving C∞ diffeomorphism which is an involution and whose set of fixed points is a submanifold with dimension one. We will prove that C1 - generically either an area-preserving R-reversible diffeomorphism, is Anosov, or, for μ-almost every x ∈ M, the Lyapunov exponents at x vanish or else the orbit of x belongs to a compact hyperbolic set with an empty interior. We will also describe a nonempty C1-open subset of area-preserving R-reversible diffeomorphisms where for C1 - generically each map is either Anosov or its Lyapunov exponents vanish from almost everywhere.

  17. Reverse Phase Protein Arrays for Compound Profiling.

    PubMed

    Moerke, Nathan; Fallahi-Sichani, Mohammad

    2016-01-01

    Reverse phase protein arrays (RPPAs), also called reverse phase lysate arrays (RPLAs), involve immobilizing cell or tissue lysates, in small spots, onto solid supports which are then probed with primary antibodies specific for proteins or post-translational modifications of interest. RPPA assays are well suited for large-scale, high-throughput measurement of protein and PTM levels in cells and tissues. RPPAs are affordable and highly multiplexable, as a large number of arrays can readily be produced in parallel and then probed separately with distinct primary antibodies. This article describes a procedure for treating cells and preparing cell lysates, as well as a procedure for generating RPPAs using these lysates. A method for probing, imaging, and analyzing RPPAs is also described. These procedures are readily adaptable to a wide range of studies of cell signaling in response to drugs and other perturbations. © 2016 by John Wiley & Sons, Inc. PMID:27622568

  18. Forward and reverse characteristics of irradiated MOSFETs

    SciTech Connect

    Paccagnella, A.; Ceschia, M.; Verzellesi, G.; Dalla Betta, G.F.; Soncini, G.; Bellutti, P.; Fuochi, P.G.

    1996-06-01

    pMOSFETs biased with V{sub gs} < V{sub gd} during Co{sup 60} {gamma} irradiation have shown substantial differences between the forward and reverse subthreshold characteristics, induced by a non-uniform charge distribution in the gate oxide. Correspondingly, modest differences have been observed in the over-threshold I-V characteristics. After irradiation, the forward subthreshold curves can shift at higher or lower gate voltages than the reverse ones. The former behavior has been observed in long-channel devices, in agreement with the classical MOS theory and numerical simulations. The latter result has been obtained in short-channel devices, and it has been correlated to a parasitic punch-through conduction mechanism.

  19. HDL Function, Dysfunction, and Reverse Cholesterol Transport

    PubMed Central

    Fisher, Edward A.; Feig, Jonathan E.; Hewing, Bernd; Hazen, Stanley L.; Smith, Jonathan D.

    2012-01-01

    Although high HDL-cholesterol levels are associated with decreased cardiovascular risk in epidemiological studies, recent genetic and pharmacological findings have raised doubts about the beneficial effects of HDL. Raising HDL levels in animal models by infusion or over expression of apolipoprotein A-I has shown clear vascular improvements, such as delayed atherosclerotic lesion progression and accelerated lesion regression, along with increased reverse cholesterol transport. Inflammation and other factors, such as myeloperoxidase mediated oxidation, can impair HDL production and HDL function, in regard to its reverse cholesterol transport, antioxidant, and anti-inflammatory activities. Thus, tests of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels. PMID:23152494

  20. Casimir-Polder Force Reversal with Metamaterials

    NASA Astrophysics Data System (ADS)

    Pappakrishnan, Venkatesh; Genov, Dentcho

    2010-10-01

    A promising system design aiming to demonstrate Casimir-Polder force (CPF) reversal is proposed. The constraints when using naturally available materials in designing the system with air as an intermediate medium is resolved by using artificial electromagnetic materials. The parametric space in terms of the plate's magnetic and dielectric plasma frequencies, gap thickness and temperature is investigated. The parametric domain for achieving CPF reversal is obtained. Furthermore, a simple analytical expression for the CPF is derived. The analytical expression accurately describes the large and short distance asymptotics and allows extraction of important parameters such as lower and upper cutoff gap distances that define the repulsive force window. This study could possibly lead us to design of quantum levitation system, frictionless bio-fluid transport devices, etc.

  1. Reverse surface-polariton cherenkov radiation

    PubMed Central

    Tao, Jin; Wang, Qi Jie; Zhang, Jingjing; Luo, Yu

    2016-01-01

    The existence of reverse Cherenkov radiation for surface plasmons is demonstrated analytically. It is shown that in a metal-insulator-metal (MIM) waveguide, surface plasmon polaritons (SPPs) excited by an electron moving at a speed higher than the phase velocity of SPPs can generate Cherenkov radiation, which can be switched from forward to reverse direction by tuning the core thickness of the waveguide. Calculations are performed in both frequency and time domains, demonstrating that a radiation pattern with a backward-pointing radiation cone can be achieved at small waveguide core widths, with energy flow opposite to the wave vector of SPPs. Our study suggests the feasibility of generating and steering electron radiation in simple plasmonic systems, opening the gate for various applications such as velocity-selective particle detections. PMID:27477061

  2. Reversible thermodynamic cycle for AMTEC power conversion

    NASA Technical Reports Server (NTRS)

    Vining, Cronin B.; Williams, Roger M.; Underwood, Mark L.; Ryan, M. A.; Suitor, Jerry W.

    1992-01-01

    The thermodynamic cycle appropriate to an AMTEC (alkali metal thermal-to-electric converter) cell is discussed for both liquid- and vapor-fed modes of operation, under the assumption that all processes can be performed reversibly. In the liquid-fed mode, the reversible efficiency is greater than 89.6 percent of Carnot efficiency for heat input and rejection temperatures (900-1300 K and 400-800 K, respectively) typical of practical devices. Vapor-fed cells can approach the efficiency of liquid-fed cells. Quantitative estimates confirm that the efficiency is insensitive to either the work required to pressurize the sodium liquid or the details of the state changes associated with cooling the low pressure sodium gas to the heat rejection temperature.

  3. Time-Reversal Generation of Rogue Waves

    NASA Astrophysics Data System (ADS)

    Chabchoub, Amin; Fink, Mathias

    2014-03-01

    The formation of extreme localizations in nonlinear dispersive media can be explained and described within the framework of nonlinear evolution equations, such as the nonlinear Schrödinger equation (NLS). Within the class of exact NLS breather solutions on a finite background, which describe the modulational instability of monochromatic wave trains, the hierarchy of rational solutions localized in both time and space is considered to provide appropriate prototypes to model rogue wave dynamics. Here, we use the time-reversal invariance of the NLS to propose and experimentally demonstrate a new approach to constructing strongly nonlinear localized waves focused in both time and space. The potential applications of this time-reversal approach include remote sensing and motivated analogous experimental analysis in other nonlinear dispersive media, such as optics, Bose-Einstein condensates, and plasma, where the wave motion dynamics is governed by the NLS.

  4. Reversible cerebral vasoconstriction syndrome: a comprehensive update.

    PubMed

    Mehdi, Ali; Hajj-Ali, Rula A

    2014-09-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological syndrome characterized by recurrent thunderclap headache, with or without neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS affects patients in various racial and ethnic groups and in all age groups, although most commonly in the fourth decade of life. Many conditions and exposures have been linked to RCVS, including vasoactive drugs and the peripartum period. Disturbance of the cerebral vascular tone is thought to contribute to the disease's pathophysiology. RCVS generally follows a monophasic course. Associated strokes and cerebral hemorrhages are not uncommon. In this review we will attempt to provide a comprehensive overview of RCVS, with emphasis on the controversies in the field and the newest findings in the reported literature. PMID:25138149

  5. Reversible Bergman cyclization by atomic manipulation

    NASA Astrophysics Data System (ADS)

    Schuler, Bruno; Fatayer, Shadi; Mohn, Fabian; Moll, Nikolaj; Pavliček, Niko; Meyer, Gerhard; Peña, Diego; Gross, Leo

    2016-03-01

    The Bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. Here we demonstrate a reversible Bergman cyclization for the first time. We induced the on-surface transformation of an individual aromatic diradical into a highly strained ten-membered diyne using atomic manipulation and verified the products by non-contact atomic force microscopy with atomic resolution. The diyne and diradical were stabilized by using an ultrathin NaCl film as the substrate, and the diyne could be transformed back into the diradical. Importantly, the diradical and the diyne exhibit different reactivity, electronic, magnetic and optical properties associated with the changes in the bond topology, and spin multiplicity. With this reversible, triggered Bergman cyclization we demonstrated switching on demand between the two reactive intermediates by means of selective C-C bond formation or cleavage, which opens up the field of radical chemistry for on-surface reactions by atomic manipulation.

  6. Arthroscopic Reverse Remplissage for Posterior Instability

    PubMed Central

    Lavender, Chad D.; Hanzlik, Shane R.; Pearson, Sara E.; Caldwell, Paul E.

    2016-01-01

    Posterior shoulder dislocation is an unusual injury often associated with electrical shock or seizure. As with anterior instability, patients frequently present with an impaction injury to the anterior aspect of the humeral head known as a “reverse Hill-Sachs lesion.” The treatment of this bony defect is controversial, and multiple surgical procedures to fill the defect in an effort to decrease recurrence have been described. Most of the reports have focused on an open approach using variations of lesser tuberosity and subscapularis transfers, bone allograft, and even arthroplasty to assist with persistent instability. We advocate an arthroscopic technique that involves a suture anchor–based distal tenodesis of the subscapularis tendon or a reverse remplissage procedure. PMID:27073776

  7. Time-reversal asymmetry in financial systems

    NASA Astrophysics Data System (ADS)

    Jiang, X. F.; Chen, T. T.; Zheng, B.

    2013-11-01

    We investigate the large-fluctuation dynamics in financial markets, based on the minute-to-minute and daily data of the Chinese Indices and the German DAX. The dynamic relaxation both before and after the large fluctuations is characterized by a power law, and the exponents p± usually vary with the strength of the large fluctuations. The large-fluctuation dynamics is time-reversal symmetric at the time scale in minutes, while asymmetric at the daily time scale. Careful analysis reveals that the time-reversal asymmetry is mainly induced by external forces. It is also the external forces which drive the financial system to a non-stationary state. Different characteristics of the Chinese and German stock markets are uncovered.

  8. A reverse evidence of rotavirus vaccines impact.

    PubMed

    Martinón-Torres, Federico; Aramburo, Angela; Martinón-Torres, Nazareth; Cebey, Miriam; Seoane-Pillado, María Teresa; Redondo-Collazo, Lorenzo; Martinón-Sánchez, Jose Maria

    2013-06-01

    In 2010, and due to a quality problem identified in the vaccine manufacture, the rotavirus (RV) vaccination was withheld in Spain during 5 months. Our study aimed to evaluate the impact that this sudden cease had on rotavirus acute gastroenteritis (RAGE) hospitalizations. An increase in RAGE hospitalization was observed in parallel to the drop in vaccine coverage. Here, we report the first reverse evidence of rotavirus vaccine impact. PMID:23836258

  9. A reverse evidence of rotavirus vaccines impact

    PubMed Central

    Martinón-Torres, Federico; Aramburo, Angela; Martinón-Torres, Nazareth; Cebey, Miriam; Seoane-Pillado, María Teresa; Redondo-Collazo, Lorenzo; Martinón-Sánchez, Jose Maria

    2013-01-01

    In 2010, and due to a quality problem identified in the vaccine manufacture, the rotavirus (RV) vaccination was withheld in Spain during 5 months. Our study aimed to evaluate the impact that this sudden cease had on rotavirus acute gastroenteritis (RAGE) hospitalizations. An increase in RAGE hospitalization was observed in parallel to the drop in vaccine coverage. Here, we report the first reverse evidence of rotavirus vaccine impact. PMID:23836258

  10. Reverse Schottky-asymmetry spin current detectors

    NASA Astrophysics Data System (ADS)

    Lu, Yuan; Appelbaum, Ian

    2010-10-01

    By reversing the Schottky barrier-height asymmetry in hot-electron semiconductor-metal-semiconductor ballistic spin filtering spin detectors, we have achieved the following: (1) demonstration of >50% spin polarization in silicon, resulting from the increase of detection efficiency by elimination of the ferromagnet/silicon interface on the transport channel detector contact and (2) evidence of spin transport at temperatures as high as 260 K, enabled by an increase in detector Schottky barrier height.

  11. Orifice Blocks Heat Pipe in Reverse Mode

    NASA Technical Reports Server (NTRS)

    Alario, J. P.

    1982-01-01

    High forward-mode conductance is combined with rapid reverse-mode shutoff in a heat pipe originally developed to cool spacecraft payloads. A narrow orifice within the pipe "chokes off" the evaporator if heat sink becomes warmer than source. During normal operation, with source warmer than sink, orifice has little effect. Design is simpler and more compact than other thermal-diode heat pipes and requires no special materials, forgings, or unusual construction techniques.

