bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory processing skills and phonological representation in Dyslexic children
Authors: Richardson Ulla , Thomson Jennifer M. , Scott Sophie K. , Goswami Usha
Published: July 2004

It is now well‐established that there is a causal connection between children's phonological skills and their acquisition of reading and spelling. Here we study low‐level auditory processes that may underpin the development of phonological representations in children. Dyslexic and control children were given a battery of phonological tasks, reading and spelling tasks and auditory processing tasks. Potential relations between deficits in dyslexic performance in the auditory processing tasks and phonological awareness were explored. It was found that individual differences in auditory tasks requiring amplitude envelope rise time processing explained significant variance in phonological processing. It is argued that developmentally, amplitude envelope cues may be primary in establishing well‐specified phonological representations, as these cues should yield important rhythmic and syllable‐level information about speech. Copyright © 2004 John Wiley & Sons, Ltd.
Evaluation of DNA intercalation potential of pharmaceuticals and other chemicals by cell‐based and three‐dimensional computational approaches
Authors: Snyder Ronald D. , Ewing Douglas E. , Hendry Lawrence B.
Published: July 2004

To what extent noncovalent chemical‐DNA interactions, in particular weak nonbonded DNA intercalation, contribute to genotoxic responses in mammalian cells has not been fully elucidated. Moreover, with the exception of predominantly flat, multiple‐fused‐ring structures, our ability to predict intercalation ability of novel compounds is nearly completely lacking. Computational programs such as DEREK and MCASE recognize primarily those molecules that can form irreversible covalent adducts with DNA since their learning sets, for the most part, have not been populated by compounds for which a relationship between noncovalent interaction and genotoxicity exists. We describe here a novel three‐dimensional (3D) computational DNA‐docking model for prediction of DNA intercalative activity of molecules with both classical and nonclassical intercalating structures. The 3D docking results show a remarkable concordance with results obtained from testing these molecules directly in the Chinese hamster V79 cell‐based bleomycin amplification system suggesting that either or both of these approaches may have utility in defining noncovalent chemical‐DNA interactions. The ability to predict and/or demonstrate cellular DNA intercalation of novel molecules may well provide fresh insights into the nature and mechanistic basis of structurally unexpected genotoxicity observed during safety testing. Environ. Mol. Mutagen. 44:163–173, 2004. © 2004 Wiley‐Liss, Inc.
Wind effects on sediment transport by raindrop‐impacted shallow flow: a wind‐tunnel study
Authors: Erpul G. , Gabriels D. , Norton L. D.
Published: July 2004

In wind‐driven rains, wind velocity and direction are expected to affect not only energy input of rains but also shallow ﬂow hydraulics by changing roughness induced by raindrop impacts with an angle on ﬂow and the unidirectional splashes in the wind direction. A wind‐tunnel study under wind‐driven rains was conducted to determine the effects of horizontal wind velocity and direction on sediment transport by the raindrop‐impacted shallow ﬂow. Windless rains and the rains driven by horizontal wind velocities of 6 m s−1, 10 m s−1, and 14 m s−1 were applied to three agricultural soils packed into a 20 by 55 cm soil pan placed on both windward and leeward slopes of 7 per cent, 15 per cent, and 20 per cent. During each rainfall application, sediment and runoff samples were collected at 5‐min intervals at the bottom edge of the soil pan with wide‐mouth bottles and were determined gravimetrically. Based on the interrill erosion mechanics, kinetic energy ﬂux (Ern) as a rainfall parameter and product of unit discharge and slope in the form of qbSco as a ﬂow parameter were used to explain the interactions between impact and ﬂow parameters and sediment transport (qs). The differential sediment transport rates occurred depending on the variation in raindrop trajectory and rain intensity with the wind velocity and direction. Flux of rain energy computed by combining the effects of wind on the velocity, frequency, and angle of raindrop impact reasonably explained the characteristics of wind‐driven rains and acceptably accounted for the differences in sediment delivery rates to the shallow ﬂow transport (R2 ≥ 0·78). Further analysis of the Pearson correlation coefﬁcients between Ern and qSo and qs also showed that wind velocity and direction signiﬁcantly affected the hydraulics of the shallow ﬂow. Ern had a smaller correlation coefﬁcient with the qs in windward slopes where not only reverse splashes but also reverse lateral raindrop stress with respect to the shallow ﬂow direction occurred. However, Ern was as much effective as qSo in the sediment transport in the leeward slopes where advance splashes and advance lateral raindrop stress on the ﬂow occurred. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of sill spacing and sediment size grading on scouring at grade‐control structures
Authors: Marion Andrea , Lenzi Mario A. , Comiti Francesco
Published: July 2004

Sequences of artiﬁcial steps are sometimes used to reproduce the natural step–pool morphology of high‐gradient streams. The depth, length and shape of the scour holes in gravel‐bed rivers can be predicted reasonably using recently developed formulae. However, the properties of the scour holes can sometimes be affected by the distance between structures. This effect is called ‘geometrical interference’ and leads to a reduction of the scour hole compared to its potential size. Geometrical interference may occur in sequences of artiﬁcial steps in high‐gradient torrents, where structures are sometimes built at distances of a few tens of metres apart, but may also apply to natural step–pool systems. In this paper, a series of tests have been conducted to determine the effect of bed sill spacing and sediment grading on the potential erosion by jets forming over the sills. A new formula is derived, applicable to high‐gradient streams (slope > 0·04), which can be applied to the special case of scour holes developed by interfering sills. Sediment size gradation, not accounted for in previous formulae, is found to have a signiﬁcant effect on the scour dimensions and is included in the new predictive formula. Copyright © 2004 John Wiley & Sons, Ltd.
Flow threads in surface run‐off: implications for the assessment of flow properties and friction coefficients in soil erosion and hydraulics investigations
Authors: Dunkerley David
Published: July 2004

