bluuebunny/crossref_metadata_2025 huggingface dataset:
Preconditioning of Low-Frequency Repetitive Transcranial Magnetic Stimulation with Transcranial Direct Current Stimulation: Evidence for Homeostatic Plasticity in the Human Motor Cortex
Authors: Siebner Hartwig R. , Lang Nicolas , Rizzo Vincenzo , Nitsche Michael A. , Paulus Walter , Lemon Roger N. , Rothwell John C.
Published: March 2004

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. “Facilitatory preconditioning” with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, “inhibitory preconditioning” with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.
Glutamate Transporters Prevent the Generation of Seizures in the Developing Rat Neocortex
Authors: Demarque Michael , Villeneuve Nathalie , Manent Jean-Bernard , Becq Hélène , Represa Alfonso , Ben-Ari Yehezkel , Aniksztejn Laurent
Published: March 2004

Glutamate transporters are operative at an early developmental stage well before synapse formation, but their functional significance has not been determined. We now report that blockade of glutamate transporters in the immature neocortex generates recurrent NMDA receptor-mediated currents associated with synchronous oscillations of [Ca2+]iin the entire neuronal population. Intracerebroventricular injections of the blocker to pups generate seizures that are prevented by coinjections of NMDA receptor blockers. Therefore, the early expression of glutamate transporters plays a central role to prevent the activation by local glutamate concentrations of NMDA receptors and the generation of seizures that may alter the construction of cortical networks. A dysfunction of glutamate transporters may be a central event in early infancy epilepsy syndromes.
Differential Effects of Cerebellar, Amygdalar, and Hippocampal Lesions on Classical Eyeblink Conditioning in Rats
Authors: Lee Taekwan , Kim Jeansok J.
Published: March 2004

Eyeblink conditioning has been hypothesized to engage two successive stages of nonspecific emotional (fear) and specific musculature (eyelid) learning, during which the nonspecific component influences the acquisition of the specific component. Here we test this notion by investigating the relative contributions of the cerebellum, the amygdala, and the hippocampus to the emergence of conditioned eyelid and fear responses during delay eyeblink conditioning in freely moving rats. Periorbital electromyography (EMG) and 22 kHz ultrasonic vocalization (USV) activities were measured concurrently from the same subjects and served as indices of conditioned eyeblink and fear responses, respectively. In control animals, conditioned EMG responses increased across training sessions, whereas USV responses were initially robust but decreased across training sessions. Animals with electrolytic lesions to their cerebellum (targeting the interpositus nucleus) were completely unable to acquire conditioned EMG responses but exhibited normal USV behavior, whereas animals with lesions to the amygdala showed decelerated acquisition of conditioned EMG responses and displayed practically no USV behavior. In contrast, hippocampal lesioned rats demonstrated facilitated acquisition of conditioned EMG responses, whereas the USV behavior was unaffected. The amygdalar involvement in eyeblink conditioning was examined further by applying the GABAAagonist muscimol directly into the amygdala either before or immediately after training sessions. Although pretraining muscimol infusions impaired conditioned EMG responses, post-training infusions did not. Together, these results suggest that, even during a simple delay eyeblink conditioning, animals learn about different aspects associated with the behavioral task that are subserved by multiple brain-memory systems that interact to produce the overall behavior.
Does Paranode Formation and Maintenance Require Partitioning of Neurofascin 155 into Lipid Rafts?
Authors: Schafer Dorothy P. , Bansal Rashmi , Hedstrom Kristian L. , Pfeiffer Steven E. , Rasband Matthew N.
Published: March 2004

Paranodal axoglial junctions in myelinated nerve fibers are essential for efficient action potential conduction and ion channel clustering. We show here that, in the mature CNS, a fraction of the oligodendroglial 155 kDa isoform of neurofascin (NF-155), a major constituent of paranodal junctions, has key biochemical characteristics of a lipid raft-associated protein. However, despite its robust expression, NF-155 is detergent soluble before paranodes form and in purified oligodendrocyte cell cultures. Only during its progressive localization to paranodes is NF-155 (1) associated with detergent-insoluble complexes that float at increasingly lower densities of sucrose and (2) retainedin situafter detergent treatment. Finally, mutant animals with disrupted paranodal junctions, including those lacking specific myelin lipids, have significantly reduced levels of raft-associated NF-155. Together, these results suggest thattransinteractions between oligodendroglial NF-155 and axonal ligands result in cross-linking, stabilization, and formation of paranodal lipid raft assemblies.
Contribution of Calcium Ions to P2X Channel Responses
Authors: Egan Terrance M. , Khakh Baljit S.
Published: March 2004

