39 results on '"HUGHES, LARRY"'
Search Results
2. Evaluating the effectiveness of electric vehicle subsidies in Canada
- Author
-
Thorne, Zachary and Hughes, Larry
- Published
- 2019
- Full Text
- View/download PDF
3. Future world oil production: growth, plateau, or peak?
- Author
-
Hughes, Larry and Rudolph, Jacinda
- Published
- 2011
- Full Text
- View/download PDF
4. Semi-continuous emulsion co-polymerisation of methylmethacrylate and butylacrylate using zwitterionic surfactants as emulsifiers: Evidence of coagulative nucleation above the critical micelle concentration
- Author
-
Parker, Andrew P., Reynolds, Paul A., Lewis, Andrew L., and Hughes, Larry
- Published
- 2005
- Full Text
- View/download PDF
5. Cartesian routing
- Author
-
Hughes, Larry, Banyasad, Omid, and Hughes, Evan
- Published
- 2000
- Full Text
- View/download PDF
6. A generic method for analyzing the risks to energy systems.
- Author
-
Hughes, Larry, de Jong, Moniek, and Wang, Xiao Qin
- Subjects
- *
ENERGY security , *STRAINS & stresses (Mechanics) , *FOSSIL fuels , *POWER resources , *CLIMATE change - Abstract
At any particular moment, the energy security of an energy system is at risk from events, both external and internal, that can affect its operation. By analyzing these risks, the state of the system’s energy security can be determined. If the method is generic, it can be applied to any energy system and the entities that support its operation. Despite the potential benefits of such a method, a review of the literature shows that existing methods of analysis focus on, for example, limited parts of the system or specific types of energy. To address this shortcoming, this paper presents a method for analyzing the risks to the energy security of any entity in an energy system. The method, derived from work at the National Institute for Statistics and Technology (NIST), determines the risks to an entity using the well-known properties of events (rate-of-occurrence and expected stress) and entities (flows, time-to-recover, and stress-tolerance). The paper demonstrates how the method can be applied using both qualitative and quantitative data to measure, analyze, and potentially improve a system’s energy security. Several examples are included. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
7. The effects of event occurrence and duration on resilience and adaptation in energy systems.
- Author
-
Hughes, Larry
- Subjects
- *
ENERGY economics , *ENERGY security , *RELIABILITY in engineering , *ECONOMIC indicators , *ENERGY policy - Abstract
Energy security exists in an energy system until an event occurs which increases the stress on one or more of its entities. A resilient entity, designed to recover quickly from an event, will return the system (and, by extension, the affected entity) to its previous secure state. However, if the event occurs repeatedly or the time to recover is deemed too slow, or both, the system may remain in a high-stress, insecure state. In these situations, if the stress is to be reduced, the entity must be adapted to handle the event and put the system into a new, secure state. This paper applies research from a variety of disciplines to analyze the temporal effects of events on entities, and shows how resilience and adaptation contribute to the existence of energy security in energy systems. It underscores the importance of time when discussing the impact of events on an energy system and employs methods associated with reliability, notably mean time between failures (MTBF), mean time to recover (MTTR), and tolerance, to describe resilience and adaptation. The analysis is presented and discussed with examples using three common energy security indicators. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
8. Energy security and the diversity of energy flows in an energy system.
- Author
-
Ranjan, Ashish and Hughes, Larry
- Subjects
- *
ENERGY security , *ENERGY consumption , *INFORMATION measurement , *QUANTITATIVE research , *ENERGY policy - Abstract
In order to maintain or improve a jurisdiction's energy security, its energy system needs to meet the demands of its energy services with affordable and preferably environmentally acceptable flows of energy. Since diversity can be a factor in the long-term survival of a system, having a diversity of energy flows is frequently treated as a proxy for energy security. This paper examines the relationship between energy security and the diversity of an energy system's energy flows using a set of energy security indicators and the Shannon-Wiener diversity index. Although diversity may be considered necessary for maintaining and improving energy security, the quantitative analysis of the relationship shows that an energy flow considered diverse need not be secure and that a secure energy flow need not be considered diverse. Examples of this relationship are included. These findings can prove useful to policy makers and energy analysts when developing transition strategies for a jurisdiction's energy system. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
9. Dynorphin release by the lateral olivocochlear efferents may inhibit auditory nerve activity: A cochlear drug delivery study.
- Author
-
Le Prell, Colleen G., Hughes, Larry F., and Bledsoe, Sanford C.
