bluuebunny/crossref_metadata_2025 huggingface dataset:
αCaMKII and NMDA‐Receptor Subunit Expression in Epileptogenic Cortex from Human Periventricular Nodular Heterotopia
Authors: Battaglia Giorgio , Pagliardini Silvia , Ferrario Arianna , Gardoni Fabrizio , Tassi Laura , Setola Veronica , Garbelli Rita , LoRusso Giorgio , Spreafico Roberto , Di Luca Monica , Avanzini Giuliano
Published: March 2003

Summary:  Purpose: Periventricular nodular heterotopia (PNH) is the most common human brain dysgenesis, very frequently characterized by focal drug‐resistant epilepsy. To understand the cellular mechanisms underlying its intrinsic hyperexcitability, we investigated the expression of glutamate‐receptor subunits and related proteins in four human patients affected by PNH.

Methods: PNH was diagnosed by means of magnetic resonance imaging. The epileptogenic area was revealed by depth electrode recordings and removed during epilepsy surgery. Sections from the removed cerebral tissue were analyzed by means of immunocytochemistry (ICC), with antibodies directed against N‐methyl‐d‐aspartate (NMDA)‐receptor subunits, the α subunit of the Ca2+/calmodulin‐dependent kinase II (αCaMKII), and its active phosphorylated form.

Results: The ICC data demonstrated that the subcortical heterotopic nodules were consistently characterized by lower expression of αCaMKII and its activated form. In more pronounced cases (i.e., when the extension of the nodules to the neocortex determined clear layering abnormalities), the heterotopic tissue also was characterized by a decreased expression of NMDA‐receptor subunits, which was particularly evident in the dendritic compartment.

Conclusions: These data suggest the existence of an alteration of αCaMKII and the NMDA‐receptor complex in the epileptogenic brain tissue of human PNH, which may play a role in the basic mechanisms of hyperexcitability associated with this brain dysgenesis.
Impaired M‐Current and Neuronal Excitability
Authors: Okada Motohiro , Wada Kazumaru , Kamata Akihisa , Murakami Takuya , Zhu Gang , Kaneko Sunao
Published: March 2003

Summary:  Purpose: Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ‐related K+‐channel (KCNQ‐channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ‐related M‐ current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability.

Methods: To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64‐channel multielectrode dish (MED64) system for novel two‐dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP).

Results: Dup996, a selective KCNQ‐channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The γ‐aminobutyric acid (GABA)A‐receptor antagonist, bicuculline, enhanced their propagation, whereas α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)/glutamate‐receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABAA‐receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX.

Conclusions: These results suggest that the occurrence of BFNC cannot be produced by KCNQ‐channel dysfunction alone but by reciprocal action between impaired KCNQ channel and the other unknown.
Epidemiology of Epilepsy in India
Authors: Bharucha N. E.
Published: March 2003

Summary: The article briefly reviews literature pertinent to the incidence, prevalence, prognosis, etiology, and treatment gap of epilepsy in India. Despite defective methodology, Indian studies have shown prevalence rates comparable with those from other countries. No incidence studies exist. Prognosis for those with epilepsy is worse in developing countries. The role of infection, especially neurocysticercosis, in the etiology of epilepsy has still to be fully worked out, as must the relative contributions of the other known etiological factors. Neuroimaging is needed to calculate attributable risk. Reasons for the treatment gap are discussed briefly, pointing out that in India, people seek alternative forms of treatment concurrently. The occurrence and effects of stigma are mentioned. The article ends with the author's opinion on how and where the epidemiology of epilepsy should proceed in the future.
Research in Epilepsy: Development Priorities for Developing Nations
Authors: Krishnamoorthy E. S. , Satishchandra P. , Sander J. W.
Published: March 2003

Summary:  Purpose: To identify research priorities in epilepsy for developing nations.

Methods: A panel discussion with audience participation at the Indo‐U.K. Workshop on Epilepsy. This included short presentations by panelists, the presentation of a research proposal, and debate on research priorities.

Results: The need to focus on primary‐care populations; to use a multi‐centre random block design; to incorporate rural areas and a service component; to study incidence, natural history, and aetiology; to focus on problems, such as cysticercosis, and to adopt a comprehensive public health–centred approach in doing so; to study disorders of local interest, such as hot water epilepsy; to pilot both pharmacological and nonpharmacological interventions; to incorporate comprehensive measures of cognition, behaviour, and psychosocial outcome in all studies; and to examine the role of novel diagnostic tools (imaging for example) and therapy (surgery for example) on cost were all outlined as priority areas.

Discussion: There is a felt need for greater and better‐quality research output from the developing world. The development of uniform research protocols, the twinning of developed and developing nations for research, and training of developing nations' personnel are likely to increase research output in the years that come.
The GABAA Receptor: Subunit-Dependent Functions and Absence Seizures
Authors: Wong C. Guin-Ting , Snead O. Carter
Published: March 2003

GABAA receptors on thalamic relay and reticular (nRT) neurons play a critical role in thalamocortical mechanisms underlying absence seizures. Studies with absence seizure-prone rats and transgenic mice have taken advantage of differences in the subunit compositions of GABAA receptors in the two thalamic cell populations to clarify thalamocortical rhythm generating mechanisms and explain the antiabsence activity of benzodiazepines. The relevance of this work is highlighted by the recent finding of a mutation in the GABAA receptor γ2 subunit in a family with childhood absence seizures.
Sudden Unexplained Death in Epilepsy
Authors: Sperling Michael R.
Published: March 2003