  12. Cyclic AMP and the reverse transformation reaction.

    PubMed

    Puck, Theodore T; Webb, Patricia; Johnson, Robert

    2002-06-01

    Traditional methods for cancer treatment have been aimed at killing the cancer cells. Unfortunately this approach all too often is accompanied by harmful killing of normal cells. The present paper describes an experimental program in our laboratory in which cancer cells are treated so as to revert to normal cell behavior. This process, which we have named reverse transformation, appears to offer considerable hope in the treatment of a large number of malignancies. PMID:12119272

  13. Reversibility of strontium sorption on fracture fillings

    SciTech Connect

    Cui, D.; Eriksen, T.E.

    1995-12-31

    Granite has been chosen by several countries as a major candidate for deep geologic disposal of radioactive waste. The authors have carried out a comparative study of sorption and desorption of strontium in groundwater on separated size and magnetic fractions of fracture fillings from deep granite. Complete reversibility of the sorption process was demonstrated by identical Freundlich isotherms, isotopic exchangeability and pH dependence of the distribution coefficient R{sub d}.

  14. Reverse Genetics Approaches to Control Arenavirus.

    PubMed

    Martínez-Sobrido, Luis; Cheng, Benson Yee Hin; de la Torre, Juan Carlos

    2016-01-01

    Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors. PMID:27076139

  15. 2004 Reversible Associations in Structure & Molecular Biology

    SciTech Connect

    Edward Eisenstein Nancy Ryan Gray

    2005-03-23

    The Gordon Research Conference (GRC) on 2004 Gordon Research Conference on Reversible Associations in Structure & Molecular Biology was held at Four Points Sheraton, CA, 1/25-30/2004. The Conference was well attended with 82 participants (attendees list attached). The attendees represented the spectrum of endeavor in this field coming from academia, industry, and government laboratories, both U.S. and foreign scientists, senior researchers, young investigators, and students.

  16. A Reverse Stroop Task with Mouse Tracking

    PubMed Central

    Yamamoto, Naohide; Incera, Sara; McLennan, Conor T.

    2016-01-01

    In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed—for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants’ responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants’ performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse’s approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID:27199881

  17. A Reverse Stroop Task with Mouse Tracking.

    PubMed

    Yamamoto, Naohide; Incera, Sara; McLennan, Conor T

    2016-01-01

    In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed-for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants' responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants' performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse's approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID:27199881

  18. On the design of reversible QDCA systems.

    SciTech Connect

    DeBenedictis, Erik P.; Frank, Michael P. (Florida State University, Tallahassee, FL); Ottavi, Marco; Frost-Murphy, Sarah E.

    2006-10-01

    This work is the first to describe how to go about designing a reversible QDCA system. The design space is substantial, and there are many questions that a designer needs to answer before beginning to design. This document begins to explicate the tradeoffs and assumptions that need to be made and offers a range of approaches as starting points and examples. This design guide is an effective tool for aiding designers in creating the best quality QDCA implementation for a system.

  19. Analysis of microalloy precipitate reversion in steels

    NASA Technical Reports Server (NTRS)

    Michal, G. M.; Locci, I. E.

    1988-01-01

    The influence of the ferrite to austenite allotropic transformation on the stability of MXn precipitates in an iron matrix is studied. In the MX phase, M is a group IVb or Vb transition metal, such as niobium, titanium, or vanadium. X is carbon or nitrogen and n is in the range of 0.75-1.0. The application of the present model to the case of vanadium carbide reversion in a microalloyed steel is discussed.

  20. Forward and reverse mutagenesis in C. elegans

    PubMed Central

    Kutscher, Lena M.; Shaham, Shai

    2014-01-01

    Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

  1. Reversible Projection Technique for Colon Unfolding

    PubMed Central

    Yao, Jianhua; Chowdhury, Ananda S.; Aman, Javed; Summers, Ronald M.

    2015-01-01

    Colon unfolding provides an efficient way to navigate the colon in CT colonography. Most existing unfolding techniques only computed forward projections. When radiologists find abnormalities or conduct measurements on the unfolded view (which is often quicker and easier), it is difficult to locate the corresponding region on the 3D view for further examination (which is more accurate and reliable). To address this, we propose a reversible projection technique for colon unfolding. The method makes use of advanced algorithms including rotation-minimizing frames, recursive ring sets, mesh skinning and cylindrical projection. Both forward and reverse transformations are computed for points on the colon surface. Therefore, it allows for detecting and measuring polyps on the unfolded view and mapping them back to the 3D surface. We generated realistic colon simulation incorporating most colon characteristics such as curved centerline, variable distention, haustral folds, teniae coli and colonic polyps. Our method was tested on both the simulated data and 110 clinical CT colonography data. Comparison of polyp size measurements on the unfolded view and the 3D view clearly demonstrates the importance of our reversible projection technique. PMID:20542756

  2. On the reversibility of mandibular symphyseal fusion.

    PubMed

    Scott, Jeremiah E; Lack, Justin B; Ravosa, Matthew J

    2012-09-01

    Experimental and comparative studies suggest that a major determinant of increased ossification of the mandibular symphysis is elevated masticatory stress related to a mechanically challenging diet. However, the morphology of this joint tracks variation in dietary properties in only some mammalian clades. Extant anthropoid primates are a notable exception: synostosis is ubiquitous in this speciose group, despite its great age and diverse array of feeding adaptations. One possible explanation for this pattern is that, once synostosis evolves, reversion to a lesser degree of fusion is unlikely or even constrained. If correct, this has important implications for functional and phylogenetic analyses of the mammalian feeding apparatus. To test this hypothesis, we generated a molecular tree for 76 vespertilionoid and noctilionoid chiropterans using Bayesian phylogenetic analysis and examined character evolution using parsimony and likelihood ancestral-state reconstructions along with the binary state speciation and extinction (BiSSE) model. Results indicate that reversals have occurred within Vespertilionoidea. In contrast, noctilionoids exhibit an anthropoid-like pattern, which suggests that more detailed comparisons of the functional and developmental bases for fusion in these bat clades may provide insight into why fusion is maintained in some lineages but not in others. Potential functional and developmental explanations for the lack of reversal are discussed. PMID:22946814

  3. Thermal magnetization reversal in arrays of nanoparticles

    SciTech Connect

    Brown, Gregory; Novotny, M. A.; Rikvold, Per Arne

    2001-06-01

    The results of large-scale simulations investigating the dynamics of magnetization reversal in arrays of single-domain nanomagnets after a rapid reversal of the applied field at nonzero temperature are presented. The numerical micromagnetic approach uses the Landau{endash}Lifshitz{endash}Gilbert equation including contributions from thermal fluctuations and long-range dipole{endash}dipole demagnetizing effects implemented using a fast-multipole expansion. The individual model nanomagnets are 9 nm{times}9 nm{times}150 nm iron pillars similar to those fabricated on a surface with scanning tunneling microscope assisted chemical vapor deposition [S. Wirth , J. Appl. Phys. 85, 5249 (1999)]. Nanomagnets oriented perpendicular to the surface and spaced 300 nm apart in linear arrays are considered. The applied field is always oriented perpendicular to the surface. When the magnitude of the applied field is less than the coercive value, about 2000 Oe for an individual nanomagnet, magnetization reversal in the nanomagnets can only occur by thermally activated processes. Even though the interaction from the dipole moment of neighboring magnets in this geometry is only about 1 Oe, less than 1% of the coercive field, it can have a large impact on the switching dynamics. What determines the height of the free-energy barrier is the difference between the coercive and applied fields, and 1 Oe can be a significant fraction of that. The magnetic orientations of the neighbors are seen to change the behavior of the nanomagnets in the array significantly. {copyright} 2001 American Institute of Physics.

  4. Perceptual learning can reverse subliminal priming effects.

    PubMed

    Przekoracka-Krawczyk, Anna; Jaśkowski, Piotr

    2007-05-01

    Masked primes presented prior to a target can result in inverse priming (i.e., benefits on trials in which the prime and the target are mapped onto opposite responses). In five experiments, time-of-task effects on subliminal priming of motor responses were investigated. First, we replicated Klapp and Hinkley's (2002) finding that the priming effect is initially straight (i.e., it benefits congruent trials, in which the prime and targets are mapped onto the same response) or absent, and only later reverses (i.e., faster responses in incongruent than in congruent trials). We show that the presentation of the mask plays a crucial role in this reversal and that the reversal occurs later if the mask pattern is very complex. We suggest that perceptual learning improves the recognition of task-relevant features. Once recognized, these features can trigger the preparation of the alternative response and/or inhibit the prime-activated response. These findings support an active role of the mask in priming. PMID:17727109

  5. Unsteady Airloads on Airfoils in Reverse Flow

    NASA Astrophysics Data System (ADS)

    Lind, Andrew; Jones, Anya

    2014-11-01

    This work gives insight into the influence of airfoil characteristics on unsteady airloads for rotor applications where local airfoil sections may operate at high and/or reverse flow angles of attack. Two-dimensional wind tunnel experiments have been performed on four airfoil sections to investigate the effects of thickness, camber, and trailing edge shape on unsteady airloads (lift, pressure drag, and pitching moment). These model rotor blades were tested through 360 deg of incidence for 104 <=Re <=106 . Unsteady pressure transducers were mounted on the airfoil surface to measure the high frequency, dynamic pressure variations. The temporal evolution of chordwise pressure distributions and resulting airloads is quantified for each airfoil in each of the three unsteady wake regimes present in reverse flow. Specifically, the influence of the formation, growth, and shedding of vortices on the surface pressure distribution is quantified and compared between airfoils with a sharp geometric trailing edge and those with a blunt geometric trailing edge. These findings are integral to mitigation of rotor blade vibrations for applications where airfoil sections are subjected to reverse flow, such as high-speed helicopters and tidal turbines.

  6. Fouling in reverse electrodialysis under natural conditions.

    PubMed

    Vermaas, David A; Kunteng, Damnearn; Saakes, Michel; Nijmeijer, Kitty

    2013-03-01

    Renewable energy can be generated from mixing salt water and fresh water in reverse electrodialysis. The potential for energy generation from mixing seawater and river water is enormous. To investigate the effect of fouling when such natural feed waters are used, the performance of three different setups for reverse electrodialysis was evaluated for 25 days using seawater and river water as feed water, with no other (pre-)treatment than a 20 μm filter. Due to the absence of other anti-fouling treatments, a mixture of fouling is observed on the membranes, composed of remnants of diatoms, clay minerals, organic fouling and scaling. The fouling type was dependent on the different membrane types. The anion exchange membranes attract mainly diatoms and clay minerals, whereas scaling was only found on the cation exchange membranes. As a reference, plastic sheets without charge were used, which results in significant cleaner surfaces. Additionally, the setups without spacers in between the membranes (i.e. profiled membranes) appear significant less sensitive to fouling. This was quantified by the pressure drop over the feed waters and the power density obtained from the membrane piles. The pressure drop increases four times slower and the power density remains higher when profiled membranes are use instead of flat membranes with spacers. Although the obtained power density reduced with approximately 40% in the first day under these conditions, caused by organic fouling, several strategies are available to maintain a high power output using reverse electrodialysis. PMID:23266386

  7. Reversible nanodiamond-carbon onion phase transformations.

    PubMed

    Xiao, J; Ouyang, G; Liu, P; Wang, C X; Yang, G W

    2014-06-11

    Because of their considerable science and technical interest, nanodiamonds (3-5 nm) are often used as a model to study the phase transformation between graphite and diamond. Here we demonstrated that a reversible nanodiamond-carbon onion phase transformation can become true when laser irradiates colloidal suspensions of nanodiamonds at the ambient temperature and pressure. Nanodiamonds are first transformed to carbon onions driven by the laser-induced high temperature in which an intermediary bucky diamond phase is observed. Sequentially, carbon onions are transformed back to nanodiamonds driven by the laser-induced high temperature and high pressure from carbon onions as nanoscaled temperature and pressure cell upon the laser irradiation process in liquid. Similarly, the same bucky diamond phase serving as an intermediate phase is found during the carbon onion-to-nanodiamond transition. To have a clear insight into the unique phase transformation the thermodynamic approaches on the nanoscale were proposed to elucidate the reversible phase transformation of nanodiamond-to-carbon onion-to-nanodiamond via an intermediary bucky diamond phase upon the laser irradiation in liquid. This reversible transition reveals a series of phase transformations between diamond and carbon allotropes, such as carbon onion and bucky diamond, having a general insight into the basic physics involved in these phase transformations. These results give a clue to the root of meteoritic nanodiamonds that are commonly found in primitive meteorites but their origin is puzzling and offers one suitable approach for breaking controllable pathways between diamond and carbon allotropes. PMID:24823241