Soil surface microtopography produces non‐uniform surface run‐off, in which narrow threads of relatively deep and fast ﬂow move within broader, shallower, slower‐moving regions. This kind of ﬂow is probably widespread, given that microtopography is itself common. Methods used to record the properties of surface run‐off include grid‐ or transect‐based depth observations, with a single mean ﬂow speed derived by calculation from V = Q/WD, and the use of dye timing to estimate velocity, with an effective mean depth calculated from D = Q/WV.

Because these methods allow only single, ﬂow‐ﬁeld mean values to be derived for V or D, neither is well suited to non‐uniform ﬂows. The use of depth data to derive a ﬂow‐ﬁeld mean V furthermore implicitly applies area weighting to the depth data; likewise, the use of dye speeds for V inherently overestimates mean V because dye dominantly follows the faster ﬂow threads. The associated errors in derived parameters such as friction coefﬁcients are not readily quantiﬁed and appear not to have been addressed previously.

New ﬁeld experiments made on untilled soil surfaces in arid western NSW, Australia, explore these circumstances and the implications for deriving meaningful measures of ﬂow properties, including friction coefﬁcients. On surfaces deliberately chosen for their very subtle microtopography, average thread velocities are shown to be commonly 2·5 times greater than the ﬂow‐ﬁeld mean, and locally 6–7 times greater. On the other hand, non‐thread ﬂow speeds lie below the ﬂow‐ﬁeld mean, on average reaching only 84 per cent of this value, and often considerably less. Flow‐ﬁeld means conceal the existence of regions of the ﬂow ﬁeld whose properties are statistically distinct. Results conﬁrm that a reliance on ﬂow‐ﬁeld average depths yields estimates of friction coefﬁcients that are biased toward the shallower, high‐roughness parts of the ﬂow, while if dye speeds are relied upon the results are biased toward the deeper, smoother threads of ﬂow. A new approach to the evaluation of friction coefﬁcients in non‐uniform ﬂows is advanced, involving the determination of separate coefﬁcients for threads and non‐thread zones of the ﬂow ﬁeld. In contrast, ﬂow‐ﬁeld friction coefﬁcients as they are customarily derived in run‐off plot experiments subsume these distinct coefﬁcients in proportions that are generally unknown. The value of such coefﬁcients is therefore questionable. Copyright © 2004 John Wiley & Sons, Ltd.
Spatial evaluation of a multi‐class sediment transport and deposition model
Authors: Van Oost K. , Beuselinck L. , Hairsine P. B. , Govers G.
Published: July 2004

This paper presents a model for the description of sediment ﬂuxes and deposition processes in a two‐dimensional spatial context using the multiple‐class Hairsine et al. sediment deposition equations. The model describes size‐selective net deposition as a result of simultaneous deposition by settling and non‐selective re‐entrainment of previously deposited sediment. A critical comparison of ﬁeld observations of net erosion and deposition in a watershed with complex topography with this physically based model is presented. The evaluation shows that the deposition model is capable of simulating reasonably both the observed size selectivity and spatial patterns of the deposition process. In this ﬁeld study, the zone where a net deposit of sediment is re‐entrained by overland ﬂow was predicted to be quite limited spatially due to low sediment concentrations and the absence of aggregates in the eroded soil. Copyright © 2004 John Wiley & Sons, Ltd.
Rate of sediment yield following small‐scale volcanic eruptions: a quantitative assessment at the Merapi and Semeru stratovolcanoes, Java, Indonesia
Authors: Lavigne Franck
Published: July 2004

Sediment yields were calculated on the ﬂanks of Merapi and Semeru volcanoes in Java, Indonesia, using two different methods. During the ﬁrst year following the 22 November 1994 eruption of Merapi, a sediment yield in excess of 1·5 × 105 m3 km−2 yr−1 was calculated in the Boyong River drainage basin, based on the volumes of sediment that were trapped by ﬁve check dams. At Semeru, sediment discharges were assessed in the Curah Lengkong River from direct measurements on the lahars in motion and on the most signiﬁcant streamﬂows. The calculated rate of sediment yield during one year of data in 2000 was 2·7 × 105 m3 km−2 yr−1.

Sediment yields are dominated by rain‐triggered lahars, which occur every rainy season in several drainage basins of Merapi and Semeru volcanoes, mostly during the rainy season extending from October to April. The return period of lahars carrying sediment in excess of 5 × 105 m3 is about one year in the Curah Lengkong River at Semeru. At Merapi, the volume of sediments transported by a lahar did not exceed 2·8 × 105 m3 in the Boyong River during the rainy season 1994–95.