Sudden unexplained death in epilepsy (SUDEP) accounts for 7–17% of deaths among people with epilepsy. Both cardiac and pulmonary derangement have been postulated as proximate causes. Patients with uncontrolled seizures are at greatest risk for SUDEP, and experiencing tonic-clonic seizures, taking multiple antiepileptic drugs and having coexisting neurologic disease further increase the risk.
Treatment of Epilepsy in the Elderly
Authors: Leppik Ilo E.
Published: March 2003

The diagnosis and treatment of seizures and epilepsy in the elderly will become a greater concern because the number of elderly is rapidly increasing, the complexities of diagnosis are more challenging, and drug therapy is affected by interactions and altered pharmacokinetics.
A Rare Cause of Mitral Insufficiency:
Authors: Baran Türker , Küçükoğlu M. Serdar , Ökçün Barış , Çetin Gürkan , Hatemi Ali Can , Üner Sinan
Published: March 2003

Anomalous muscular bands have been seen in the left ventricle and right and left atria. Although the significance of left ventricular false tendons and right atrial anomalous muscular bands have been reported previously, the importance of anomalous muscular bands observed in the left atrium is not clearly defined. They have been found to be associated with Chiari's network, patent foramen ovale, and supraventricular arrhythmias. We describe a left atrial anomalous band causing mitral valve prolapse and mitral regurgitation. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Aortokoronare Bypassdysfunktion – Wertigkeit klinischer, laborchemischer und elektrokardiographischer Parameter
Authors: Weber T. , Berent R. , Kirchgatterer A. , Auer J. , Mayr H. , Schwarz C. , Maurer E. , Punzengruber C. , Hartl P. , Eber B.
Published: March 2003

Zusammenfassung: Ein Wiederauftreten kardialer Beschwerden nach aortokoronarer Bypassoperation (ACBP‐Op) ist häufig durch eine Dysfunktion der Bypässe bedingt. Die vorliegende Arbeit untersucht, welche Parameter mit der Langzeitfunktion der arteriellen und venösen Bypässe korrelieren.  Es wurden alle im Jahre 1998 an unserer Abteilung koronarangiographierten Patienten mit Zustand nach ACBP‐Op inkludiert (n = 163 Patienten, mittleres Alter 67 Jahre, mittleres Intervall seit der Operation 79 Monate, insgesamt 341 venöse Bypässe [VBP] mit 386 peripheren Anastomosen sowie 85 Arteria‐mammaria‐Bypässe [LIMA]). Die Gewinnung der Daten erfolgte durch eine retrospektive Analyse der Krankengeschichten. Für die statistische Auswertung wurde der Wilcoxon‐Mann‐Whitney‐U‐Test herangezogen.  Die stenosefreie Offenheit der LIMA betrug nach durchschnittlich 53 Monaten 92 %. Bei nur 2 % der Patienten wurde eine Dysfunktion der LIMA als ursächlich für die Klinik angesehen.  Die Offenheit der VBP nahm mit der Zeit ab (nach 5 Jahren 74 % stenosefrei, nach 5 – 10 Jahren 56 %, nach über 10 Jahren 35 %, p < 0,01). Es bestand ein klarer Zusammenhang der Funktion venöser Bypässe mit der Klinik (43 % stenosefrei bei akuten Koronarsyndromen, 57 % bei Belastungs‐Angina‐pectoris [p = 0,08] und 86 % bei atypischer Angina pectoris [p < 0,0001 für die Unterscheidung von den beiden anderen Gruppen]), dem Ruhe‐EKG (65 % stenosefrei bei normalen ST‐Strecken, 49 % stenosefrei bei pathologischen Endstrecken, p < 0,01), dem Body‐Mass‐Index (70 % stenosefreie Bypässe bei Normalgewicht vs. 56 % bei Adipositas, p = 0,05) sowie der Blutkörperchensenkungsgeschwindigkeit nach 2 Stunden (bei Blutkörperchensenkungsgeschwindigkeit (BSG < 20 mm Offenheit der Venenbypässe 79 % vs. 64 % bei BSG > 49 mm, p = 0,02).  Die Funktion venöser Bypässe nach ACBP‐Operation hängt in erster Linie vom Intervall seit dem Eingriff ab. Weiters zeigen sich Zusammenhänge mit der Klinik, dem Ruhe‐EKG, dem Body‐Mass‐Index sowie der BSG als möglichem Marker einer chronischen Entzündung bei der Bypass‐Atherosklerose. Somit scheinen inflammatorische Vorgänge eine wichtige Rolle für die Dysfunktion von venösen Bypässen zu spielen.
Stellenwert eines strukturierten Befundschemas zur Interpretation der Nebenschilddrüsenszintigraphie bei primärem Hyperparathyreoidismus
Authors: Zettinig G. , Prager G. , Kurtaran A. , Kaserer K. , Czerny C. , Dudczak R. , Niederle B.
Published: March 2003

