bluuebunny/crossref_metadata_2025 huggingface dataset:
The Werner Syndrome: A Model for the Study of Human Aging
Authors: NEHLIN JAN O. , SKOVGAARD GUNHILD LANGE , BOHR VILHELM A.
Published: July 2010

Abstract: Human aging is a complex process that leads to the gradual deterioration of body functions with time. Various models to approach the study of aging have been launched over the years such as the genetic analysis of life span in the yeast S. cerevisiae, the worm C. elegans, the fruitfly, and mouse, among others. In human models, there have been extensive efforts using replicative senescence, the study of centenerians, comparisons of young versus old at the organismal, cellular, and molecular levels, and the study of premature aging syndromes to understand the mechanisms leading to aging. One good model for studying human aging is a rare autosomal recessive disorder known as the Werner syndrome (WS), which is characterized by accelerated aging in vivo and in vitro. A genetic defect implicated in WS was mapped to the WRN locus. Mutations in this gene are believed to be associated, early in adulthood, with clinical symptoms normally found in old individuals. WRN functions as a DNA helicase, and recent evidence, summarized in this review, suggests specific bio‐chemical roles for this multifaceted protein. The interaction of WRN protein with RPA (replication protein A) and p53 will undoubtedly direct efforts to further dissect the genetic pathway(s) in which WRN protein functions in DNA metabolism and will help to unravel its contribution to the human aging process.
Inherited Variability of the Mitochondrial Genome and Successful Aging in Humans
Authors: DE BENEDICTIS G. , CARRIERI G. , VARCASIA O. , BONAFÈ M. , FRANCESCHI C.
Published: July 2010

Abstract: Increasing data indicate that polymorphic variants of nuclear loci can affect rate and quality of aging in humans. However, the mitochondrial genome is another good candidate, because of the central role played by mitochondrial genes in oxidative phosphorylation (OXPHOS) and cell metabolism. A characteristic of the mitochondrial genome (mtDNA) is the high level of interindividual variability that ensues from high mutation rate and unilinear inheritance. Related groups of germline/inherited mtDNA polymorphisms (haplogroups) have been identified as continent‐specific sets of stable/ancient/associated restriction fragment length polymorphisms in the mtDNA coding region, representing markers capable of exactly depicting the mtDNA pool of a specific population. The hypothesis can be put forward that mtDNA variants included in a haplogroup may have similar OXPHOS efficiency and therefore act as genetic factors predisposing to individual successful or unsuccessful aging. This idea can be explored by sampling groups of individuals of different ages from a well‐defined population and comparing the pools of mtDNA haplogroups between samples. The results obtained by screening mtDNA haplogroups in about 800 Italians of different ages, including more that 200 centenarians, agree with the hypothesis that the inherited variability of the mitochondrial genome is associated with the chance of successful aging and longevity in humans.
Partial Opioids: Medications for the Treatment of Pain and Drug Abuse
Authors: BIDLACK JEAN M. , McLAUGHLIN JAY P. , WENTLAND MARK P.
Published: July 2010

Abstract:Pentazocine and cyclazocine are two benzomorphans that were synthesized by the late Sydney Archer in 1962. These benzomorphans were synthesized as part of an effort to develop analgesics with little or no abuse potential. Pentazocine is used as an analgesic, often in individuals who have sever pain or in those who have drug‐abuse problems. Cyclazocine is a low‐liability analgesic and potential therapeutic for the treatment of drug abuse. The risk of drug dependence is lower with the benzomorphans, which usually act as partial agonists at the μ opioid receptor and as κ agonists. In an attempt to synthesize analogs of cyclazocine with increased bioavailability and varying κ agonist and partial μ agonist properties, a series of 8‐amino derivatives of cyclazocine were synthesized. These compounds were characterized in radioligand binding assays for their affinity and selectivity for the μ, δ, and κ opioid receptors. Mouse antinociceptive tests were used to characterize the agonist and antagonist properties of each compound at the μ, δ and κ receptors.
Spinal and Supraspinal Mechanisms of Neuropathic Pain
Authors: OSSIPOV MICHAEL H. , LAI JOSEPHINE , MALAN T. PHILIP , PORRECA FRANK
Published: July 2010

Abstract:Neuropathic pain is associated with abnormal tactile and thermal responses that may be extraterritorial to the injured nerve. Importantly, tactile allodynia and thermal hyperalgesia may involve separate pathways, since complete and partial spinal cord lesions have blocked allodynia, but not hyperalgesia, after spinal nerve ligation (SNL). Furthermore, lesions of the dorsal column, and lidocaine microinjected into dorsal column nuclei block only tactile allodynia. Conversely, thermal hyperalgesia, but not tactile allodynia was blocked by desensitizatin of C‐fibers with resiniferotoxin. Therefore, it seems that tactile allodynia is likely to be mediated by large diameter Aβ fibers, and not susceptible to modulation by spinal opioids, whereas hyperalgesia is mediated by unmyelinated C‐fibers, and is sensitive to blockade by spinal opioids. Additionally, abnormal, spontaneous afferent drive in neuropathic pain may contribute to NMDA‐mediated central sensitization by glutamate and by non‐opioid actions of spinal dynorphin. Correspondingly, SNL elicited elevation in spinal dynorphin content in spinal segments at and adjacent to the zone of entry of the injured nerve along with signs of neuropathic pain. Antiserum to dynorphin A(1–17)or MK‐801 given spinally blocked thermal hyperalgesia, but not tactile allodynia, after SNL, and also restored diminished morphine antinociception. Finally, afferent drive may induce descending facilitation from the rostroventromedial medulla (RVM). Blocking afferent drive with bupivicaine also restored lost potency of PAG morphine, as did CCK antagonists in the RVM. This observation is consistent with afferent drive activating descending facilitation from the RVM, and thus diminishing opioid activity, and may underlie the clinical observation of limited responsiveness of neuropathic pain to opioids
Effects of the Novel D1Dopamine Receptor Agonist ABT‐431 on Cocaine Self‐Administration and Reinstatement
Authors: SELF DAVID W. , KARANIAN DAVID A. , SPENCER JENNIFER J.
Published: July 2010

