bluuebunny/crossref_metadata_2025 huggingface dataset:
An effective terrain model for web‐based 3D geographic information systems
Authors: Araya Shinji , Hyunsuk Jin , Araya Ryo
Published: September 2002

The needs of three‐dimensional implementation and WWW‐based geographic information systems are increasing. In this paper, we propose a flexible and efficient VRML‐based terrain model. In the proposed model, by placing side by side the terrain models (tiles) of fixed size in 3D space, the simplification of display range change, the utilization of a caring mechanism, and the attachment of an automatic changeover mechanism for the level of detail of the model will become possible. Each tile is modeled by combining multiple grid models, and the useless polygons in the sea and lakes are curtailed. Moreover, we propose an automatic changeover mechanism of the level of detail of the model, which regenerates the shape features of the terrain objects such as square and flat. Furthermore, for curtailing the transmitted data, we also propose a method for automatically generating simplified models from the detailed model on WWW terminal side. Finally, the effectiveness of the proposed model is shown by 3D spatial navigation experiments using automatic viewpoint motion. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 85(9): 43–52, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10071
Low‐bit‐rate image coding with metaballs
Authors: Masukura Koichi , Kumazawa Itsuo
Published: September 2002

As new coding methods using the two‐dimensional structure of images instead of JPEG which is an image coding method based on signal processing, the coding methods using sketch‐based coding or region splitting have been attracting attention in recent years. However, in these techniques, it is difficult to represent with good efficiency the image composed of complicated gradations. Accordingly, in this paper, will extend the metaballs which can represent arbitrary functional shapes efficiently to the image representation by density sum of the multiple distribution functions, and propose an image coding scheme using them. Moreover, we have performed a comparison with JPEG for performance evaluation of the proposed technique; as a result, it has become clear that the image quality of the proposed technique is excellent especially at low bit rates. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 85(9): 53–62, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10072
A WWW‐based melody retrieval system
Authors: Sonoda Tomonari , Goto Masataka , Muraoka Yoichi
Published: September 2002

This paper discusses a system that operates on the WWW and retrieves the song title from the melody of a song. In retrieval from a sung tune, it is not always true that the input melody information (such as pitch and span) is exact. The result of coarse conversion of the input data to the melody information based on thresholds is used as the retrieval key, and the matching to a song in the database is attempted. It has been difficult, however, to define adequate thresholds. In particular, it has been difficult to derive effective retrieval keys for the span. It has also been difficult to make the process converge toward the correct solution by using the coarse information. From such a viewpoint, this study proposes the following two approaches in matching: (1) A method is presented to set optimal thresholds for deriving an effective retrieval key. (2) A matching procedure to restrict precisely the candidates for the correct song from the database song is presented. Retrieval with a higher matching accuracy than in the conventional method is realized, and a system that can be utilized by multiple users on the WWW is constructed. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 85(9): 63–74, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10073
Construction of a geothermal power generation model based on characteristics of geothermal steam wells and its applications
Authors: Nakamura Masatoshi , Kajiwara Masaru , Goto Satoru , Jitsuhara Sadayuki , Hatazaki Hironori
Published: September 2002

Electricity generation in geothermal power plants depends on the characteristics of geothermal steam wells. In this research, a geothermal power generation model was constructed based on the characteristics of the steam well, and the generation of electricity was estimated precisely by the constructed model. Many applications of the geothermal power generation model are introduced. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 39–49, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10039
Quantitative evaluation of perpendicular‐field losses in stacked high‐Tc superconducting tapes
Authors: Kajikawa Kazuhiro , Nishimura Motoaki , Moriyama Hiroyuki , Iwakuma Masataka , Funaki Kazuo
Published: September 2002

The influence of stacks of Bi‐2223 multifilamentary tape‐shaped wires without twisting on AC losses observed in an external magnetic field perpendicular to their wide faces is investigated. The perpendicular‐field losses decrease with increasing number of tapes in the range of small field amplitudes. At larger amplitudes, on the other hand, the AC losses have little dependence on the stack number. This can be attributed to the effect of magnetic interaction between wires. By taking into account effective demagnetization factors on the basis of theoretical consideration, the perpendicular‐field losses are plotted on a master curve for the maximum magnetic field applied to the wires. Furthermore, the perpendicular‐field losses measured as a function of the field amplitude are well reproduced by the numerical evaluation of AC losses for a slab with infinitely wide surfaces. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 50–57, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10050
Studies of characteristics and design of superconducting fault current limiter with adjustable trigger current level in current limiting operation
Authors: Hatta Hiroyuki , Nitta Tanzo , Shirai Yasuyuki , Fujikawa Kazuhiro
Published: September 2002

Superconducting fault current limiters (SCFCLs) are expected to improve not only reliability but also stability of power systems. To introduce an SCFCL in a power system, various specifications such as trigger current level, impedance in current limiting operation, recovery time, and so on are necessary. Fault analyses point out that accuracy of the trigger current level is necessary. Therefore, an SCFCL of a transformer type with adjustable trigger current level was proposed and manufactured. Using the trial SCFCL, adjustability of the trigger current level was confirmed. It is found that the SCFCL has good limiting and recovery characteristics. In this paper, characteristics of the SCFCL are considered from a design point of view. Most of the specifications necessary for design depend on the characteristics in current limiting operation. Therefore, the characteristics of the SCFCL in current limiting operation are discussed. It is shown that this kind of SCFCL has good property for easy design, and its design principle is summarized. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 30–38, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10054
A new position‐sensorless position control method for high‐speed spindle systems
Authors: Shinnaka Shinji
Published: September 2002