Zusammenfassung: Obwohl die Tc‐99 m Sestamibi‐Szintigraphie als beste Methode zur präoperativen Lokalisationsdiagnostik angesehen wird, erreichen Sensitivität und positiver Vorhersagewert der Methode nicht 100 %. Ziel dieser Untersuchung war es, herauszufinden, ob durch ein vierstufiges Befundschema die diagnostische Wertigkeit der Zweiphasen‐Tc‐99 m Sestamibi‐Szintigraphie zur präoperativen Lokalisationsdiagnostik bei primärem Hyperparathyreoidismus verbessert werden kann.  Es wurden die Befunde von 35 Zweiphasen‐Tc‐99 m Sestamibi‐Szintigraphien von Patienten mit primärem Hyperparathyreoidismus analysiert und mit Sonographie und Operationsergebnis verglichen. Die Szintigramme wurden nach einem vierstufigen Befundschema interpretiert: Gruppe A – typisches Bild einer Eindrüsenerkrankung, Gruppe B – mit Eindrüsenerkrankung vereinbar, Gruppe C – primär Mehrdrüsenerkrankung, Gruppe D – inkonklusiv.  Gruppe A umfaßte 23 Patienten. Bei allen lokalisierte die Szintigraphie sowohl Seite als auch Lokalisation des Adenom korrekt. Aus dieser Gruppe waren 21/23 sonographische Befunde korrekt und 2/23 falsch positiv. In Gruppe B fielen 10 Scans; 7/10 lokalisierten sowohl Seite als auch Lokalisation korrekt, bei 2/10 Scans konnte lediglich die Seite angegeben werden. Eine Vierdrüsenhyperplasie wurde fälschlich als „vereinbar mit Eindrüsenerkrankung links kaudal” klassifiziert. Die sonographischen Befunde der Patienten aus dieser Gruppe waren in 8/10 Fällen korrekt und bei je 1/10 Patienten falsch positiv bzw. falsch negativ. Kein Scan wurde primär als Mehrdrüsenerkrankung (Gruppe C) gewertet und 2 Scans wurden als „inkonklusiv” (Gruppe D) klassifiziert. In beiden Patienten aus Gruppe D konnte sonographisch das Adenom korrekt lokalisiert werden.  Unsere Daten weisen darauf hin, daß bei Vorliegen eines typischen szintigraphischen Bildes (Gruppe A) aufgrund des hohen positiven Vorhersagewertes bei minimal‐invasiver chirurgischer Technik primär der szintigraphische und nicht der sonographische Befund zur präoperativen Lokalisationsdiagnostik herangezogen werden soll.
Modulation of Inflammation by Vasoactive Intestinal Peptide and Bombesin: Lack of Effects on Neutrophil Apoptosis
Authors: Djanani Angela M. , Kähler Ch. M.
Published: March 2003

Summary: Inhibition of neutrophil apoptosis has been identified as a prominent feature in chronic inflammation, parenchymal damage, and unresolved organ dysfunction. Lung injury animal models suggest that the neuropeptides vasoactive intestinal peptide and bombesin are protective. Therefore, in vitro effects of VIP and bombesin on apoptosis of normal human neutrophils were tested. For measuring effects on cell survival and apoptosis, trypan dye exclusion, colorimetric MTT assay to assess cell survival, and caspase‐3 assay and annexin‐V binding for analysing apoptosis rates were used. Foetal calf serum, Fas ligand, and tumour necrosis factor‐alpha served as modulatory control agents; survival‐promoting and apoptosis‐inducing activities of the respective agents were confirmed. Vasoactive intestinal peptide and bombesin, however, failed to significantly affect cell death in neutrophils. Data suggest that direct regulation of neutrophil apoptosis is unlikely to be among the mechanisms of lung‐protective actions of VIP and bombesin.
Pharmacokinetics of Ciprofloxacin in Patients with Acute Renal Failure Undergoing Continuous Venovenous Haemofiltration: Influence of Concomitant Liver Cirrhosis
Authors: Bellmann R. , Egger Petra , Gritsch W. , Bellmann‐Weiler Rosa , Joannidis M. , Dunzendorfer St. , Wiedermann Ch. J.
Published: March 2003

Summary: To determine an adequate dosage of ciprofloxacin in critically ill medical patients on continuous venovenous haemofiltration, we studied the pharmacokinetics of ciprofloxacin in eight critically ill medical patients with renal failure treated with continuous venovenous haemofiltration using polysulfone membranes. Three of those patients also presented with severe liver dysfunction. For comparison, three patients with approximately normal renal function and two patients with impaired renal function were included. During haemofiltration, plasma concentrations of ciprofloxacin were variable. In all critically ill patients ciprofloxacin elimination was significantly slowed; the mean half‐life was similarly prolonged to about 14 h in patients on haemofiltration and those with approximately normal renal function. In critically ill patients with impaired renal function not on haemofiltration, the mean half‐life was longest. Ciprofloxacin clearance by haemofiltration was a quarter of the total clearance. Although a unique dose recommendation can hardly be made because of the high variability of pharmacokinetics during haemofiltration, a daily dose of 800 mg (400 mg b. i. d.) in average can be regarded as appropriated for reaching a target plasma concentration of 2 to 3 µg/mL (mean concentration). Because the half‐life of ciprofloxacin was further prolonged by the presence of liver cirrhosis, the dose should be reduced to 600 mg in patients on haemofiltration with concomitant severe liver dysfunction.
18F‐Fluorodeoxyglukose‐Positronenemissionstomographie zur Diagnostik des Bronchialkarzinoms
Authors: Bares R. , Eschmann S. M. , Friedel G.
Published: March 2003