- Subjects
- *
DYNORPHINS , *EFFERENT pathways , *ACOUSTIC nerve , *DRUG delivery systems , *OPIOID receptors , *AUDITORY evoked response , *PHYSIOLOGY - Abstract
Highlights: [•] The kappa opioid receptor agonist (−)pentazocine was applied to the cochlea. [•] Sound evoked neural potentials were reduced in amplitude after drug treatment. [•] Endogenous dynorphin at biologically plausible levels has an inhibitory effect. [•] Higher (nonbiological) concentrations of drugs excite the auditory nerve. [•] Transmitter effects should be assessed at biologically plausible concentrations. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
10. Barriers to the Development of Electrical Energy Storage: A North American Perspective.
- Author
-
Wilson, David and Hughes, Larry
- Subjects
- *
ENERGY storage , *ACTIVATION energy , *ENERGY development , *ENERGY policy - Abstract
Interest in electrical energy storage is growing despite the many barriers preventing it from competing against technologies that provide similar services. While technical issues remain at the forefront, barriers also exist in the policy and regulatory sphere, but some potential solutions are being explored in North American jurisdictions. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
11. Event-related stresses in energy systems and their effects on energy security.
- Author
-
Hughes, Larry and Ranjan, Ashish
- Subjects
- *
ENERGY security , *POWER resources , *ENERGY economics , *ENERGY policy , *STAKEHOLDERS , *PHYSIOLOGICAL stress - Abstract
Abstract: Energy systems change over time as events, such as grid failures, new energy sources, and extreme weather conditions, occur, often affecting the system's energy security. Understanding events, their causes, and how they are handled, can help a jurisdiction and its energy stakeholders develop better, evidence-based energy policy. This paper employs a definition of stress in combination with systems analysis to specify methods for explaining the states through which an energy process, chain, or system passes in response to an event and how this response results in energy security improving, deteriorating, or being maintained. The definition uses three dimensions-availability, affordability, and acceptability-derived from the International Energy Agency's definition of energy security to show when and how a system's energy security will change. Examples are used to illustrate the application of the methods. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
12. Age-related GABAA receptor changes in rat auditory cortex
- Author
-
Caspary, Donald M., Hughes, Larry F., and Ling, Lynne L.
- Subjects
- *
GABA receptors , *LABORATORY rats , *AUDITORY cortex , *SYNAPSES , *AGING , *BIOMARKERS , *PROTEINS - Abstract
Abstract: Auditory cortex (AI) shows age-related decreases in pre-synaptic markers for gamma-aminobutyric acid (GABA) and degraded AI neuronal response properties. Previous studies find age-related increases in spontaneous and driven activity, decreased spectral and directional sensitivity, and impaired novelty detection. The present study examined expression of GABAA receptor (GABAAR) subunit message, protein, and quantitative GABAAR binding in young, middle-aged, and aged rat AI, with comparisons with adjoining parietal cortex. Significant loss of GABAAR α1 subunit message across AI layers was observed in middle-aged and aged rats and α1 subunit protein levels declined in layers II and III. Age-related increases in GABAAR α3 subunit message and protein levels were observed in certain AI layers. GABAAR subunits, including β1, β2, γ1, γ2s, and γ2L, primarily, but not exclusively, showed age-related declines at the message and protein levels. The ability of GABA to modulate [3H]t-butylbicycloorthobenzoate binding in the chloride channel showed age-related decreases in peak binding and changes in desensitization kinetics. Collectively, age-related changes in GABAAR subunit composition would alter the magnitude and temporal properties of inhibitory synaptic transmission and could underpin observed age-related functional changes seen in the elderly. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
13. Forecasting the reliability of wind-energy systems: A new approach using the RL technique
- Author
-
Chaudhry, Nikhil and Hughes, Larry
- Subjects
- *
ELECTRIC power consumption forecasting , *RELIABILITY in engineering , *WIND power , *GREENHOUSE gases , *ELECTRIC power production , *RENEWABLE energy sources , *SIMULATION methods & models , *ENERGY consumption - Abstract
Abstract: Two of the most significant challenges in the 21st century will be to improve energy security and reduce the greenhouse gas emissions associated with energy consumption. A co-beneficial solution to these challenges is seen as increasing the use of renewable energy for the production of electricity. Some renewable sources, such as wind are often presented as a way to reduce greenhouse gas emissions; however, since wind’s variability increases uncertainty and risk in expected generation, it can be detrimental to energy security. One of the ways in which wind’s contribution to a jurisdiction’s energy security and greenhouse gas reduction strategies can be improved is to employ a forecasting method that can help reduce risks. This paper proposes a method that applies risk and reliability analysis techniques to obtain the most-likely RL (Resistance–Load) scenario using a set of historical data for wind-supply or generation and load. RL estimates the reliability of a wind-energy system by simulating an anticipated resistance (the electrical generation) attempting to meet a load (the electricity demand) for a future year. The method is demonstrated through a case study and its results are compared with real-time data from a 12MW wind farm to prove its efficacy. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