Abstract:Selective D1dopamine agonists represent a potential pharmacotherapy for the treatment of cocaine addiction. Here we report that systemic injections of the novel D1agonist ABT‐431 lack the ability to induce cocaine‐seeking behavior, and completely attenuate the ability of cocaine to induce this behavior in rats tested in a reinstatement paradigm. Similar doses suppress the initiation of cocaine self‐administration, and produce an extinction‐like response pattern in animals that subsequently initiate self‐administration, without altering responding maintained by food pellets. There was no tolerance to this effect over 4 days of testing. The results suggest that ABT‐431 attenuates the motivation to seek cocaine, and masks the reinforcing effects of cocaine during self‐administration. The profile of ABT‐431 is similar to the behavioral effects of other structurally distinct D1agonists, and is consistent with the desired profile of a “methadone‐like” compound for cocaine addiction.
Mimicking Gene Defects to Treat Drug Dependence
Authors: SELLERS EDWARD M. , TYNDALE RACHEL F.
Published: July 2010

Abstract:The genetic basis for drug dependence has focused on genes that encode receptors involved in the reinforcing properties of drugs of abuse or that determine drug‐taking behavior (e.g. impulsivity, etc.). Pharmacogenetic variations in the patterns of metabolism among individuals can also importantly modulate the risk of drug dependence. Cytochrome P450 drug metabolizing enzymes (CYPs), can activate (e.g. codeine to morphine) or deactivate (e.g. nicotine to cotinine) drugs of abuse. Some CYPs are polymorphic, that is, there are gene mutations which result in individuals with no (null mutations) or decreased enzyme activity (e.g. CYP2D6*10). Individuals with two null mutations appear in the population as phenotypic poor metabolizers. Usingin vitrostudies, we have identified drugs of abuse that are substrates of the polymorphic enzymes CYP2D6 (codeine, amphetamines, dextromethorphan), CYP2A6 (nicotine) and CYP2C19 (flunitrazepam). In human experimental studies, we have shown that CYP phenotype and genotype affect abuse liability of CYP2D6 metabolized drugs of abuse. In addition, we inhibited CYP2D6 and decreased individuals' risk of dependence experimentally (codeine, dextromethorphan) and treated codeine dependence. In epidemiologic studies CYP2D6 and CYP2A6 null mutations protect individuals from becoming codeine and tobacco dependent, respectively. With respect to CYP2A6, individuals with mutations, smoke fewer cigarettes and can quit more easily. Inhibiting CYP2A6 (e.g. tranylcypromine, methoxsalen) decreases smoking and the activation of procarcinogens. By mimicking these gene defects the risk of dependence can be decreased in individuals and new treatments developed.
CD44 Acts Both as a Growth‐ and Invasiveness‐Promoting Molecule and as a Tumor‐Suppressing Cofactor
Authors: HERRLICH PETER , MORRISON HELEN , SLEEMAN JONATHAN , ORIAN‐ROUSSEAU VÉRONIQUE , KÖNIG HARALD , WEG‐REMERS SUSANNE , PONTA HELMUT
Published: July 2010

Abstract: High‐molecular‐weight splice variants of the CD44 transmembrane protein family have been implicated in tumorigenesis and metastasis formation. By contrast, in certain tumors‐for example, Burkitt's lymphoma, neuroblastomas, and prostate cancer‐loss of CD44 expression seems to accompany transformation. Here we describe two modes of action of CD44 proteins. They can bind growth factors and present them to their authentic high‐affinity receptors, and thus promote proliferation and invasiveness of cells. Under these conditions the CD44 proteins recruit ERM proteins‐for example, ezrin or moesin‐to their cytoplasmic tails, thereby producing links to the cytoskeleton. This mode of action could account for the tumor‐promoting action of CD44 proteins. The second mode of action of CD44 proteins comes into play when cells reach confluent growth conditions. Under specific conditions, binding of another ligand, the ECM component hyaluronate, leads to the activation and binding to the CD44 cytoplasmic tail of the tumor suppressor protein merlin. The activation of merlin confers growth arrest, so‐called contact inhibition. This function of CD44 proteins defines them as tumor suppressors. The type of action of CD44 on a given cell will depend on the isoform pattern of CD44 expressed, on the cellular equipment with ERM protein members, on the nature of the ECM, and on yet‐unknown conditions.
How Does DNA Methyltransferase Cause Oncogenic Transformation?
Authors: SZYF MOSHE , KNOX DAVID J. , MILUTINOVIC SNEZANA , SLACK ANDREW D. , ARAUJO FELIPE D.
Published: July 2010