Zusammenfassung: Die Positronenemissionstomographie ist ein nuklearmedizinisches Untersuchungsverfahren, welches mit hoher räumlicher Auflösung die biochemische Charakterisierung menschlicher Gewebe erlaubt. Durch bildliche Darstellung von Stoffwechsel‐ oder Transportraten lassen sich Bronchialkarzinome, deren Metastasen und Rezidive nachweisen, auch ohne daß entsprechende morphologische Veränderungen vorliegen. Dies kann zu einer Verbesserung der Differentialdiagnose pulmonaler Rundherde sowie der präoperativen Ausbreitungsdiagnostik nicht‐kleinzelliger Bronchialkarzinome beitragen, wie inzwischen in zahlreichen Studien belegt wurde. Neue Anwendungsmöglichkeiten ergeben sich durch Proliferations‐ und Hypoxiemarker, von denen Informationen über die individuelle Prognose, insbesondere das Ansprechen einer späteren Radiotherapie, erhofft werden.
Selection for developmental time in bean weevil (Acanthoscelides obtectus): correlated responses for other life history traits and genetic architecture of line differentiation
Authors: Šešlija Darka , Tucić Nikola
Published: March 2003

In this article we investigate the direct and correlated responses to selection for developmental time in order to discern differences between lines in several preadult and adult life history traits ofAcanthoscelides obtectus(Coleoptera, Bruchidae). Selection for fast development was about five times as effective as selection for slow development, as judged by realized heritabilities. The correlated responses on the following life‐history traits were studied: egg size, hatching success, embryonic developmental time, egg‐to‐adult viability, body weight, first day of egg laying, total fecundity, and longevity. Analyses of the terminal generation of selection showed that all life history traits examined, except for hatching success, were affected by selection. The findings suggest that body weight, total fecundity, and longevity traded off to preadult developmental time. Unlike the adult traits, none of the preadult traits showed negative correlations with developmental time. We also present data concerning the underlying genetic basis that produces changes in preadult developmental time, body weight, and egg‐to‐adult viability in the lines selected for fast and slow preadult developmental time. Additive‐dominance genetic architecture for both preadult developmental time and body weight was found. In addition, it appears that the responses to selection for preadult developmental time involved between 10 and 28 loci, which were correlated with at least one to four genes for body weight. Epistasis makes a significant contribution to genetic divergence between fast and slow selected lines only with respect to preadult viability. The observed levels of dominance and epistasis underscore the important role of nonadditive genetic effects to the adaptive diversifications of bean weevil populations.
Preweaning enrichment has no lasting effects on adult hippocampal neurogenesis in four‐month‐old mice
Authors: Kohl Z. , Kuhn H. G. , Cooper‐Kuhn C. M. , Winkler J. , Aigner L. , Kempermann G.
Published: March 2003

Since both living in an enriched environment and physical activity stimulate hippocampal neurogenesis in adult mice, we endeavored to examine whether preweaning enrichment, a sensory enrichment paradigm with very limited physical activity, had similar effects on neurogenesis later in life. Mice were removed from the dams for periods of increasing length from postnatal day 7 to 21, and exposed to a variety of sensory stimuli. At the age of 4 months, significant differences could be found between previously enriched and non‐enriched animals when spontaneous activity was monitored. Enriched mice moved longer distances, and spent more time in a defined center zone of the open field. Adult neurogenesis was examined by labeling proliferating cells in the dentate gyrus with bromodeoxyuridine (BrdU). Cell proliferation, survival of the newborn cells, and net neurogenesis were similar in both groups. Volumetric measurements and stereological assessment of total granule cell counts revealed no difference in size of the dentate gyrus between both groups. Thus, in contrast to postweaning enrichment, preweaning enrichment had no lasting measurable effect on adult neurogenesis. One of the parameters responsible for this effect might be the lack of physical activity in preweaning enrichment. As physical activity is an integral part of postweaning enrichment, it might be a necessary factor to elicit a neurogenic response to environmental stimuli. The result could also imply that baseline adult hippocampal neurogenesis is independent of the changes induced by preweaning enrichment and might not contribute to the sustained types of plasticity seen in enriched animals.
Harnessing the mouse to unravel the genetics of human disease
Authors: Phillips T. J. , Belknap J. K. , Hitzemann R. J. , Buck K. J. , Cunningham C. L. , Crabbe J. C.
Published: March 2003

Complex traits, i.e. those with multiple genetic and environmental determinants, represent the greatest challenge for genetic analysis, largely due to the difficulty of isolating the effects of any one gene amid the noise of other genetic and environmental influences. Methods exist for detecting and mapping the Quantitative Trait Loci (QTLs) that influence complex traits. However, once mapped, gene identification commonly involves reduction of focus to single candidate genes or isolated chromosomal regions. To reach the next level in unraveling the genetics of human disease will require moving beyond the focus on one gene at a time, to explorations of pleiotropism, epistasis and environment‐dependency of genetic effects. Genetic interactions and unique environmental features must be as carefully scrutinized as are single gene effects. No one genetic approach is likely to possess all the necessary features for comprehensive analysis of a complex disease. Rather, the entire arsenal of behavioral genomic and other approaches will be needed, such as random mutagenesis, QTL analyses, transgenic and knockout models, viral mediated gene transfer, pharmacological analyses, gene expression assays, antisense approaches and importantly, revitalization of classical genetic methods. In our view, classical breeding designs are currently underutilized, and will shorten the distance to the target of understanding the complex genetic and environmental interactions associated with disease. We assert that unique combinations of classical approaches with current behavioral and molecular genomic approaches will more rapidly advance the field.
Neue Entwicklungen in der systemischen Psoriasistherapie
Authors: Friedrich Markus , Sterry Wolfram , Asadullah Khusru
Published: March 2003