14. Meeting residential space heating demand with wind-generated electricity
- Author
-
Hughes, Larry
- Subjects
- *
HEATING , *WIND power , *ELECTRIC power production , *HEAT storage , *ENERGY consumption , *ELECTRIC power distribution , *ELECTRIC utilities - Abstract
Abstract: Worldwide, many electricity suppliers are faced with the challenge of trying to integrate intermittent renewables, notably wind, into their energy mix to meet the needs of those services that require a continuous supply of electricity. Solutions to intermittency include the use of rapid-response backup generation and chemical or mechanical storage of electricity. Meanwhile, in many jurisdictions with lengthy heating seasons, finding secure and preferably environmentally benign supplies of energy for space heating is also becoming a significant challenge because of volatile energy markets. Most, if not all, electricity suppliers treat these twin challenges as separate issues: supply (integrating intermittent renewables) and demand (electric space heating). However, if space heating demand can be met from an intermittent supply of electricity, then both of these issues can be addressed simultaneously. One such approach is to use off-the-shelf electric thermal storage systems. This paper examines the potential of this approach by applying the output from a 5.15 MW wind farm to the residential heating demands of detached households in the Canadian province of Prince Edward Island. The paper shows that for the heating season considered, up to 500 households could have over 95 percent of their space heating demand met from the wind farm in question. The benefits as well as the limitations of the approach are discussed in detail. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
15. Processing of broadband stimuli across A1 layers in young and aged rats
- Author
-
Hughes, Larry F., Turner, Jeremy G., Parrish, Jennifer L., and Caspary, Donald M.
- Subjects
- *
AUDITORY perception , *PRESBYCUSIS , *AUDITORY cortex , *GABA , *AMPLITUDE modulation , *SOUND pressure , *LABORATORY rats , *AGE differences - Abstract
Abstract: Presbycusis can be considered a slow age-related peripheral and central deterioration of auditory function which manifests itself as deficits in speech comprehension, especially in noisy environments. The present study examined neural correlates of a simple broadband noise stimulus in primary auditory cortex (A1) of young and aged Fischer–Brown Norway (FBN) rats. Age-related changes in unit responses to broadband noise bursts and spontaneous activity were simultaneously recorded across A1 layers using a single shank, 16-channel electrode. Noise bursts were presented contralateral to the left A1 at 80dB SPL. Aged A1 units displayed increased spontaneous (29%), peak (24%), and steady state response rates (38%) than did young A1 units. This was true across all A1 layers, although age-related differences were significantly greater for layers I–III (43% vs 18%) than lower layers. There was a significant age-related difference in the depth and duration of post-onset suppression between young and aged upper layer A1 units. The present functional differences across layers were consistent with studies showing greatest losses of gamma-aminobutyric acid (GABA) markers in superficial layers of A1 and with anatomic studies showing highest levels of inhibitory neurons located in superficial cortical layers. The present findings were also consistent with aging studies suggesting loss of functional inhibition in other cortical sensory systems. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
16. Sleep, activity, temperature and arousal responses of mice deficient for muscarinic receptor M2 or M4
- Author
-
Turner, Jeremy, Hughes, Larry F., and Toth, Linda A.
- Subjects
- *
AROUSAL (Physiology) , *MUSCARINIC receptors , *SLEEP deprivation , *G proteins , *BODY temperature , *SLOW wave sleep , *CANDIDA albicans , *CHOLINERGIC receptors - Abstract
Abstract: Aims: The type 2 muscarinic receptor (M2R) differs from the other G-protein-coupled muscarinic receptor (type 4, or M4R) in tissue distribution and physiologic effects. We studied the impact of these receptors on sleep and arousal by using M2R and M4R knock-out (KO) mice. Main methods: M2R and M4R KO and genetically intact mice were compared in terms of normal patterns of sleep, responses to sleep loss, infectious challenge and acoustic startle, and acoustic prepulse inhibition of startle (PPI). Key findings: Under basal conditions, M2R and M4R KO mice do not differ from the background strain or each other in the amount or diurnal pattern of sleep, locomotor activity, and body temperature. After enforced sleep loss, M2R KO mice, in contrast to the other two strains, show no rebound in slow-wave sleep (SWS) time, although their SWS is consolidated, and they show a greater rebound in time spent in REMS (rapid-eye-movement sleep) and REMS consolidation. During influenza infection, M2R KO mice, as compared with the other strains, show marked hypothermia and a less robust increase in SWS. During Candida albicans infection, M2R KO mice show a greater increase in SWS and a greater inflammatory response than do the other strains. M2R KO mice also show greater acoustic startle amplitude than does the background strain, although PPI was not different across the 3 strains over a range of stimulus intensities. Significance: Taken together, these findings support different roles for M2R and M4R in the modulation of sleep and arousal during homeostatic challenge. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
17. Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma
- Author
-
Le Prell, Colleen G., Hughes, Larry F., and Miller, Josef M.