Ca2+entry through transmitter-gated cation channels, including ATP-gated P2X channels, contributes to an array of physiological processes in excitable and non-excitable cells, but the absolute amount of Ca2+flowing through P2X channels is unknown. Here we address the issue of precisely how much Ca2+flows through P2X channels and report the finding that the ATP-gated P2X channel family has remarkably high Ca2+flux compared with other channels gated by the transmitters ACh, serotonin, protons, and glutamate. Several homomeric and heteromeric P2X channels display fractional Ca2+currents equivalent to NMDA channels, which hitherto have been thought of as the largest source of transmitter-activated Ca2+flux. We further suggest that NMDA and P2X channels may use different mechanisms to promote Ca2+flux across membranes. We find that mutating three critical polar amino acids decreases the Ca2+flux of P2X2receptors, suggesting that these residues cluster to form a novel type of Ca2+selectivity region within the pore. Overall, our data identify P2X channels as a large source of transmitter-activated Ca2+influx at resting membrane potentials and support the hypothesis that polar amino acids contribute to Ca2+selection in an ATP-gated ion channel.
ParallelFoxP1andFoxP2Expression in Songbird and Human Brain Predicts Functional Interaction
Authors: Teramitsu Ikuko , Kudo Lili C. , London Sarah E. , Geschwind Daniel H. , White Stephanie A.
Published: March 2004

Humans and songbirds are two of the rare animal groups that modify their innate vocalizations. The identification ofFOXP2as the monogenetic locus of a human speech disorder exhibited by members of the family referred to as KE enables the first examination of whether molecular mechanisms for vocal learning are shared between humans and songbirds. Here,in situhybridization analyses forFoxP1andFoxP2in a songbird reveal a corticostriatal expression pattern congruent with the abnormalities in brain structures of affected KE family members. The overlap in FoxP1 and FoxP2 expression observed in the songbird suggests that combinatorial regulation by these molecules during neural development and within vocal control structures may occur. In support of this idea, we find thatFOXP1andFOXP2expression patterns in human fetal brain are strikingly similar to those in the songbird, including localization to subcortical structures that function in sensorimotor integration and the control of skilled, coordinated movement. The specific colocalization ofFoxP1andFoxP2found in several structures in the bird and human brain predicts that mutations in FOXP1 could also be related to speech disorders.
Expression of Connexin36 in Cone Pedicles and OFF-Cone Bipolar Cells of the Mouse Retina
Authors: Feigenspan Andreas , Janssen-Bienhold Ulrike , Hormuzdi Sheriar , Monyer Hannah , Degen Joachim , Söhl Goran , Willecke Klaus , Ammermüller Josef , Weiler Reto
Published: March 2004

Transgenic technology, immunocytochemistry, electrophysiology, intracellular injection techniques, and reverse transcription PCR were combined to study the expression of neuronal connexin36 (Cx36) in the outer plexiform layer of the mouse retina. Transgenic animals expressed either a fusion protein of full-length Cx36 with enhanced green fluorescent protein (EGFP) attached at the C terminus or exon 2 of Cx36 was replaced byβ-galactosidase (β-gal). In the outer nuclear layer,β-gal-positive cell bodies, which were confined to the most distal region close to the outer limiting membrane, displayed immunoreactivity against S-cone opsin. Cx36–EGFP puncta colocalized with cone pedicles, which were visualized by intracellular injection. In reverse transcriptase PCR experiments, Cx36 mRNA was never detected in samples of rods harvested from the outer nuclear layer. These results strongly suggest expression of Cx36 in cones but not in rods. In vertical sections, Cx36 expression in the vitreal part of the outer plexiform layer was characterized by a patchy distribution. Immunocytochemistry with antibodies against the neurokinin-3 receptor and the potassium channel HCN4 (hyperpolarization-activated cyclic nucleotide-gated potassium channel) displayed clusters of the Cx36 label on the dendrites of OFF-cone bipolar cells. In horizontal sections, these clusters of Cx36 appeared as round or oval-shaped groups of individual puncta, and they were always aligned with the base of cone pedicles. Double-labeling experiments and single-cell reverse transcriptase PCR ruled out expression of Cx36 in horizontal cells and rod bipolar cells. At light microscopic resolution, we found close association of Cx36–EGFP with the AMPA-type glutamate receptor subunit GluR1 but not with GluR2–GluR4, the kainate receptor subunit GluR5, or the metabotropic glutamate receptor mGluR6.
Towards the “Pressure and Materials Gap”: Hydrogenation of Acrolein Using Silver Catalysts
Authors: Bron M. , Kondratenko E. , Trunschke A. , Claus P.
Published: April 2004