Abstract: Global hypomethylation of genes and repetitive sequences, as well as hypermethylation of certain genes known to be involved in tumor suppression, are observed concurrently in cancer cells. Aberrant expression of DNA methyltransferase 1 (dnmt1) is a downstream effector of multiple tumorigenic pathways, and several data suggest that dnmt1 plays a causal role in these pathways. These data raise two critical questions: Why does ectopic expression of dnmt1 transform cells? and How can global hypomethylation exist in a cell that bears high levels of DNMT1 activity? It is proposed that DNMT1 induces cellular transformation by a mechanism that does not involve DNA methylation and that the low level of methylation in cancer cells is a result of induction of a DNA demethylase in these cells. Both DNMT1 and the demethylase play a causal role in cellular transformation and are candidate anticancer targets.
Translational Studies on Cox‐2 Inhibitors in the Prevention and Treatment of Colon Cancer
Authors: GUPTA RAJNISH A. , DuBOIS RAYMOND N.
Published: July 2010

Abstract: Inhibitors of the inducible cyclooxygenase (COX‐2) have emerged as a promising new class of drugs that may be useful for the prevention of colorectal cancer. Experimental evidence to support such a claim has come from both clinical and laboratory findings that show that both selective and nonselective COX inhibitors effectively block tumor growth. Although the precise mechanism(s) by which these drugs modulate tumor growth is not known, there is evidence from colon carcinoma cell culture studies that COX‐2 activity may play an important role in regulating angiogenesis and apoptosis. Recent data obtained in animal studies suggest that COX‐2 inhibitors may also be useful in the treatment of established colorectal tumors. Treatment of COX‐2 expressing tumor cells with selective COX‐2 inhibitors appears to reset the balance between cell proliferation and cell death such that there is no increase in tumor volume.
Inhibition of CDKs as a Therapeutic Modality
Authors: SAUSVILLE EDWARD A. , JOHNSON JILL , ALLEY MICHAEL , ZAHAREVITZ DANIEL , SENDEROWICZ ADRIAN M.
Published: July 2010

Abstract: Altered cell cycle control has emerged as a recurring theme in neoplasia. Strategies that would return toward normal the altered cell cycle control present in tumor cells have appeal as novel approaches to cancer treatment. Cyclin‐dependent kinases (CDKs) control the progression through the cell cycle, operating at the transition from the G2 to M and G1 to S phases, and progression through S. CDKs are regulated by a complex set of mechanisms, including the presence of activating cyclins, regulatory phosphorylations, and endogenous CDK inhibitors at “checkpoints.” This overview focuses on progress in defining compounds that can antagonize directly the action of CDKs. These have emerged as various types of ATP site‐directed inhibitors, including flavopiridol, N‐substituted adenine derivatives, the natural product butyrolactone, staurosporine derivatives, and, more recently, the synthetic paullones. Paullones appear to be of interest in that one of the most active members of the class, 9‐nitropaullone (alsterpaullone), requires relatively brief periods of exposure to living cells in order to effect lasting effects on cellular and proliferative potential. Two of these compounds, flavopiridol and UCN‐01 (7‐hydroxy‐staurosporine), have entered early clinical trials and achieved concentrations that might potentially modulate CDK function. In the case of UCN‐01, unexpected human plasma protein binding might prevent direct inhibition of CDKs but allow drug concentrations to be achieved that indirectly affect CDKs by checkpoint abrogation. Further studies with CDK inhibitors should define the expected end point of CDK inhibition more clearly in preclinical models and clinical systems, including cytostasis, apoptosis, or differentiation.
Radioimmunotherapy of Colorectal Cancer Liver Metastases: Combination with Radiotherapy
Authors: BUCHEGGER F. , ROTH A. , ALLAL A. , DUPERTUIS Y. M. , SLOSMAN D. O. , DELALOYE A. BISCHOF , MACH J‐P.
Published: July 2010

Abstract: The expected therapeutic gain of a combined radioimmunotherapy (RIT) with conventional radiotherapy (RT) would be a synergy of tumor irradiation, provided that toxic, dose‐limiting side effects concern different organs. We have shown in a model of subcutaneous human colon cancer transplants in nude mice that RIT with 131I‐labeled anti‐CEA antibody fragments combined with fractionated RT give an additive therapeutic effect without increase of side effects. A second study of different timing schedules of RIT and RT has shown that close association of both therapies without delay is more efficient than a therapy with a treatment‐free interval of two weeks. In a new model of human colon cancer liver metastases in nude mice, early treatment with RIT and with RT has been curative, whereas therapies initiated later were less efficient, suggesting that the combined therapy is likely to be more efficient in an adjuvant situation after surgery. At the clinical level, six patients with limited liver metastatic disease from colorectal cancer were treated with RIT using 200 mCi 131I‐labeled anti‐CEA MAb F(ab′)2 fragments combined with fractionated external beam RT of 20 Gy to the entire liver. As expected, spontaneously reversible bone marrow toxicity grade 3 to 4 and reversible liver toxicity grade 1 to 3 have been observed. By computerized tomography, three patients showed stable disease and one patient partial remission, whereas two patients had progressive disease. In conclusion, animal experiments have shown a clear advantage of combined RT and RIT, and the clinical study shows the feasibility of such a therapy in patients with colorectal cancer liver metastases.
Physiology of the Entorhinal and Perirhinal Projections to the Hippocampus Studied by Current Source Density Analysis
Authors: CANNING KEVIN J. , WU KUN , PELOQUIN PASCAL , KLOOSTERMAN FABIAN , LEUNG L. STAN
Published: July 2010