- Subjects
- *
NOISE-induced deafness , *FREE radicals , *VITAMINS , *MAGNESIUM - Abstract
Abstract: Free radical formation in the cochlea plays a key role in the development of noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant formation of both reactive oxygen species and reactive nitrogen species 7–10 days after noise exposure. Reduction in cochlear blood flow as a result of free radical formation has also been described. Here we report that the antioxidant agents vitamins A, C, and E act in synergy with magnesium to effectively prevent noise-induced trauma. Neither the antioxidant agents nor the magnesium reliably reduced NIHL or sensory cell death with the doses we used when these agents were delivered alone. In combination, however, they were highly effective in reducing both hearing loss and cell death even with treatment initiated just 1 h before noise exposure. This study supports roles for both free radical formation and noise-induced vasoconstriction in the onset and progression of NIHL. Identification of this safe and effective antioxidant intervention that attenuates NIHL provides a compelling rationale for human trials in which free radical scavengers are used to eliminate this single major cause of acquired hearing loss. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
18. Age-related changes in the response properties of cartwheel cells in rat dorsal cochlear nucleus
- Author
-
Caspary, Donald M., Hughes, Larry F., Schatteman, Tracy A., and Turner, Jeremy G.
- Subjects
- *
CELLS , *NEURONS , *NERVOUS system , *BRAIN stem - Abstract
Abstract: The fusiform cell and deep layers of the dorsal cochlear nucleus (DCN) show neurotransmitter and functional age-related changes suggestive of a downregulation of inhibitory efficacy onto DCN output neurons. Inhibitory circuits implicated in these changes include vertical and D-multipolar cells. Cartwheel cells comprise a large additional population of DCN inhibitory neurons. Cartwheel cells receive excitatory inputs from granule cell parallel fibers and provide a source of glycinergic inhibitory input onto apical dendrites of DCN fusiform cells. The present study compared the response properties from young and aged units meeting cartwheel-cell criteria in anesthetized rats. Single unit recordings from aged cartwheel cells revealed significantly higher thresholds, increased spontaneous activity and significantly altered rate-level functions characterized by hyperexcitability at higher intensities. Aged cartwheel cells showed a significant reduction in off-set suppression. Collectively, these findings suggest a loss of tonic and perhaps response inhibition onto aged DCN cartwheel neurons. These changes likely reflect a compensatory downregulation of synaptic inhibition in response to a loss of excitatory drive from auditory and non-auditory excitatory inputs via granule cells. The impact of increased excitability of cartwheel cells on DCN output neurons is likely to be complex, influenced by loss of glycinergic release and/or subunit receptor changes which would only partially off-set age-related loss of inhibition onto the somata and basal dendrites of fusiform cells. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
19. Divergent response properties of layer-V neurons in rat primary auditory cortex
- Author
-
Turner, Jeremy G., Hughes, Larry F., and Caspary, Donald M.
- Subjects
- *
NEURONS , *AUDITORY cortex , *CELLS , *NERVOUS system - Abstract
Abstract: Layer-V pyramidal cells comprise a major output of primary auditory cortex (A1). At least two cell types displaying different morphology, projections and in vitro physiology have been previously identified in layer-V. The focus of the present study was to characterize extracellular receptive field properties of layer-V neurons to determine whether a similar breakdown of responses can be found in vivo. Recordings from 105 layer-V neurons revealed two predominant receptive field types. Thirty-two percent displayed strong excitatory V/U-shaped receptive field maps and spiking patterns with shorter stimulus-driven interspike intervals (ISIs), reminiscent of the bursting cells discussed in the in vitro literature. V/U-shaped maps remained relatively unchanged across the three sequential repetitions of the map run on each neuron. Neurons with V/U-shaped maps were also easily depolarized with extracellular current pulse stimulation. In contrast, 47% of the neurons displayed Complex receptive field maps characterized by weak and/or inconsistent excitatory regions and were difficult to depolarize with current pulses. These findings suggest that V/U-shaped receptive fields could correspond to previously described intrinsic bursting (IB) cells with corticotectal projections, and that neurons with Complex receptive fields might represent the regular spiking (RS) cells with their greater inhibitory input and corticocortical/corticostriatal projection pattern. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
20. Survey of multicast address handling techniques for Ethernet communication controllers
- Author
-
Hughes, Larry
- Published
- 1989
- Full Text
- View/download PDF
21. Design and implementation of a multicast messaging kernel
- Author
-
Hughes, Larry
- Published
- 1988
- Full Text
- View/download PDF
22. Fault-tolerant process tracking in Lego
- Author
-
Hughes, Larry and Stoddart, Glenn
- Published
- 1995
- Full Text
- View/download PDF
23. Identifying migrated objects using multicast addresses
- Author
-
Hughes, Larry
- Published
- 1991
- Full Text
- View/download PDF
24. Chat: an N-party talk facility for the Unix 4.2 operating system
- Author
-
Hughes, Larry
- Published
- 1988
- Full Text
- View/download PDF
25. Gateway designs for internetwork multicast communication
- Author
-
Hughes, Larry
- Published
- 1989
- Full Text
- View/download PDF
26. Multicast response handling taxonomy
- Author
-
Hughes, Larry
- Published
- 1989
- Full Text
- View/download PDF
27. Process migration and its influence on interprocess communication
- Author
-
Hughes, Larry
- Published
- 1998
- Full Text
- View/download PDF
28. Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity.