On both volcanoes, the sediments are derived from similar sources: pyroclastic‐ﬂow/surges deposits, rockfalls from the lava domes, and old material from the riverbed and banks. However, daily explosions of vulcanian type at Semeru provide a more continuous sediment supply than at Merapi. Therefore, sediment yields are larger at Semeru. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis of stable isotope labeled PNU‐95666
Authors: Jian Zhigang
Published: July 2004

Studies towards the synthesis of stable isotope labeled PNU‐95666, a CNS agent currently under development for the treatment of Parkinson's disease, is described. The synthesis of non‐labeled PNU‐95666 starts using a large excess of methylamine. While the non‐labeled methylamine is inexpensive and in plentiful supply, the stable isotope labeled form is expensive and limited availability. Different synthetic routes and conditions, including the use of different aminating agents and various amounts of methylamine were explored and new synthetic conditions were established. Copyright © 2004 John Wiley & Sons, Ltd.
HLA‐DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes
Authors: Finn Thomas P. , Jones Richard E. , Rich Cathleen , Dahan Rony , Link Jason , David Chella S. , Chou Yuan K. , Offner Halina , Vandenbark Arthur A.
Published: July 2004

Susceptibility to multiple sclerosis (MS) is associated genetically with human leucocyte antigen (HLA) class II alleles, including DRB1*1501, DRB5*0101, and DQB1*0602, and it is possible that these alleles contribute to MS through an enhanced ability to present encephalitogenic myelin peptides to pathogenic T cells. HLA‐DRB1*1502, which contains glycine instead of valine at position 86 of the P1 peptide‐binding pocket, is apparently not genetically associated with MS. To identify possible differences between these alleles in their antigen‐presenting function, we determined if T‐cell responses to known DRB1*1501‐restricted myelin peptides might be diminished or absent in transgenic (Tg) DRB1*1502‐expressing mice. We found that Tg DRB1*1502 mice had moderate to strong T‐cell responses to several myelin peptides with favorable DRB1*1501 binding motifs, notably myelin oligodendrocyte glycoprotein (MOG)‐35‐55 (which was also encephalitogenic), proteolipid protein (PLP)‐95‐116, and MOG‐194‐208, as well as other PLP and MOG peptides. These peptides, with the exception of MOG‐194‐208, were also immunogenic in healthy human donors expressing either DRB1*1502 or DRB1*1501. In contrast, the DRB1*1502 mice had weak or absent responses to peptides with unfavorable DRB1*1501 binding motifs. Overall, none of the DRB1*1501‐restricted myelin peptides tested selectively lacked immunogenicity in association with DRB1*1502. These results indicate that the difference in risk association with MS of DRB1*1501 versus DRB1*1502 is not due to a lack of antigen presentation by DRB1*1502, at least for this set of myelin peptides, and suggest that other mechanisms involving DRB1*1501 may account for increased susceptibility to MS. © 2004 Wiley‐Liss, Inc.
Failure of neuronal protection by inhibition of glial activation in a rat model of striatonigral degeneration
Authors: Stefanova Nadia , Mitschnigg Monika , Ghorayeb Imad , Diguet Elsa , Geser Felix , Tison Francois , Poewe Werner , Wenning Gregor K.
Published: July 2004

Previous studies in rodent models of neurodegenerative disorders have demonstrated that minocycline exerts neuroprotective effects unrelated to its antimicrobial action. The purpose of the present study was to analyze whether minocycline exhibits neuroprotective activity in a rat model of striatonigral degeneration (SND), the core pathology underlying levodopa‐unresponsive parkinsonism associated with multiple system atrophy (MSA). We observed no significant effect of minocycline on locomotor impairment in double‐lesioned SND rats. Minocycline significantly suppressed astroglial and microglial activation (P < 0.01); however, 3′5′‐monophosphate‐regulated phosphoprotein (DARPP 32) immunohistochemistry revealed no significant differences in striatal lesion volume of minocycline‐treated versus untreated control SND rats. Furthermore, there was no protection of nigral dopaminergic neurons in the double‐lesion model. We conclude that despite its astrocytic and microglial suppression, minocycline failed to attenuate lesion‐induced neuronal damage in the SND rat model. © 2004 Wiley‐Liss, Inc.
α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors signaling complexes in Bergmann glia
Authors: Millán Alejandro , Arias‐Montaño José Antonio , Méndez J. Alfredo , Hernández‐Kelly L. Clara R. , Ortega Arturo
Published: July 2004

Glutamate, the major excitatory neurotransmitter, induces a wide array of signals from the membrane to the nucleus regulating gene expression. In Bergmann glia, Ca2+‐permeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐ propionic acid (AMPA) receptors are involved in the short‐ and long‐term interactions between these cells and the neurons that they surround. After activation, AMPA receptors become tyrosine phosphorylated and by these means form multiprotein signaling complexes. To characterize these events, cultured chick Bergmann glia cells as well as chick cerebellar slices were exposed to glutamate, and, by using a combination of immunoprecipitation assays coupled to Western blot analysis, we identified several signaling proteins that become associated with these receptors. A dose‐ and time‐dependent association among AMPA receptors, the focal adhesion kinase pp125FAK, the phosphatidylinositol‐3 kinase and paxillin was found. These results extend the concept of the transducisome to AMPA receptors and provide a framework in which a plausible control of the cytoskeletal network by glutamate is taking place, most possibly through AMPA receptors. © 2004 Wiley‐Liss, Inc.
Ermittlung von Berechnungskennwerten an Karosseriewerkstoffen – Bericht über ein Gemeinschaftsprojekt der Stahl‐ und Automobilindustrie
Authors: Bleck W. , Engl B. , Frehn A. , Nicklas D. , Steinbeck G.
Published: July 2004

