Irene C. Solomon, Tami J. Halat, M.Raafat El-Maghrabi, Marvin H. O'Neal III
{"title":"Localization of connexin26 and connexin32 in putative CO2-chemosensitive brainstem regions in rat","authors":"Irene C. Solomon, Tami J. Halat, M.Raafat El-Maghrabi, Marvin H. O'Neal III","doi":"10.1016/S0034-5687(01)00299-7","DOIUrl":"10.1016/S0034-5687(01)00299-7","url":null,"abstract":"<div><p>Recent studies have suggested that cell-to-cell coupling, which occurs via gap junctions, may play a role in CO<sub>2</sub> chemoreception. Here, we used immunoblot and immunohistochemical analyses to investigate the presence, distribution, and cellular localization of the gap junction proteins connexin26 (Cx26) and connexin32 (Cx32) in putative CO<sub>2</sub>-chemosensitive brainstem regions in both neonatal and adult rats. Immunoblot analyses revealed that both Cx subtypes were expressed in putative CO<sub>2</sub>-chemosensitive brainstem regions; however, regional differences in expression were observed. Immunohistochemical experiments confirmed Cx expression in each of the putative CO<sub>2</sub>-chemosensitive brainstem regions, and further demonstrated that Cx26 and Cx32 were found in neurons and Cx26 was also found in astrocytes in these regions. Thus, our findings suggest the potential for gap junctional communication in these regions in both neonatal and adult rats. We propose that the gap junction proteins Cx26 and Cx32, at least in part, form the neuroanatomical substrate for this gap junctional communication, which is hypothesized to play a role in central CO<sub>2</sub> chemoreception.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 101-121"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00299-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81619500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ventrolateral neurons of medullary organotypic cultures: intracellular pH regulation and bioelectric activity","authors":"Martin Wiemann, Dieter Bingmann","doi":"10.1016/S0034-5687(01)00282-1","DOIUrl":"10.1016/S0034-5687(01)00282-1","url":null,"abstract":"<div><p>The hypothesized role of the intracellular pH (pH<sub>i</sub>) as a proximate stimulus for central chemosensitive neurons is reviewed on the basis of data obtained from organotypic cultures of the medulla oblongata (obex level) of new born rats (OMC). Within OMC a subset of neurons responds to hypercapnia as do neurons in the same (or similar) brain areas in vivo. Maneuvers altering intra- and/or extracellular pH (pH<sub>o</sub>) such as hypercapnia, bicarbonate-withdrawal, or ammonium pre-pulses, evoked well defined changes of the neuronal pH<sub>i</sub>. During hypercapnia (pH<sub>o</sub> 7.0) or bicarbonate-withdrawal (pH<sub>o</sub> 7.4) most ventrolateral neurons adopted a pH<sub>i</sub> which was ≤0.2 pH units below the steady state pH<sub>i</sub>, while signs of pH<sub>i</sub>-regulation occurred only in a small fraction of neurons. During all treatments leading to intracellular acidosis, bioelectric activity of chemosensitive neurons increased and was often indistinguishable from the response to hypercapnia, regardless of whether pH<sub>o</sub> was unchanged, decreased or increased during the treatment. These data strongly suggest that the pH<sub>i</sub> acts as proximate stimulus. The mode of acid extrusion of chemosensitive neurons is, therefore, of major importance for the control of central chemosensitivity. Immunocytochemical data, pH<sub>i</sub> measurements and neuropharmacological studies with novel drugs pointed to the Na<sup>+</sup>/H<sup>+</sup> exchanger subtype 3 (NHE3) as a main acid extruder in ventrolateral chemosensitive neurons. Possible functions and neuropharmacological strategies arising from this very local NHE3 expression are discussed.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 57-70"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00282-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82129786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytoarchitecture of central chemoreceptors in the mammalian ventral medulla","authors":"Yasumasa Okada , Zibin Chen , Shun-ichi Kuwana","doi":"10.1016/S0034-5687(01)00279-1","DOIUrl":"10.1016/S0034-5687(01)00279-1","url":null,"abstract":"<div><p>We reviewed the previous reports on the fine anatomy of the mammalian ventral medulla with special attention to the cytoarchitecture of the superficial chemosensitive regions to summarize what is known, what is not yet known, and what should be studied in the future. We also reviewed studies on anatomical relationship between neurons and vessels, and morphological studies on dendrites of respiratory or chemosensitive neurons. When we compared the morphological reports on the ventral and dorsal putative chemosensitive regions, similarities were found as follows. Chemosensitive cells were often found not only near the ventral surface but near the dorsal surface of the brainstem. Dendritic projection towards the surface was a common characteristic in the ventral and dorsal chemosensitive neurons. Morphological abnormality in the brainstem of sudden infant death syndrome victims was also summarized. On the basis of the previous reports we discussed the perspective on the future study on central chemoreception. Among various unanswered questions in central chemosensitivity studies, physiological significance of surface cells and surface extending dendrites is the most important topic, and must be thoroughly investigated.