Abstract: Evoked field potentials and current‐source‐density analysis were used to study the olfactory, entorhinal, and perirhinal projections to the hippocampus. In urethane‐anesthetized rats, various structures were electrically stimulated, and evoked potentials were mapped using glass micropipettes or multichannel silicon probes. Stimulation of the olfactory bulb, lateral olfactory tract, piriform cortex, amygdala‐entorhinal transition, lateral entorhinal cortex, or lateral perforant path (LPP) evoked an outer molecular layer sink (inferred distal dendritic excitation) in the dentate gyrus, with progressively decreasing onset latency. Medial perforant path (MPP) stimulation evoked a middle molecular layer sink (mid‐dendritic excitation) in the dentate gyrus. LPP and MPP were also inferred to monosynaptically excite the distal dendrites of CA3, often resulting in a population spike in CA3. CA3 spiking, in turn, was often followed by excitation at the inner molecular layer of the dentate gyrus. LPP and MPP evoked distal dendritic sinks but no population spikes in CA1. Stimulation of the perirhinal cortex activated a sink in the subiculum/CA1 border without activating the dentate gyrus. In addition, reverberatory activity through a hippocampal‐entorhinal‐hippocampal pathway may be activated by MPP or CA3 stimulation. It is suggested that the parallel projections of the entorhinal and perirhinal inputs to the distal dendrites of hippocampal principal neurons enhance local and distributed processing as characterized by CA3 to dentate gyrus feedback, and hippocampal‐entorhinal reverberation.
Two‐Phase Computational Model Training Long‐Term Memories in the Entorhinal‐Hippocampal Region
Authors: LÖRINCZ ANDRÁS , BUZSÁKI GYÖRGY
Published: July 2010

Abstract:The computational model described here is driven by the hypothesis that a major function of the entorhinal cortex (EC)‐hippocampal system is to alter synaptic connections in the neocortex. It is based on the following postulates: (1) The EC compares the difference between neocortical representations (primary input) and feedback information conveyed by the hippocampus (the “reconstructed input”). The difference between the primary input and the reconstructed input (termed “error”) initiates plastic changes in the hippocampal networks (error compensation). (2) Comparison of the primary input and reconstructed input requires that these representations are available simultaneously in the EC network. We suggest that compensation of time delays is achieved by predictive structures, such as the CA3 recurrent network and EC‐CA1 connections. (3) Alteration of intrahippocampal connections gives rise to a new hippocampal output. The hippocampus generates separated (independent) outputs, which, in turn, train long‐term memory traces in the EC (independent components, IC). The ICs of the long‐term memory trace are generated in a two‐step manner, the operations of which we attribute to the activities of the CA3 (whitening) and CA1 (separation) fields. (4) The different hippocampal fields can perform both nonlinear and linear operations, albeit at different times (theta and sharp phases). We suggest that long‐term memory is represented in a distributed and hierarchical reconstruction network, which is under the supervision of the hippocampal output. Several of these model predictions can be tested experimentally.
The Parahippocampal Region and Object Identification
Authors: MURRAY E. A. , BUSSEY T. J. , HAMPTON R. R. , SAKSIDA L. M.
Published: July 2010

Abstract: The hippocampus has long been thought to be critical for memory, including memory for objects. However, recent neuropsychological studies in nonhuman primates have indicated that other regions within the medial temporal lobe, specifically, structures in the parahippocampal region, are primarily responsible for object recognition and object identification. This article reviews the behavioral effects of removal of structures within the parahippocampal region in monkeys, and cites relevant work in rodents as well. It is argued that the perirhinal cortex, in particular, contributes to object identification in at least two ways: (i) by serving as the final stage in the ventral visual cortical pathway that represents stimulus features, and (ii) by operating as part of a network for associating together sensory inputs within and across sensory modalities.
Reorganization of the Rat Fascia Dentata after a Unilateral Entorhinal Cortex Lesion: Role of the Extracellular Matrix
Authors: DELLER THOMAS , HAAS CAROLA A. , FROTSCHER MICHAEL
Published: July 2010

Abstract: Entorhinal cortex lesion (ECL) partially denervates the fascia dentata of the hippocampus. This is said to induce the sprouting of intact fibers from neighboring layers that invade the zone of the degenerating axons. However, recent studies using anterograde tracing failed to demonstrate sprouting across laminar boundaries. Sprouting does occur, but it mainly involves unlesioned fiber systems terminating within the layer of fiber degeneration. It is now of interest to identify the cues that could underlie this layer‐specific sprouting response. Since extracellular matrix (ECM) molecules delineate boundaries of axonal growth during development, it was tested whether these molecules play a similar role during the sprouting process following ECL. After ECL, reactive astrocytes rapidly synthesize and secrete growth‐inhibiting ECM molecules, such as tenascin‐C and the chondroitin sulfate proteoglycan neurocan, into the ECM of the outer molecular layer. These molecules form a sharp border against the nondenervated inner molecular layer. This pattern of ECM molecule expression may contribute to the layer‐specific sprouting response of surviving afferents after ECL: axons trying to grow into the denervated outer molecular layer, for example, from the inner molecular layer, would be deflected by a growth‐inhibiting ECM barrier.
Pathological Changes in the Parahippocampal Region in Select Non‐Alzheimer's Dementias
Authors: BRAAK HEIKO , DEL TREDICI KELLY , BOHL JÜRGEN , BRATZKE HANSJÜRGEN , BRAAK EVA
Published: July 2010