Im Rahmen eines gemeinschaftlichen Projektes der Stahl‐ und Automobilindustrie wurden an insgesamt 20 Stählen für Feinblech Kennwerte für die FEM‐Simulation ermittelt. Im Einzelnen handelte es sich um elastische, plastische und zyklische Kennwerte, die über einen Zeitraum von 3 Jahren von unterschiedlichen Prüfstellen erarbeitet wurden. Die untersuchten Stähle unterschieden sich hinsichtlich ihrer Ausgangsgefüge und Werkstoffkonzepte, wobei neben verschiedenen einphasigen ferritischen Stahlsorten auch Mehrphasen‐Stähle wie Dualphasen‐, Complexphasen‐ und TRIP‐Stähle sowie 2 austenitische nicht rostende Stähle zum Einsatz kamen. Die Stähle wurden sowohl im Ausgangszustand als auch in definierten Vorverformungs‐ und Wärmebehandlungszuständen untersucht. Die Vorgaben für die Herstellung dieser Zustände und für die anschließende Prüfung wurden von den Projektpartnern in der sogenannten „Prüf‐ und Dokumentationsrichtlinie”︁ festgelegt, mit deren Hilfe eine standardisierte Kennwertermittlung und Datenaufbereitung für eine von der Automobilindustrie realisierte Werkstoffdatenbank möglich wurde. Den elastischen, plastischen und zyklischen Prüfungen wurde eine Eingangsprüfung vorgeschaltet, in der die Stähle hinsichtlich ihrer Gefügeausbildung, Oberfläche, chemischen Zusammensetzung und mechanischen Eigenschaften im quasistatischen Zugversuch vollständig charakterisiert wurden. Die Ergebnisse der einzelnen Prüfbereiche (plastisch, elastisch, zyklisch) werden in separaten Veröffentlichungen ausführlich vorgestellt. Es hat sich gezeigt, dass Werkstoffgruppen mit nahezu gleicher Verfestigungscharakteristik existieren, so dass eine rechnerische Vorhersage von Kennwerten und Fließkurven artverwandter Stähle möglich erscheint. Diese Thematik wird in einem am 01. Januar 2003 angelaufenen Nachfolgeprojekt im Mittelpunkt der Untersuchungen stehen.
Increased DNA methylation in the HoxA5 promoter region correlates with decreased expression of the gene during tumor promotion
Authors: Watson Rebecca E. , Curtin Geoffrey M. , Hellmann Gary M. , Doolittle David J. , Goodman Jay I.
Published: July 2004

Promoter‐region DNA methylation inhibits transcription. A two‐stage SENCAR (sensitive to mouse carcinogenesis) mouse skin carcinogenicity model was used to examine gene‐specific changes in methylation during skin tumor promotion. Analysis was performed on 7,12‐dimethylbenz[a]anthracene (DMBA)‐initiated skin promoted with 9, 18, 27, or 36 mg cigarette smoke condensate (CSC) for 9 wk, or 27 mg CSC for 9 wk and sacrificed 6 wk afterwards (recovery group). Additionally, tumors arising following promotion with 27 mg CSC for 29 wk were assessed. Gene array analysis identified differentially expressed genes. Expression of HoxA5, a tumor suppressor gene, was decreased following 9 wk of treatment with 27 mg CSC, and returned to control levels during recovery. HoxA5 promoter methylation was measured with the enzymatic regional methylation assay (ERMA). DNA was bisulfite‐modified, PCR‐amplified with primers containing dam sites, incubated with [14C‐methyl] S‐adenosyl‐l‐methionine (SAM) and dam methyltransferase for DNA quantification, then incubated with [3H‐methyl] SAM and SssI methylase to quantify methylation status. Higher 3H/14C ratios indicate increased methylation. The 3H/14C ratios of animals promoted with 27 or 36 mg CSC (48.2 ± 6.9 and 24.2 ± 6.1, respectively) were higher than the control or recovery group ratios (12.3 ± 0.1 and 12.6 ± 0.3, respectively); sequence analysis supported these findings. Increased methylation of p16 or O6 methylguanine methyltranferase (MGMT) was detected in 4/8 (50%) of the tumor samples from mice promoted with 27 mg CSC. These data suggest that increased DNA methylation contributes to the downregulation of HoxA5, and combined with hypermethylation of p16 or MGMT, this might facilitate the clonal expansion of increasingly aberrant cells during promotion. © 2004 Wiley‐Liss, Inc.
Prolonged practice is of scarce benefit in improving motor performance in Parkinson's disease
Authors: Agostino Rocco , Currà Antonio , Soldati Giampiero , Dinapoli Loredana , Chiacchiari Luigi , Modugno Nicola , Pierelli Francesco , Berardelli Alfredo
Published: July 2004

Many studies have addressed practice effects in motor sequences in Parkinson's disease (PD). Most studied short‐term practice and showed that treated patients with mild‐to‐moderate disease achieve normal or slightly abnormal improvement. Less attention has focused on practice effects after prolonged training (days), and the results are inconclusive. Here, we studied the kinematic changes induced by prolonged practice in a group of medicated patients with mild‐to‐moderate PD and a healthy control group. We did so by analyzing an internally determined sequential arm movement performed as fast and accurately as possible before and after a 2‐week training period. After 1‐day's practice, movement duration, pause duration, and movement accuracy improved similarly in patients and controls, indicating that patients benefitted normally from short‐term practice. After 1‐week's practice, movement and pause duration improved further in both groups, whereas movement accuracy remained unchanged. After 2‐weeks' practice, healthy controls continued to improve but patients did not, indicating reduced prolonged practice benefit in PD. Because short‐term practice benefit on motor performance is thought to be mediated predominantly by cerebellar activation, whereas long‐term practice benefit relies predominantly on the basal ganglia, we attribute our findings to the underlying basal ganglia dysfunction in PD. Our study may be relevant for planning and executing rehabilitation programs in these patients. © 2004 Movement Disorder Society
Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's disease
Authors: O'Suilleabhain Padraig E. , Bottiglieri Teodoro , Dewey Richard B. , Sharma Shailja , Diaz‐Arrastia Ramon
Published: July 2004

Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) μmol/L increased to 10.1 (3.1) μmol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L‐dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 μmol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined. © 2004 Movement Disorder Society
Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene in patients with essential tremor in Turkey
Authors: Sazci Ali , Ergul Emel , Bayulkem Kemal
Published: July 2004

Essential tremor (ET) is a most common human movement disorder of unknown etiology. Previous reports have shown that the C677T polymorphism of methylenetetrahydrofolate reductase gene has been associated with neurodegenerative disorders. To investigate the role of methylenetetrahydrofolate reductase gene polymorphisms in essential tremor, we analyzed the alleles and genotypes of methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C in a total of 158 unrelated essential tremor patients and compared them with those of 246 unrelated healthy control subjects, using a polymerase chain reaction restriction fragment length polymorphism method. The allele frequency of MTHFR 677T was 35.76% in the essential tremor cases and 30.08% in the controls. We obtained statistically significant results for MTHFR677 and also for MTHFR1298. The MTHFR T677T genotype was overrepresented and was statistically significant. The T677T/A1298A and C677C/C1298C compound genotypes were similarly statistically significant. The C677C/A1298A compound genotype provided protection for essential tremor. In conclusion, the MTHFR 677T, 1298C alleles and MTHFR T677T genotype and T677T/A1298A, and C677C/C1298C compound genotypes are genetic risk factors for essential tremor in Turkey. © 2004 Movement Disorder Society
Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: A 12‐week, double‐blind, randomized, parallel‐group, placebo‐controlled study
Authors: Walters Arthur S. , Ondo William G. , Dreykluft Tilman , Grunstein Ron , Lee Daniel , Sethi Kapil ,   on behalf of the TREAT RLS 2 (Therapy with Ropinirole: Efficacy And Tolerability in RLS 2) Study Group
Published: July 2004

Restless legs syndrome (RLS) is a neurological condition with significant impact on sleep and quality of life (QoL). This double‐blind, randomized, 12‐week, multinational study compared the efficacy and safety of ropinirole and placebo in RLS. In total, 267 outpatients with moderate‐to‐severe RLS were randomly assigned to ropinirole (0.25–4.0 mg/day) or placebo, 1 to 3 hours before bedtime. The primary endpoint was the change in International Restless Legs Scale (IRLS) score at week 12. Key secondary endpoints were the percentage of patients showing significant improvement on the Clinical Global Impression‐Improvement (CGI‐I) scale at week 12 and changes in IRLS and CGI‐I scale scores at week 1. Other measures included the Medical Outcomes Study sleep scale and Restless Legs Syndrome Quality of Life questionnaire. Improvements were significantly greater for ropinirole than placebo for change in IRLS score at week 12 (−11.2 [SE 0.76] vs. −8.7 [0.75], respectively; adjusted treatment difference −2.5 [95% confidence interval [CI], −4.6, −0.4], P = 0.0197); all key secondary endpoints; sleep and QoL parameters. Adverse events were typical for dopamine agonists; disease augmentation, although not directly assessed, was not reported during treatment. Ropinirole improves symptoms, associated sleep disturbance, and QoL of RLS patients and is generally well tolerated. © 2004 Movement Disorder Society
Re: Hypothyroidism and Parkinson's disease
Authors: Deuschl Günther , Goetz Christopher G.
Published: July 2004

The original letter to which this reply refers is published in DOI 10.1002/mds.20249 Movement Disorders, 2004.
Fate of the first polar bodies in mouse oocytes
Authors: Miao Yiliang , Ma Suofeng , Liu Xinyong , Miao Deqiang , Chang Zhongle , Luo Mingjiu , Tan Jinghe
Published: July 2004

Both nuclear transfer and intracytoplasmic sperm injection (ICSI) practice necessitates studies on the spatial relationship between the MII spindle and the first polar bodies (FPB). Although recent observations have shown that the FPB position does not predict accurately the location of the meiotic spindle in metaphase II oocytes of monkey, hamster, and human, detailed studies on FPB deviation and its affecting factors are lacking. Since polar bodies can be used for genetic testing and oocyte quality grading, their life span under different conditions should be studied. The timing of formation and degeneration and the position relative to the MII spindle of the FPB and the factors affecting FPB deviation and degeneration during in vivo and in vitro aging of both in vivo and in vitro matured mouse oocytes were investigated in this study. Mice of the Kun‐ming breed were used, and the intact and degenerated FPB were identified through microscopic morphology in combination with propidium iodide (PI) exclusion test and the chromosomes visualized by Hoechst staining. Results are summarized as follows: (i) oocytes started FPB extrusion at 8 hr after the onset of in vivo or in vitro maturation, but the number of FPB reached maximum much later in vitro (14 hr of culture) than in vivo (10 hr post hCG). (ii) Some FPB began to degenerate before ovulation and around 70% became degenerated within 6 hr after maximal nuclear maturation both in vivo and in vitro; they disappeared faster during in vivo than in vitro aging but turned from intact to degenerated at a similar tempo. (iii) Some FPB began to deviate from the MII spindle 10 hr after hCG injection or in vitro culture and the distance between FPB and the spindle increased with time during both in vivo and in vitro aging. (iv) FPB deviated more slowly in the in vitro matured oocytes than in in vivo matured. (v) Denudation performed after FPB extrusion markedly enhanced its deviation. (vi) The perivitelline space (PVS) increased with time during maturation and aging in vivo and in vitro and the values of PVS and the percentages of FPB adjacent to the spindle were significantly negatively correlated. (vii) Cytochalasin B and colchicine had no effect on FPB deviation. (viii) None of the more than 3,500 FPBs observed was found to be dividing or have divided into two cells at any time points before or after ovulation or in vitro maturation. Our results were consistent with the possibility that the displacement of the FPB was a time‐ and PVS‐dependent process, indicating that PVS would increase with time and its formation and enlargement would facilitate the lateral displacement of the degenerating FPB. Mol. Reprod. Dev. 69: 66–76, 2004. © 2004 Wiley‐Liss, Inc.
Differential expression and activation of Stat3 during mouse embryo implantation and decidualization
Authors: Teng Chun‐Bo , Diao Hong‐Lu , Ma Xing‐Hong , Xu Li‐Bin , Yang Zeng‐Ming
Published: July 2004