  8. MDR-reversal activity of chalcones.

    PubMed

    Ivanova, Antoaneta; Batovska, Daniela; Engi, Helga; Parushev, Stoyan; Ocsovszki, Imre; Kostova, Ivanka; Molnar, Joseph

    2008-01-01

    The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was applied as a positive control. The majority of the tested compounds were proved to be effective inhibitors of the outward transport of rhodamine-123. In the MTT test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects, with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 microg/mL, respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values in the range of 1.5-3.5 microg/mL. The antiproliferative effect was shown to be affected by the type of substitution at the p-position on ring B. Chalcone 7, with a p-chloro group on ring B, was the most effective in MDR reversal, causing a marked increase in drug accumulation from 0.4 to 40 microg/mL. In combination with epirubicin, compound 7 displayed synergistic properties while compound 3 exhibited an additive effect. The data presented here indicated that some calcone derivatives can be regarded as effective compounds for reversal of MDR. PMID:18610751

  9. Reversible RNA adenosine methylation in biological regulation

    PubMed Central

    Jia, Guifang; Fu, Ye; He, Chuan

    2012-01-01

    N6-methyladenosine (m6A) is a ubiquitous modification in messenger RNA (mRNA) and other RNAs across most eukaryotes. For many years, however, the exact functions of m6A were not clearly understood. The discovery that the fat mass and obesity associated protein (FTO) is an m6A demethylase indicates that this modification is reversible and dynamically regulated, suggesting it has regulatory roles. In addition, it has been shown that m6A affects cell fate decisions in yeast and plant development. Recent affinity-based m6A profiling in mouse and human cells further showed that this modification is a widespread mark in coding and non-coding RNA transcripts and is likely dynamically regulated throughout developmental processes. Therefore, reversible RNA methylation, analogous to reversible DNA and histone modifications, may affect gene expression and cell fate decisions by modulating multiple RNA-related cellular pathways, which potentially provides rapid responses to various cellular and environmental signals, including energy and nutrient availability in mammals. PMID:23218460

  10. Reversible colorimetric probes for mercury sensing.

    PubMed

    Coronado, Eugenio; Galán-Mascarós, José R; Martí-Gastaldo, Carlos; Palomares, Emilio; Durrant, James R; Vilar, Ramón; Gratzel, M; Nazeeruddin, Md K

    2005-09-01

    The selectivity and sensitivity of two colorimetric sensors based on the ruthenium complexes N719 [bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II) bis(tetrabutylammonium) bis(thiocyanate)] and N749 [(2,2':6',2' '-terpyridine-4,4',4' '-tricarboxylate)ruthenium(II) tris(tetrabutylammonium) tris(isothiocyanate)] are described. It was found that mercury ions coordinate reversibly to the sulfur atom of the dyes' NCS groups. This interaction induces a color change in the dyes at submicromolar concentrations of mercury. Furthermore, the color change of these dyes is selective for mercury(II) when compared with other ions such as lead(II), cadmium(II), zinc(II), or iron(II). The detection limit for mercury(II) ions--using UV-vis spectroscopy--in homogeneous aqueous solutions is estimated to be approximately 20 ppb for N719 and approximately 150 ppb for N749. Moreover, the sensor molecules can be adsorbed onto high-surface-area mesoporous metal oxide films, allowing reversible heterogeneous sensing of mercury ions in aqueous solution. The results shown herein have important implications in the development of new reversible colorimetric sensors for the fast, easy, and selective detection and monitoring of mercuric ions in aqueous solutions. PMID:16131215

  11. Therapeutic Drug Monitoring By Reverse Iontophoresis

    PubMed Central

    Nair, Anroop B; Goel, Ankit; Prakash, Shashi; Kumar, Ashok

    2011-01-01

    Therapeutic molecules possessing distinct pharmacokinetic variation, narrow therapeutic index and concentration dependent therapeutic/adverse effects demand constant monitoring. The current methods for blood sampling are invasive and possess low patient compliance. Human skin, selective and effective membrane to chemical permeation, offers an alternative route for the extraction of endogenous molecules in the body. Significant attention has been received in the application of reverse iontophoresis in extracting drugs/biomaterials from the subdermal region. This technique involves transiting of a low electric current across the skin usually with couple of skin electrodes to extract charged as well as neutral molecules. Electromigration and electroosmosis are the two basic mechanisms involved in transport of molecules. Several in vitro and in vivo experiments demonstrated the potential of reverse iontophoresis as a noninvasive tool in clinical chemistry and therapeutic drug monitoring. This technology is currently being used in device such as Glucowatch Biogrpaher which allows blood glucose detection across skin layers. Advances in technology and rapid progress in research has widely improved the opportunity of this system, and the recent trend indicates that several products are likely to be developed very soon. This review provides an overview about the recent developments in reverse iontophoresis for therapeutic drug monitoring. PMID:24826025

  12. Reversal by pronethalol of dibenamine blockade

    PubMed Central

    Guimarães, S.

    1969-01-01

    1. The guinea-pig seminal vesicle has been shown to be a very suitable test object for the study of mechanisms involving α-adrenoceptive receptors, because no β-receptors were found in this preparation. 2. Adrenaline, noradrenaline and phenylephrine were directly acting agonists, their ED50 values being 7·1 × 10-6M, 1·5 × 10-5M and 2·7 × 10-5M, respectively. 3. Pretreatment with reserpine had no influence on the contractions caused by adrenaline, noradrenaline and phenylephrine but abolished or greatly reduced the contractions caused by dopamine. Cocaine enhanced the effects of adrenaline, noradrenaline and phenylephrine and reduced those of dopamine. 4. Pronethalol (6·8 × 10-5M) reversed the α-receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine; it did not affect the blockade by dibenamine of responses to histamine. 5. Reversal of the blockade by dibenamine was observed only when its concentration was such that it caused a parallel shift of the dose-effect curves of the agonists to the right; higher concentrations, which caused an unsurmountable depression of the maximal contraction, were not antagonized by pronethalol. 6. It is assumed that the reversal is dependent on a direct action on α-receptors, “spare receptors” being probably involved. PMID:4389284

  13. Coevolution can reverse predator-prey cycles.

    PubMed

    Cortez, Michael H; Weitz, Joshua S

    2014-05-20

    A hallmark of Lotka-Volterra models, and other ecological models of predator-prey interactions, is that in predator-prey cycles, peaks in prey abundance precede peaks in predator abundance. Such models typically assume that species life history traits are fixed over ecologically relevant time scales. However, the coevolution of predator and prey traits has been shown to alter the community dynamics of natural systems, leading to novel dynamics including antiphase and cryptic cycles. Here, using an eco-coevolutionary model, we show that predator-prey coevolution can also drive population cycles where the opposite of canonical Lotka-Volterra oscillations occurs: predator peaks precede prey peaks. These reversed cycles arise when selection favors extreme phenotypes, predator offense is costly, and prey defense is effective against low-offense predators. We present multiple datasets from phage-cholera, mink-muskrat, and gyrfalcon-rock ptarmigan systems that exhibit reversed-peak ordering. Our results suggest that such cycles are a potential signature of predator-prey coevolution and reveal unique ways in which predator-prey coevolution can shape, and possibly reverse, community dynamics. PMID:24799689

  14. Domino model for geomagnetic field reversals.

    PubMed

    Mori, N; Schmitt, D; Wicht, J; Ferriz-Mas, A; Mouri, H; Nakamichi, A; Morikawa, M

    2013-01-01

    We solve the equations of motion of a one-dimensional planar Heisenberg (or Vaks-Larkin) model consisting of a system of interacting macrospins aligned along a ring. Each spin has unit length and is described by its angle with respect to the rotational axis. The orientation of the spins can vary in time due to spin-spin interaction and random forcing. We statistically describe the behavior of the sum of all spins for different parameters. The term "domino model" in the title refers to the interaction among the spins. We compare the model results with geomagnetic field reversals and dynamo simulations and find strikingly similar behavior. The aggregate of all spins keeps the same direction for a long time and, once in a while, begins flipping to change the orientation by almost 180 degrees (mimicking a geomagnetic reversal) or to move back to the original direction (mimicking an excursion). Most of the time the spins are aligned or antialigned and deviate only slightly with respect to the rotational axis (mimicking the secular variation of the geomagnetic pole with respect to the geographic pole). Reversals are fast compared to the times in between and they occur at random times, both in the model and in the case of the Earth's magnetic field. PMID:23410284

  15. Model of reversible vesicular transport with exclusion

    NASA Astrophysics Data System (ADS)

    Bressloff, Paul C.; Karamched, Bhargav R.

    2016-08-01

    A major question in neurobiology concerns the mechanics behind the motor-driven transport and delivery of vesicles to synaptic targets along the axon of a neuron. Experimental evidence suggests that the distribution of vesicles along the axon is relatively uniform and that vesicular delivery to synapses is reversible. A recent modeling study has made explicit the crucial role that reversibility in vesicular delivery to synapses plays in achieving uniformity in vesicle distribution, so called synaptic democracy (Bressloff et al 2015 Phys. Rev. Lett. 114 168101). In this paper we generalize the previous model by accounting for exclusion effects (hard-core repulsion) that may occur between molecular motor-cargo complexes (particles) moving along the same microtubule track. The resulting model takes the form of an exclusion process with four internal states, which distinguish between motile and stationary particles, and whether or not a particle is carrying vesicles. By applying a mean field approximation and an adiabatic approximation we reduce the system of ODEs describing the evolution of occupation numbers of the sites on a 1D lattice to a system of hydrodynamic equations in the continuum limit. We find that reversibility in vesicular delivery allows for synaptic democracy even in the presence of exclusion effects, although exclusion does exacerbate nonuniform distributions of vesicles in an axon when compared with a model without exclusion. We also uncover the relationship between our model and other models of exclusion processes with internal states.

  16. Preference reversal in quantum decision theory

    PubMed Central

    Yukalov, Vyacheslav I.; Sornette, Didier

    2015-01-01

    We consider the psychological effect of preference reversal and show that it finds a natural explanation in the frame of quantum decision theory. When people choose between lotteries with non-negative payoffs, they prefer a more certain lottery because of uncertainty aversion. But when people evaluate lottery prices, e.g., for selling to others the right to play them, they do this more rationally, being less subject to behavioral biases. This difference can be explained by the presence of the attraction factors entering the expression of quantum probabilities. Only the existence of attraction factors can explain why, considering two lotteries with close utility factors, a decision maker prefers one of them when choosing, but evaluates higher the other one when pricing. We derive a general quantitative criterion for the preference reversal to occur that relates the utilities of the two lotteries to the attraction factors under choosing vs. pricing and test successfully its application on experiments by Tversky et al. We also show that the planning paradox can be treated as a kind of preference reversal. PMID:26500592

  17. Coevolution can reverse predator–prey cycles

    PubMed Central

    Cortez, Michael H.; Weitz, Joshua S.

    2014-01-01

    A hallmark of Lotka–Volterra models, and other ecological models of predator–prey interactions, is that in predator–prey cycles, peaks in prey abundance precede peaks in predator abundance. Such models typically assume that species life history traits are fixed over ecologically relevant time scales. However, the coevolution of predator and prey traits has been shown to alter the community dynamics of natural systems, leading to novel dynamics including antiphase and cryptic cycles. Here, using an eco-coevolutionary model, we show that predator–prey coevolution can also drive population cycles where the opposite of canonical Lotka–Volterra oscillations occurs: predator peaks precede prey peaks. These reversed cycles arise when selection favors extreme phenotypes, predator offense is costly, and prey defense is effective against low-offense predators. We present multiple datasets from phage–cholera, mink–muskrat, and gyrfalcon–rock ptarmigan systems that exhibit reversed-peak ordering. Our results suggest that such cycles are a potential signature of predator–prey coevolution and reveal unique ways in which predator–prey coevolution can shape, and possibly reverse, community dynamics. PMID:24799689

  18. Dipole collapse and reversal precursors in a numerical dynamo

    NASA Astrophysics Data System (ADS)

    Olson, Peter; Driscoll, Peter; Amit, Hagay

    2009-03-01

    Precursors to extreme geomagnetic field changes are examined in a numerical dynamo with a reversing dipolar magnetic field. A dynamo model with compositional convection in a rotating spherical shell produces a strongly dipolar external magnetic field over 6 Myr of simulated paleomagnetic time, with stable polarity epochs and occasional dipole collapses, some of which result in polarity reversals or dipole axis excursions. We analyze the model behavior during two dipole collapses, one that leads to a polarity reversal and one that does not, focusing on observable precursors. Reversed magnetic field induced in the dynamo interior by intermittent convective variability is the primary cause of dipole collapse. Spots of reversed magnetic flux emerge on the outer boundary at an early stage, then re-emerge with greater intensity at the height of the collapse. The energy in the external field cascades to higher harmonics as these reversed patches appear. Butterfly diagrams showing the reversed and normal flux contributions to the axial dipole reveal poleward migration of the patches during dipole collapse. Axial dipole reduction by precursory reversed flux is several times larger in the reversing case, compared to the non-reversing case. A butterfly diagram of the geomagnetic field since 1840 shows high latitude reversed flux emerging on the core-mantle boundary. Although the reversed geomagnetic flux is presently too weak to be labeled a reversal precursor, it is consistent with early stage dipole collapse in the dynamo model.