Abstract: The transentorhinal and entorhinal regions of the human brain extend over the ambient gyrus and anterior portions of the parahippocampal gyrus. They are important components of the limbic loop which receives its major afferents from the neocortical sensory association areas and generates powerful efferent projections both directly and via intermediary relay stations to the prefrontal cortex. The bilateral structural preservation of limbic loop components is a prerequisite for the maintenance of intact memory functions. In progressive neurodegenerative diseases, such as Alzheimer's disease, argyrophilic grain disease, Pick's disease, idiopathic Parkinson syndrome, and Huntington's disease, the transentorhinal and entorhinal regions are particularly susceptible to severe pathological changes. The transentorhinal region typically registers the initial alterations and becomes the most severely involved. From this transitional region of the mesocortex, the alterations usually invade with decreasing severity both the entorhinal region and temporal proneocortex. Each type of lesion that develops in the above‐mentioned neurode‐generative disorders hampers or even interrupts data‐transport from the sensory neocortex to the prefrontal neocortex, thereby contributing to the insidious development of progressive changes in personality, cognitive decline, and, ultimately, dementia.
The Parahippocampal Cortices and Kindling
Authors: McINTYRE DAN C. , KELLY MARY ELLEN
Published: July 2010

Abstract: The piriform and perirhinal cortices are parahippocampal structures with strong connections to limbic structures, including the amygdala and hippocampus, as well as other parahippocampal structures such as the entorhinal cortex. In this paper, we present results, based on anatomical, physiological, and kindling studies, that suggest that the perirhinal and piriform cortices might be very important in the secondary generalization of limbic seizures, particularly those with convulsive expression. These kindling data further suggest that the progressive lowering of afterdischarge thresholds in the parahippocampal structures, due to insult and/or genetic predisposition, might provide the neural basis for the clinical presentation of temporal lobe epilepsy.
Memory Deficits Characterized by Patterns of Lesions to the Hippocampus and Parahippocampal Cortex
Authors: BOHBOT VÉRONIQUE D. , ALLEN JOHN J.B. , NADEL LYNN
Published: July 2010

Abstract: Spatial and nonspatial memory tests were given to patients with small thermal lesions administered to the medial temporal lobes in an attempt at alleviating pharmacologically resistant epilepsy. In all three spatial memory experiments presented in this paper, patients with lesions that included the right parahippocampal cortex were seriously impaired. Their impairment, together with the performance of patients with lesions to the right hippocampus (sparing the right parahippocampal cortex), provides the different patterns of deficits that lead to different interpretations of the function of the parahippocampal cortex. The distinction between the effects of functional damage in hippocampus and the effects of a lesion to the hippocampus or to regions surrounding the hippocampus, such as the parahippocampal cortex, is emphasized. We conclude that the right parahippocampal cortex participates in spatial memory beyond serving as a gateway to the hippocampus.
Reciprocal Connections between the Amygdala and the Hippocampal Formation, Perirhinal Cortex, and Postrhinal Cortex in Rat: A Review
Authors: PITKÄNEN ASLA , PIKKARAINEN MARIA , NURMINEN NINA , YLINEN AARNE
Published: July 2010

Abstract:Recent anterograde and retrograde studies in the rat have provided detailed information on the origin and termination of the interconnections between the amygdaloid complex and the hippocampal formation and parahippocampal areas (including areas 35 and 36 of the perirhinal cortex and the postrhinal cortex). The most substantial inputs to the amygdala originate in the rostral half of the entorhinal cortex, the temporal end of the CA1 subfield and subiculum, and areas 35 and 36 of the perirhinal cortex. The amygdaloid nuclei receiving the heaviest inputs are the lateral, basal, accessory basal, and central nuclei as well as the amygdalohippocampal area. The heaviest projections from the amygdala to the hippocampal formation and the parahippocampal areas originate in the lateral, basal, accessory basal, and posterior cortical nuclei. These pathways terminate in the rostral half of the entorhinal cortex, the temporal end of the CA3 and CA1 subfields or the subiculum, the parasubiculum, areas 35 and 36 of the perirhinal cortex, and the postrhinal cortex. The connectional data are summarized and the underlying principles of organization of these projections are discussed.
Imaging Epileptiform Discharges in Slices of Piriform Cortex with Voltage‐sensitive Fluorescent Dyes
Authors: DEMIR REZAN , HABERLY LEWIS B. , JACKSON MEYER B.
Published: July 2010

Abstract: Voltage imaging techniques were used to investigate epileptiform discharges in brain slices containing piriform cortex (PC). These experiments pinpointed the site of discharge onset in the endopiriform nucleus (En). Under some conditions, discharge onset also occurred simultaneously in adjoining neocortex. With slightly suprathreshold electrical stimulation, discharge generation was a two‐stage process in which onset was preceded by a sustained spatially localized depolarization denoted as plateau activity. Plateau activity was seen away from the onset site, in a border region between En and layer III of PC. A similar two‐stage sequence was seen for slices taken from a variety of planes, using two different interictal models as well as an ictal model. Plateau activity was found to be necessary for the generation of both kinds of discharge. Synaptic transmission at the site of onset was found to be required for the generation of interictal‐like discharges, but ictal‐like discharges were different in that they could still be generated when synaptic transmission at this site was impaired. These studies identify specialized regions with potentially important roles in epileptogenesis and help to elucidate the neuronal circuitry that can produce epileptiform activity.
Gas Hydrate and Humans
Authors: KVENVOLDEN KEITH A.
Published: July 2010