- Author
-
Le Prell, Colleen G., Dolan, David F., Hughes, Larry F., Altschuler, Richard A., Shore, Susan E., and Jr, Sanford C. Bledsoe
- Subjects
- *
DOPAMINERGIC mechanisms , *NEUROTOXIC agents , *ACOUSTIC nerve , *AUDITORY pathways , *NEURONS , *BRAIN stem , *GUINEA pigs as laboratory animals - Abstract
Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
29. Current practice patterns in tonsillectomy and perioperative care
- Author
-
Krishna, Priya, LaPage, Martin J., Hughes, Larry F., and Lin, Sandra Y.
- Subjects
- *
TONSILLECTOMY , *SLEEP apnea syndromes , *PEDIATRICS - Abstract
Objectives: Tonsillectomy is one of the most commonly performed otolaryngologic procedures in the United States. Many options and controversies exist regarding techniques and peri-operative management. The purpose of the study was to examine current practice patterns among otolaryngologists regarding tonsillectomy. Methods: A 13 question survey regarding tonsillectomy techniques and peri-operative management was mailed to 10% of randomly selected board certified otolaryngologists of the AAO-HNS in the spring of 2002. Four hundred and eighteen anonymously completed questionnaires were returned, for a response rate of 58.5%. Statistical analysis of survey data was performed by means of cross tabulation and Pearson Chi-Square Calculation. Results: Monopolar electrocautery was the most common technique used among those surveyed (53.5%). There was a significant correlation between choice of monopolar electrocautery and the cited reason for choice of technique being decreased blood loss (
P<0.001 ). There was no relationship between pediatric fellowship training and choice of technique. 97.7% routinely admitted sleep apnea patients for post-operative observation. There was no significant correlation between practice setting (tertiary versus community) and type of post-operative monitoring for sleep apnea patients, with patients most commonly admitted to an intermediate care setting. Conclusion: In our survey, the most common surgical technique for tonsillectomy was monopolar electrocautery, chosen for the reason of decreased blood loss. [Copyright &y& Elsevier]- Published
- 2004
- Full Text
- View/download PDF
30. GABAergic inputs shape responses to amplitude modulated stimuli in the inferior colliculus
- Author
-
Caspary, Donald M., Palombi, Peggy Shadduck, and Hughes, Larry F.
- Subjects
- *
INFERIOR colliculus , *BRAIN stem - Abstract
The inferior colliculus (IC) is an important auditory processing center receiving inputs from lower brainstem nuclei, higher auditory and nonauditory structures, and contralateral IC. The IC, along with other auditory structures, is involved in coding information about the envelope of complex signals. Biologically relevant acoustic signals, including animal vocalizations and speech, are spectrally and temporally complex and display amplitude and frequency variations over time. Certain IC neurons respond selectively over a narrow range of modulation frequencies to sinusoidally amplitude modulated (SAM) stimuli. Responses to SAM stimuli can be measured in terms of discharge rate, with rate plotted against the modulation frequency to generate rate modulation transfer functions (rMTF). A role for the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in shaping selective responses to SAM stimuli has been suggested. The present study examined the role of GABA in shaping responses to SAM stimuli in the IC of anesthetized chinchilla. Responses from 94 IC neurons were obtained before, during and after iontophoretic application of the GABAA receptor antagonist bicuculline methiodide. Complete responses to SAM stimuli were obtained from 55 extensively tested neurons, displaying band-pass (38) and low-pass rMTFs (17). For neurons showing band-pass rMTFs, GABAA receptor blockade selectively increased discharge rate at low modulation frequencies for 14 units, increased discharge near the best modulation frequency for 12 units. For neurons showing low-pass rMTFs, GABAA receptor blockade selectively increased discharge rate at low modulation frequencies for nine units. GABAA receptor blockade consistently reduced peak modulation gain, producing low-pass gain functions in a subset of IC neurons. In support of previous findings suggesting that selective temporal responses to SAM stimuli are coded in lower brainstem nuclei, temporal responses to SAM stimuli were relatively unaffected by GABAA receptor blockade. These findings support a role for GABA in shaping selective rate responses to SAM stimuli for a subset of chinchilla IC neurons. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
31. l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice
- Author
-
Wise, Laura E., Premaratne, Ishani D., Gamage, Thomas F., Lichtman, Aron H., Hughes, Larry D., Harris, Louis S., and Aceto, Mario D.