  19. Reverse Discrimination in Professional Schools' Admissions and in Employment.

    ERIC Educational Resources Information Center

    Brown, Frank

    1979-01-01

    Discusses equal opportunity in America, the antecedents of present reverse discrimination cases, discrimination in professional schools' admissions, and reverse discrimination in employment. Concludes that the American people are ready to accept limited affirmative action programs. (Author/IRT)

  20. Defunctioning Ileostomy Reversal Rates and Reasons for Delayed Reversal: Does Delay Impact on Complications of Ileostomy Reversal? A Study of 170 Defunctioning Ileostomies

    PubMed Central

    Waterland, Peter; Goonetilleke, Kolitha; Naumann, David N.; Sutcliff, Mathew; Soliman, Faris

    2015-01-01

    Background Temporary defunctioning ileostomy can reduce the consequences of anastomotic leak following low anterior resection. However, some patients never have their ileostomy reversed and in other cases the time to reversal of ileostomy can be delayed. The aim of this study was to identify the ileostomy closure rate following anterior resection, time to closure of ileostomy, reasons for delay in reversal and whether delay was associated with an increased complication rate. Methods Data were collected retrospectively on consecutive patients undergoing defunctioning ileostomy following anterior resection for rectal cancer, between January 2009 and August 2013. Data were collected on reversal of ileostomy rates, time to reversal, reasons for delayed reversal (defined as > 6 months) and complications following reversal. Results One hundred seventy patients were studied (median age 69 years, range 41 - 90 years), of whom 117 (69%) were male. One hundred twenty-seven (75%) patients had their ileostomies reversed. Median time to reversal was 6 months (range 1 - 42). In 63 patients who had delayed reversal, reasons were adjuvant chemotherapy (22, 35%), medical illness (14, 22%), anastomotic leak (9, 14%), and others (4, 7%). Postoperative complications occurred in 33 patients (26%). There was no postoperative mortality. Univariate analysis showed that delayed reversal was associated with an increased rate of complications and longer length of hospital stay following reversal (P < 0.05). Conclusions One in four defunctioning ileostomies are not closed following anterior resection in our unit. Of those that are closed, approximately 50% have delayed closure beyond 6 months which is associated with increased risk of complications following their ileostomy reversal. PMID:26251682

  1. Reversible catalytic dehydrogenation of alcohols for energy storage

    PubMed Central

    Bonitatibus, Peter J.; Chakraborty, Sumit; Doherty, Mark D.; Siclovan, Oltea; Jones, William D.; Soloveichik, Grigorii L.

    2015-01-01

    Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels. PMID:25588879

  2. A study on dynamic heat assisted magnetization reversal mechanisms under insufficient reversal field conditions

    SciTech Connect

    Chen, Y. J.; Yang, H. Z.; Leong, S. H.; Yu Ko, Hnin Yu; Wu, B. L.; Ng, V.; Asbahi, M.; Yang, J. K. W.

    2014-10-20

    We report an experimental study on the dynamic thermomagnetic (TM) reversal mechanisms at around Curie temperature (Tc) for isolated 60 nm pitch single-domain [Co/Pd] islands heated by a 1.5 μm spot size laser pulse under an applied magnetic reversal field (Hr). Magnetic force microscopy (MFM) observations with high resolution MFM tips clearly showed randomly trapped non-switched islands within the laser irradiated spot after dynamic TM reversal process with insufficient Hr strength. This observation provides direct experimental evidence by MFM of a large magnetization switching variation due to increased thermal fluctuation/agitation over magnetization energy at the elevated temperature of around Tc. The average percentage of non-switched islands/magnetization was further found to be inversely proportional to the applied reversal field Hr for incomplete magnetization reversal when Hr is less than 13% of the island coercivity (Hc), showing an increased switching field distribution (SFD) at elevated temperature of around Tc (where main contributions to SFD broadening are from Tc distribution and stronger thermal fluctuations). Our experimental study and results provide better understanding and insight on practical heat assisted magnetic recording (HAMR) process and recording performance, including HAMR writing magnetization dynamics induced SFD as well as associated DC saturation noise that limits areal density, as were previously observed and investigated by theoretical simulations.

  3. Time Reversal in Solids (Linear and Nonlinear Elasticity): Multimedia Resources in Time Reversal

    DOE Data Explorer

    Dynamic nonlinear elastic behavior, nonequilibrium dynamics, first observed as a curiosity in earth materials has now been observed in a great variety of solids. The primary manifestations of the behavior are characteristic wave distortion, and slow dynamics, a recovery process to equilibrium that takes place linearly with the logarithm of time, over hours to days after a wave disturbance. The link between the diverse materials that exhibit nonequilibrium dynamics appears to be the presence of soft regions, thought to be 'damage' at many scales, ranging from order 10-9 m to 10-1 m at least. The regions of soft matter may be distributed as in a rock sample, or isolated, as in a sample with a single crack [LANLhttp://www.lanl.gov/orgs/ees/ees11/geophysics/nonlinear/nonlinear.shtml]. The Geophysics Group (EES-11) at Los Alamos National Laboratory has posted two or more multimedia items under each of the titles below to demonstrate aspects of their work: 1) Source Reconstruction Using Time Reversal; 2) Robustness and Efficiency of Time Reversal Acoustics in Solid Media; 3) Audio Example of Time Reversal - Speech Privacy; 4) Crack Imagining with Time Reversal - Experimental Results; 5) Time Reversal of the 2004 (M9.0) Sumatra Earthquake.

  4. Analytical prediction of reverse buckling pressure for thin shells

    NASA Technical Reports Server (NTRS)

    Martindale, D. L.; Urbanac, C.

    1970-01-01

    Analytical technique is developed for prediction of reverse buckling in thin curved shells. Test data indicate technique predicts actual reverse buckling pressure within 10 percent, and should be useful for analytical prediction of reversed condition failure for problems such as explosive decomposition through vacuum failure.

  5. Study of a new airfoil used in reversible axial fans

    NASA Technical Reports Server (NTRS)

    Li, Chaojun; Wei, Baosuo; Gu, Chuangang

    1991-01-01

    The characteristics of the reverse ventilation of axial flow are analyzed. An s shaped airfoil with a double circular arc was tested in a wind tunnel. The experimental results showed that the characteristics of this new airfoil in reverse ventilation are the same as those in normal ventilation, and that this airfoil is better than the existing airfoils used on reversible axial fans.

  6. Study on the reversibility of the diffraction light path

    NASA Astrophysics Data System (ADS)

    Zhang, Weiping; Wan, Lingyu; Liu, Yun; Dong, Jianjie; Shen, Xiaoming

    2009-08-01

    of grating. First, we studied the reversibility of optical path of grating illuminated by monochromatic light, and then illuminated by polychromatic light. We found that the optical path of diffraction of grating has partial reversibility. Using the partial reversibility of optical path of diffraction of grating, we analyzed the spectral combination characteristic of grating and the bi-grating diffraction imaging effect.

  7. 21 CFR 177.2550 - Reverse osmosis membranes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Reverse osmosis membranes. 177.2550 Section 177... Components of Articles Intended for Repeated Use § 177.2550 Reverse osmosis membranes. Substances identified in paragraph (a) of this section may be safely used as reverse osmosis membranes intended for use...

  8. 21 CFR 177.2550 - Reverse osmosis membranes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Reverse osmosis membranes. 177.2550 Section 177... Components of Articles Intended for Repeated Use § 177.2550 Reverse osmosis membranes. Substances identified in paragraph (a) of this section may be safely used as reverse osmosis membranes intended for use...

  9. 21 CFR 177.2550 - Reverse osmosis membranes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Reverse osmosis membranes. 177.2550 Section 177... Components of Articles Intended for Repeated Use § 177.2550 Reverse osmosis membranes. Substances identified in paragraph (a) of this section may be safely used as reverse osmosis membranes intended for use...

  10. 21 CFR 177.2550 - Reverse osmosis membranes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Reverse osmosis membranes. 177.2550 Section 177... Components of Articles Intended for Repeated Use § 177.2550 Reverse osmosis membranes. Substances identified in paragraph (a) of this section may be safely used as reverse osmosis membranes intended for use...

  11. 21 CFR 177.2550 - Reverse osmosis membranes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Reverse osmosis membranes. 177.2550 Section 177... Use § 177.2550 Reverse osmosis membranes. Substances identified in paragraph (a) of this section may be safely used as reverse osmosis membranes intended for use in processing bulk quantities of...

  12. Summary of Scale-Model Thrust-Reverser Investigation

    NASA Technical Reports Server (NTRS)

    Povolny, John H; Steffen, Fred W; Mcardle, Jack G

    1957-01-01

    An investigation was undertaken to determine the characteristics of several basic types of thrust-reverser. Models of three types, target, tailpipe cascade, and ring cascade, were tested with unheated air. The effects of design variables on reverse-thrust performance, reversed-flow boundaries, and thrust modulation characteristics were determined.

  13. Correlation of electrostatic fluctuation and reversal of toroidal field in the reversed-field pinch plasma

    SciTech Connect

    Yambe, Kiyoyuki; Koguchi, Haruhisa; Sakakita, Hajime; Hirano, Yoichi; Kiyama, Satoru

    2011-06-15

    The magnetic fluctuations and electrostatic probe potential have been measured in the Toroidal Pinch Experiment - RX (TPE-RX) reversed-field pinch plasma [Y. Yagi et al., Fusion Eng. Des. 45, 421 (1999)] (at the plasma surface r/a = 1.00). Fast electrons with energy comparable to or slightly higher than the core electron temperature are observed as many spikes in the electrostatic probe signal. These electrons are diffused by a fluctuating magnetic field from the core region. During the period of mild deepening of the reversal of the edge toroidal field, a significant reduction in the spike signal, increases in electron density and soft x-ray radiation, and a decrease in the D{alpha} line radiation are observed, even though the reduction in magnetic fluctuations is not significant during the same period, which indicates that the mild deepening of the reversal of the toroidal field can improve the confinement of fast electrons.

  14. Cascade Reverse Osmosis Air Conditioning System: Cascade Reverse Osmosis and the Absorption Osmosis Cycle

    SciTech Connect

    2010-09-01

    BEETIT Project: Battelle is developing a new air conditioning system that uses a cascade reverse osmosis (RO)-based absorption cycle. Analyses show that this new cycle can be as much as 60% more efficient than vapor compression, which is used in 90% of air conditioners. Traditional vapor-compression systems use polluting liquids for a cooling effect. Absorption cycles use benign refrigerants such as water, which is absorbed in a salt solution and pumped as liquid—replacing compression of vapor. The refrigerant is subsequently separated from absorbing salt using heat for re-use in the cooling cycle. Battelle is replacing thermal separation of refrigerant with a more efficient reverse osmosis process. Research has shown that the cycle is possible, but further investment will be needed to reduce the number of cascade reverse osmosis stages and therefore cost.

  15. Time reversal invariance in polarized neutron decay

    SciTech Connect

    Wasserman, E.G.

    1994-03-01

    An experiment to measure the time reversal invariance violating (T-violating) triple correlation (D) in the decay of free polarized neutrons has been developed. The detector design incorporates a detector geometry that provides a significant improvement in the sensitivity over that used in the most sensitive of previous experiments. A prototype detector was tested in measurements with a cold neutron beam. Data resulting from the tests are presented. A detailed calculation of systematic effects has been performed and new diagnostic techniques that allow these effects to be measured have been developed. As the result of this work, a new experiment is under way that will improve the sensitivity to D to 3 {times} 10{sup {minus}4} or better. With higher neutron flux a statistical sensitivity of the order 3 {times} 10{sup {minus}5} is ultimately expected. The decay of free polarized neutrons (n {yields} p + e + {bar v}{sub e}) is used to search for T-violation by measuring the triple correlation of the neutron spin polarization, and the electron and proton momenta ({sigma}{sub n} {center_dot} p{sub p} {times} p{sub e}). This correlation changes sign under reversal of the motion. Since final state effects in neutron decay are small, a nonzero coefficient, D, of this correlation indicates the violation of time reversal invariance. D is measured by comparing the numbers of coincidences in electron and proton detectors arranged symmetrically about a longitudinally polarized neutron beam. Particular care must be taken to eliminate residual asymmetries in the detectors or beam as these can lead to significant false effects. The Standard Model predicts negligible T-violating effects in neutron decay. Extensions to the Standard Model include new interactions some of which include CP-violating components. Some of these make first order contributions to D.