Die etablierten systemischen Therapien zur Behandlung der Psoriasis sind durch ein hohes Nebenwirkungspotential gekennzeichnet. Fortschritte im Verständnis der Pathophysiologie der Psoriasis, als T‐Zell‐vermittelte Dermatose, eröffnen Möglichkeiten für neue, gezieltere therapeutische Ansätze. Diese immunologischen Behandlungsstrategien zielen im wesentlichen auf eine Inhibition/Depletion von aktivierten T‐Lymphozyten, eine Hemmung der Antigenpräsentation und damit auf die Regulation der T‐Zellaktivierung, die Hemmung der Adhäsion inflammatorischer Zellen, die Hemmung der Wirkung von proinflammatorischen Mediatoren und die Applikation von antiinflammatorischen Zytokinen ab. Der Artikel gibt eine Übersicht über diese neuen systemischen Therapieansätze. Die klinischen Ergebnisse aus den ersten Anwendungen sind heterogen. Einige der hier diskutierten Ansätze könnten zu neuen zugelassenen Medikamenten zur Behandlung der Psoriasis führen und so die bestehenden therapeutischen Optionen ergänzen oder aber sogar auch ablösen. Die Ergebnisse aus den experimentellen Therapieversuchen tragen zudem auch zum besseren Verständnis der Erkrankung bei. So lernen wir, welche Mechanismen eine mehr oder weniger große Bedeutung bei der Erkrankung haben, was wiederum Impulse für noch gezieltere pharmakologische Beeinflussungen geben wird.
Characterization of a New γTuRC Subunit with WD Repeats
Authors: Gunawardane Ruwanthi N. , Martin Ona C. , Zheng Yixian
Published: March 2003

The γ-tubulin ring complex (γTuRC), consisting of multiple protein subunits, can nucleate microtubule assembly. Although many subunits of the γTuRC have been identified, a complete set remains to be defined in any organism. In addition, how the subunits interact with each other to assemble into γTuRC remains largely unknown. Here, we report the characterization of a novel γTuRC subunit, Drosophila gamma ring protein with WD repeats (Dgp71WD). With the exception of γ-tubulin, Dgp71WD is the only γTuRC component identified to date that does not contain the grip motifs, which are signature sequences conserved in γTuRC components. By performing immunoprecipitations after pair-wise coexpression in Sf9 cells, we show that Dgp71WD directly interacts with the grip motif–containing γTuRC subunits, Dgrips84, 91, 128, and 163, suggesting that Dgp71WD may play a scaffolding role in γTuRC organization. We also show that Dgrips128 and 163, like Dgrips84 and 91, can interact directly with γ-tubulin. Coexpression of any of these grip motif–containing proteins with γ-tubulin promotes γ-tubulin binding to guanine nucleotide. In contrast, in the same assay Dgp71WD interacts with γ-tubulin but does not facilitate nucleotide binding.
Sequential Entry of Components of Gene Expression Machinery into Daughter Nuclei
Authors: Prasanth Kannanganattu V. , Sacco-Bubulya Paula A. , Prasanth Supriya G. , Spector David L.
Published: March 2003

In eukaryotic cells, RNA polymerase II (RNA pol II) transcription and pre-mRNA processing are coordinated events. We have addressed how individual components of the transcription and pre-mRNA processing machinery are organized during mitosis and subsequently recruited into the newly formed daughter nuclei. Interestingly, localization studies of numerous RNA pol II transcription and pre-mRNA processing factors revealed a nonrandom and sequential entry of these factors into daughter nuclei after nuclear envelope/lamina formation. The initiation competent form of RNA pol II and general transcription factors appeared in the daughter nuclei simultaneously, but prior to pre-mRNA processing factors, whereas the elongation competent form of RNA pol II was detected even later. The differential entry of these factors rules out the possibility that they are transported as a unitary complex. Telophase nuclei were competent for transcription and pre-mRNA splicing concomitant with the initial entry of the respective factors. In addition, our results revealed a low turnover rate of transcription and pre-mRNA splicing factors during mitosis. We provide evidence to support a model in which the entry of the RNA pol II gene expression machinery into newly forming daughter nuclei is a staged and ordered process.
A Novel Golgi Membrane Protein Is a Partner of the ARF Exchange Factors Gea1p and Gea2p
Authors: Chantalat Sophie , Courbeyrette Rëgis , Senic-Matuglia Francesca , Jackson Catherine L. , Goud Bruno , Peyroche Anne
Published: March 2003