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 13-23"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00279-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83416754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intracellular pH regulation of neurons in chemosensitive and nonchemosensitive areas of brain slices","authors":"Robert W Putnam","doi":"10.1016/S0034-5687(01)00281-X","DOIUrl":"10.1016/S0034-5687(01)00281-X","url":null,"abstract":"<div><p>The role of changes of intracellular pH (pH<sub>i</sub>) as the proximal signal in central chemosensitive neurons has been studied. pH<sub>i</sub> recovery from acidification is mediated by Na<sup>+</sup>/H<sup>+</sup> exchange in all medullary neurons and pH<sub>i</sub> recovery from alkalinization is mediated by Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup> exchange in most medullary neurons. These exchangers are more sensitive to inhibition by changes in extracellular pH (pH<sub>o</sub>) in neurons from chemosensitive regions compared to those from nonchemosensitive regions. Thus, neurons from chemosensitive regions exhibit a maintained intracellular acidification in response to hypercapnic acidosis but they show pH<sub>i</sub> recovery in response to isohydric hypercapnia. A similar pattern of pH<sub>i</sub> response is seen in other CO<sub>2</sub>/H<sup>+</sup>-responsive cells, including glomus cells, sour taste receptor cells, and chemosensitive neurons from snails, suggesting that a maintained fall of pH<sub>i</sub> is a common feature of the proximal signal in all CO<sub>2</sub>/H<sup>+</sup>-sensitive cells. To further evaluate the potential role of pH<sub>i</sub> changes as proximal signals for chemosensitive neurons, studies must be done to: determine why a lack of pH<sub>i</sub> recovery from hypercapnic acidosis is seen in some nonchemosensitive neurons; establish a correlation between hypercapnia-induced changes of pH<sub>i</sub> and membrane potential (V<sub>m</sub>); compare the hypercapnia-induced pH<sub>i</sub> changes seen in neuronal cell bodies with those in dendritic processes; understand why the V<sub>m</sub> response to hypercapnia of many chemosensitive neurons is washed out when using whole cell patch pipettes; and employ knock out mice to investigate the role of certain proteins in the CO<sub>2</sub>/H<sup>+</sup> response of chemosensitive neurons.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 37-56"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00281-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75306630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An alternative approach to the identification of respiratory central chemoreceptors in the brainstem","authors":"Chun Jiang, Haoxing Xu, Ningren Cui, Jianping Wu","doi":"10.1016/S0034-5687(01)00301-2","DOIUrl":"10.1016/S0034-5687(01)00301-2","url":null,"abstract":"<div><p>Central chemoreceptors (CCRs) play a crucial role in autonomic respiration. Although a variety of brainstem neurons are CO<sub>2</sub> sensitive, it remains to know which of them are the CCRs. In this article, we discuss a potential alternative approach that may allow an access to the CCRs. This approach is based on identification of specific molecules that are CO<sub>2</sub> or pH sensitive, exist in brainstem neurons, and regulate cellular excitability. Their molecular identity may provide another measure in addition to the electrophysiologic criteria to indicate the CCRs. The inward rectifier K<sup>+</sup> channels (Kir) seem to be some of the CO<sub>2</sub> sensing molecules, as they regulate membrane potential and cell excitability and are pH sensitive. Among homomeric Kirs, we have found that even the most sensitive Kir1.1 and Kir2.3 have pK∼6.8, suggesting that they may not be capable of detecting hypocapnia. We have studied their biophysical properties, and identified a number of amino acid residues and molecular motifs critical for the CO<sub>2</sub> sensing. By comparing all Kirs using the motifs, we found the same amino acid sequence in Kir5.1, and demonstrated the pH sensitivity in heteromeric Kir4.1 and Kir5.1 channels to be pK∼7.4. In current clamp, we show evidence that the Kir4.1–Kir5.1 can detect P<sub>CO<sub>2</sub></sub> changes in either hypercapnic or hypocapnic direction. Our in-situ hybridization studies have indicated that they are coexpressed in brainstem cardio–respiratory nuclei. Thus, it is likely that the heteromeric Kir4.1–Kir5.1 contributes to the CO<sub>2</sub>/pH sensitivity in these neurons. We believe that this line of research intended to identify CO<sub>2</sub> sensing molecules is an important addition to current studies on the CCRs.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 141-157"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00301-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87965458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Andrzejewski, K Mückenhoff, P Scheid, D Ballantyne