This paper proposes a new position‐sensorless position control method for high‐speed spindle drive systems. Mechanical vulnerability of position sensors such as an encoder mounted on a spindle motor is becoming a serious problem as required speed increases. For high speeds above 1500 rad/s, sensorless drive is preferred. It is possible for current technologies to control spindle motor in speed control mode without the sensor, but not in position control mode without the sensor. In the example of high‐speed spindle systems of automatic machine tools, implements must be automatically attached to and removed from the spindle at standstill. Automation necessitates position control, for which current technologies require a sensor. The proposed method makes it possible to realize pure sensorless high‐speed spindle systems performing in both speed and a position control modes. The method can attain a position control performance with quick settling from speed control and a repetitive positioning precision of 0.006 rad, 0.4°, which is comparable to that achieved by current sensor‐based methods. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 58–69, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10059
A particle simulation of negative corona discharge in SF6 gas
Authors: Sasano Shuichi , Cho Mengu
Published: September 2002

In order to study partial discharge phenomena in a gas‐insulated system, we have developed a simulation code using the MC‐PIC (Monte Carlo Particle‐in‐Cell) method. The MC‐PIC code can simulate ionization and attachment in a nonuniform unsteady electric field with sufficient quantitative accuracy by considering collision cross‐section data as close as possible to the real data. A negative DC corona discharge in SF6 is simulated. The electric field is distorted near the rod electrode once the corona discharge starts, because the positive ions and negative ions are polarized near the rod electrode after the electron avalanche ends. The electric field strength decreases in comparison with the initial condition due to the negative space charge. The image current due to the motion of electrons dominates the current pulse. The simulation result agrees well with the experimental result. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 1–8, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10065
Cutting plane methods for Lagrangian relaxation‐based unit commitment algorithm
Authors: Murai Masahiko , Kato Masakazu
Published: September 2002

In this paper, we study cutting plane methods for a Lagrangian relaxation‐based unit commitment algorithm. In the algorithm, nondifferentiable optimization methods can be applied to optimize the dual function, and a subgradient method which needs parameter tuning and has some drawbacks such as computational inefficiency and oscillating behavior is commonly used. The cutting plane method and the central cutting plane method are applied to the algorithm and implemented using reoptimization techniques. A numerical example shows that both methods are accelerated by the reoptimization techniques and have good convergence without parameter tuning. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 17–29, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10066
Induction of the SOS response in starved Escherichia coli
Authors: Janion Celina , Sikora (nee Wójcik) Anna , Nowosielska Anetta , Grzesiuk Elżbieta
Published: September 2002

The SOS system in Escherichia coli is induced in response to DNA damage and the arrest of DNA synthesis. Here we show that in AB1157 bacteria starved for arginine, conditions for induction of adaptive mutations, the LexA‐dependent SOS system is induced, but that this occurs only when the bacteria resume growth and when the source of carbon is glycerol rather than glucose (glycerol, but not glucose, enables synthesis of cAMP). Therefore, we conclude that starved cells accumulate some lesions in DNA, which in growth conditions may trigger SOS induction by a process that is cAMP‐dependent. Environ. Mol. Mutagen. 40:129–133, 2002. © 2002 Wiley‐Liss, Inc.
Removal of benzo(a)pyrene diol epoxide (BPDE)‐DNA adducts as a measure of DNA repair capacity in lymphoblastoid cell lines from sisters discordant for breast cancer
Authors: Motykiewicz Grazyna , Faraglia Beatrice , Wang Lian Wen , Terry Mary Beth , Senie Ruby T. , Santella Regina M.
Published: September 2002

The mutagen sensitivity assay is one of the approaches used to investigate individual DNA repair capacity. This method is based on the premise that after in vitro treatment with a test mutagen, DNA from subjects with defective repair will be more damaged than DNA from those with an efficient repair system. However, very little is known about unmeasured processes that occur between cell treatment and final assessment of DNA damage. To develop a more precise assay, we modified the traditional mutagen sensitivity assay to also include measurement of DNA damage after culturing cells in the absence of mutagen. First, we treated apparently normal and xeroderma pigmentosum lymphoblastoid cell lines with various doses of benzo(a)pyrene diol epoxide (BPDE) and harvested cells at different time points. A polyclonal antiserum against BPDE‐DNA was used to quantitate levels of adducts by immunoslot‐blot and immunohistochemistry. Selected conditions included treatment with 10 μM BPDE, a 4‐hr culture in mutagen‐free medium, and immunohistochemical measurement of BPDE‐DNA adducts. The method was then applied in a pilot study to 50 lymphoblastoid lines from sisters discordant for breast cancer. There was no significant difference between cases and controls in the level of BPDE‐DNA adducts in lymphoblasts harvested immediately after BPDE treatment. However, after a 4‐hr culture in mutagen‐free medium, the level of adducts was significantly higher (P = 0.006) among cases than in controls. There was a two‐fold increase in mean adduct removal in lines from nonaffected as compared to affected sisters (44% and 22% decrease, respectively). DNA repair capacity was predictive of case status (P = 0.04) in logistic regression analysis. This method, which can be easily applied to large numbers of samples, should be useful in studies to investigate the role of DNA repair in cancer risk. Environ. Mol. Mutagen. 40:93–100, 2002. © 2002 Wiley‐Liss, Inc.
Sex‐specific induction of mutations by PhIP in the kidney of male and female rats and its modulation by conjugated linoleic acid
Authors: Yang Haiyan , Glickman Barry W. , de Boer Johan G.
Published: September 2002

The heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) is a recognized mutagen and carcinogen in the colon and prostate of male rats and in the mammary gland of female rats. In the current study, we examined the mutagenicity of PhIP in the kidney of male and female lacI transgenic rats and its modulation by a dietary chemopreventive agent, conjugated linoleic acid (CLA). Sex‐specific changes in mutation were observed following PhIP and CLA treatment. Exposure to 100 ppm PhIP through dietary supplementation for 47 days induced a lacI mutation frequency (MF) of 7.7 ± 0.3 × 10‐5 and 4.7 ± 1.0 × 10‐5 in the kidney of male and female rats, respectively. The PhIP‐induced MFs in the kidney of male and female rats were significantly different from each other and were 300% (P < 0.001) and 60% (P < 0.05) higher than the corresponding controls, respectively. When rats were given CLA along with PhIP, CLA completely inhibited the formation of PhIP‐induced mutations in the kidney of female rats, but not in male rats. Comparison of mutational spectra did not detect significant differences between male rats treated with PhIP and PhIP + CLA. However, unlike the ‐1 frameshifts induced by PhIP in the colon and prostate, which consist primarily of G:C deletions, ‐1 frameshifts in the kidney involved the loss of both G:C and A:T basepairs. Our data indicate that the kidney of the rats responds in a sex‐dependent way to mutagenesis and antimutagenesis by PhIP and CLA. These differences may be related to hormonally regulated induction of P450 enzymes or cell proliferation. Environ. Mol. Mutagen. 40:116–121, 2002. © 2002 Wiley‐Liss, Inc.
Short Communication: application of a surrogate material in assessing the impact of porosity on re‐ignition of wood‐based materials
Authors: Moghtaderi Behdad , Poespowati Tri , Dlugogorski Bogdan , Kennedy Eric
Published: September 2002

Re‐ignition behaviour of charred solid fuels after extinction by water is studied. In this communication the effect of material porosity on re‐ignition is investigated. A surrogate ceramic material is used so as to separate the pyrolysis and combustion processes from those associated with heat transfer. Experimental data are reported for different sample thickness and porosity, and varying heat flux and water application time. Copyright © 2002 John Wiley & Sons, Ltd.
Prediction of heat release in the single burning item test
Authors: Hansen Anne Steen
Published: September 2002

This paper presents a modification of an existing mathematical model that uses cone calorimeter test results to predict heat release rate in the single burning item (SBI) test. A method for classification of cases based on multivariate statistical analysis is incorporated in the modified model. This makes it possible to determine the development of the heat release curve in the SBI test with better precision than the original version was able to. The model has been applied to 100 cases of cone calorimeter test results from 33 different products. For most of the products the predicted shape and level of the heat release curves are close to measurements in the SBI test. Using the predicted heat release results as input to calculation of FIGRA0.2MJ and THR600s within the new European system for reaction‐to‐fire classification, we were able to predict membership of the correct class in 90% of the analysed cases. Copyright © 2002 John Wiley & Sons, Ltd.
Chemical composition and bioactivity of essential oil from Syzygium travancoricum Gamble
Authors: Radha R. , Latha R. , Swaminathan M. S.
Published: September 2002

An Erratum has been published for this article in Flavour and Fragrance Journal 17 (6) 2002, 478.

The antimicrobial and antifungal activity of the volatile oil from the leaves of Syzygium travancoricum Gamble from Kerala (South India) has been discussed in this paper. Copyright © 2002 John Wiley & Sons, Ltd.
Volatile components associated with freshly cooked and oxidized off‐flavours in turkey breast meat
Authors: Brunton N. P. , Cronin D. A. , Monahan F. J.
Published: September 2002

Cooked turkey breast is particularly susceptible to lipid oxidation‐mediated off‐flavour development during refrigerated storage. Volatile aroma compounds present in freshly cooked turkey breast muscle after cooling in air and under nitrogen, and also those in air‐cooled meat stored for 3 days at 4 °C, were examined using headspace solid phase microextraction (SPME) combined with gas chromatography–mass spectrometry (GC–MS). Odour‐port sensory assessment of the separated volatiles was carried out, using a modified form of aroma extract dilution analysis (AEDA). Compared to weakly aromatic nitrogen‐cooled turkey breast, the levels of a number of unsaturated carbonyl compounds were much higher in freshly cooked air‐cooled samples and showed further large increases in the oxidized chilled meat. Among these, the most potent odour contributors to both fresh and oxidized turkey samples were 1‐octen‐3‐one, (E,E)‐2,4‐decadienal and (E,Z)‐2,6‐nonadienal. The concentration of the only moderately potent sulphur‐containing compound identified, viz. 2‐pentylthiophene, was significantly lower in the oxidized compared to the fresh samples, and gas chromatography–olfactometry (GCO) suggested that this compound made a contribution to the aroma of freshly cooked turkey. Copyright © 2002 John Wiley & Sons, Ltd.
Composition of the essential oil from roots and rhizomes of Valeriana pancicii Halácsy & Bald
Authors: Kovacevic N. , Pavlovic M. , Menkovic N. , Tzakou O. , Couladis M.
Published: September 2002