Signal transducer and activator of transcription (STATs) can be activated by many cytokines and growth factors. Stat3, a member of STAT family, is essential for embryonic development. Stat3 is specifically activated during mouse embryo implantation. This study was to investigate the expression, activation, and regulation of Stat3 in mouse uterus during early pregnancy, pseudopregnancy, delayed implantation, artificial decidualization, and hormonal treatments using in situ hybridization and immunohistochemistry. There was a strong level of Stat3 phosphorylation in the luminal epithelium only at the midnight of day 4 pregnancy, which coincides with attachment reaction between the blastocyst and luminal epithelium. However, there was no detectable Stat3 phosphorylation at the corresponding period during pseudopregnancy. On day 5 of pregnancy, Stat3 phosphorylation was strongly observed in the luminal epithelium and the stroma surrounding the implanting blastocyst at implantation sites, but not at the inter‐implantation sites. Stat3 phosphorylation was also not detected on day 5 of pseudopregnancy. Stat3 phosphorylation was at a high level in the decidual cells on days 6–8 of pregnancy. Under artificial decidualization, Stat3 was also phosphorylated in the decidual cells. In the ovariectomized mice, there was no Stat3 expression and activation in the uterus. Progesterone had no obvious effects. However, Stat3 mRNA expression and phosphorylation were significantly stimulated by estrogen treatment. Our data suggest that Stat3 phosphorylation may be important for mouse embryo implantation and decidualization, and may also be regulated by maternal estrogen. Mol. Reprod. Dev. 69: 1–10, 2004. © Wiley‐Liss, Inc.
Retinoid‐dependent mRNA expression and poly‐(A) contents in bovine oocytes meiotically arrested and/or matured in vitro
Authors: Gomez Enrique , Rodríguez Aida , Goyache Felix , Dd́ez Carmen , José Royo Luis , Moreira Pedro N. , Néstor Caamaño José , Morán Erica , Gutiérrez‐Adán Alfonso
Published: July 2004

The presence of retinoic acid (RA) during in vitro maturation (IVM) improves bovine oocyte quality and developmental potential. In this work, we investigated the underlying molecular mechanisms. Cumulus–oocyte complexes were meiotically arrested by roscovitine and/or matured in defined medium containing RA, 1% ethanol (vehicle), or no additives. Cumulus‐free oocytes were analyzed for poly‐(A) mRNA contents and relative mRNA expression of genes involved in cell cycle regulation (cyclin B1 and H1) and antioxidative defence (Mn‐superoxide dismutase and glucose‐6‐phosphate dehydrogenase). Poly‐(A) mRNA increased after meiotic inhibition and decreased with IVM completion, both in meiotically arrested and permissively matured oocytes, i.e., matured without previous meiotic arrest. RA dramatically increased poly‐(A) mRNA in meiotically arrested oocytes, but more than half of the poly‐(A) mRNA disappeared during maturation. Irrespective of oocyte origin, transcripts were detected for all the genes analyzed. IVM, with or without previous meiotic inhibition, increased expression of cyclin B1 and glucose‐6‐phosphate dehydrogenase, and decreased cyclin H1 and Mn‐superoxide dismutase. Except for a decreasing of Mn‐superoxide dismutase in meiotically arrested and matured oocytes, RA did not affect mRNA expression. Ethanol led to an abnormal poly‐(A) mRNA profile and expression of all the genes analyzed. RA does not modify expression of cyclin B1 and HI genes in the bovine oocyte, and probably does not generate oxidative stress. In addition, RA enhanced mRNA amount as measured by poly‐(A) mRNA contents. Mol. Reprod. Dev. 69: 101–108, 2004. © 2004 Wiley‐Liss, Inc.
Effect of paternal tamoxifen on the expression of insulin‐like growth factor 2 and insulin‐like growth factor type 1 receptor in the post‐implantation rat embryos
Authors: Kedia Neelam , Gill‐Sharma Manjit K. , Parte Priyanka , Juneja Harbans S. , Balasinor Nafisa
Published: July 2004