  16. Reversible (unitized) PEM fuel cell devices

    SciTech Connect

    Mitlitsky, F; Myers, B; Smith, W F; Weisberg, Molter, T M

    1999-06-01

    Regenerative fuel cells (RFCs) are enabling for many weight-critical portable applications, since the packaged specific energy (>400 Wh/kg) of properly designed lightweight RFC systems is several-fold higher than that of the lightest weight rechargeable batteries. RFC systems can be rapidly refueled (like primary fuel cells), or can be electrically recharged (like secondary batteries) if a refueling infrastructure is not conveniently available. Higher energy capacity systems with higher performance, reduced weight, and freedom from fueling infrastructure are the features that RFCs promise for portable applications. Reversible proton exchange membrane (PEM) fuel cells, also known as unitized regenerative fuel cells (URFCs), or reversible regenerative fuel cells, are RFC systems which use reversible PEM cells, where each cell is capable of operating both as a fuel cell and as an electrolyzer. URFCs further economize portable device weight, volume, and complexity by combining the functions of fuel cells and electrolyzers in the same hardware, generally without any system performance or efficiency reduction. URFCs are being made in many forms, some of which are already small enough to be portable. Lawrence Livermore National Laboratory (LLNL) has worked with industrial partners to design, develop, and demonstrate high performance and high cycle life URFC systems. LLNL is also working with industrial partners to develop breakthroughs in lightweight pressure vessels that are necessary for URFC systems to achieve the specific energy advantages over rechargeable batteries. Proton Energy Systems, Inc. (Proton) is concurrently developing and commercializing URFC systems (UNIGEN' product line), in addition to PEM electrolyzer systems (HOGEN' product line), and primary PEM fuel cell systems. LLNL is constructing demonstration URFC units in order to persuade potential sponsors, often in their own conference rooms, that advanced applications based on URFC s are feasible. Safety

  17. Thermodynamically reversible generalization of diffusion limited aggregation.

    PubMed

    D'Souza, R M; Margolus, N H

    1999-07-01

    We introduce a lattice gas model of cluster growth via the diffusive aggregation of particles in a closed system obeying a local, deterministic, microscopically reversible dynamics. This model roughly corresponds to placing the irreversible diffusion limited aggregation model (DLA) in contact with a heat bath. Particles release latent heat when aggregating, while singly connected cluster members can absorb heat and evaporate. The heat bath is initially empty, hence we observe the flow of entropy from the aggregating gas of particles into the heat bath, which is being populated by diffusing heat tokens. Before the population of the heat bath stabilizes, the cluster morphology (quantified by the fractal dimension) is similar to a standard DLA cluster. The cluster then gradually anneals, becoming more tenuous, until reaching configurational equilibrium when the cluster morphology resembles a quenched branched random polymer. As the microscopic dynamics is invertible, we can reverse the evolution, observe the inverse flow of heat and entropy, and recover the initial condition. This simple system provides an explicit example of how macroscopic dissipation and self-organization can result from an underlying microscopically reversible dynamics. We present a detailed description of the dynamics for the model, discuss the macroscopic limit, and give predictions for the equilibrium particle densities obtained in the mean field limit. Empirical results for the growth are then presented, including the observed equilibrium particle densities, the temperature of the system, the fractal dimension of the growth clusters, scaling behavior, finite size effects, and the approach to equilibrium. We pay particular attention to the temporal behavior of the growth process and show that the relaxation to the maximum entropy state is initially a rapid nonequilibrium process, then subsequently it is a quasistatic process with a well defined temperature. PMID:11969759

  18. Explaining Polarization Reversals in STEREO Wave Data

    NASA Technical Reports Server (NTRS)

    Breneman, A.; Cattell, C.; Wygant, J.; Kersten, K.; Wilson, L, B., III; Dai, L.; Colpitts, C.; Kellogg, P. J.; Goetz, K.; Paradise, A.

    2012-01-01

    Recently Breneman et al. reported observations of large amplitude lightning and transmitter whistler mode waves from two STEREO passes through the inner radiation belt (L<2). Hodograms of the electric field in the plane transverse to the magnetic field showed that the transmitter waves underwent periodic polarization reversals. Specifically, their polarization would cycle through a pattern of right-hand to linear to left-hand polarization at a rate of roughly 200 Hz. The lightning whistlers were observed to be left-hand polarized at frequencies greater than the lower hybrid frequency and less than the transmitter frequency (21.4 kHz) and right-hand polarized otherwise. Only righthand polarized waves in the inner radiation belt should exist in the frequency range of the whistler mode and these reversals were not explained in the previous paper. We show, with a combination of observations and simulated wave superposition, that these polarization reversals are due to the beating of an incident electromagnetic whistler mode wave at 21.4 kHz and linearly polarized, symmetric lower hybrid sidebands Doppler-shifted from the incident wave by +/-200 Hz. The existence of the lower hybrid waves is consistent with the parametric decay mechanism of Lee and Kuo whereby an incident whistler mode wave decays into symmetric, short wavelength lower hybrid waves and a purely growing (zero-frequency) mode. Like the lower hybrid waves, the purely growing mode is Doppler-shifted by 200 Hz as observed on STEREO. This decay mechanism in the upper ionosphere has been previously reported at equatorial latitudes and is thought to have a direct connection with explosive spread F enhancements. As such it may represent another dissipation mechanism of VLF wave energy in the ionosphere and may help to explain a deficit of observed lightning and transmitter energy in the inner radiation belts as reported by Starks et al.

  19. Secondary Reverse Slide Tracheoplasty for Airway Rescue.

    PubMed

    Kopelovich, Jonathan C; Wine, Todd M; Rutter, Michael J; Mitchell, Max B; Prager, Jeremy D

    2016-03-01

    Slide tracheoplasty is used in cases of tracheal stenosis or injury. With expanding indications for its use at tertiary centers, salvage techniques for dehiscence or restenosis after slide tracheoplasty are increasingly relevant. We present a case in which slide tracheoplasty was augmented with an anterior costochondral graft that stenosed again and ultimately failed. We salvaged this airway emergency by performing a secondary reverse slide tracheoplasty. Using this technique, we were able to establish a safe and durable airway using only native airway tissue. PMID:26897214

  20. Time-reversal violation in beta decay

    SciTech Connect

    Herczeg, P.

    2003-01-01

    At present there is no unambigous direct evidence for time-reversal (T) violation in the fundamental interactions. But T-violation is intimately connected with CP-violation by the CPT theorem. A stringent bound on possible violation of CPT invariance comes from the properties of K{sup 0} - {bar K}{sup 0} mixing [I]. In the following we shall assume that CPT violating interactions, if present, can be neglected, and use the terms 'T-violation' and 'CP-violation' interchangably.

  1. Reversed rainbow with a nonlocal metamaterial

    NASA Astrophysics Data System (ADS)

    Morgado, Tiago A.; Marcos, João S.; Costa, João T.; Costa, Jorge R.; Fernandes, Carlos A.; Silveirinha, Mário G.

    2014-12-01

    One of the intriguing potentials of metamaterials is the possibility to realize a nonlocal electromagnetic reaction, such that the effective medium response at a given point is fundamentally entangled with the macroscopic field distribution at long distances. Here, it is experimentally and numerically verified that a microwave nonlocal metamaterial formed by crossed metallic wires enables a low-loss broadband anomalous material response such that the refractive index decreases with frequency. Notably, it is shown that an electromagnetic beam refracted by our metamaterial prism creates a reversed microwave rainbow.

  2. Reversed rainbow with a nonlocal metamaterial

    SciTech Connect

    Morgado, Tiago A. Marcos, João S.; Silveirinha, Mário G.; Costa, João T.; Costa, Jorge R.; Fernandes, Carlos A.

    2014-12-29

    One of the intriguing potentials of metamaterials is the possibility to realize a nonlocal electromagnetic reaction, such that the effective medium response at a given point is fundamentally entangled with the macroscopic field distribution at long distances. Here, it is experimentally and numerically verified that a microwave nonlocal metamaterial formed by crossed metallic wires enables a low-loss broadband anomalous material response such that the refractive index decreases with frequency. Notably, it is shown that an electromagnetic beam refracted by our metamaterial prism creates a reversed microwave rainbow.

  3. Reverse genetics: Its origins and prospects

    SciTech Connect

    Berg, P. )

    1991-04-01

    The nucleotide sequence of a gene and its flanking segments alone will not tell us how its expression is regulated during development and differentiation, or in response to environmental changes. To comprehend the physiological significance of the molecular details requires biological analysis. Recombinant DNA techniques provide a powerful experimental approach. A strategy termed reverse genetics' utilizes the analysis of the activities of mutant and normal genes and experimentally constructed mutants to explore the relationship between gene structure and function thereby helping elucidate the relationship between genotype and phenotype.

  4. Reversible Stochastically Gated Diffusion-Influenced Reactions.

    PubMed

    Gopich, Irina V; Szabo, Attila

    2016-08-25

    An approximate but accurate theory is developed for the kinetics of reversible binding of a ligand to a macromolecule when either can stochastically fluctuate between reactive and unreactive conformations. The theory is based on a set of reaction-diffusion equations for the deviations of the pair distributions from their bulk values. The concentrations are shown to satisfy non-Markovian rate equations with memory kernels that are obtained by solving an irreversible geminate (i.e., two-particle) problem. The relaxation to equilibrium is not exponential but rather a power law. In the Markovian limit, the theory reduces to a set of ordinary rate equations with renormalized rate constants. PMID:26956646

  5. Time-reversal and the Bessel equation

    NASA Astrophysics Data System (ADS)

    Alfinito, Eleonora; Vitiello, Giuseppe

    2015-07-01

    The system of two damped/amplified oscillator equations is of widespread interest in the study of many physical problems and phenomena, from inflationary models of the Universe to thermal field theories, in condensed matter physics as well in high energy physics, and also in neuroscience. In this report we review the equivalence, in a suitable parametrization, between such a system of equations and the Bessel equations. In this connection, we discuss the breakdown of loop-antiloop symmetry, its relation with time-reversal symmetry and the mechanism of group contraction. Euclidean algebras such as e(2) and e(3) are also discussed in relation with Virasoro-like algebra.

  6. Reverse transcriptase: mediator of genomic plasticity.

    PubMed

    Brosius, J; Tiedge, H

    1995-01-01

    Reverse transcription has been an important mediator of genomic change. This influence dates back more than three billion years, when the RNA genome was converted into the DNA genome. While the current cellular role(s) of reverse transcriptase are not yet completely understood, it has become clear over the last few years that this enzyme is still responsible for generating significant genomic change and that its activities are one of the driving forces of evolution. Reverse transcriptase generates, for example, extra gene copies (retrogenes), using as a template mature messenger RNAs. Such retrogenes do not always end up as nonfunctional pseudogenes but form, after reinsertion into the genome, new unions with resident promoter elements that may alter the gene's temporal and/or spatial expression levels. More frequently, reverse transcriptase produces copies of nonmessenger RNAs, such as small nuclear or cytoplasmic RNAs. Extremely high copy numbers can be generated by this process. The resulting reinserted DNA copies are therefore referred to as short interspersed repetitive elements (SINEs). SINEs have long been considered selfish DNA, littering the genome via exponential propagation but not contributing to the host's fitness. Many SINEs, however, can give rise to novel genes encoding small RNAs, and are the migrant carriers of numerous control elements and sequence motifs that can equip resident genes with novel regulatory elements [Brosius J. and Gould S.J., Proc Natl Acad Sci USA 89, 10706-10710, 1992]. Retrosequences, such as SINEs and portions of retroelements (e.g., long terminal repeats, LTRs), are capable of donating sequence motifs for nucleosome positioning, DNA methylation, transcriptional enhancers and silencers, poly(A) addition sequences, determinants of RNA stability or transport, splice sites, and even amino acid codons for incorporation into open reading frames as novel protein domains. Retroposition can therefore be considered as a major

  7. Toward postnatal reversal of ocular congenital malformations

    PubMed Central

    Sahel, José-Alain; Marazova, Katia

    2013-01-01

    Aniridia is a panocular disorder that severely affects vision in early life. Most cases are caused by dominantly inherited mutations or deletions of the PAX6 gene, which encodes a transcription factor that is essential for the development of the eye and the central nervous system. In this issue of the JCI, Gregory-Evans and colleagues demonstrate that early postnatal topical administration of an ataluren-based formulation reverses congenital malformations in the postnatal mouse eye, providing evidence that manipulation of PAX6 after birth may lead to corrective tissue remodeling. These findings offer hope that ataluren administration could be a therapeutic paradigm applicable to some major congenital eye defects. PMID:24355915

  8. What is a Reversed Field Pinch?

    NASA Astrophysics Data System (ADS)

    Escande, D. F.