The essential oil of subterranean parts of the endemic plant Valeriana pancicii was obtained by hydrodistillation and analysed by GC–MS. Plant material was collected in summer (sample A) and autumn (sample B) from the same location in Montenegro (Mountain Ljevorecki Kom). The main characteristic of V. pancicii essential oil was the low content of monoterpenoids and the high percentage of sesquiterpenoid compounds. The major compounds in the essential oil of both samples were patchouli alcohol, an unidentified oxygenated monoterpene, α‐guaiene and γ‐patchoulene. Copyright © 2002 John Wiley & Sons, Ltd.
The essential oil of ‘greater galangal’ [Alpinia galanga (L.) Willd.] from the lower Himalayan region of India
Authors: Raina V. K. , Srivastava S. K. , Syamasunder K. V.
Published: September 2002

The volatile constituents of the rhizomes and leaves of Alpinia galanga, growing in the arboretum of CIMAP Field Station Pant Nagar, were analysed by GC and GC–MS. The main constituents identified in the rhizome oil were 1,8‐cineole (39.4%) and β‐pinene (11.9%). The leaf oil contained 1,8‐cineole (32.5%), β‐pinene (22.7%) and camphor (12.8%), as major constituents. Copyright © 2002 John Wiley & Sons, Ltd.
Studies on the essential oil‐bearing plants of Bangladesh. Part VIII. Composition of some Ocimum oils O. basilicum L. var. purpurascens; O. sanctum L. green; O. sanctum L. purple; O. americanum L., citral type; O. americanum L., camphor type
Authors: Mondello Luigi , Zappia Giovanni , Cotroneo Antonella , Bonaccorsi Ivana , Chowdhury Jasim Uddin , Yusuf Mohammed , Dugo Giovanni
Published: September 2002

The essential oils of Ocimum basilicum L. var. purpurascens, O. sanctum L. green, O. sanctum L. purple, O. americanum L. (citral type) and, O. americanum L. (camphor type) obtained from plants grown in Bangladesh were analysed by GC and GC–MS. The oil obtained from O. basilicum L. var. purpurascens was classified as a monoterpene alcohol‐type according to its monoterpene alcohol content (64.5%); the oil obtained from O. Sanctum L. green was classified as a eugenol/sesquiterpene‐type according to its content of eugenol (41.7%) and of sesquiterpene components (45.9%); while the oil from O. sanctum purple was classified as an eugenol‐type according to its content of eugenol (77.5%). One of the two O. americanum was classified as a citral‐type oil, according to its content of neral (27.9%) and geranial (37.7%), whereas the other oil of the same species was characterized by a high content of camphor (38.6%). Copyright © 2002 John Wiley & Sons, Ltd.
The effect of exogenous pectinase on DMHF and derivatives in clarified strawberry juice (Fragaria × ananassa, cv. Elsanta)
Authors: Mura Emanuela , Zabetakis Ioannis
Published: September 2002

The effect of exogenous pectinase on the levels of 2,5‐dimethyl‐4‐hydroxy‐2H‐furan‐one (DMHF) and DMHF‐glucoside was studied in clarified strawberry juice (Fragaria × ananassa, cv. Elsanta). The extent of conversion of DMHF‐malonyl glucoside to DMHF‐glucoside and DMHF was monitored at three different temperatures (45 °C, 50 °C and 60 °C) and at three different pH values (pH 3.0, 4.0 and 5.4). The effect of using two different concentrations of pectinase was also studied. Based on these results, the endogenous levels of DMHF‐malonyl glucoside were calculated for the first time in strawberries. Copyright © 2002 John Wiley & Sons, Ltd.
In vitro radical scavenging activity of essential oils from Columbian plants and fractions from oregano (Origanum vulgare L.) essential oil
Authors: Puertas‐Mejía Miguel , Hillebrand Silke , Stashenko Elena , Winterhalter Peter
Published: September 2002

Antioxidant activities of essential oils from anise (Pimpinella anisum L.), fennel (Foeniculum vulgare Mill.), coriander (Coriandrum sativum L.), rosemary (Rosmarinus officinalis L.), oregano (Origanum vulgare L.), ylang‐ylang (Cananga odorata Hook.), verbena (Lippia alba Mill.) and salvia negra (Lepechinia schiedeana (Schlecht) Vatke, syn. Stachys schiedeana Schlecht) were determined using the free radical α‐α‐diphenyl‐β‐picrylhydrazyl (DPPH·) and the preformed radical monocation 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS·+). Some of the oils under investigation had antioxidant capacities in a range comparable to that of α‐tocopherol, BHA, ascorbic acid and Trolox, which were used as reference antioxidants. The all‐liquid chromatographic technique of multilayer coil countercurrent chromatography (MLCCC) was applied to the fractionation of oregano essential oil. For oregano, a high antioxidant activity was observed, which is mainly due to the presence of thymol and carvacrol in the essential oil. Copyright © 2002 John Wiley & Sons, Ltd.
Composition and antimicrobial activity of the essential oil of Hypericum maculatum Crantz
Authors: Gudžić Branislav , Djokovic Dejan , Vajs Vlatka , Palić Radosav , Stojanovic Gordana
Published: September 2002