The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserved regulators of membrane dynamics and protein trafficking. The interactions of large ARF GEFs with cellular membranes for localization and/or activation are likely to participate in regulated recruitment of ARF and effectors. However, these interactions remain largely unknown. Here we characterize Gmh1p, the first Golgi transmembrane-domain partner of any of the high-molecular-weight ARF-GEFs. Gmh1p is an evolutionarily conserved protein. We demonstrate molecular interaction between the yeast Gmh1p and the large ARF-GEFs Gea1p and Gea2p. This interaction involves a domain of Gea1p and Gea2p that is conserved in the eukaryotic orthologues of the Gea proteins. A single mutation in a conserved amino acid residue of this domain is sufficient to abrogate the interaction, whereas the overexpression of Gmh1p can compensate in vivo defects caused by mutations in this domain. We show that Gmh1p is an integral membrane protein that localizes to the early Golgi in yeast and in human HeLa cells and cycles through the ER. Hence, we propose that Gmh1p acts as a positive Golgi-membrane partner for Gea function. These results are of general interest given the evolutionary conservation of both ARF-GEFs and the Gmh proteins.
Pex15p of Saccharomyces cerevisiae Provides a Molecular Basis for Recruitment of the AAA Peroxin Pex6p to Peroxisomal Membranes
Authors: Birschmann Ingvild , Stroobants An K. , van den Berg Marlene , Schäfer Antje , Rosenkranz Katja , Kunau Wolf-H. , Tabak Henk F.
Published: March 2003

The gene products (peroxins) of at least 29 PEX genes are known to be necessary for peroxisome biogenesis but for most of them their precise function remains to be established. Here we show that Pex15p, an integral peroxisomal membrane protein, in vivo and in vitro binds the AAA peroxin Pex6p. This interaction functionally interconnects these two hitherto unrelated peroxins. Pex15p provides the mechanistic basis for the reversible targeting of Pex6p to peroxisomal membranes. We could demonstrate that the N-terminal part of Pex6p contains the binding site for Pex15p and that the two AAA cassettes D1 and D2 of Pex6p have opposite effects on this interaction. A point mutation in the Walker A motif of D1 (K489A) decreased the binding of Pex6p to Pex15p indicating that the interaction of Pex6p with Pex15p required binding of ATP. Mutations in Walker A (K778A) and B (D831Q) motifs of D2 abolished growth on oleate and led to a considerable larger fraction of peroxisome bound Pex6p. The nature of these mutations suggested that ATP-hydrolysis is required to disconnect Pex6p from Pex15p. On the basis of these results, we propose that Pex6p exerts at least part of its function by an ATP-dependent cycle of recruitment and release to and from Pex15p.
Guidelines for the design of robotic gripping systems
Authors: Causey Greg
Published: March 2003

This paper describes guidelines for the design of grippers for use in modular manufacturing workcells. Gripper design is an important and often overlooked aspect of the design of a complete assembly system. Here, guidelines are presented which can be applied to a wide variety of grippers. Guidelines are divided into three major categories: those that improve system throughput, those that increase system reliability, and those that decrease cost. Designs of several grippers, currently being used in a modular manufacturing workcell, are presented as examples of the application of the guidelines to real world problems.
A non‐linear sensitivity analysis of cross‐country growth regressions
Authors: Kalaitzidakis Pantelis , Mamuneas Theofanis P. , Stengos Thanasis
Published: March 2003

We extend the sensitivity analysis of cross‐country growth regressions of Levine and Renelt (1992) by introducing a semi‐parametric formulation of their regression function. Our results differ from theirs in how certain policy variables affect growth rates. We find that distortion variables, such as the standard deviation of gross domestic credit and inflation and real exchange rate distortions, have a robust negative effect on growth. JEL Classification: O47, C14

Une analyse de sensibilité non‐linéaire des régressions de croissance pour divers pays. Les auteurs utilisent une formulation semi‐paramétrique des équations de croissance de Levine et Renelt (1992) pour divers pays afin de rendre leur analyse de sensibilité plus compréhensive. Les résultats different de ceux de Levine et Renelt en ce que certaines variables de politique affectent les taux de croissance. On découvre que certains facteurs comme l'écart type du crédit intérieur brut et de l'inflation, et des distorsions des taux de change réels, ont un effet négatif important sur la croissance.
Technology and the demand for skills in Canada: an industry‐level analysis
Authors: Gera Surendra , Gu Wulong , Lin Zhengxi
Published: March 2003

In this paper we examine the effect of technological change on the relative demand for skilled workers across Canadian industries. We find that skill upgrading at the aggregate level is less evident in Canada than in the United States and other industrialized economies over the 1981–94 period. Behind this overall trend on skill upgrading, there is substantial variation across industrial sectors. Consistent with the skill‐biased technological change hypothesis, the technology indicators – the stock of patents used by the industry and the age of capital stock – are found to be significantly correlated with skill intensity. JEL Classification: E24, J23, J31, O33

Technologie et demande de travailleurs qualifiés: une analyse au niveau de l'industrie. Ce mémoire examine les effets du changement technologique sur la demande de travailleurs qualifiés dans les industries canadiennes. On montre que l'amélioration du niveau des compétences au niveau agrégé est moins claire au Canada qu'aux Etats‐Unis et dans les autres économies industrialisées au cours de la période 1981–94. Derrière cette tendance générale, il y a cependant des variations importantes entre les secteurs industriels. On trouve que les indicateurs de niveau technologique (le stock de brevets, l'âge du stock de capital) sont co‐reliés positivement au degré d'intensité d'utilisation des compétences – ce qui s'arrime bien avec l'hypothèse du changement technologique liéà une amélioration du niveau des compétences
Ethnic Conflict and Urban Redevelopment in Downtown Beirut
Authors: Nagle Caroline
Published: March 2003