    2015-12-01

    The following sections are included: * Introduction * Short description * Usefulness of the RFP configuration for fusion science and dynamo physics * Attractivity of the RFP configuration for a reactor * Challenges ahead * Lawson criterion * Intuitive model of magnetic self-reversal * Intuitive description of the dynamo * Necessity of a helical deformation * MHD simulations * From single to multiple helicity * Single helicity * Multiple helicity * Quasi single helicity * Experimental results * Multiple helicity * Quasi single helicity * Upgrade of the RFX device * From double to single magnetic axis * Analytical description of the single helicity RFP * Helical Grad-Shafranov equation * Parallel Ohm's law * Pinch-stellarator equation * Single helicity ohmic RFP states * Calculation of the dynamo * Conclusion * Acknowledgments * References

  9. Implant shape optimization using reverse FEA

    NASA Astrophysics Data System (ADS)

    Gladilin, Evgeny; Ivanov, A.; Roginsky, V.

    2005-04-01

    This work presents a novel approach for the physically-based optimization of individual implants in cranio-maxillofacial surgery. The proposed method is based on solving an inverse boundary value problem of the cranio-maxillofacial surgery planning, i.e. finding an optimal implant shape for a desired correction of soft tissues. The paper describes the methodology for the generation of individual geometrical models of human head, the reverse finite element approach for solving biomechanical boundary value problems and two clinical studies dealing with the computer aided design of individual craniofacial implants.

  10. Confinement of translated field-reversed configurations

    NASA Astrophysics Data System (ADS)

    Tuszewski, M.; Armstrong, W. T.; Chrien, R. E.; Klingner, P. L.; McKenna, K. F.; Rej, D. J.; Sherwood, E. G.; Siemon, R. E.

    1986-03-01

    The confinement properties of translating field-reversed configurations (FRC) in the FRX-C/T device [Phys. Fluids 29, (1986)] are analyzed and compared to previous data without translation and to available theory. Translation dynamics do not appear to appreciably modify the FRC confinement. Some empirical scaling laws with respect to various plasma parameters are extracted from the data. These are qualitatively similar to those obtained in the TRX-1 device [Phys. Fluids 28, 888 (1985)] without translation and with a different formation method. Translation with a static gas fill offers new opportunities such as improved particle confinement or refueling of the FRC particle inventory.

  11. Reversible optical-to-microwave quantum interface.

    PubMed

    Barzanjeh, Sh; Abdi, M; Milburn, G J; Tombesi, P; Vitali, D

    2012-09-28

    We describe a reversible quantum interface between an optical and a microwave field using a hybrid device based on their common interaction with a micromechanical resonator in a superconducting circuit. We show that, by employing state-of-the-art optoelectromechanical devices, one can realize an effective source of (bright) two-mode squeezing with an optical idler (signal) and a microwave signal, which can be used for high-fidelity transfer of quantum states between optical and microwave fields by means of continuous variable teleportation. PMID:23030075

  12. Evidence for reversible motoneurone dysfunction in thyrotoxicosis

    PubMed Central

    McComas, A. J.; Sica, R. E. P.; McNabb, A. R.; Goldberg, W. M.; Upton, A. R. M.

    1974-01-01

    Motor unit estimating techniques have been employed as part of a comprehensive electrophysiological survey of peripheral nerve and muscle in 20 patients with thyrotoxicosis. In all patients there was evidence of a loss of operational motor units; the selective nature of this involvement suggested that the motoneurone soma was the site of the primary lesion. The reversible nature of the postulated motoneurone dysfunction was demonstrated by the increased motor unit counts in six patients who were studied again after treatment of their thyrotoxicosis. PMID:4836749

  13. Interaction between Reverse Transcriptase and Integrase Is Required for Reverse Transcription during HIV-1 Replication

    PubMed Central

    Tekeste, Shewit S.; Wilkinson, Thomas A.; Weiner, Ethan M.; Xu, Xiaowen; Miller, Jennifer T.; Le Grice, Stuart F. J.; Clubb, Robert T.

    2015-01-01

    ABSTRACT Human immunodeficiency virus type 1 (HIV-1) replication requires reverse transcription of its RNA genome into a double-stranded cDNA copy, which is then integrated into the host cell chromosome. The essential steps of reverse transcription and integration are catalyzed by the viral enzymes reverse transcriptase (RT) and integrase (IN), respectively. In vitro, HIV-1 RT can bind with IN, and the C-terminal domain (CTD) of IN is necessary and sufficient for this binding. To better define the RT-IN interaction, we performed nuclear magnetic resonance (NMR) spectroscopy experiments to map a binding surface on the IN CTD in the presence of RT prebound to a duplex DNA construct that mimics the primer-binding site in the HIV-1 genome. To determine the biological significance of the RT-IN interaction during viral replication, we used the NMR chemical shift mapping information as a guide to introduce single amino acid substitutions of nine different residues on the putative RT-binding surface in the IN CTD. We found that six viral clones bearing such IN substitutions (R231E, W243E, G247E, A248E, V250E, and I251E) were noninfectious. Further analyses of the replication-defective IN mutants indicated that the block in replication took place specifically during early reverse transcription. The recombinant INs purified from these mutants, though retaining enzymatic activities, had diminished ability to bind RT in a cosedimentation assay. The results indicate that the RT-IN interaction is functionally relevant during the reverse transcription step of the HIV-1 life cycle. IMPORTANCE To establish a productive infection, human immunodeficiency virus type 1 (HIV-1) needs to reverse transcribe its RNA genome to create a double-stranded DNA copy and then integrate this viral DNA genome into the chromosome of the host cell. These two essential steps are catalyzed by the HIV-1 enzymes reverse transcriptase (RT) and integrase (IN), respectively. We have shown previously that IN

  14. Flow reversals in turbulent convection via vortex reconnections.

    PubMed

    Chandra, Mani; Verma, Mahendra K

    2013-03-15

    We employ detailed numerical simulations to probe the mechanism of flow reversals in two-dimensional turbulent convection. We show that the reversals occur via a vortex reconnection of two attracting corner rolls having the same sign of vorticity, thus leading to major restructuring of the flow. Large fluctuations in heat transport are observed during the reversal due to the flow reconfiguration. The flow configurations during the reversals have been analyzed quantitatively using large-scale modes. Using these tools, we also show why flow reversals occur for a restricted range of Rayleigh and Prandtl numbers. PMID:25166544

  15. Optimization Approaches for Designing a Novel 4-Bit Reversible Comparator

    NASA Astrophysics Data System (ADS)

    Zhou, Ri-gui; Zhang, Man-qun; Wu, Qian; Li, Yan-cheng

    2013-02-01

    Reversible logic is a new rapidly developed research field in recent years, which has been receiving much attention for calculating with minimizing the energy consumption. This paper constructs a 4×4 new reversible gate called ZRQ gate to build quantum adder and subtraction. Meanwhile, a novel 1-bit reversible comparator by using the proposed ZRQC module on the basis of ZRQ gate is proposed as the minimum number of reversible gates and quantum costs. In addition, this paper presents a novel 4-bit reversible comparator based on the 1-bit reversible comparator. One of the vital important for optimizing reversible logic is to design reversible logic circuits with the minimum number of parameters. The proposed reversible comparators in this paper can obtain superiority in terms of the number of reversible gates, input constants, garbage outputs, unit delays and quantum costs compared with the existed circuits. Finally, MATLAB simulation software is used to test and verify the correctness of the proposed 4-bit reversible comparator.

  16. Intrinsic anisotropy-defined magnetization reversal in submicron ring magnets

    NASA Astrophysics Data System (ADS)

    Li, S. P.; Lew, W. S.; Bland, J. A. C.; Natali, M.; Lebib, A.; Chen, Y.

    2002-12-01

    We report a study of the effect of magnetocrystalline anisotropy in the magnetization reversal of submicron Co rings fabricated by nanoimprint lithography. For weak magnetocrystalline anisotropy, the complete reversal takes place via a transition from saturation at large negative fields, into a vortex configuration at small fields, and back to reverse saturation at large positive fields. When the anisotropy strength is increased to a critical value, the intermediate vortex configuration no longer exists in the magnetization reversal along the easy axis; instead, the reversal occurs through a rapid jump. However, when the applied field direction is far from the easy axis, the presence of the magnetocrystalline anisotropy favors local vortex nucleation, and this leads to a similar switching process as found for low anisotropy. Micromagnetic simulations indicate that the magnetization reversal process of the rings, starts from a buckling-like reverse domain nucleation, followed by local vortex formation and an avalanche process of local vortex nucleation.

  17. A novel reversible carry-selected adder with low latency

    NASA Astrophysics Data System (ADS)

    Li, Ming-Cui; Zhou, Ri-Gui

    2016-07-01

    Reversible logic is getting more and more attention in quantum computing, optical computing, nanotechnology and low-power complementary metal oxide semiconductor designs since reversible circuits do not loose information during computation and have only small energy dissipation. In this paper, a novel carry-selected reversible adder is proposed primarily optimised for low latency. A 4-bit reversible full adder with two kinds of outputs, minimum delay and optimal quantum cost is presented as the building block for ?-bit reversible adder. Three new reversible gates NPG (new Peres gate), TEPG (triple extension of Peres gate) and RMUX21 (reversible 2-to-1 multiplexer) are proposed and utilised to design efficient adder units. The secondary carry propagation chain is carefully designed to reduce the time consumption. The novelty of the proposed design is the consideration of low latency. The comparative study shows that the proposed adder achieves the improvement from 61.46% to 95.29% in delay over the existing designs.

  18. Magnetization reversal in exchange biased nanocap arrays

    NASA Astrophysics Data System (ADS)

    Guhr, I. L.; van Dijken, S.; Malinowski, G.; Fischer, P.; Springer, F.; Hellwig, O.; Albrecht, M.

    2007-05-01

    Arrays of self-assembled polystyrene spheres with various particle sizes have been used as a substrate to study the exchange bias effect along the out-of-plane direction of Pt/Co multilayers capped with IrMn layers. The evolution of the reversal process of the resulting magnetic nanocaps was investigated by magnetic force microscopy (MFM) and magnetic transmission x-ray microscopy (M-TXM). Tip-sample interaction-induced irreversible and reversible switching events have been observed during multiple scanning cycles in MFM imaging which are ascribed to the so-called training effect. During M-TXM imaging a drastic change in morphology has been found due to the x-ray exposure, leading to the formation of much larger spherical particles. Interestingly, these merged particles reveal again an exchange coupled single-domain magnetic cap with magnetic behaviour similar to magnetic films deposited directly on spheres of similar size. This paper was presented at the Materials Research Society Fall 2006 Meeting, 27 November-1 December 2006, as part of Symposium P: Nanoscale Magnets-Synthesis, Self-assembly, Properties and Applications, organized by J Fassbender, J Chapman and C A Ross.

  19. Comprehensive phylogenetic analysis of bacterial reverse transcriptases.

    PubMed

    Toro, Nicolás; Nisa-Martínez, Rafael

    2014-01-01

    Much less is known about reverse transcriptases (RTs) in prokaryotes than in eukaryotes, with most prokaryotic enzymes still uncharacterized. Two surveys involving BLAST searches for RT genes in prokaryotic genomes revealed the presence of large numbers of diverse, uncharacterized RTs and RT-like sequences. Here, using consistent annotation across all sequenced bacterial species from GenBank and other sources via RAST, available from the PATRIC (Pathogenic Resource Integration Center) platform, we have compiled the data for currently annotated reverse transcriptases from completely sequenced bacterial genomes. RT sequences are broadly distributed across bacterial phyla, but green sulfur bacteria and cyanobacteria have the highest levels of RT sequence diversity (≤85% identity) per genome. By contrast, phylum Actinobacteria, for which a large number of genomes have been sequenced, was found to have a low RT sequence diversity. Phylogenetic analyses revealed that bacterial RTs could be classified into 17 main groups: group II introns, retrons/retron-like RTs, diversity-generating retroelements (DGRs), Abi-like RTs, CRISPR-Cas-associated RTs, group II-like RTs (G2L), and 11 other groups of RTs of unknown function. Proteobacteria had the highest potential functional diversity, as they possessed most of the RT groups. Group II introns and DGRs were the most widely distributed RTs in bacterial phyla. Our results provide insights into bacterial RT phylogeny and the basis for an update of annotation systems based on sequence/domain homology. PMID:25423096

  20. Comprehensive Phylogenetic Analysis of Bacterial Reverse Transcriptases

    PubMed Central

    Toro, Nicolás; Nisa-Martínez, Rafael

    2014-01-01

    Much less is known about reverse transcriptases (RTs) in prokaryotes than in eukaryotes, with most prokaryotic enzymes still uncharacterized. Two surveys involving BLAST searches for RT genes in prokaryotic genomes revealed the presence of large numbers of diverse, uncharacterized RTs and RT-like sequences. Here, using consistent annotation across all sequenced bacterial species from GenBank and other sources via RAST, available from the PATRIC (Pathogenic Resource Integration Center) platform, we have compiled the data for currently annotated reverse transcriptases from completely sequenced bacterial genomes. RT sequences are broadly distributed across bacterial phyla, but green sulfur bacteria and cyanobacteria have the highest levels of RT sequence diversity (≤85% identity) per genome. By contrast, phylum Actinobacteria, for which a large number of genomes have been sequenced, was found to have a low RT sequence diversity. Phylogenetic analyses revealed that bacterial RTs could be classified into 17 main groups: group II introns, retrons/retron-like RTs, diversity-generating retroelements (DGRs), Abi-like RTs, CRISPR-Cas-associated RTs, group II-like RTs (G2L), and 11 other groups of RTs of unknown function. Proteobacteria had the highest potential functional diversity, as they possessed most of the RT groups. Group II introns and DGRs were the most widely distributed RTs in bacterial phyla. Our results provide insights into bacterial RT phylogeny and the basis for an update of annotation systems based on sequence/domain homology. PMID:25423096

  1. Periodic Reversals in Paenibacillus dendritiformis Swarming

    PubMed Central

    Strain, Shinji K.; Hernández, Roberto A.; Ben-Jacob, Eshel; Florin, E.-L.