- Subjects
- *
THEANINE , *TEMPERANCE , *MORPHINE abuse , *METHYL aspartate , *BRAIN-derived neurotrophic factor , *GREEN tea , *TRANQUILIZING drugs , *GABA , *LABORATORY monkeys - Abstract
Abstract: l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine''s stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
32. d-methionine (d-met) significantly rescues noise-induced hearing loss: Timing studies.
- Author
-
Campbell, Kathleen, Claussen, Alex, Meech, Robert, Verhulst, Steven, Fox, Daniel, and Hughes, Larry
- Subjects
- *
NOISE-induced deafness , *METHIONINE , *NOISE , *BRAIN stem , *CHINCHILLAS , *HAIR cells - Abstract
Abstract: We have previously reported rescue from noise-induced auditory brainstem response (ABR) threshold shifts with d-methionine (d-met) administration 1 h after noise exposure. The present study investigated further d-met rescue intervals at 3, 5 and 7 h post-noise exposure. Chinchillas laniger were exposed to a 6 h 105 dB sound pressure level (dB SPL) octave band noise (OBN) and then administered d-met i.p. starting 3, 5, or 7 h after noise exposure; controls received saline i.p. immediately after noise exposure. ABR assessments were performed at baseline and on post-exposure days 1 and 21. Outer hair cell (OHC) loss was measured in cochleae obtained at sacrifice 21 days post-exposure. Administration of d-met starting at any of the delay times of 3–7 h post-noise exposure significantly reduced day 21 ABR threshold shift at 2 and 4 kHz and OHC loss at all hair cell regions measured (2, 4, 6 and 8 kHz). ABR threshold shifts in the control group at 6 and 8 kHz were only 8 and 11 dB respectively allowing little opportunity to observe protection at those 2 frequencies. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
33. Adenosine receptor antagonists and behavioral activation in NF-κB p50 subunit knockout mice
- Author
-
Xie, Xiaobin, Mhaskar, Yashanad, Arbogast, Lydia A., Trammell, Rita A., Hughes, Larry F., and Toth, Linda A.
- Subjects
- *
ADENOSINES , *CELL receptors , *NF-kappa B , *LABORATORY mice , *ANIMAL locomotion , *CAFFEINE , *PHARMACOKINETICS , *HIGH performance liquid chromatography - Abstract
Abstract: Aims: Our previous work revealed that mice lacking the p50 subunit of transcription factor nuclear factor kappa B (NF-κB) (p50 KO mice) and genetically intact F2 mice have similar locomotion under basal conditions, yet p50 KO mice show greater locomotor activation after caffeine ingestion. In this report, we test whether KO mice display altered caffeine pharmacokinetics or increased caffeine-induced DA turnover relative to F2 mice, and evaluate the impact of intraperitoneal administration of specific adenosine and DA receptor antagonists on locomotor activity. Main methods: Concentrations of DA and caffeine were measured using high performance liquid chromatography. DA turnover was measured after treatment of mice with an inhibitor of tyrosine hydroxylase. Locomotor activity was measured using telemetry. Key findings: The data reveal that 1) caffeine concentrations in blood and brain are similar in KO and F2 mice after oral or intraperitoneal administration; 2) KO mice show greater DA turnover under basal conditions, but turnover is similar in both strains after caffeine administration; 3) the specific A2AAR antagonist SCH 58261 induces greater locomotion in KO versus F2 mice; and 4) the activating effect of SCH 58261 in KO mice is prevented by prior treatment with the D2R antagonist raclopride. Significance: These findings support the conclusions that 1) A2AAR has a major impact on behavioral activation of p50 KO mice, and 2) D2R mediated neurotransmission is important to this effect. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
34. Expression of striatal adenosine and dopamine receptors in mice deficient in the p50 subunit of NF-κB
- Author
-
Xie, Xiaobin, Jhaveri, Krishna A., Ding, Ming, Hughes, Larry F., Toth, Linda A., and Ramkumar, Vickram
- Subjects
- *
RODENTS , *METHYLXANTHINES , *IMMUNOCYTOCHEMISTRY , *MESSENGER RNA - Abstract
Abstract: The striatal dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AAR) exhibit mutually antagonistic effects through physical interactions and by differential modulation of post-receptor signaling pathways. The expression of the A2AAR and the D2R is differentially regulated by nuclear factor-κB (NF-κB). In this report, we determined the role of NF-κB in regulation of these receptors by comparing mice deficient in the NF-κB p50 subunit (p50 KO) with genetically intact B6129PF2/J (F2) mice. Quantification of adenosine receptor (AR) subtypes in mouse striatum by real time PCR, immunocytochemistry and radioligand binding assays showed more A2AAR but less A1AR in p50 KO mice as compared with F2 mice. Striata from p50 KO mice also had less D2R mRNA and [3H]-methylspiperone binding than did striata from F2 mice. Gαolf and Gαs proteins, which are transducers of A2AAR signals, were also present at a higher level in striata from the p50 KO versus F2 mice. In contrast, the Gαi1 protein, which transduces signals from the A1AR and D2R, was significantly reduced in striata from p50 KO mice. Behaviorally, p50 KO mice exhibited increased locomotor activity relative to that of F2 mice after caffeine ingestion. These data are consistent with a role for the NF-κB in the regulation of A1AR, A2AAR, D2R and possibly their coupling G proteins in the striatum. Dysregulation of these receptors in the striata of p50 KO mice might sensitize these animals to locomotor stimulatory action of caffeine. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
35. Prevention of noise- and drug-induced hearing loss with d-methionine
- Author
-
Campbell, Kathleen C.M., Meech, Robert P., Klemens, James J., Gerberi, Michael T., Dyrstad, Sara S.W., Larsen, Deb L., Mitchell, Diana L., El-Azizi, Mohammed, Verhulst, Steven J., and Hughes, Larry F.