The hydrogenation of acrolein has been studied over various Ag/SiO2 catalysts in a pressure range from 50mbar to 20bar. Increasing partial pressures of acrolein and/or hydrogen lead to increasing selectivities of allyl alcohol. The selectivity towards allyl alcohol also depends on the structural features of the Ag/SiO2 catalyst. Larger particles seem to favour the production of propanal. This observation is discussed in view of the different plane-to-edge-ratio of the different catalysts. The interaction of hydrogen with silver samples has been studied with TAP at very low pressures as well as with calorimetry at ambient pressures. Both methods indicate, that also the hydrogen adsorption is structure-sensitive. No interaction of hydrogen with electrolytic silver or the support material alone was observed. IR spectroscopy has been used to elucidate the interaction of acrolein with Ag/SiO2 catalysts. A strong interaction with the support material was found, hindering the observation of probable silver-acrolein interaction.
Limitations of Variational Transition State Theory for Barrierless Radical–Radical Recombination Reactions
Authors: Troe Jürgen
Published: April 2004

Variational transition state theory (VTST) is widely used for the modelling of barrierless radical-radical recombination reactions. In this application, VTST suffers from a number of limitations some of which are of more technical, others of more fundamental nature. The former are caused by inappropriate averaging over individual adiabatic channel potentials or by the neglect of quantum effects, the latter are due to deviations from adiabatic dynamics. It is shown that most radical-radical recombination reactions are characterized by Massey parameters which are smaller than unity such that the dynamics is nonadiabatic. VTST treatments which generally assume adiabatic dynamics, therefore, have a fundamental problem. Calculations of rate constants by VTST often exceed classical trajectory results by about 10 to 20percent. This is normally attributed to “recrossing trajectories”. In the present work it is shown, however, that deviations of this magnitude also have to be expected for nonadiabatic dynamics in comparison to adiabatic dynamics. It is, therefore, suggested that “recrossing” at least in part has to be attributed to nonadiabatic dynamics. A way out of the dilemma is the use of a combination of statistical adiabatic channel and classical trajectory concepts.
A Kinetic Study of the Reaction between the 2-Ċ3H7 Radical and i-C4H8: Enthalpy of Formation of the (CH3)2CHCH2Ċ(CH3)2 Radical
Authors: Seres László , Dinse Martin , Görgényi Miklós
Published: April 2004

The reversible addition reaction

2-Ċ
3H7 + i-C4H8 ⇔ (CH3)2CHCH2
Ċ(CH3)2

was studied in the temperature range 491–543K by product analysis in experiments in which 2-Ċ
3H7 radicals were generated by the thermal decomposition of azoisopropane. The enthalpy of formation of the radical (CH3)2CHCH2
Ċ(CH3)2 was determined, the value obtained being Δf
H° = -21.8 ± 5.2kJ mol-1. From this result, the following group value was deduced: Δf
H°[Ċ–(C)3] = 177.1kJ mol-1. From the latter, Δf
H°(t-Ċ
4H9) = 51.6kJ mol-1 was estimated.

The rate constant of self-combination of the radical (CH3)2CHCH2
Ċ(CH3)2 was determined for the first time: log(k
12/(dm3mol-1s-1)) = 7.3.
Direct Kinetic Study of Reactions of Hydroxyl Radicals with Alkyl Formates
Authors: Szilágyi István , Dóbé Sándor , Bérces Tibor , Márta Ferenc , Viskolcz Béla
Published: April 2004