    2013-01-01

    Bacterial swarming is a type of motility characterized by a rapid and collective migration of bacteria on surfaces. Most swarming species form densely packed dynamic clusters in the form of whirls and jets, in which hundreds of rod-shaped rigid cells move in circular and straight patterns, respectively. Recent studies have suggested that short-range steric interactions may dominate hydrodynamic interactions and that geometrical factors, such as a cell's aspect ratio, play an important role in bacterial swarming. Typically, the aspect ratio for most swarming species is only up to 5, and a detailed understanding of the role of much larger aspect ratios remains an open challenge. Here we study the dynamics of Paenibacillus dendritiformis C morphotype, a very long, hyperflagellated, straight (rigid), rod-shaped bacterium with an aspect ratio of ∼20. We find that instead of swarming in whirls and jets as observed in most species, including the shorter T morphotype of P. dendritiformis, the C morphotype moves in densely packed straight but thin long lines. Within these lines, all bacteria show periodic reversals, with a typical reversal time of 20 s, which is independent of their neighbors, the initial nutrient level, agar rigidity, surfactant addition, humidity level, temperature, nutrient chemotaxis, oxygen level, illumination intensity or gradient, and cell length. The evolutionary advantage of this unique back-and-forth surface translocation remains unclear. PMID:23603739

  2. Electroosmotic Flow Reversal Outside Glass Nanopores

    PubMed Central

    2015-01-01

    We report observations of a striking reversal in the direction of electroosmotic flow (EOF) outside a conical glass nanopore as a function of salt concentration. At high ionic strengths (>100 mM), we observe EOF in the expected direction as predicted by classical electrokinetic theory, while at low salt concentrations (<1 mM) the direction of the flow is reversed. The critical crossover salt concentration depends on the pore diameter. Finite-element simulations indicate a competition between the EOF generated from the inner and outer walls of the pore, which drives flows in opposite directions. We have developed a simple analytical model which reveals that, as the salt concentration is reduced, the flow rates inside the pore are geometrically constrained, whereas there is no such limit for flows outside the pore. This model captures all of the essential physics of the system and explains the observed data, highlighting the key role the external environment plays in determining the overall electroosmotic behavior. PMID:25490120

  3. Magnetic reversals of Jupiter and Saturn

    NASA Technical Reports Server (NTRS)

    Hathaway, D. H.; Dessler, A. J.

    1986-01-01

    The possibility that the gas-giant planets Jupiter and Saturn undergo solar-type magnetic reversals is examined using dynamo theory and radiotelescope data on decametriic emissions from Jupiter. Possible values are found for the effects of the fluctuating velocity field, the magnetic diffusivity, and change in the rotation rate of a dynamo over a characteristic length. The radio emissions from Jupiter decreased in intensity from 1961-72 and rose steadily to the end of 1978, which could have been caused by a change in the Jovian magnetic field. Since Jupiter may have a small rocky core embedded in metallic hydrogen which comprises 75 percent of the radius of the planet, the planetary magnetic field may extend into the cores of its satellites. The dynamo characteristics, like those of Saturn, would be chaotic, although quasi-periodic reversals could occur over intervals on the order of centuries instead of decades such as with the sun and much longer periods such as with the earth.

  4. Atmospheric helium and geomagnetic field reversals.

    NASA Technical Reports Server (NTRS)

    Sheldon, W. R.; Kern, J. W.

    1972-01-01

    The problem of the earth's helium budget is examined in the light of recent work on the interaction of the solar wind with nonmagnetic planets. It is proposed that the dominant mode of helium (He4) loss is ion pumping by the solar wind during geomagnetic field reversals, when the earth's magnetic field is very small. The interaction of the solar wind with the earth's upper atmosphere during such a period is found to involve the formation of a bow shock. The penetration altitude of the shock-heated solar plasma is calculated to be about 700 km, and ionization rates above this level are estimated for a cascade ionization (electron avalanche) process to average 10 to the 9th power ions/sq cm/sec. The calculated ionization rates and the capacity of the solar wind to remove ionized helium (He4) from the upper atmosphere during geomagnetic dipole reversals are sufficient to yield a secular equilibrium over geologic time scales. The upward transport of helium from the lower atmosphere under these conditions is found to be adequate to sustain the proposed loss rate.

  5. Numerical simulation of reversing buoyancy gravity currents

    NASA Astrophysics Data System (ADS)

    Radhakrishnan, Senthil; Lenk, Erik; Boekels, Michael; Meiburg, Eckart

    2012-11-01

    Sediment laden fluid propagates as an underflow when its bulk density is higher than the density of the ambient fluid. If the density of the interstitial fluid in gravity current is smaller than the density of the ambient fluid, the gravity current can become positively buoyant after sufficient particles have settled. The current then lifts off from the bottom surface and travels as a surface gravity current over the heavier ambient fluid. These types of currents, where the buoyancy reverses its direction, have been observed when sediment laden fresh water enters the sea or during volcanic eruption that creates a pyroclastic flow. We use a lock-exchange configuration with mono-disperse and bi-disperse particles to study the lofting characteristics of reversing buoyancy currents. This talk will focus on results obtained from Large-eddy Simulation of high Reynolds number currents. In particular, the deposit profiles show a sharp decay at the lift-off point unlike a ground hugging turbidity current whose deposit profile has a slow monotonic decay from the lock region.

  6. Nematic electroconvection under time-reversed excitation

    NASA Astrophysics Data System (ADS)

    Pietschmann, Dirk; John, Thomas; Stannarius, Ralf

    2010-10-01

    We study nematic electrohydrodynamic convection (EHC) under excitation with superimposed harmonic wave forms. Within the standard model for EHC, a time reversal of the excitation does not affect threshold voltages and pattern wavelengths obtained in a linear stability analysis. This was confirmed in experiments with superimposed square waves [Heuer , Phys. Rev. E 78, 036218 (2008)10.1103/PhysRevE.78.036218]. We show here that this symmetry with respect to time reversal of the excitation breaks down close to the transition from the conduction regime to the dielectric regime. The EHC standard model without flexoelectric terms fails to predict quantitatively correct threshold curves and wavelengths in a certain parameter range below the transition. This is an indication that a more elaborate description of the EHC mechanism is necessary in this range. We suggest that the weak electrolyte model has to be employed for a correct description. This is in accordance with observations of traveling rolls and of localized structures at onset of the convection in earlier experiments described in literature.

  7. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    PubMed

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade. PMID:27324403

  8. Flow reversal in enzymatic microfluidic pumps

    NASA Astrophysics Data System (ADS)

    Shum, Henry; Ortiz-Rivera, Isamar; Agrawal, Arjun; Sen, Ayusman; Balazs, Anna

    A chemical reaction occurring at an enzyme-covered patch in a closed fluid chamber generates local solute concentration gradients and, hence, fluid density gradients. This has recently been shown to drive fluid flows with speeds of the order of microns per second. We develop and analyze a model that accounts for fluid density changes due to consumption of the reaction substrate and accumulation of products for such a fluid pump based on the enzyme urease. Hydrolysis of urea by urease produces ammonium bicarbonate, which leads to a net increase in solution density. Higher density fluid is expected to sink and spread horizontally away from the pump. Modeling reveals, however, that the local fluid density is not necessarily greatest near the pump and fluid flow can even reverse in direction after some time. The qualitative behavior depends on two dimensionless parameters, the ratio of solutal expansion coefficients and the ratio of diffusion coefficients for the reaction substrate and product. The predicted reversal of pumping direction is experimentally verified and we show that the direction of pumping also depends on the amount of enzyme present on the patch. A better understanding of these pumps will aid in the design of responsive, chemically powered microfluidic flow control.

  9. Magnetic stripes and skyrmions with helicity reversals.

    PubMed

    Yu, Xiuzhen; Mostovoy, Maxim; Tokunaga, Yusuke; Zhang, Weizhu; Kimoto, Koji; Matsui, Yoshio; Kaneko, Yoshio; Nagaosa, Naoto; Tokura, Yoshinori

    2012-06-01

    It was recently realized that topological spin textures do not merely have mathematical beauty but can also give rise to unique functionalities of magnetic materials. An example is the skyrmion--a nano-sized bundle of noncoplanar spins--that by virtue of its nontrivial topology acts as a flux of magnetic field on spin-polarized electrons. Lorentz transmission electron microscopy recently emerged as a powerful tool for direct visualization of skyrmions in noncentrosymmetric helimagnets. Topologically, skyrmions are equivalent to magnetic bubbles (cylindrical domains) in ferromagnetic thin films, which were extensively explored in the 1970s for data storage applications. In this study we use Lorentz microscopy to image magnetic domain patterns in the prototypical magnetic oxide-M-type hexaferrite with a hint of scandium. Surprisingly, we find that the magnetic bubbles and stripes in the hexaferrite have a much more complex structure than the skyrmions and spirals in helimagnets, which we associate with the new degree of freedom--helicity (or vector spin chirality) describing the direction of spin rotation across the domain walls. We observe numerous random reversals of helicity in the stripe domain state. Random helicity of cylindrical domain walls coexists with the positional order of magnetic bubbles in a triangular lattice. Most unexpectedly, we observe regular helicity reversals inside skyrmions with an unusual multiple-ring structure. PMID:22615354

  10. Reverse-Time Migration Based Optical Imaging.

    PubMed

    Wang, Zhiyong; Ding, Hao; Lu, Guijin; Bi, Xiaohong

    2016-01-01

    We theoretically demonstrated a new optical imaging technique based on reverse-time migration (RTM) for reconstructing optical structures in homogeneous media for the first time. RTM is a powerful wave-equation-based method to reconstruct the image of the structure by modeling the wave propagation inside the media with both forward modeling and reverse-time extrapolation. While RTM is commonly used with acoustic seismic waves, this paper represents the first effort to develop optical RTM imaging method for biomedical research. To refine the image quality, we further developed new methods to suppress the low-wavenumber artifact (LWA). When compared with the conventional means for LWA suppression such as Laplacian filtering, illumination normalization, and the ratio method, our new derivative-based and power-image methods are able to significantly reduce LWA, resulting in high-quality reconstructed images with sufficient contrasts and spatial resolutions for structure identification. The optical RTM imaging technique may provide a new platform for non-invasive optical imaging of structures in deep layers of tissues for biomedical applications. PMID:26292337

  11. Design of a reversible single precision floating point subtractor.

    PubMed

    Anantha Lakshmi, Av; Sudha, Gf

    2014-01-01

    In recent years, Reversible logic has emerged as a major area of research due to its ability to reduce the power dissipation which is the main requirement in the low power digital circuit design. It has wide applications like low power CMOS design, Nano-technology, Digital signal processing, Communication, DNA computing and Optical computing. Floating-point operations are needed very frequently in nearly all computing disciplines, and studies have shown floating-point addition/subtraction to be the most used floating-point operation. However, few designs exist on efficient reversible BCD subtractors but no work on reversible floating point subtractor. In this paper, it is proposed to present an efficient reversible single precision floating-point subtractor. The proposed design requires reversible designs of an 8-bit and a 24-bit comparator unit, an 8-bit and a 24-bit subtractor, and a normalization unit. For normalization, a 24-bit Reversible Leading Zero Detector and a 24-bit reversible shift register is implemented to shift the mantissas. To realize a reversible 1-bit comparator, in this paper, two new 3x3 reversible gates are proposed The proposed reversible 1-bit comparator is better and optimized in terms of the number of reversible gates used, the number of transistor count and the number of garbage outputs. The proposed work is analysed in terms of number of reversible gates, garbage outputs, constant inputs and quantum costs. Using these modules, an efficient design of a reversible single precision floating point subtractor is proposed. Proposed circuits have been simulated using Modelsim and synthesized using Xilinx Virtex5vlx30tff665-3. The total on-chip power consumed by the proposed 32-bit reversible floating point subtractor is 0.410 W. PMID:24455466