Nuclear transplantation studies demonstrated the importance of paternal contribution to embryogenesis. Paternal treatment with agents like cyclophosphamide and 5‐azacytidine has been shown to cause an increase in pre‐implantation loss (PIL) and post‐implantation loss (POL). Studies from our laboratory have shown that paternal tamoxifen treatment increases PIL and POL. It was observed that the PIL occurred at day 2 of gestation (embryo at 2–4 cell stage) and the POL occurred around day 9 of gestation (mid‐gestation). The insulin‐like growth factor (IGF) system represents one of the major growth‐controlling system expressed in the embryo. Several studies suggest that in rodents, insulin‐like growth factor 2 (Igf2) signaling through the insulin‐like growth factor type 1 receptor (Igf1r) modulates embryo growth at around days 9–11 of gestation (mid‐gestation). The present study was undertaken to evaluate the expression of Igf2 and Igf1r transcript by RT‐PCR in the post‐implantation embryos obtained after paternal tamoxifen treatment. It was observed that both the genes were down regulated in resorbed embryos (POL). Since Igf2 is an imprinted gene and the imprint mark is established during spermatogenesis, the present study suggests that paternal tamoxifen treatment may have affected imprinting of the gene during spermatogenesis thereby decreasing its expression and leading to increase in POL. This is to our knowledge the first study correlating the increase in post‐implantation embryo loss obtained after paternal drug treatment with the decrease in the expression of Igf2 in these embryos. Mol. Reprod. Dev. 69: 22–30, 2004. © 2004 Wiley‐Liss, Inc.
Transcutaneous magnetic stimulation of the quadriceps via the femoral nerve
Authors: Kremenic Ian J. , Ben‐Avi S. Simon , Leonhardt Dan , McHugh Malachy P.
Published: July 2004

We investigated the efficacy of different frequencies and intensities of magnetic stimulation for activating the quadriceps muscles; a painless method for stimulating the quadriceps would be useful in the rehabilitation of patients who have difficulty in voluntarily activating their muscles after injury or surgery. Eleven subjects underwent magnetic stimulation of the femoral nerve over a range of frequencies and intensities using a MagStim Rapid magnetic stimulator. Magnetic stimulation at 30 Hz at 80% of the power output of the stimulator used was capable of generating 72% of quadriceps maximal voluntary contraction torque. Subjects reported little or no pain during the procedure. Magnetic stimulation of the femoral nerve is a well‐tolerated way to activate the quadriceps muscles. Muscle Nerve 30: 379–381, 2004
β‐synemin localizes to regions of high stress in human skeletal myofibers
Authors: Mizuno Yuji , Guyon Jeffrey R. , Watkins Simon C. , Mizushima Kazuyuki , Sasaoka Toshikuni , Imamura Michihiro , Kunkel Louis M. , Okamoto Koichi
Published: July 2004

Synemin is an intermediate filament protein shown previously to interact with α‐dystrobrevin and desmin. Immunoblot analysis detects a β‐synemin protein of 170 kDa in human skeletal muscle and an α‐synemin protein of 225 kDa in monkey brain. Low‐resolution immunohistochemical analysis localizes β‐synemin within muscle along the sarcolemma, whereas confocal microscopic analysis further refines localization to the costamere and muscle Z‐lines. In addition to these locations, β‐synemin is also enriched at the neuromuscular and myotendinous junctions, other regions that undergo high stress during myofiber contraction. Based on its localization and its expression pattern, it is proposed that β‐synemin functions as a structural protein involved in maintaining muscle integrity through its interactions with α‐dystrobrevin, desmin, and other structural proteins. Muscle Nerve 30: 337–346, 2004
Polystyrene magadiite nanocomposites
Authors: Wang Dongyan , Jiang David D. , Pabst Jaclyn , Han Zhidong , Wang Jianqi , Wilkie Charles A.
Published: July 2004

An organically modified magadiite has been prepared and used to make a mixed intercalated‐exfoliated polystyrene nanocomposite by bulk polymerization. This system gives excellent improvement in mechanical properties, but the thermogravimetric analysis curves do not show any change in the onset of the degradation and the degradation pathway is not changed from that for virgin polystyrene, unlike the situation for an aluminosilicate clay, montmorillonite. By cone calorimetry, the peak heat release rate is not changed, again unlike the results with the aluminosilicate. This suggests that not all clays exhibit the same behavior in nanocomposite formation. Polym. Eng. Sci. 44:1122–1131, 2004. © 2004 Society of Plastics Engineers.
Epoxy nanocomposites: Analysis and kinetics of cure
Authors: Ton‐That M.‐T. , Ngo T.‐D. , Ding P. , Fang G. , Cole K. C. , Hoa S. V.
Published: July 2004

The effect of organo‐nanoclay (Nanomer I30E) on the cure mechanism and kinetics of epoxy nanocomposites based on Epon 828 and Epicure 3046 was studied by means of dynamic differential scanning calorimetry (DSC) at four heating rates (2.5, 5, 10, and 20°C·min−1) and by Fourier transform infrared (FT‐IR) spectroscopy. The DSC cure data for epoxy‐amine mixtures with and without nanoclay was modeled by means of different approaches; the Kissinger and isoconversional models were used to calculate the kinetics parameters while the Avrami model was utilized to compare the cure behavior of the two systems. The Nanomer I30E was shown to initiate rapid homopolymerization of the Epon 828 resin at temperatures above 180°C. For the epoxy‐amine mixtures, the presence of nanoclay had little effect on the cure kinetics in the early stages (i.e., at lower temperatures), and the apparent activation energy was around 60 kJ·mol−1. However, in the later stages, the apparent activation energy increased significantly in the absence of nanoclay, but did not do so when it was present. The presence of nanoclay also lowered the final glass transition temperature by about 4°C. Polym. Eng. Sci. 44:1132–1141, 2004. © 2004 Society of Plastics Engineers.
Polyolefin nanocomposites: Essential work of fracture analysis
Authors: Bureau M. N. , Perrin‐Sarazin F. , Ton‐That M.‐T.
Published: July 2004