Rate coefficients were determined for the gas phase reactions of hydroxyl radicals with a series of alkyl formats. Experiments were carried out using the isothermal fast flow method coupled with resonance fluorescence detection. The obtained room temperature rate coefficients are (in 10−13cm3 molecule−1s−1 units): 1.83 ± 0.33 (methyl formate), 9.65 ± 0.43 (ethyl formate), 18.73 ± 0.83 (isopropyl formate), 6.77 ± 0.38 (tert-butyl formate) and 1.62 ± 0.13 (methyl chloroformate). These results are compared with the literature data. In addition estimations are made for the partial reactivities of the formate group and for the hydrocarbon groups adjacent to HC(O)O. Moreover, it has been found that the partial reactivity of the HC(O)O group (in reactions of OH with formates) is two orders of magnitude smaller than that of the HC(O) group (in reactions of OH with aldehydes). This has been explained using the results of ab initio calculations at the G3MP2//MP2(full)/6-31G(d) level of theory.
Gas-Phase Kinetics of the Reactions of the CH2F Radicals with the Radicals CHF2, CH3, and C2H5
Authors: Beiderhase T. , Hoyermann Karlheinz , Nothdurft Jörg , Olzmann Matthias
Published: April 2004

The mechanisms and the rates of the reactions of the fluorinated hydrocarbon radical CH2F with the fluorinated and pure hydrocarbon radicals CHF2, CH3, and C2H5, respectively, have been studied at low pressure (around 2 mbar) and room temperature using the discharge-flow reactor technique. Mass spectrometry either with electron impact or laser induced multiphoton ionization was applied for the detection of labile and stable species.

The cross combination of the radicals is mainly followed by HF elimination from the chemically activated adduct. The overall rate coefficients at 298K for

CH2F + CHF2 → C2H2F2 + HF (1)

CH2F + CH3 → C2H4 + HF (2)

CH2F + C2H5 → C3H6 + HF (3)

were derived from the analysis of the radical-time profiles by fit procedures; the following values were obtained:

CH2F + CHF2 → C2H2F2 + HF (1)

CH2F + CH3 → C2H4 + HF (2)

CH2F + C2H5 → C3H6 + HF (3)

k
1 = (3.0 + 1.5/ − 0.7) × 1012cm3mol−1s−1

k
2 = (4.0 ± 1.5) × 1013cm3mol−1s−1

k
3 = (9.0 ± 3) × 1012cm3mol−1s−1.

The results are discussed in terms of chemical activation mechanisms.
Elastic Moduli of Porous and Anisotropic Composites at High Temperatures
Authors: Loidl D. , Puchegger S. , Kromp K. , Zeschky J. , Greil P. , Bourgeon M. , Peterlik H.
Published: March 2004

The knowledge of the elastic properties of a material is essential for the purpose of designing constructive parts or simulating their behaviour by finite element calculations. In particular at high temperatures it is difficult to measure these elastic properties for porous materials – applied e.g. as shock absorbers – and for anisotropic composites – applied in aerospace technologies. The paper presents a method, which is capable to obtain the elastic moduli in a wide temperature range.
Hydrogen‐Bonding‐Directed Layer‐by‐Layer Assembly of Conjugated Polymers
Authors: Liang Z. , Cabarcos O. M. , Allara D. L. , Wang Q.
Published: April 2004

Poly(phenylenevinylene) polymers, functionalized with either amine or carboxyl acid groups (see Figure), have been synthesized and assembled using layer‐by‐layer deposition. This hydrogen‐bonding‐driven self‐assembly produces conjugated polymer multilayer films with molecular‐level controlled thickness and architecture. The approach enables the creation of robust thin films via a thermally induced cross‐linking reaction.
Polymer Complexes: supramolecular assemblies and structures of poly[N‐(2′‐pyridyl)propenamide] complexes
Authors: Mubarak A. T. A. , El‐Sonbati A. Z. , El‐Bindary A. A.
Published: April 2004