For the first time the composition of the essential oil of Hypericum maculatum Crantz has been determined by GC and GC–MS. The oil consisted of a large number of components in low percentages. Only five components exceeded a 5% level: β‐farnesene (10.0%), n‐undecane (8.2%), β‐caryophyllene (7.6%), δ‐cadinene (7.2%) and γ‐muurolene (5.2%). The oil showed strong antimicrobiological activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Klebsiella pneumoniae, Bacillus subtilis, Sarcina lutea, Aspergillus niger and Candida albicans, documented in vitro by MIC and MMC values. Copyright © 2002 John Wiley & Sons, Ltd.
Comparative genomic hybridization analysis of primary cutaneous B‐cell lymphomas: Identification of common genomic alterations in disease pathogenesis
Authors: Mao Xin , Lillington Debra , Child Fiona , Russell‐Jones Robin , Young Bryan , Whittaker Sean
Published: September 2002

To investigate genetic alterations in primary cutaneous B‐cell lymphomas (PCBCLs), we have analyzed 29 cases of PCBCL. Comparative genomic hybridization showed chromosome imbalances (CIs) in 12 cases (41%). The mean number of CIs per sample was 2.05 ± 2.97, with gains (1.48 ± 2.38) more frequent than losses (0.56 ± 1.40). The common regions of gains were 18/18q (50%), 7/7p (42%), 3/3q (33%), 20 (33%), 1p (25%), 12/12q (25%), and 13/13q (25%), whereas loss of 6q was frequent (42%). Among the different subsets of PCBCLs, CI was seen in 50% of diffuse large‐cell lymphomas (DLCLs), 33% of marginal zone lymphomas, and 8% of follicle center cell lymphomas and unclassified lymphomas. A similar pattern of CI was observed in these lymphomas, but loss of 6q and gains of 3/3q were present only in DLCLs. Microarray‐based genomic analysis of four DLCL cases identified oncogene gains of SAS/CDK4 (12q13.3) in three cases and MYCL1 (1p34.3), MYC (8q24), FGFR2 (10q26), BCL2 (18q21.3), CSE1L (20q13), and PDGFB (22q12–13) in two cases, whereas losses of AKT1 (14q32.3), IGFR1 (15q25–26), and JUNB (19p13.2) were identified in three cases, and losses of FGR (1p36), ESR (6q25.1), ABL1 (9q34.1), TOP2A (17q21–22), ERBB2 (17q21.2), CCNE1 (19q13.1), and BCR (22q11) were each identified in two cases. In addition, real‐time–polymerase chain reaction detected amplification of BCL2 in 5 of 29 cases. These findings suggest that there are complex but consistent genetic alterations associated with the pathogenesis of PCBCLs. © 2002 Wiley‐Liss, Inc.
Evidence of a role for the INK4 family of cyclin‐dependent kinase inhibitors in ovarian granulosa cell tumors
Authors: Arcellana‐Panlilio Mayi Y. , Egeler R. Maarten , Ujack Eva , Magliocco Anthony , Stuart Gavin C.E. , Robbins Stephen M. , Coppes Max J.
Published: September 2002

Granulosa cell tumors (GCTs) of the ovary are relatively rare and account for <5% of all ovarian cancers. The molecular pathogenesis of these tumors is not well understood. We tested the hypothesis that cyclin‐dependent kinase inhibitors, specifically the inhibitors of the cyclin‐dependent kinase 4 (INK4) family, are targets for altered gene expression in GCTs. The status of RB1, INK4A, INK4B, INK4C, INK4D, and ARF in 13 adult and 2 juvenile ovarian GCTs was determined by reverse transcription–polymerase chain reaction of total RNA and exon‐specific sequencing of genomic DNA. Tumors showing loss of INK4A expression were assayed further by exon‐deletion analysis and methylation‐specific PCR. None of the juvenile tumors demonstrated altered expression, but 7/12 (58%) adult GCTs lacked expression of INK4A, INK4B, or both. In one of these cases, we noted a homozygous deletion of the INK4A locus, and in the remaining tumors we found hypermethylation of the promoter region, a mechanism that can lead to gene inactivation. These data support a role for the INK4 family of CDK inhibitors in the biology of GCTs. © 2002 Wiley‐Liss, Inc.
Regulatory subunit type I‐α of protein kinase A (PRKAR1A): A tumor‐suppressor gene for sporadic thyroid cancer
Authors: Sandrini Fabiano , Matyakhina Ludmila , Sarlis Nicholas J. , Kirschner Lawrence S. , Farmakidis Constantine , Gimm Oliver , Stratakis Constantine A.
Published: September 2002

The tumor‐suppressor gene encoding the cyclic AMP‐dependent protein kinase A type I‐α regulatory subunit PRKAR1A has been mapped to chromosome 17 (17q22–24) and is mutated in Carney complex, a familial neoplasia syndrome that is associated with thyroid tumors. Other genes implicated in cyclic nucleotide‐dependent signaling have been investigated in thyroid tumorigenesis. We studied protein kinase A (PKA) activity in noninherited follicular thyroid adenomas and follicular, papillary, and undifferentiated (anaplastic) thyroid carcinomas. We then examined these and additional thyroid tumors for losses of the 17q22–24 PRKAR1A region, mutations of the PRKAR1A gene, and expression of its peptide product. Total PKA activity was markedly increased in carcinomas over that in adenomas, whereas the ratio of free vs. total PKA activity was decreased in cancer. Consistent with these findings, the 17q22–24 region was frequently lost in cancer but not in benign adenomas. A novel inactivating mutation of the PRKAR1A gene (leading to premature termination of the predicted protein) was found in an aggressive thyroid cancer. The tumor with PRKAR1A gene mutation, as well as the tumors with 17q allelic losses, showed decreased PRKAR1A expression by immunostaining. We conclude that PRKAR1A, the most abundant regulatory subunit of protein kinase A and a principal cyclic AMP‐signaling modulator, acts as a tumor‐suppressor gene in sporadic thyroid cancer. Published 2002 Wiley‐Liss, Inc.
Mycophenolic acid downregulates inducible nitric oxide synthase induction in astrocytes
Authors: Miljkovic Djordje , Samardzic Tatjana , Cvetkovic Ivana , Mostarica Stojkovic Marija , Trajkovic Vladimir
Published: September 2002