- Subjects
- *
ANTINEOPLASTIC agents , *CISPLATIN , *DRUG therapy , *DRUGS - Abstract
Abstract: A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating d-methionine (d-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented d-met’s otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further d-met has an excellent safety profile. d-Met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in d-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral d-met protection against cisplatin-induced ototoxicity, d-met protection against amikacin-induced ototoxicity, and d-met rescue from permanent noise-induced hearing loss when d-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
36. Investigation into potential mechanisms promoting biocompatibility of polymeric biomaterials containing the phosphorylcholine moiety: A physicochemical and biological study
- Author
-
Parker, Andrew P., Reynolds, Paul A., Lewis, Andrew L., Kirkwood, Laura, and Hughes, Larry G.
- Subjects
- *
POLYMERS , *BIOMEDICAL materials , *BIOCOMPATIBILITY , *MACROMOLECULES - Abstract
Abstract: Phosphorylcholine (PC) moieties were chemically attached to surfaces of polymer microparticles by addition of 2-methylacryloyloxyethyl phosphorylcholine monomer to the seeded, semi-continuous polymerisations of methyl methacrylate (MMA) and butyl acrylate (BA). The surface of the bio-functionalised polymer microparticles was principally characterised using X-ray photoelectron spectroscopy (XPS), dynamic nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), acoustophoresis and enzyme-linked immunosorbent assays (ELISA). It was found that the persulphate initiating species are concealed behind the phosphorylcholine containing monomer sequence located on the surface of the microparticles. The combination of analytical techniques showed that the surfaces of the polymer microparticles are extremely mobile above the glass transition temperature of the co-polymer and able to rearrange depending on the environment in which they are placed. This allows the phosphorylcholine moiety to be preferentially expressed at the surface in aqueous media, but not so in the dry state or conditions of ultra-high vacuum. In terms of the nature of the biocompatibility of phosphorylcholine containing polymers, no evidence was found for the irreversible structuring of water molecules around the phosphorylcholine moiety in the wet state. The results of this work suggest that a more likely contributory reason for the protein-resistant nature of phosphorylcholine containing polymers is the mobility of the phosphorylcholine moiety. Increases in biocompatibility correspond with increases in the hydrophilicity of a polymer surface when phosphorylcholine is preferentially expressed. A large free water fraction may be present in the phosphorylcholine containing monomer sequence, as part of a hydrogel structure located at the surface of the polymer microparticles. This, coupled with concomitant modification of the local electrical double-layer very close to the surface may also play a critical role in reducing protein–surface interactions. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
37. Noise induces A1 adenosine receptor expression in the chinchilla cochlea
- Author
-
Ramkumar, Vickram, Whitworth, Craig A., Pingle, Sandeep C., Hughes, Larry F., and Rybak, Leonard P.