A number of new polymer complexes of palladium(II), platinum(II) and copper(II) containing homopolymer (N‐(2′‐pyridyl)propenamide; APH) and various anions (Cl−, Br−, I− or NO3−) have been synthesized and characterized by elemental analyses, magnetic susceptibility, electron paramagnetic resonance, IR and reflectance spectral measurements. The homopolymer shows three types of coordination behavior. In the mononuclear polymer complexes 1–6 and 9 it acts as a neutral bidentate ligand chelated through the pyridine‐nitrogen and amide‐oxygen atoms, whereas in the square‐planar [Pd(APH)2X2] (X = Cl, Br) unidentate APH is coordinated through the pyridine‐nitrogen atom alone. Under alkaline conditions APH is deprotonated in the presence of palladium(II) to form [Pd(AP)2] (10), AP being an anionic bidentate ligand and chelating through the pyridine‐nitrogen and amide‐oxygen atoms. The poly‐chelates are of 1:1 and 1:3 (metal:homopolymer) stoichiometry and exhibit six‐coordination. The polymer complexes of stoichiometric [(APH)2CuX2] contain square planar (APH)2 Cu2+ units and the anions X− are in the axial positions, giving distorted octahedral configurations. From the electron paramagnetic resonance and spectral data, the orbital reduction factors were calculated. Copyright © 2004 John Wiley & Sons, Ltd.
High‐resolution 15N solid‐state NMR investigations on borazine‐based precursors
Authors: Toury Bérangère , Gervais Christel , Dibandjo Philippe , Cornu David , Miele Philippe , Babonneau Florence
Published: April 2004

Reference compounds based on borazine units and polyborylborazines have been characterized by 15N solid‐state NMR. The various nitrogen sites (B3N, B2NH, B2NX (X = H, Me, iPr), BN(H)X and BNX2 (X = Me, iPr) have been discriminated according to their cross‐polarization behaviour and chemical shift values, which range from −265 to −350 ppm. This has permitted the elucidation of the polymerization mechanism associated with the polycondensation of two borazine‐based derivatives. In particular, this technique appears to be a powerful investigation tool for finding whether the B3N3 rings are linked through three‐atom NBN aminoboryl bridges or connected by direct BN bonds. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: Bis(µ2‐chloro)‐{bis(diethylether)‐lithium}‐bis(η5‐pentamethyl‐cyclopentadienyl)samarium(III)
Authors: Junk Peter C. , Smith Matthew K.
Published: April 2004

The structure is mononuclear with samarium bound by two η5‐cyclopentadienyl ligands and two chloride ligands, the latter of which bridge to a doubly ether‐solvated lithium centre. Copyright © 2004 John Wiley & Sons, Ltd.
Photo‐induced single electron transfer addition of triphenylgermane to conjugated carbonyl compounds: competitive radical addition
Authors: Feddouli A. , El Kadib A. , Rivière P. , Delpech F. , Rivière‐Baudet M. , Castel A. , Manriquez M. J. , Chavez I. , Ait Itto M. Y. , Ahbala M.
Published: April 2004

Conjugated ketones are poorly reactive towards triphenylgermane under radical conditions, but in their excited state they can undergo single electron transfer (SET) reactions. The SET reaction, through the formation of a germanium‐centred radical, initiates a competitive and divergent radical addition. In the case of carvone, the SET adduct was isolated pure from the reaction of triphenylgermyllithium with the same ketone. Copyright © 2004 John Wiley & Sons, Ltd.
Coordination behaviour of the 2‐(N,N‐dimethylaminomethyl)phenyl ligand towards the di‐t‐butylchlorotin(IV) moiety
Authors: Novák Petr , Císařová Ivana , Jambor Roman , Rûžička Aleš , Holeček Jaroslav
Published: April 2004

{2‐(N,N‐Dimethylaminomethyl)phenyl}(di‐t‐butyl)tin(IV)chloride, {2‐[(CH3)2NCH2]C6H4}Sn(t‐Bu)2 Cl, has been prepared and characterized using NMR and crystallography. This is the first example of a triorganotin(IV) halide containing the 2‐[(CH3)2NCH2]C6H4—group as a C,N‐chelating ligand with a weak intramolecular Sn—N interaction because of the steric hindrance of t‐butyl groups. The interatomic Sn—N distance is elongated to 2.904(14) Å and the central tin atom is distorted trigonal bipyramidal. Copyright © 2004 John Wiley & Sons, Ltd.
Structural comparisons between analogously substituted gallane–pnictine adducts
Authors: Kuczkowski Andreas , Schulz Stephan , Nieger Martin
Published: April 2004