{"title":"Synchronized rhythms in chemosensitive neurons of the locus coeruleus in the absence of chemical synaptic transmission","authors":"M Andrzejewski, K Mückenhoff, P Scheid, D Ballantyne","doi":"10.1016/S0034-5687(01)00300-0","DOIUrl":"10.1016/S0034-5687(01)00300-0","url":null,"abstract":"<div><p>The activity of locus coeruleus (LC) neurons was examined in the en bloc isolated brainstem–spinal cord of the neonatal rat using paired whole cell or whole cell plus extracellular recording. In artificial cerebrospinal fluid (ACSF) LC neurons were synchronized by their respiratory innervation and in some neurons showing tonic or burst patterns of discharge these patterns of discharge could also be synchronized. Replacing ACSF with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> generated synchronized rhythmic bursts which remained synchronized at high CO<sub>2</sub> (up to 20%). This rhythm was suppressed by TTX. Substitution of Ba<sup>2+</sup> for Ca<sup>2+</sup> in ACSF generated a synchronized rhythm which was TTX-insensitive<strong>.</strong> The frequency of this rhythm increased by 31±16% on raising CO<sub>2</sub> concentration from 2 to 10%. We conclude that the capacity of chemosensitive LC neurons to generate a synchronized rhythm depends on their electrical coupling, but not on chemical synaptic transmission.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 123-140"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00300-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76026745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Douglas A Bayliss, Edmund M Talley, Jay E Sirois, Qiubo Lei
{"title":"TASK-1 is a highly modulated pH-sensitive ‘leak’ K+ channel expressed in brainstem respiratory neurons","authors":"Douglas A Bayliss, Edmund M Talley, Jay E Sirois, Qiubo Lei","doi":"10.1016/S0034-5687(01)00288-2","DOIUrl":"10.1016/S0034-5687(01)00288-2","url":null,"abstract":"<div><p>Central respiratory chemoreceptors adjust respiratory drive in a homeostatic response to alterations in brain pH and/or P<sub>CO<sub>2</sub></sub>. Multiple brainstem sites are proposed as neural substrates for central chemoreception, but molecular substrates that underlie chemosensitivity in respiratory neurons have not been identified. In rat brainstem neurons expressing transcripts for TASK-1, a two-pore domain K<sup>+</sup> channel, we characterized K<sup>+</sup> currents with kinetic and voltage-dependent properties identical to cloned rat TASK-1 currents. Native currents were sensitive to acid and alkaline shifts in the same physiological pH range as TASK-1 (pK∼7.4), and native and cloned pH-sensitive currents were modulated similarly by neurotransmitters and inhalational anesthetics. This pH-sensitive TASK-1 channel is an attractive candidate to mediate chemoreception because it is functionally expressed in respiratory-related neurons, including airway motoneurons and putative chemoreceptor neurons of locus coeruleus (LC). Inhibition of TASK-1 channels by extracellular acidosis can depolarize and increase excitability in those cells, thereby contributing to chemoreceptor function in LC neurons and directly enhancing respiratory motoneuronal output.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 159-174"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00288-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81119324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell–cell coupling in CO2/H+-excited neurons in brainstem slices","authors":"Jay B Dean, Elizabeth A Kinkade, Robert W Putnam","doi":"10.1016/S0034-5687(01)00284-5","DOIUrl":"10.1016/S0034-5687(01)00284-5","url":null,"abstract":"<div><p>The indirect and direct electrical and anatomical evidence for the hypothesis that central chemoreceptor neurons in the dorsal brainstem (solitary complex, SC; locus coeruleus, LC) are coupled by gap junctions, as reported primarily in rat brainstem slices, and the methods used to study gap junctions in brain slices, are critiqued and reviewed. Gap junctions allow intercellular communication that could be important in either electrical coupling (intercellular flow of ionic current), metabolic coupling (intercellular flow of signaling molecules), or both, ultimately influencing excitability within the SC and LC during respiratory acidosis. Gap junctions may also provide a mechanism for modulating neuronal activity in the network under conditions that lead to increased or decreased central respiratory chemosensitivity. Indirect measures of electrical coupling suggest that junctional conductance between chemosensitive neurons is relatively insensitive to a broad range of intracellular pH (pH<sub>i</sub>), ranging from pH<sub>i</sub> ≈7.49 to ≈6.71 at 35–37 °C. In contrast, further reductions in pH<sub>i</sub>, down through pH<sub>i</sub> ≈6.67, abolish indirect measures of electrical coupling.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 83-100"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00284-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89903592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