Abstract: The potential effects of naturally occurring gas hydrate on humans are not understood with certainty, but enough information has been acquired over the past 30 years to make preliminary assessments possible. Three major issues are gas hydrate as (1) a potential energy resource, (2) a factor in global climate change, and (3) a submarine geohazard. The methane content is estimated to be between 1015 to 1017 m3 at STP and the worldwide distribution in outer continental margins of oceans and in polar regions are significant features of gas hydrate. However, its immediate development as an energy resource is not likely because there are various geological constraints and difficult technological problems that must be solved before economic recovery of methane from hydrate can be achieved. The role of gas hydrate in global climate change is uncertain. For hydrate methane to be an effective greenhouse gas, it must reach the atmosphere. Yet there are many obstacles to the transfer of methane from hydrate to the atmosphere. Rates of gas hydrate dissociation and the integrated rates of release and destruction of the methane in the geo/hydro/atmosphere are not adequately understood. Gas hydrate as a submarine geohazard, however, is of immediate and increasing importance to humans as our industrial society moves to exploit seabed resources at ever‐greater depths in the waters of our coastal oceans. Human activities and installations in regions of gas‐hydrate occurrence must take into account the presence of gas hydrate and deal with the consequences of its presence.
Comparisons of In Situ and Core Gas Measurements in ODP Leg 164 Bore Holes
Authors: PAULL C. K. , LORENSON T. D. , DICKENS G. , BOROWSKI W. S. , USSLER W. , KVENVOLDEN K.
Published: July 2010

Abstract: During Ocean Drilling Program Leg 164, an unprecedented effort was made to determine the amounts of gas and gas hydrate in the sediments from Sites 994, 995, and 997. For the first time in the history of academic drilling, a pressure core sampler (PCS) worked well enough to generate an independent stratigraphy of in situ gas concentrations and compositions with depth. Here, gas concentrations and composition data produced by routine shipboard gas sampling techniques are compared with PCS data.
The Nature of Gas Hydrates on the Nigerian Continental Slope
Authors: BROOKS JAMES M. , BRYANT WILLIAM R. , BERNARD BERNIE B. , CAMERON NICK R.
Published: July 2010

Abstract: Gas hydrates were collected in six‐meter piston cores during surface geochemical exploration (SGE) surveys in the deep and ultra deepwaters of Nigeria during 1991, 1996, and 1998. To date, gas hydrates have been collected in about 21 cores out of the more than 800 core collections on the Nigerian margin. This represents a 2.5% recovery ratio of gas hydrated cores on this margin at sites that are potential conduits for the upward migration of hydrocarbons (i.e., the core locations are sited based on two‐ and three‐dimensional seismic overfaults, mounds, acoustic wipe‐outs, etc.). Unlike the Northern Gulf of Mexico where the authors have retrieved a significant percentage of thermogenic hydrates in piston cores, all the gas hydrate collections offshore Nigeria to date are primarily biogenic in nature (methane more than 99% of the hydrocarbon gases; δ13C generally light, −60 to −117%). A few of these gas hydrated sites do contain a mixed thermogenic gas component (ethane to butane gases up to a few hundred ppm of total hydrocarbon gas) but even at these sites the primary gas in the hydrates is methane.
Methane Hydrate Accumulation along the Western Nankai Trough
Authors: AOKI YUTAKA , SHIMIZU SHOSHIRO , YAMANE TERUMASA , TANAKA TOMOYUKI , NAKAYAMA KAZUO , HAYASHI TSUTOMU , OKUDA YOSHIHISA
Published: July 2010

Abstract: A one‐dimensional gas hydrate accumulation model is developed to simulate the existence of hydrate in the Nankai Trough margin, where the total organic carbon content is extremely low. In order to study the accumulation of gas hydrate along a seismic profile, our model assumes an initial 1000 m thick turbidite sedimentation at the trench axis, and then the sediment experiences tectonic uplift to form the Nankai accretionary prism. Methane generated by microbial processes during the sedimentation is partly trapped in the pore space and partly migrated upwards due to compaction and subsequent porosity decrease at deeper levels. Upward methane gas flux from the deeper part (below 1000 m) is predicted by the model because the maximum thickness of the accreted sediment exceeds ten kilometers in the Nankai Trough accretionary prism. The basic geological parameters input to the model are those obtained from the ODP site 808, which was drilled at the lower inner trench slope. The methane hydrate stability zone is essentially controlled by bottom water temperature, regional heat flow and hydrostatic pressure. The simulation shows that methane hydrate will not accumulate in the Nankai Trough margin if only microbial methane generation is considered because the organic carbon content in the Nankai Trough area is as low as 0.75%. However, if we assume an upward flux of 5 kg of methane per square meters per 10,000 years, it will cause approximately 10 to 25% hydrate saturation under current physical conditions. The origin of the methane may be thermogenic and/or microbial. The resultant distribution of methane hydrate shows very good correlation with the distribution of the BSR.
Gas Hydrates and Global Climate Change
Authors: BREWER PETER G.
Published: July 2010

Abstract: The gas hydrate phenomenon intersects with societal concerns about global climate change in at least two distinct ways: the possibility of destruction of gas hydrates exposed on or near the sea floor by global warming; and the possibility of avoiding this and other problems by taking advantage of CO2 hydrate formation during active disposal of fossil fuel CO2 in the deep ocean. This extraordinary picture of contemporary discussion of the possible destruction by mankind of one hydrate, and the creation of another, both in vast quantities in the ocean, is a tribute to the unusual nature and power of this chemical cage.
A Calculation Model for Liquid CO2 Injection into Shallow Sub‐Seabed Aquifer
Authors: SASAKI KYURO , AKIBAYASHI SATOSHI
Published: July 2010