- Subjects
- *
OXIDATIVE stress , *ISCHEMIA , *ADENOSINES , *RADIOLIGAND assay - Abstract
Adenosine plays a major cytoprotective role during ischemia and conditions of oxidative stress. Previous studies in our laboratory indicate that oxidative stress induces expression of the A1 adenosine receptor (A1AR) via activation of nuclear factor (NF)-κB. In this study, we tested whether noise exposure could induce oxidative stress and determine whether this induces expression of the A1AR in the chinchilla cochlea. Chinchillas were exposed to a 96 dB 4 kHz octave band of noise for 6 h of daily exposure, followed by an 18 h noise-free period. This noise paradigm resulted in threshold shifts of 10–60 dB over the frequency range (1–16 kHz) tested. Radioligand binding studies for the A1AR indicate a significant increase in receptor (∼2-fold) expression soon after the first noise exposure period (usually within ∼8 h of the initiation of noise), which gradually returned to basal levels by day 7. The rise in A1AR levels was followed by a significant increase in malondialdehyde levels by day 3, which also recovered by day 7. Assessment of the activity of NADPH oxidase in the cochlea indicates a significant increase in enzyme activity which was evident by ∼8 h following initiation of noise exposure, and which persisted for at least up to day 3. Electrophoretic mobility shift assays indicate that the increase in A1AR was associated with a significant increase in NF-κB activity following noise exposure. We conclude that noise exposure induces A1AR expression, which might be mediated, in part, through generation of reactive oxygen species and activation of NF-κB. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
38. Age-related synaptic changes in the anteroventral cochlear nucleus of Fischer-344 rats
- Author
-
H. Helfert, Robert, Krenning, Judyann, Wilson, Teresa S., and Hughes, Larry F.
- Subjects
- *
GLYCINE , *COCHLEAR nucleus , *COMPUTER software , *DENDRITES - Abstract
Previous studies have demonstrated age-related decreases in the transmitters glycine and glutamate in the cochlear nucleus (CN) of the Fischer-344 (F344) rat, along with declining levels of binding for glycine receptors. The purpose of this study was to evaluate structural correlates to the transmitter and receptor losses that accompany aging in the anteroventral CN (AVCN). Thin sections were obtained from the middle-frequency area of the right AVCNs from five 3-month-, four 19-month-, and five 28-month-old F344 rats. Montages were constructed from electron micrographs taken of several sites in each AVCN section. The presynaptic terminals were classified by vesicle type and postsynaptic target, and their perimeters and synaptic lengths were traced using morphometry software. The calibers of all dendritic profiles were also measured, and cell counts were performed on semi-thin sections. The data were compared among the three age groups using analysis of variance followed by Tukey’s Honestly Significant Difference for pairwise comparisons. There were significant age-related decreases in the size of terminals contacting small-caliber (<2 μm) dendrites. Dendrites of this size comprised the largest percentage of dendrites in the AVCN. On these targets, round and pleomorphic-vesicle terminals were reduced in volume by nearly 44% and 24%, respectively, in 28-month olds when compared to the 3-month olds. On the other hand, the densities and numbers of synaptic terminals and dendritic profiles did not differ among age groups, and no neuronal losses were evident in the older animals. Also, there were no detectable changes in synaptic area among groups. The decrease in terminal size may be related to age-associated reductions in neurotransmitter levels previously described in the F344 CN. The observations presented here contrast with those previously described in the inferior colliculus (IC), in which there were significant age-related losses of synaptic terminals and dendrites, but no change in the size of synaptic terminals. The lack of synaptic and dendritic losses suggests that the structural connectivity of the rat AVCN remains relatively intact during aging, which is interesting in light of the synaptic and dendritic changes evident in the IC, a major target of its projections. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
39. Hsp70 in the inferior colliculus of Fischer-344 rats: effects of age and acoustic stress
- Author
-
Helfert, Robert H., Glatz III, Frank R., Wilson, Teresa S., Ramkumar, Vickram, and Hughes, Larry F.
- Subjects
- *
HEAT shock proteins , *INFERIOR colliculus , *AGING - Abstract
Heat shock proteins 72 and 73 (hsp72 and hsp73) were studied in the inferior colliculus (IC) of Fischer-344 rats to determine if their levels are altered during normal aging and following exposure to intense acoustic noise. Three age groups of rats (3, 18, and 25 months) were exposed to ambient sound (control) or broad-band noise at 108 dB sound pressure level (0.0004 dyn/cm2) for 30 min. Western blotting procedures were used to measure hsp72 and hsp73 in ICs and cerebella (positive control). Immunohistochemistry was performed using 3-month olds to study the localization patterns of hsp72 and hsp73 in both structures. The IC and cerebellum exhibited immunolabeling over neuronal somata and proximal dendrites. Ambient levels of hsp72 in supernatants from aged rats were reduced 56.5%±7.8% in the IC relative to 3-month olds. This decrease may render the IC more susceptible to stress-related damage. An increase in constitutive hsp73 (350.7%±70.4%) was observed in IC pellet fractions from animals exposed to the 108-dB noise when compared to the ambient-noise controls, suggestive of a lipoprotective role for hsp73. This elevation was consistent across age groups. No noise-induced changes in hsp72 were detectable in the IC, indicating that loud sounds may not be an appropriate stimulus for hsp72 induction in this structure. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.