Free radical nitric oxide (NO), generated by inducible nitric oxide synthase (iNOS) in astrocytes and macrophages, has been implicated in CNS inflammatory disorders such as multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Mycophenolic acid (MPA), a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibited interferon‐γ (IFN‐γ) + lipopolysaccharide (LPS)‐induced NO production dose‐dependently in astrocytes, but not in macrophages. The effect of MPA was not mediated through interference with IMPDH‐dependent synthesis of iNOS cofactor BH4 and subsequent suppression of iNOS enzymatic activity, as direct BH4 precursor sepiapterin failed to block the action of the drug. However, MPA markedly inhibited IFN‐γ + LPS‐triggered astrocyte expression of mRNA for iNOS and its transcription factor IRF‐1, while the expression of tumor necrosis factor‐α (TNF‐α) gene was not altered. The observed MPA suppression of NO release and iNOS and IRF‐1 induction in astrocytes were efficiently prevented by exogenous guanosine, indicating that the drug acted through reduction of IMPDH‐dependent synthesis of guanosine nucleotides. This IRF‐1‐dependent inhibition of iNOS activation might be partly responsible for the protective effect of MPA in EAE, prompting investigation of its potential use in multiple sclerosis. GLIA 39:247–255, 2002. © 2002 Wiley‐Liss, Inc.
Human cortical glial tumors contain neural stem‐like cells expressing astroglial and neuronal markers in vitro
Authors: Ignatova Tatyana N. , Kukekov Valery G. , Laywell Eric D. , Suslov Oleg N. , Vrionis Frank D. , Steindler Dennis A.
Published: September 2002

Neural stem cells from neurogenic regions of mammalian CNS are clonogenic in an in vitro culture system exploiting serum and anchorage withdrawal in medium supplemented with methyl cellulose and the pleiotropic growth factors EGF, FGF2, and insulin. The aim of this study was to test whether cortical glial tumors contain stem‐like cells capable, under this culture system, of forming clones showing intraclonal heterogeneity in the expression of neural lineage‐specific proteins. The high frequencies of clone‐forming cells (about 0.1–10 × 10−3) in clinical tumor specimens with mutated p53, and in neurogenic regions of normal human CNS, suggest that the ability to form clones in this culture system is induced epigenetically. RT‐PCR analyses of populations of normal brain‐ and tumor‐derived sister clones revealed transcripts for nestin, neuron‐specific enolase, and glial fibrillary acidic protein (GFAP). However, the tumor‐derived clones were different from clones derived from neurogenic regions of normal brain in the expression of transcripts specific for genes associated with neural cell fate determination via the Notch‐signaling pathway (Delta and Jagged), and cell survival at G2 or mitotic phases (Survivin). Moreover, the individual glioma‐derived clones contain cells immunopositive separately for GFAP or neuronal β‐III tubulin, as well as single cells coexpressing both glial and neuronal markers. The data suggest that the latent critical stem cell characteristics can be epigenetically induced by growth conditions not only in cells from neurogenic regions of normal CNS but also in cells from cortical glial tumors. Moreover, tumor stem‐like cells with genetically defective responses to epigenetic stimuli may contribute to gliomagenesis and the developmental pathological heterogeneity of glial tumors. GLIA 39:193–206, 2002. © 2002 Wiley‐Liss, Inc.
Intracellular chloride modulates A‐type potassium currents in astrocytes
Authors: Bekar Lane K. , Walz Wolfgang
Published: September 2002

Application of the GABAA receptor agonist muscimol to astrocytes in situ or in vitro results in a receptor‐mediated Cl− current with a concomitant block of outward K+ currents. The effect on K+ current is largely selective for the inactivating A‐type current. Parallel experiments with various Cl− pipette concentrations show a significant reduction in A‐type current under low Cl− conditions with minimal effect on delayed current. In addition, lower Cl− conditions caused a depolarizing shift of steady‐state inactivation (V1/2, −68 to −57 mV) and activation (V1/2, −5.8 to 34 mV) kinetics of A‐type current only. Cl− had no effect on the time course of inactivation or reactivation kinetics, suggesting the Cl−‐mediated effect is largely on activation kinetics, indirectly affecting steady‐state inactivation. Muscimol application to astrocytes under perforated patch control (gramicidin) displayed a similar block of A‐type current to that of conventional whole cell patch at 40 or 20 mM pipette Cl− concentrations. With barium application under perforated patch conditions, the study of muscimol‐mediated Cl− current in isolation of the effect on K+ currents was possible. This allowed estimation of intracellular Cl− concentration from receptor current reversal information. The average intracellular Cl− concentration was found to be 29 ± 3.2 mM. The effect on activation kinetics and lack of effect on time course of inactivation or reactivation suggest that intracellular anion concentrations have an effect on the K+ channel voltage sensor region. Cl− may modulate K+ currents by altering membrane field potentials surrounding K+ channel proteins. GLIA 39:207–216, 2002. © 2002 Wiley‐Liss, Inc.
High‐affinity GABA uptake in retinal glial (Müller) cells of the guinea pig: Electrophysiological characterization, immunohistochemical localization, and modeling of efficiency
Authors: Biedermann Bernd , Bringmann Andreas , Reichenbach Andreas
Published: September 2002