Abstract: This study provided a model for calculating the aquifer transmissibility, the CO2 injection rate, the inner diameter of the injection well, and the number of wells for liquid CO2 disposal in the aquifer. The possibility of disposing liquid CO2 in an aquifer just beneath the sea floor was shown, based on the equilibrium lines in the pressure and temperature map. Our study focused on the feasibility of liquid CO2 disposal below the critical temperature because CO2 can be denser in the low‐pressure range (below the critical temperature) than above the critical temperature. An aquifer about 200 m under the sea floor, at a water depth of around 500 m (700 m below the sea surface), will serve for liquid CO2 disposal. In the aquifer the absolute pressure is approximately 7.3 MPa, sea‐floor temperature is about 4–6°C, and aquifer temperature is about 15–20°C. Therefore, it can be assumed that CO2 dissolves in the aquifer water, and liquid CO2 replaces the water. This means that under the previous conditions, more CO2 can be injected into the aquifer compared to supercritical conditions. Furthermore, by forming a cap of CO2 hydrates, the sediment between the sea floor and the aquifer, prevents CO2 leakage to the sea. Even without the cap, liquid CO2 and CO2 hydrates form at the sea floor, so the CO2 exerts no large environmental impact.
The Impact of CO2 Clathrate Hydrate on Deep Ocean Sequestration of CO2: Experimental Observations and Modeling Results
Authors: WARZINSKI ROBERT P. , LYNN RONALD J. , HOLDER GERALD D.
Published: July 2010

Abstract: CO2 clathrate hydrate is a crystalline compound that can form under temperature and pressure conditions associated with the injection and storage of CO2 in the deep ocean (below 500 m). At depths being considered for injection of CO2 (between 1,000 and 1,500 m), in the absence of hydrate formation, the buoyant CO2 would simply rise as it dissolved in the seawater. If, however, the hydrate phase forms, it will affect this process. The impact could be positive or negative, depending on how hydrate forms and whether it is associated with undissolved CO2. This paper summarizes experimental and theoretical information relating to formation conditions for the hydrate, the relative density of the hydrate, the formation of a hydrate shell on drops of liquid CO2, and the impact that a hydrate shell has on dissolution of CO2. The future direction of the work is also briefly described.
Hydrate Plug Properties: Formation and Removal of Plugs
Authors: AUSTVIK TORSTEIN , LI XIAOYUN , GJERTSEN LARS HENRIK
Published: July 2010

Abstract: The properties of hydrate plugs have been demonstrated to vary from case to case. Plugs formed in a gas/HC liquid/water system consist of hydrate particles and pores with gas and liquid constituting both water and HC at different portions. The composition of the gas and liquids trapped in the pores plays a major role in the probability of plugging as well as the behavior of plugs during melting.
Comparison of Laboratory Results on Hydrate Induction Rates in a THF Rig, High‐Pressure Rocking Cell, Miniloop, and Large Flowloop
Authors: TALLEY LARRY D. , MITCHELL GARRICK F. , OELFKE RUSSELL H.
Published: July 2010

Abstract: This paper compares experimental data obtained on three high‐pressure devices and one atmospheric apparatus that measure hydrate formation onset and dissociation temperatures. The high‐pressure devices are rocking sapphire tubes, a 0.5‐inch diameter miniloop, and a 4‐inch diameter flowloop. High‐pressure miniloop results are compared to atmospheric pressure, tetrahydrofuran (THF) rig results in which chemically similar inhibitors ranked in different order. Although high‐pressure, stirred tank apparatus is considered by many to be effective in obtaining data of this kind, this paper does not include any stirred‐tank data. Many kinetics experiments are insensitive to the high‐pressure apparatus used. However, results of kinetic experiments obtained in different types of screening apparatus may not agree if the methods of hydrate detection are different. An example of a gas/condensate/brine system that would be difficult to characterize in a rocking‐cell or stirred‐tank apparatus is discussed.
Flow Properties of Hydrate‐in‐Water Slurries
Authors: ANDERSSON VIBEKE , GUDMUNDSSON JÓN STEINAR
Published: July 2010

Abstract: Natural gas hydrates have been proposed as a means to capture associated gas produced on offshore oil platforms. Hydrates are produced by bringing the gas into contact with liquid water, resulting in a hydrate‐in‐water slurry. It is further suggested that the hydrates be mixed with the crude oil, resulting in an hydrate‐in‐oil slurry that might be transported to shore in shuttle tankers, or in long‐distance pipelines. A hydrate laboratory has been built to obtain the data necessary to evaluate such processes. The laboratory contains a high‐pressure tube viscometer in which the flow properties of water‐based and oil‐based hydrate slurries can be studied under laminar and turbulent pipe flow conditions. In this paper, the experimental equipment is described, and experiments on the flow properties of hydrate‐in‐water slurries are presented. It was found that the slurry viscosity increases with increasing hydrate concentration, and also that the hydrate slurries approach the same frictional pressure drop as the carrying water in the turbulent flow regime, regardless of hydrate concentration.
Mathematical Models of Gas Hydrates Dissociation in Porous Media
Authors: TSYPKIN GEORGE G.
Published: July 2010

