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Search Results: 1 - 10 of 191342 matches for " D. Henshall "
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Shuffling and Unshuffling
D. Henshall,N. Rampersad,J. Shallit
Computer Science , 2011,
Abstract: We consider various shuffling and unshuffling operations on languages and words, and examine their closure properties. Although the main goal is to provide some good and novel exercises and examples for undergraduate formal language theory classes, we also provide some new results and some open problems.
Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
David C Henshall, Nick Dürmüller, H Steve White, Robert Williams, et al.
Neuropsychiatric Disease and Treatment , 2009, DOI: http://dx.doi.org/10.2147/NDT.S4714
Abstract: troencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents Original Research (3911) Total Article Views Authors: David C Henshall, Nick Dürmüller, H Steve White, Robert Williams, et al. Published Date March 2009 Volume 2009:5 Pages 189 - 206 DOI: http://dx.doi.org/10.2147/NDT.S4714 David C Henshall1, Nick Dürmüller2, H Steve White3, Robert Williams4, Paul Moser2, Mark Dunleavy1, Peter H Silverstone5 1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; 2Porsolt and Partners Pharmacology, Le Genest-Saint-Isle, France; 3NeuroAdjuvants, Inc., Salt Lake City, UT, USA; 4Biovail Technologies, Ltd., Dublin, Ireland; 5Biovail Corporation, Mississauga, ON, Canada Abstract: A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 ± 2.56 vs 0.75 ± 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in signifi cantly (p < 0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p < 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.
A sampling algorithm for segregation analysis
Bruce Tier, John Henshall
Genetics Selection Evolution , 2001, DOI: 10.1186/1297-9686-33-6-587
Abstract: (To access the full article, please see PDF)
Parallel computations on pedigree data through mapping to configurable computing devices
Henshall John,Little Bryce
Genetics Selection Evolution , 2006,
Abstract: Pedigree data structures have a number of applications in genetics, including the estimation of allelic or haplotype probabilities in humans and agricultural species, and the estimation of breeding values in agricultural species. Sequential algorithms for general purpose CPU-based computers are commonly used, but are inadequate for some tasks on large data sets. We show that pedigree data can be directly represented on Field Programmable Gate Arrays (FPGA), allowing highly efficient massively parallel simulation of the flow of genes. Operating on the whole pedigree in parallel, the transmission of genes can occur for all individuals in a single clock cycle. By using FPGA, the algorithms to estimate inbreeding coefficients and allelic probabilities are shown to operate hundreds to thousands of times faster than the corresponding sequentially based algorithms. Where problems can be largely represented in an integer form, FPGA provide an efficient platform for computations on pedigree data.
MicroRNAs in the pathophysiology and treatment of status epilepticus
David C. Henshall
Frontiers in Molecular Neuroscience , 2013, DOI: 10.3389/fnmol.2013.00037
Abstract: MicroRNA (miRNA) are an important class of non-coding RNA which function as post-transcriptional regulators of gene expression in cells, repressing and fine-tuning protein output. Prolonged seizures (status epilepticus, SE) can cause damage to brain regions such as the hippocampus and result in cognitive deficits and the pathogenesis of epilepsy. Emerging work in animal models has found that SE produces select changes to miRNAs within the brain. Similar changes in over 20 miRNAs have been found in the hippocampus in two or more studies, suggesting conserved miRNA responses after SE. The miRNA changes that accompany SE are predicted to impact levels of multiple proteins involved in neuronal morphology and function, gliosis, neuroinflammation, and cell death. miRNA expression also displays select changes in the blood after SE, supporting blood genomic profiling as potential molecular biomarkers of seizure-damage or epileptogenesis. Intracerebral delivery of chemically modified antisense oligonucleotides (antagomirs) has been shown to have potent, specific and long-lasting effects on brain levels of miRNAs. Targeting miR-34a, miR-132 and miR-184 has been reported to alter seizure-induced neuronal death, whereas targeting miR-134 was neuroprotective, reduced seizure severity during status epilepticus and reduced the later emergence of recurrent spontaneous seizures. These studies support roles for miRNAs in the pathophysiology of status epilepticus and miRNAs may represent novel therapeutic targets to reduce brain injury and epileptogenesis.
Automatic Theorem-Proving in Combinatorics on Words
Dane Henshall,Jeffrey Shallit
Computer Science , 2012,
Abstract: We describe a technique for mechanically proving certain kinds of theorems in combinatorics on words, using automata and a package for manipulating them. We illustrate our technique by solving, purely mechanically, an open problem of Currie and Saari on the lengths of unbordered factors in the Thue-Morse sequence.
Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
David C Henshall,Nick Dürmüller,H Steve White,Robert Williams, et al.
Neuropsychiatric Disease and Treatment , 2009,
Abstract: David C Henshall1, Nick Dürmüller2, H Steve White3, Robert Williams4, Paul Moser2, Mark Dunleavy1, Peter H Silverstone51Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; 2Porsolt and Partners Pharmacology, Le Genest-Saint-Isle, France; 3NeuroAdjuvants, Inc., Salt Lake City, UT, USA; 4Biovail Technologies, Ltd., Dublin, Ireland; 5Biovail Corporation, Mississauga, ON, Canada Abstract: A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 ± 2.56 vs 0.75 ± 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in signifi cantly (p < 0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p < 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.Keywords: bupropion hydrobromide, bupropion hydrochloride, EEG, seizures, mice, rats, motor impairment
Parallel computations on pedigree data through mapping to configurable computing devices
John M Henshall, Bryce Little
Genetics Selection Evolution , 2006, DOI: 10.1186/1297-9686-38-3-265
Abstract: (To access the full article, please see PDF)
Use of the EM algorithm to detect QTL affecting multiple-traits in an across half-sib family analysis
RJ Kerr, GM McLachlan, JM Henshall
Genetics Selection Evolution , 2005, DOI: 10.1186/1297-9686-37-1-83
Abstract: (To access the full article, please see PDF)
Cell Signaling Underlying Epileptic Behavior
Yuri Bozzi,Mark Dunleavy,David C. Henshall
Frontiers in Behavioral Neuroscience , 2011, DOI: 10.3389/fnbeh.2011.00045
Abstract: Epilepsy is a complex disease, characterized by the repeated occurrence of bursts of electrical activity (seizures) in specific brain areas. The behavioral outcome of seizure events strongly depends on the brain regions that are affected by overactivity. Here we review the intracellular signaling pathways involved in the generation of seizures in epileptogenic areas. Pathways activated by modulatory neurotransmitters (dopamine, norepinephrine, and serotonin), involving the activation of extracellular-regulated kinases and the induction of immediate early genes (IEGs) will be first discussed in relation to the occurrence of acute seizure events. Activation of IEGs has been proposed to lead to long-term molecular and behavioral responses induced by acute seizures. We also review deleterious consequences of seizure activity, focusing on the contribution of apoptosis-associated signaling pathways to the progression of the disease. A deep understanding of signaling pathways involved in both acute- and long-term responses to seizures continues to be crucial to unravel the origins of epileptic behaviors and ultimately identify novel therapeutic targets for the cure of epilepsy.
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