Glial cells may act as important modulators of neuronal information processing, in particular, via fast uptake of neuronally released transmitters. Here, we characterize the electrogenic γ‐aminobutyric acid (GABA) transporters present in the plasma membranes of Müller (glial) cells of the guinea pig retina and present an estimate of their functional efficiency. The GABA‐evoked whole‐cell currents are voltage‐dependent, with increasing amplitudes and decreasing affinity constants at more negative membrane potentials. The transmembranal GABA transport is concentration‐dependent, with near‐maximal currents at 100 μM GABA, and is dependent on extracellular sodium and chloride ions; the stoichiometry is 1 GABA/2 Na+/1 Cl−. Immunohistochemical labeling and whole‐cell voltage‐clamp records reveal that Müller cells express both GAT‐1 and GAT‐3 (but not GAT‐2), and that the transporter proteins are expressed predominantly at plasma membrane sites that, in situ, are localized in the outer retina where GABA uptake is performed exclusively by Müller cells. When extracellular GABA enters the cell interior, it evokes, via activation of the GABA transaminase, an NAD(P)H fluorescence signal selectively in the distal region of the Müller cells where their mitochondria are located. Using our experimental data, we simulated the GABA clearance from the extracellular space surrounding one Müller cell; these estimates show that a pulse of 100 μM extracellular GABA is fully cleared after 70 ms. It is suggested that Müller cells may be involved in the regulation of GABAergic transmission within the retina by providing a fast termination of GABAergic signaling via their highly efficient GABA uptake. GLIA 39:217–228, 2002. © 2002 Wiley‐Liss, Inc.
Y1 receptor of neuropeptide Y as a glial marker in proliferative vitreoretinopathy and diseased human retina
Authors: Soler M. Valeria Cantó , Gallo Juan E. , Dodds Ricardo A. , Hökfelt Tomas , Villar Marcelo J. , Suburo Angela M.
Published: September 2002

The Y1 receptor of neuropeptide Y (NPY) has been demonstrated in glial cells of astrocytic lineage in vitro. We have studied the immunohistochemical expression of Y1 receptors in the glia of the diseased human retina, in tissue samples obtained after surgery for proliferative vitreoretinopathy. In this condition, glia and other cell types migrate and form epi‐ or subretinal membranes. Both diseased retinas (n = 8) and PVR membranes (n = 43) contained numerous Y1‐immunoreactive cells. In the diseased retina, the Y1 antiserum labeled cells with the morphological radial pattern characteristic of Müller cells, whereas in the membranes, label appeared in a large population of elongate cells, measuring up to 250 μm. In both retina and membranes, double labeling demonstrated that the vast majority of Y1‐immunoreactive cells were also labeled by a glial fibrillary acidic protein (GFAP) antibody, indicating their glial origin. Retinal regions devoid of GFAP immunoreactivity also lacked the Y1 label. None of these markers was detected in Müller cells of normal retina. Y1 immunoreactivity did not co‐localize with smooth muscle actin immunoreactivity, a marker of myofibroblasts. Expression of Y1 receptors would characterize reactive and proliferating glial cells of the diseased retina and could perhaps be involved in the proliferation of injured glial cells causing regrowth of PVR membranes and the consequent secondary retinal detachments. GLIA 39:320–324, 2002. © 2002 Wiley‐Liss, Inc.
Functional melatonin receptors and metabolic coupling in cultured chick astrocytes
Authors: Adachi Akihito , Natesan Arjun K. , Whitfield‐Rucker Melissa G. , Weigum Shannon E. , Cassone Vincent M.
Published: September 2002

Melatonin is an important hormone regulating circadian clocks in birds, but the specific cellular sites of action are not completely known. The present study was designed to determine whether astrocytes derived from chick brain contained functional melatonin receptors. Primary cell cultures of diencephalon astrocytes that express glial fibrillary acidic protein (GFAP), but not neuron‐specific enolase (NSE) immunoreactivity, were employed to determine the cellular distribution and physiological role for the three known receptor subtypes. Saturation and Scatchard analysis of 2‐[125I]iodomelatonin binding demonstrated melatonin receptor binding with a high affinity and a pharmacological profile similar to that obtained from brain. In situ hybridization for receptor subtypes revealed Mel1A and Mel1C receptor mRNA, but not Mel1B. Administration of pharmacological levels of melatonin acutely inhibited forskolin‐stimulated 2‐deoxyglucose (2DG) uptake, while rhythmic administration of physiological levels of melatonin gradually imposed a rhythm in 2DG uptake and of the release of both lactate and pyruvate into the medium. These results indicate that (1) there are functional Mel1A and Mel1C melatonin receptors in astrocyte‐rich cultures, and (2) rhythmic administration of melatonin plays an important role in the regulation of astrocytic metabolic activity. Together, the data suggest that the circadian secretion of melatonin probably plays a role in the global metabolic economy of the avian brain through rhythmic regulation of metabolism in astrocytes. GLIA 39:268–278, 2002. © 2002 Wiley‐Liss, Inc.
Kir potassium channel subunit expression in retinal glial cells: Implications for spatial potassium buffering†
Authors: Kofuji Paulo , Biedermann Bernd , Siddharthan Venkatraman , Raap Maik , Iandiev Ian , Milenkovic Ivan , Thomzig Achim , Veh Rüdiger W. , Bringmann Andreas , Reichenbach Andreas
Published: September 2002