George B Richerson , Wengang Wang , Jyoti Tiwari , Stefania Risso Bradley
{"title":"Chemosensitivity of serotonergic neurons in the rostral ventral medulla","authors":"George B Richerson , Wengang Wang , Jyoti Tiwari , Stefania Risso Bradley","doi":"10.1016/S0034-5687(01)00289-4","DOIUrl":"10.1016/S0034-5687(01)00289-4","url":null,"abstract":"<div><p>The medullary raphé contains two subtypes of chemosensitive neuron: one that is stimulated by acidosis and another that is inhibited. Both types of neuron are putative chemoreceptors, proposed to act in opposite ways to modulate respiratory output and other pH sensitive brain functions. In this review, we will discuss the cellular properties of these chemosensitive raphé neurons when studied in vitro using brain slices and primary dissociated cell culture. Quantification of chemosensitivity of raphé neurons indicates that they are highly sensitive to small changes in extracellular pH (pH<sub>o</sub>) between 7.2 and 7.6. Stimulation by acidosis occurs only in the specific phenotypic subset of neurons within the raphé that are serotonergic. These serotonergic neurons also have other properties consistent with a specialized role in chemoreception. Homologous serotonergic neurons are present within the ventrolateral medulla (VLM), and may have contributed to localization of respiratory chemoreception to that region. Chemosensitivity of raphé neurons increases in the postnatal period in rats, in parallel with development of respiratory chemoreception in vivo. An abnormality of serotonergic neurons of the ventral medulla has been identified in victims of sudden infant death syndrome (SIDS). The cellular properties of serotonergic raphé neurons suggest that they play a role in the CNS response to hypercapnia, and that they may contribute to interactions between the sleep/wake cycle and respiratory control.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 175-189"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00289-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88214066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John A. DeSimone , Vijay Lyall , Gerard L. Heck , George M. Feldman
{"title":"Acid detection by taste receptor cells","authors":"John A. DeSimone , Vijay Lyall , Gerard L. Heck , George M. Feldman","doi":"10.1016/S0034-5687(01)00293-6","DOIUrl":"10.1016/S0034-5687(01)00293-6","url":null,"abstract":"<div><p>Sourness is a primary taste quality that evokes an innate rejection response in humans and many other animals. Acidic stimuli are the unique sources of sour taste so a rejection response may serve to discourage ingestion of foods spoiled by acid producing microorganisms. The investigation of mechanisms by which acids excite taste receptor cells (TRCs) is complicated by wide species variability and within a species, apparently different mechanisms for strong and weak acids. The problem is further complicated by the fact that the receptor cells are polarized epithelial cells with different apical and basolateral membrane properties. The cellular mechanisms proposed for acid sensing in taste cells include, the direct blockage of apical K<sup>+</sup> channels by protons, an H<sup>+</sup>-gated Ca<sup>2+</sup> channel, proton conduction through apical amiloride-blockable Na<sup>+</sup> channels, a Cl<sup>−</sup> conductance blocked by NPPB, the activation of the proton-gated channel, BNC-1, a member of the Na<sup>+</sup> channel/degenerin super family, and by stimulus-evoked changes in intracellular pH. Acid-induced intracellular pH changes appear to be similar to those reported in other mammalian acid-sensing cells, such as type-I cells of the carotid body, and neurons found in the ventrolateral medulla, nucleus of the solitary tract, the medullary raphe, and the locus coceuleus. Like type-I carotid body cells and brainstem neurons, isolated TRCs demonstrate a linear relationship between intracellular pH (pH<sub>i</sub>) and extracellular pH (pH<sub>o</sub>) with slope, ΔpH<sub>i</sub>/ΔpH<sub>o</sub> near unity. Acid-sensing cells also appear to regulate pH<sub>i</sub> when intracellular pH changes occur under iso-extracellular pH conditions, but fail to regulate their pH when pH<sub>i</sub> changes are induced by decreasing extracellular pH. We shall discuss the current status of proposed acid-sensing taste mechanisms, emphasizing pH-tracking in receptor cells.</p></div>","PeriodicalId":20976,"journal":{"name":"Respiration physiology","volume":"129 1","pages":"Pages 231-245"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0034-5687(01)00293-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75119554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}