The tensile properties and the fracture toughness, based on the essential work of fracture (EWF) method, of melt‐compounded polymer nanocomposites based on polypropylene (PP) with organo‐modified clays (montmorillonite) and maleic anhydride (MA)–grafted PP coupling agents were studied. Depending on the compounding sequence and on whether a coupling agent was used, some improvements in tensile properties were observed. These improvements were related to the level of dispersion of clay particles. The highest tensile properties were obtained for the PP/clay compound showing the highest surface density of uniform sub‐micron particles. The mechanical improvements of the PP/clay compounds were those of a microcomposite in which the fiber reinforcement has an average aspect ratio of 17–35. The PP/clay compounds with coupling agents and with highest surface density of uniform sub‐micron particles showed very good fracture toughness, with EWF values slightly higher than those of unfilled PP. Fractographic observations showed that clay particles acted as void nucleation sites, which then grew and coalesced, promoting fibrillation of the remaining material between the voids. The EWF results indicated that the void nucleation density determined the fracture toughness. The EWF results also indicated that the plastic work dissipation related to the stability of the fibrillation, which was promoted by the use of a coupling agent. Polym. Eng. Sci. 44:1142–1151, 2004. © 2004 Society of Plastics Engineers.
Bending behavior of hydrogels composed of poly(methacrylic acid) and alginate by electrical stimulus
Authors: Kim Seon Jeong , Yoon Seoung Gil , Lee Yong Hee , Kim Sun I
Published: July 2004

Interpenetrating polymer networks (IPNs) prepared from poly(methacrylic acid) (PMAAc) and sodium alginate (SA) exhibited electrical sensitive behavior. The swelling behavior of the PMAAc/SA IPN hydrogel was studied by immersion of the gel into aqueous HCl solutions at various concentrations and into various pH buffer solutions, and their responses to electric fields were also investigated. When swollen IPN hydrogel was placed between a pair of electrodes it exhibited bending behavior on application of an electric field, and showed stepwise bending behavior depending on the magnitude of the electrical stimulus. Copyright © 2004 Society of Chemical Industry
First hyperpolarizabilities of 1,3,5‐tricyano‐2,4,6‐tris(styryl)benzene derivatives: ab initio studies and Hammett correlation
Authors: Park Gyoosoon , Cho Bong Rae
Published: July 2004

First hyperpolarizabilities (β) of the 1,3,5‐tricyano‐2,4,6‐tris(styryl)benzene derivatives were studied by an ab initio method (HF/6–31G). The β values of these molecules increase with increase in donor strength, reaching a maximum value of 262 × 10−30 esu with an oxyanion as the donor. Also, the electronic charge is more delocalized, and the HOMO–LUMO energy gap (ΔE) and the bond length alternation (BLA) decrease with the same variation of the donor. Noteworthy is the excellent linear relationship between β and 1/ΔE2 and σgas+. These results may serve as a useful guideline for the design of two‐dimensional octupoles with large first hyperpolarizabilities. Copyright © 2004 John Wiley & Sons, Ltd.
Tuning carbanion reactivity by complexing with boranes: γ‐elimination reaction as a model
Authors: Habusha Uri , Rozental Esther , Hoz Shmaryahu
Published: July 2004

The anion of 3‐chloro‐3‐phenylselenocyclobutanecarbonitrile undergoes in DME, in the presence of alcohols, competitive protonation and γ‐elimination reactions [Eqn (1)]. With highly acidic alcohols such as trifluoroethanol the protonation is diffusion controlled and the rate for the cross ring elimination reaction is greater by a factor of three (at an alcohol concentration of 1 M). However, in the presence of BH3 or Bu3B, the protonated product becomes dominant. This result is attributed to the binding of the carbanion by the boranes. Experimental data as well as ab initio calculations show that the preferred complexation site is the ring carbon and not the cyano nitrogen of the complex. The results also show that direct protonation of the complex is not a viable rationalization of the findings. It is suggested that the enhanced protonation results from the formation of a hydrogen bond between the alcohol and the cyano nitrogen, thus increasing the effective molarity of the proton donor which migrates to the α‐carbon upon dissociation of the C—B bond. Copyright © 2004 John Wiley & Sons, Ltd.
Preparation and Screening of Diboronate Arrays for Identification of Carbohydrate Binders
Authors: Hoeg‐Jensen Thomas
Published: July 2004

Boronic acids and their anionic counterpart, boronates, are known to bind reversibly to polyols, such as carbohydrates, under aqueous conditions. Monoboronic acids generally display a common selectivity rank exemplified by fructose>galactose>mannose>glucose. This order can however be modulated by the use of diboronic acids, which may give increased selectivity for e.g. glucose. Diboronic acids have previously typically been prepared and tested individually, but this paper reports a solid‐phase method for parallel synthesis of diboronate arrays, along with visual screening of the compounds for carbohydrate binding by competitive binding to alizarin. Diboronate arrays were prepared based on Fmoc‐Lys(Boc) and related amino acids, and screening identified diboronates with enhanced affinity to melibiose and glucose.