Abstract: In strata hydrates may exist in different forms: as hydrates alone, hydrates in conjunction with free gas, or with gas and water in state of thermodynamic equilibrium, hydrates with excess ice or water, and other forms. A series of new mathematical models of gas production from gas hydrate reservoirs are proposed. The purpose of this work is to investigate dissociation problem for various initial states of gas hydrates fields under thermal stimulation and depressurization. The simplest case of a stratum in which the gas hydrate completely fills the pore space is proposed. It is shown that there are two different regimes of hydrate dissociation. In the strata with a positive initial temperature, the calculated dissociation temperature at the front may fall below the water crystallization temperature. This means that the hydrate does not satisfy the assumed decomposition into gas and water and the mathematical model has internal thermodynamic contradiction. In this case the hydrate dissociates with formation of an ice‐gas mixture zone. The gas hydrate dissociation problem coexisting with gas is considered. It is shown that for high permeability the front solution does not apply, because the local temperature of the hydrate in the zone ahead of the dissociation front is higher than the local phase transition temperature calculated from the pressure distribution. In this case there are three zones: gas‐water, gas‐hydrate‐water, and gas‐hydrate. If the stratum initially contains gas, water, and hydrate in thermodynamic equilibrium the frontal model always gives a contradiction. It is shown that hydrate dissociation takes place in the extended gas‐hydrate‐water zone. For media with high permeability the amount of gas hydrate dissociated in this zone exceeds the amount of hydrate decomposed in the total dissociation zone by several orders.
Growth and Inhibition of Ethylene Oxide Clathrate Hydrate
Authors: LARSEN ROAR , KNIGHT CHARLES A. , RIDER KEVIN T. , SLOAN E. DENDY
Published: July 2010

Abstract: Growth and inhibition of single crystals of ethylene oxide clathrate hydrate provide experimental accessibility to similar phenomena in methane clathrate hydrates. Ethylene oxide hydrate single crystals were grown in a simple experimental setup. The crystals grew from the subcooled melt as rhombic dodecahedra, macroscopically exhibiting {110} as the slowest growing faces. The addition of minute amounts of poly(N‐vinylcaprolactam) (PVCap) or a random terpolymer of PVCap, poly(N‐vinylpyrrolidone), and dimethylaminoethylmethacrylate (VC‐713) caused small‐scale branching of crystals, but with a seemingly uniform crystal orientation. A few tenths of a weight percent of these additives caused complete crystal growth inhibition at several degrees of subcooling.
Hydrogen and Oxygen Isotope Fractionation in Water during Gas Hydrate Formation
Authors: MAEKAWA TATSUO , IMAI NOBORU
Published: July 2010

Abstract: Isotope fractionation of hydrogen and oxygen in water caused by methane hydrate formation in saline water was investigated experimentally. The isotope fractionation factors were calculated by measuring the concentration of salts and hydrogen and oxygen isotopic ratios of water in both initial solution and residual solution after formation of methane hydrate. The amount of methane hydrates was estimated using two assumptions: complete desalination and gas consumption. As methane hydrate forms in saline water, the concentration of salt in solution increases and gas pressure decreases. We estimated the amount of methane hydrate not only from the increase of concentration of salts in the solution, but also from the decrease in gas pressure. The isotope fractionation factors of hydrogen and oxygen in the water between methane hydrate and saline water were obtained as 1.016 to 1.020 and 1.0028 to 1.0032, respectively. These are similar to the factors between ice and water.
A Unified Nucleation Theory for the Kinetics of Hydrate Formation
Authors: KVAMME BJØRN
Published: July 2010

Abstract: In this work I present a nucleation theory for the kinetics of hydrate nucleation and growth. The first stage of the theory is the kinetic transport of hydrate formers towards the surface, calculations of average surface density, and composition of adsorbed molecules. The second step is molecular agglomeration and clustering, with a matrix approach for evaluation of cluster distribution, and a subsequent cluster stability analysis. Growth rates for metastable clusters are obtained from an extended diffuse interface theory. The final step is the calculation of growth rates for stable cores according to an explicit solution of the classical nucleation theory. Preliminary results from the theory are very promising. The deviations from the experiments are also in directions that are to be expected from the simplifications made at this stage in the development of the theory.
The Occurrence of Methane Hydrate in Ternary and Quaternary Systems of Methane, Water, Certain Organics, and Sodium Chloride
Authors: MOOIJER‐van den HEUVEL M. M. , REUVERS M. , De DEUGD R. M. , PETERS C. J. , De SWAAN ARONS J.
Published: July 2010

Abstract: From literature it is known that sodium chloride (NaCl) exerts a strong pressure enhancing effect on the three‐phase equilibrium liquid water‐hydrate‐vapor (Lw‐H‐V) in the ternary system water + methane + sodium chloride (H2O + CH4+?NaCl). However, on the other hand, it recently became apparent that certain water‐soluble organic components, present in low concentrations in the aqueous phase, exert the opposite effect on the equilibrium pressure of the three‐phase equilibrium Lw‐H‐V. Compared to the hydrate equilibrium pressure of the organic free liquid phase, pressure reductions as high as 80% have been observed. This paper reports on experimental results of the competitive effect on the equilibrium pressure of the three‐phase equilibrium Lw‐H‐V, of both NaCl and the water‐soluble organic component 1,3‐dioxolane. We also consider the effect on the hydrate equilibrium pressure of organic components that are very poorly soluble in water, for example, tetrahydropyran, cyclobutanone, methylcyclohexane, fluoroform (CHF3), and tetrafluoromethane (CF4). These poorly water‐soluble components are referred to as water‐insoluble.