  12. The human LINE-1 reverse transcriptase:effect of deletions outside the common reverse transcriptase domain.

    PubMed Central

    Clements, A P; Singer, M F

    1998-01-01

    Heterologous expression of human LINE-1 ORF2 in yeast yielded a single polypeptide (Mr145 000) which reacted with specific antibodies and co-purified with a reverse transcriptase activity not present in the host cells. Various deletion derivatives of the ORF2 polypeptide were also synthesized. Reverse transcriptase assays using synthetic polynucleotides as template and primer revealed that ORF2 protein missing a significant portion of the N-terminal endonuclease domain still retains some activity. Deletion of the C-terminal cysteine-rich motif reduces activity only a small amount. Three non-overlapping deletions spanning 144 amino acids just N-terminal to the common polymerase domain of the ORF2 protein were analyzed for their effect on reverse transcriptase activity; this region contains the previously-noted conserved Z motif. The two deletions most proximal to the polymerase domain eliminate activity while the third, most-distal deletion had no effect. An inactive enzyme was also produced by substitution of two different amino acids in a highly-conserved octapeptide sequence, Z8, located within the region removed to make the deletion most proximal to the polymerase domain; substitution of a third had no effect. We conclude that the octapeptide sequence and neighboring amino acids in the Z region are essential for reverse transcriptase activity, while the endonuclease and cysteine-rich domains are not absolutely required. PMID:9671814

  13. Wavefield separation and polarity reversal correction in elastic reverse time migration

    NASA Astrophysics Data System (ADS)

    Li, Zhiyuan; Ma, Xiaona; Fu, Chao; Liang, Guanghe

    2016-04-01

    In elastic reverse time migration (RTM), one of the problems that are often encountered is the cross-talk between P- and S-wavefields. A useful processing technique to reduce the cross-talk is separating the P- and S-wavefields by using divergence and curl operators before applying an elastic imaging condition. However, the separated wavefields lose their physical meaning because their phase and amplitude are changed. In this paper, we modify the divergence and curl operators to give the separated wavefields a clear physical meaning: the separated wavefield is the first derivative of the input wavefield with respect to time. Another problem often encountered is polarity reversals in PS and SP images, which can cause destructive interference in the final stacked image and thus destroy the migrated events. In this paper we also develop a procedure for polarity reversal correction based on the polarization vectors of the P- and S-wavefields in the common-shot domain. The correction factor is first calculated at every imaging point during the wavefield reconstruction and is then multiplied by the PS and SP images at each time step when an elastic imaging condition is applied. Numerical examples with synthetic data have shown that the modified wavefield separation method is correct, and the procedure of polarity reversal correction is effective for a complex model.

  14. Magnetic flux trapping during field reversal in the formation of a field-reversed configuration

    NASA Astrophysics Data System (ADS)

    Steinhauer, Loren C.

    1985-11-01

    The flow of plasma and magnetic flux toward a wall is examined in a slab geometry where the magnetic field is parallel to the wall. Magnetohydrodynamic (MHD) flow with a quasisteady approximation is assumed that reduces the problem to three coupled ordinary differential equations. The calculated behavior shows that a thin current sheath is established at the wall in which a variety of phenomena appear, including significant resistive heating and rapid deceleration of the plasma flow. The sheath physics determines the speed at which flux and plasma flow toward the wall. The model has been applied to the field-reversal phase of a field-reversed theta pinch, during which the reduced magnetic field near the wall drives an outward flow of plasma and magnetic flux. The analysis leads to approximate expressions for the instantaneous flow speed, the loss of magnetic flux during the field reversal phase, the integrated heat flow to the wall, and the highest possible magnetic flux retained after reversal. Predictions from this model are compared with previous time-dependent MHD calculations and with experimental results from the TRX-1 [Proceedings of the 4th Symposium on the Physics and Technology of Compact Toroids, 27-29 October 1981 (Lawrence Livermore National Laboratory, Livermore, CA, 1982), p. 61] and TRX-2 [Proceedings of the 6th U.S. Symposium on Compact Toroid Research, 20-23 February, 1984 (Princeton Plasma Physics Laboratory, Princeton, NJ, 1984), p. 154] experiments.

  15. Nigella Sativa reverses osteoporosis in ovariectomized rats

    PubMed Central

    2014-01-01

    Background Osteoporosis poses a significant public health issue. It is a skeletal disorder characterized by compromised bone strength that predisposes to increased risk of fracture. There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis. About 33% of women over 50 will experience bone fractures as a result of osteoporosis. Nigella Sativa (NS) has been shown to have beneficial effects on bone and joint diseases. The present study was conducted to elucidate the protective effect of Nigella Sativa on osteoporosis produced by ovariectomy in rats. Methods Female Wistar rats aged 12–14 months were divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized supplemented with nigella sativa (OVX-NS) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. After 12 weeks, plasma levels of calcium (Ca+2), phosphorous (Pi), alkaline phosphatase (ALP), amino terminal collagen type 1 telopeptide, malondialdehyde (MDA), nitrates, nitric oxide surrogate, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Histological examination of the liver and the tibia was conducted. Histomorphometric analysis of the tibia was also performed. Results OVX rats showed significant decrease in plasma Ca+2, accompanied by a significant increase in plasma ALP, amino terminal collagen type 1 telopeptide, MDA, nitrates, TNF-α and IL-6. These changes were reversed by NS supplementation in OVX-NS group to be near SHAM levels. Histological examination of the tibias revealed discontinuous eroded bone trabeculae with widened bone marrow spaces in OVX rats accompanied by a significant decrease in both cortical and trabecular bone thickness compared to Sham rats. These parameters were markedly reversed in OVX-NS rats. Histological examination of the liver showed mononuclear cellular infiltration and congestion of blood vessels at the portal area in OVX rats which were not found

  16. Synthetic Antibodies for Reversible Cell Recognition

    NASA Astrophysics Data System (ADS)

    Zhou, Jing Zhou

    2011-12-01

    Antibody-mediated cell recognition plays a critical role in various biological and biomedical applications. However, strong antibody-cell interactions can lead to the difficulty of separating antibodies from the bound cells in a simple and non-destructive manner, which is often necessary to numerous applications such as cell sorting or separation. Thus, this thesis research is aimed to create an antibody-like nanomaterial with the function of reversible cell recognition It was hypothesized that nucleic acid aptamer and dendrimer could be used as fundamental structural components to develop an antibody-like nanomaterial. The aptamer functions as the binding site of an antibody; the dendrimer is used as a robust, defined nano-scaffold to support the aptamer and to carry small molecules (e.g., fluorophores). To test this hypothesis, a novel method was first developed to discover the essential nucleotides of full-length aptamers to mimic the binding sites of antibodies. The essential nucleotides were further conjugated with a dendrimer to synthesize a monovalent aptamer-dendrimer nanomaterial. The results clearly showed that the essential nucleotides could maintain high affinity and specificity after tethered on dendrimer surface. To further test the hypothesis that antibody-like nanomaterials can be rationally designed to acquire the capability of reversible cell recognition, an aptamer that was selected at 0 °C was used as a model to synthesize a "Y-shaped" nanomaterial by conjugating two aptamers to the same dendrimer. The results showed that the nanomaterial-cell interaction could be affected by the distance between two binding aptamers. In addition, the "Y-shaped" antibody-like nanomaterial could bind target cells more strongly than its monovalent control. Importantly, the strong cell-nanomaterial interaction could be rapidly reversed when the temperature was shifted from 0 °C to 37 °C. In summary, we developed a synthetic antibody that can not only mimic the

  17. Towards reversible basic linear algebra subprograms: A performance study

    SciTech Connect

    Perumalla, Kalyan S.; Yoginath, Srikanth B.

    2014-12-06

    Problems such as fault tolerance and scalable synchronization can be efficiently solved using reversibility of applications. Making applications reversible by relying on computation rather than on memory is ideal for large scale parallel computing, especially for the next generation of supercomputers in which memory is expensive in terms of latency, energy, and price. In this direction, a case study is presented here in reversing a computational core, namely, Basic Linear Algebra Subprograms, which is widely used in scientific applications. A new Reversible BLAS (RBLAS) library interface has been designed, and a prototype has been implemented with two modes: (1) a memory-mode in which reversibility is obtained by checkpointing to memory in forward and restoring from memory in reverse, and (2) a computational-mode in which nothing is saved in the forward, but restoration is done entirely via inverse computation in reverse. The article is focused on detailed performance benchmarking to evaluate the runtime dynamics and performance effects, comparing reversible computation with checkpointing on both traditional CPU platforms and recent GPU accelerator platforms. For BLAS Level-1 subprograms, data indicates over an order of magnitude better speed of reversible computation compared to checkpointing. For BLAS Level-2 and Level-3, a more complex tradeoff is observed between reversible computation and checkpointing, depending on computational and memory complexities of the subprograms.

  18. Towards reversible basic linear algebra subprograms: A performance study

    DOE PAGESBeta

    Perumalla, Kalyan S.; Yoginath, Srikanth B.

    2014-12-06

    Problems such as fault tolerance and scalable synchronization can be efficiently solved using reversibility of applications. Making applications reversible by relying on computation rather than on memory is ideal for large scale parallel computing, especially for the next generation of supercomputers in which memory is expensive in terms of latency, energy, and price. In this direction, a case study is presented here in reversing a computational core, namely, Basic Linear Algebra Subprograms, which is widely used in scientific applications. A new Reversible BLAS (RBLAS) library interface has been designed, and a prototype has been implemented with two modes: (1) amore » memory-mode in which reversibility is obtained by checkpointing to memory in forward and restoring from memory in reverse, and (2) a computational-mode in which nothing is saved in the forward, but restoration is done entirely via inverse computation in reverse. The article is focused on detailed performance benchmarking to evaluate the runtime dynamics and performance effects, comparing reversible computation with checkpointing on both traditional CPU platforms and recent GPU accelerator platforms. For BLAS Level-1 subprograms, data indicates over an order of magnitude better speed of reversible computation compared to checkpointing. For BLAS Level-2 and Level-3, a more complex tradeoff is observed between reversible computation and checkpointing, depending on computational and memory complexities of the subprograms.« less

  19. Topoisomerase 1 inhibition reversibly impairs synaptic function

    PubMed Central

    Mabb, Angela M.; Kullmann, Paul H. M.; Twomey, Margaret A.; Miriyala, Jayalakshmi; Philpot, Benjamin D.; Zylka, Mark J.

    2014-01-01

    Topotecan is a topoisomerase 1 (TOP1) inhibitor that is used to treat various forms of cancer. We recently found that topotecan reduces the expression of multiple long genes, including many neuronal genes linked to synapses and autism. However, whether topotecan alters synaptic protein levels and synapse function is currently unknown. Here we report that in primary cortical neurons, topotecan depleted synaptic proteins that are encoded by extremely long genes, including Neurexin-1, Neuroligin-1, Cntnap2, and GABAAβ3. Topotecan also suppressed spontaneous network activity without affecting resting membrane potential, action potential threshold, or neuron health. Topotecan strongly suppressed inhibitory neurotransmission via pre- and postsynaptic mechanisms and reduced excitatory neurotransmission. The effects on synaptic protein levels and inhibitory neurotransmission were fully reversible upon drug washout. Collectively, our findings suggest that TOP1 controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission. PMID:25404338

  20. Hepatotoxicity of nucleoside reverse transcriptase inhibitors.

    PubMed

    Montessori, Valentina; Harris, Marianne; Montaner, Julio S G

    2003-05-01

    Hepatotoxicity is an adverse effect of all available classes of antiretrovirals, including nucleoside reverse transcriptase inhibitors (NRTI). A syndrome of hepatic steatosis and lactic acidosis has been recognized as a rare, potentially fatal complication since the advent of NRTI monotherapy in the early 1990s. Today, NRTI remain the backbone of antiretroviral combination regimens, and, with the success of current treatment strategies, exposure to two or more of these agents may occur over a number of years. Hepatic steatosis and lactic acidosis are accordingly being observed more frequently, along with a more recently recognized syndrome of chronic hyperlactatemia. These as well as other adverse effects of NRTI are mediated by inhibition of human DNA polymerase gamma, resulting in mitochondrial dysfunction in the liver and other tissues. Early recognition and intervention are essential to avert serious outcomes. PMID:12800069