The concept of globalization has become almost ubiquitous in contemporaryaccounts of urban development and cultural transformations. In these accounts, questions of globalization, urbanization, and ethnicity increasingly intersect. But this burgeoning literature, while laudably integrating cultural concerns into political‐economic understandings of globalization, tends to rely on a dualistic sense of scale which treats localities as points of reaction to and resistance against global forces. Ethnicity and identity, situated in a rigid local scale, are reduced to either primordial communal sentiments or commodified symbols in the global economy. This paper advocates a conceptualization of ethnicity and locality not in opposition to the global, but in relation to social, political, and economic relationships that operate within and beyond particular spaces. These arguments are illustrated with the case of downtown Beirut. Beirut's reconstruction epitomizes the commodification of place identities. But the marketing of place identity is significant beyond the immediate investment goals of the city's investors. Indeed, this new identity and the new Beirut have been generated in a hotly‐contested terrain of sectarian allegiances and state legitimacy. The redevelopment of Beirut and the re‐creation of Lebanese identity are embedded not only in the imperatives of the contemporary global economy, but also in the troublesome legacies of a violent past and in the day‐to‐day lives of the Lebanese populace.
Sacred Space in Conflict in India: The Babri Masjid Affair
Authors: Bacchetta Paola
Published: March 2003

The focus of this paper is on the demolition of a sacred space, the Babri Masjid, a sixteenth century mosque, in Ayodhya, India, in December 1992, an illegal albeit well‐organized act by the Hindu right. Drawing on postcolonial theory, and feminist geographical theory, and using a discourse analysis primarily of Hindu nationalist texts, and of significant action as text, the author examines the strategic construction and deployment of cultural meanings pertaining to space, and the engagement of social actors on that basis, towards political, violent ends. The author argues, firstly, that Hindu nationalist ideologues, notwithstanding pretensions to Hindu ‘authenticity,’ make use of Western thought to rewrite Hindu‐Muslim relations in antagonistic terms, and to signify these oppositional relations through sacred spatialities (mosque, temple, and Motherland as the body of the mother goddess Bharatmata). Secondly, in this framework, the Babri Masjid, one particular mosque, became a site of conflict because Hindu nationalists were able to transform it into a symbol of Muslim military invasions and Muslim male sexual aggression against Hindu femininity (as Motherland and Hindu women's bodies). Thirdly, Hindu nationalists, through a well‐orchestrated campaign, were able to convince a wider audience that these violations could only be avenged by the demolition of the Babri mosque (while also unofficially and inadvertently targeting Muslim women's bodies for sexual violation). Finally, this analysis should have wider implications for understanding the place of space, gender, sexuality, and sexual violation, in religio‐political and ethnic conflicts elsewhere.
Reasoning about Locations in Theory and Practice
Authors: Myers Karen L. , Wilkins David E.
Published: March 2003

Locational reasoning plays an important role in many applications of AI problem‐solving systems, yet has remained a relatively unexplored area of research. This paper addresses both theoretical and practical issues relevant to reasoning about locations. We define several theories of location designed for use in various settings, along with a sound and complete belief revision calculus for each that maintains a STRIPS‐style database of locational facts. Techniques for the efficient operationalization of the belief revision rules in planning frameworks are presented. These techniques were developed during application of the location theories to several large‐scale planning tasks within the Sipe planning framework.
Scalability in Formal Concept Analysis
Authors: Cole Richard , Eklund Peter W.
Published: March 2003

Formal Concept Analysis is a symbolic learning technique derived from mathematical algebra and order theory. The technique has been applied to a broad range of knowledge representation and exploration tasks in a number of domains. Most recorded applications of Formal Concept Analysis deal with a small number of objects and attributes, in which case the complexity of the algorithms used for indexing and retrieving data is not a significant issue. However, when Formal Concept Analysis is applied to exploration of a large numbers of objects and attributes, the size of the data makes issues of complexity and scalability crucial.

This paper presents the results of experiments carried out with a set of 4,000 medical discharge summaries in which were recognized 1,962 attributes from the Unified Medical Language System (UMLS). In this domain, the objects are medical documents (4,000) and the attributes are UMLS terms extracted from the documents (1,962). When Formal Concept Analysis is used to iteratively analyze and visualize these data, complexity and scalability become critically important.

Although the amount of data used in this experiment is small compared with the size of primary memory in modern computers, the results are still important because the probability distributions that determine the efficiencies are likely to remain stable as the size of the data is increased.

Our work presents two outcomes. First, we present a methodology for exploring knowledge in text documents using Formal Concept Analysis by employing conceptual scales created as the result of direct manipulation of a line diagram. The conceptual scales lead to small derived purified contexts that are represented using nested line diagrams. Second, we present an algorithm for the fast determination of purified contexts from compressed representation of the large formal context. Our work draws on existing encoding and compression techniques to show how rudimentary data analysis can lead to substantial efficiency improvements in knowledge visualization.
English‐Thai Translation: Initial Experiments with a Multiphase Translation System
Authors: Naruedomkul Kanlaya , Cercone Nick , Sirinaovakul Booncharoen
Published: March 2003

A multiphase machine translation approach, Generate and Repair Machine Translation (GRMT), is proposed. GRMT is designed to generate accurate translations that focus primarily on retaining the linguistic meaning of the source language sentence. GRMT presently incorporates a limited multilingual translation capability. The central idea behind the GRMT approach is to generate a translationcandidate (TC) by quick and dirty machine translation (QDMT), then investigate the accuracy of that TC by translation candidate evaluation (TCE), and, if necessary, revise the translation in the repair and iterate (RI) phase. To demonstrate the GRMT approach, a translation system that translates from English to Thai has been developed. This paper presents the design characteristics and some experimental results of QDMT and also the initial design, some experiments, and proposed ideas behind TCE and RI.
Time Series Prediction With Genetic‐Algorithm Designed Neural Networks: An Empirical Comparison With Modern Statistical Models
Authors: Hansen James V. , McDonald James B. , Nelson Ray D.
Published: March 2003