To understand the role of different K+ channel subtypes in glial cell‐mediated spatial buffering of extracellular K+, immunohistochemical localization of inwardly rectifying K+ channel subunits (Kir2.1, Kir2.2, Kir2.3, Kir4.1, and Kir5.1) was performed in the retina of the mouse. Stainings were found for the weakly inward‐rectifying K+ channel subunit Kir4.1 and for the strongly inward‐rectifying K+ channel subunit Kir2.1. The most prominent labeling of the Kir4.1 protein was found in the endfoot membranes of Müller glial cells facing the vitreous body and surrounding retinal blood vessels. Discrete punctate label was observed throughout all retinal layers and at the outer limiting membrane. By contrast, Kir2.1 immunoreactivity was located predominantly in the membrane domains of Müller cells that contact retinal neurons, i.e., along the two stem processes, over the soma, and in the side branches extending into the synaptic layers. The results suggest a model in which the glial cell‐mediated transport of extracellular K+ away from excited neurons is mediated by the cooperation of different Kir channel subtypes. Weakly rectifying Kir channels (Kir4.1) are expressed predominantly in membrane domains where K+ currents leave the glial cells and enter extracellular “sinks,” whereas K+ influxes from neuronal “sources” into glial cells are mediated mainly by strongly rectifying Kir channels (Kir 2.1). The expression of strongly rectifying Kir channels along the “cables” for spatial buffering currents may prevent an unwarranted outward leak of K+, and, thus, avoid disturbances of neuronal information processing. GLIA 39:292–303, 2002. © 2002 Wiley‐Liss, Inc.
CD38 expression and NAD+‐induced intracellular Ca2+ mobilization in isolated retinal Müller cells
Authors: Esguerra Manuel , Miller Robert F.
Published: September 2002

Müller cells of the vertebrate retina are prominent radial glia that provide essential support to sustain homeostasis of the tissue, including redistribution of external potassium, uptake and metabolism of neurotransmitters, and secretion of factors that stabilize the retina. Meeting this diversity of functional supports requires that Müller cells express numerous receptors, transporters, enzymes, and tissue factors. In this study, we provide evidence that adds to the dimensions of Müller cell function by demonstrating a unique relationship between external NAD+ and the mobilization of internal calcium, expressed in the form of calcium waves. The cellular mechanism that supports internal mobilization of calcium appears to depend on a complex multifunctional ectoenzyme, CD38, which converts NAD+ into the intracellular Ca2+‐mobilizing second‐messenger cyclic ADP‐ribose (cADPR) and could function as a detector for extracellular NAD+, thus providing a novel signal detection system for evaluating the extracellular environment. Our results are consistent with a model of intracellular Ca2+ mobilization in which membrane‐bound CD38 binds extracellular NAD+ and triggers intracellular Ca2+ waves either by direct conversion of NAD+ to cADPR or by activating intracellular cADPR synthesis. Our preliminary results indicate that the Ca2+ waves induced by external NAD+ propagate through an internal pathway that depends on the activation of ryanodine receptors, which appear to be distributed throughout the Müller cell cytosol. Because NAD+ is likely to be enhanced when cells are stress or damaged, CD38 could enable Müller cells to detect NAD+ under these circumstances and respond appropriately. Alternatively, NAD+ could also represent a novel extracellular, paracrine function that mediates signaling between glial cells and/or other cellular elements of the retina. GLIA 39:314–319, 2002. © 2002 Wiley‐Liss, Inc.
Motor cortex activation is related to force of squeezing
Authors: Cramer Steven C. , Weisskoff Robert M. , Schaechter Judith D. , Nelles Gereon , Foley Mary , Finklestein Seth P. , Rosen Bruce R.
Published: September 2002

Primate studies have demonstrated that motor cortex neurons show increased activity with increased force of movement. In humans, this relationship has received little study during a power grip such as squeezing, and has previously only been evaluated across a narrow range of forces. Functional MRI was performed in eight healthy subjects who alternated between rest and right hand squeezing at one of three force levels. During scanning, motor performances were recorded using a dynamometer. At each force level, activation volume was measured within left sensorimotor cortex, right sensorimotor cortex, and a midline supplementary motor area. In left sensorimotor cortex, % signal change was also assessed. The range of force generated across the three force levels varied from 4.9 N to 276 N. In left sensorimotor cortex, activation volume increased significantly with greater force. The % signal change also increased with greater force and correlated closely with activation volume. In supplementary motor area, activation volume increased significantly with increasing force, but with greater intersubject variability. In right sensorimotor cortex, a trend for larger activation volumes with greater force did not reach significance. The laterality index, an expression of the relative degree of contralateral vs. ipsilateral sensorimotor cortex activation, did not change across the three force levels. Increased force of squeezing is associated with increased contralateral sensorimotor cortex and supplementary motor area activation. This relationship was found across the full spectrum of forces that the human hand is capable of generating. Use of a valid, reliable method for assessing motor behavior during functional MRI may be important to clinical applications. Hum. Brain Mapping 16:197–205, 2002. © 2002 Wiley‐Liss, Inc.