Neural networks whose architecture is determined by genetic algorithms outperform autoregressive integrated moving average forecasting models in six different time series examples. Refinements to the autoregressive integrated moving average model improve forecasting performance over standard ordinary least squares estimation by 8% to 13%. In contrast, neural networks achieve dramatic improvements of 10% to 40%. Additionally, neural networks give evidence of detecting patterns in data which remain hidden to the autoregression and moving average models. The consequent forecasting potential of neural networks makes them a very promising addition to the variety of techniques and methodologies used to anticipate future movements in time series.
An Integrated Instance‐Based Learning Algorithm
Authors: Wilson D. Randall , Martinez Tony R.
Published: March 2003

The basic nearest‐neighbor rule generalizes well in many domains but has several shortcomings, including inappropriate distance functions, large storage requirements, slow execution time, sensitivity to noise, and an inability to adjust its decision boundaries after storing the training data. This paper proposes methods for overcoming each of these weaknesses and combines the methods into a comprehensive learning system called the Integrated Decremental Instance‐Based Learning Algorithm (IDIBL) that seeks to reduce storage, improve execution speed, and increase generalization accuracy, when compared to the basic nearest neighbor algorithm and other learning models. IDIBL tunes its own parameters using a new measure of fitness that combines confidence and cross‐validation accuracy in order to avoid discretization problems with more traditional leave‐one‐out cross‐validation. In our experiments IDIBL achieves higher generalization accuracy than other less comprehensive instance‐based learning algorithms, while requiring less than one‐fourth the storage of the nearest neighbor algorithm and improving execution speed by a corresponding factor. In experiments on twenty‐one data sets, IDIBL also achieves higher generalization accuracy than that reported for sixteen major machine learning and neural network models.
Probability‐Based Chinese Text Processing and Retrieval
Authors: Huang Xiangji , Robertson Stephen , Cercone Nick , An Aijun
Published: March 2003

We discuss the use of probability‐based natural language processing for Chinese text retrieval. We focus on comparing different text extraction methods and probabilistic weighting methods. Several document processing methods and probabilistic weighting functions are presented. A number of experiments have been conducted on large standard text collections. We present the experimental results that compare a word‐based text processing method with a character‐based method. The experimental results also compare a number of term‐weighting functions including both single‐unit weighting and compound‐unit weighting functions.
From Safety Net To Trampoline: Labor Market Activation in the Netherlands and Denmark
Authors: Cox Robert Henry
Published: March 2003

In recent years Denmark and the Netherlands have made dramatic shifts from passive to active labor market policies. Though often portrayed as a necessary response to high levels of structural unemployment, such changes are more than a mere technical adjustment of welfare programs to a changing economic climate. They represent new ideas about the goals of public policy and the social rights of citizenship. This article surveys the politics of labor market policies in the two countries to demonstrate that the recent activation programs reflect a departure from the ideas and goals of the postwar welfare state.
Managed Liberalization of the Dutch Welfare State: A Review and Analysis of the Reform of the Dutch Social Security System, 1985–1998
Authors: Van Der Veen Romke , Trommel Willem
Published: March 2003

In this article the changes that have been implemented in the Dutch social security system are analyzed. The extensive changes are characterized as a form of “managed liberalization.” This characterization points to the paradoxical nature of these changes. On the one hand a certain liberalization can be observed (an increase of social insurance and the administration of social security via the market) while on the other hand the control of the system by the state is also increasing. This process of managed liberalization, however, takes place under an umbrella of lasting universal social protection: entitlements are still determined by law and remain collective. In this article the changes in the Dutch social security are described extensively, interpreted theoretically and analyzed in their consequences for the level of social protection. By following the process of institutional change the system of social security has undergone, the authors also try to find out what the causes of the changes are and what determines the direction the process has taken.
Institutional Reforms and Democratization in Korea: the Case of the Kim Young Sam Administration, 1993–1998
Authors: Hahm Sung Deuk , Kim Kwang Woong
Published: March 2003

This article examines the nature of political and institutional reform initiatives that have been carried out under former president Kim Young Sam. How effective have they been in consolidating democracy in Korea? Specifically, we examine why the Kim Young Sam government's political reform campaigns have been limited, and explore the impact of this limitation on his institutional reform initiatives and the process of consolidation of democracy in Korea.

We argue that Kim Young Sam's initial political reform campaigns have contributed to creating a favorable environment for his institutional reform efforts. However, limitations of these initial political reform campaigns such as political funding and bribery scandals have hampered institutional reforms. We also argue that these difficulties were intensified by public dissatisfaction with Korea's poor economic performance and International Monetary Fund (IMF) financial assistance. As a result, Kim Young Sam's moral legitimacy as a civilian and reform‐oriented leader toward the public has totally evaporated.

Therefore, experiences under the Kim Young Sam administration are just trials and errors of democratization that show another failure in presidential leadership in Korea. These experiences will negatively affect the consolidation process of democracy in Korea by increasing the public's distrust of government as a whole. As a result, democratic consolidation in Korea is being delayed.