The syntheses and solid‐state structures of five Lewis acid–base adducts Et3Ga–E(SiMe3)3 (E = P (1), As (2), Sb (3)), i‐Bu(t‐Bu)2Ga–P(i‐Pr)3 (4) and (t‐Bu)3Ga–As(i‐Pr)3 (5) are described and the structural trends observed within these adducts are discussed and compared with those reported for the corresponding alane adducts. GaC bond distances and CGaC bond angles were found to be useful structural parameters to estimate the strength of the Lewis acid–base interaction in the solid state. In addition, the solid‐state structure of uncomplexed t‐Bu3Ga (6) is reported. Copyright © 2004 John Wiley & Sons, Ltd.
Improving performance of text categorization by combining filtering and support vector machines
Authors: Díaz Irene , Ranilla José , Montañes Elena , Fernández Javier , Combarro Elías F.
Published: April 2004

Text Categorization is the process of assigning documents to a set of previously fixed categories. A lot of research is going on with the goal of automating this time‐consuming task. Several different algorithms have been applied, and Support Vector Machines (SVM) have shown very good results. In this report, we try to prove that a previous filtering of the words used by SVM in the classification can improve the overall performance. This hypothesis is systematically tested with three different measures of word relevance, on two different corpus (one of them considered in three different splits), and with both local and global vocabularies. The results show that filtering significantly improves the recall of the method, and that also has the effect of significantly improving the overall performance.
Information retrieval by metabrowsing
Authors: Wiesman F. , van den Herik H.J. , Hasman A.
Published: April 2004

This article investigates a new, effective browsing approach called metabrowsing. It is an alternative for current information retrieval systems, which still face six prominent difficulties. We identify and classify the difficulties and show that the metabrowsing approach alleviates the difficulties associated with query formulation and missing domain knowledge. Metabrowsing is a high‐level way of browsing through information: instead of browsing through document contents or document surrogates, the user browses through a graphical representation of the documents and their relations to the domain. The approach requires other cognitive skills from the user than what is currently required. Yet, a user evaluation in which the metabrowsing system was compared with an ordinary query‐oriented system showed only some small indicatory differences in effectiveness, efficiency, and user satisfaction. We expect that more experience with metabrowsing will result in a significantly better performance difference. Hence, our conclusion is that the development of new cognitive skills requires some time before the technologies are ready to be used.
An entropy‐based interpretation of retrieval status value‐based retrieval, and its application to the computation of term and query discrimination value
Authors: Dominich Sándor , Góth Júlia , Kiezer Tamás , Szlávik Zoltán
Published: April 2004

The concepts of Shannon information and entropy have been applied to a number of information retrieval tasks such as to formalize the probabilistic model, to design practical retrieval systems, to cluster documents, and to model texture in image retrieval. In this report, the concept of entropy is used for a different purpose. It is shown that any positive Retrieval Status Value (RSV)‐based retrieval system may be conceived as a special probability space in which the amount of the associated Shannon information is being reduced; in this view, the retrieval system is referred to as Uncertainty Decreasing Operation (UDO). The concept of UDO is then proposed as a theoretical background for term and query discrimination power, and it is applied to the computation of term and query discrimination values in the vector space retrieval model. Experimental evidence is given as regards such computation; the results obtained compare well to those obtained using vector‐based calculation of term discrimination values. The UDO‐based computation, however, presents advantages over the vector‐based calculation: It is faster, easier to assess and handle in practice, and its application is not restricted to the vector space model. Based on the ADI test collection, it is shown that the UDO‐based Term Discrimination Value (TDV) weighting scheme yields better retrieval effectiveness than using the vector‐based TDV weighting scheme. Also, experimental evidence is given to the intuition that the choice of an appropriate weighting scheme and similarity measure depends on collection properties, and thus the UDO approach may be used as a theoretical basis for this intuition.
Interaction of dexloxiglumide, a cholecystokinin type‐1 receptor antagonist, with human cytochromes P450
Authors: Hall Michael , Persiani Stefano , Cheung Yen‐Ling , Matthews Anne , Cybulski Z. Richard , Holding Jeremy D. , Kapil Ram , D'Amato Massimo , Makovec Francesco , Rovati Lucio C.
Published: March 2004

Dexloxiglumide (DEX) is a cholecystokinin type‐1 receptor antagonist under development for the treatment of constipation‐predominant irritable bowel syndrome. Studies of the potential interaction of DEX with human cytochromes P450 (CYPs) were conducted in vitro. DEX (300µM), both with and without a 15‐min pre‐incubation, was incubated with pooled human liver microsomes and substrates selective for each of eight CYPs. This resulted in >30% inhibition of tolbutamide 4‐methyl‐hydroxylase (CYP2C9/10) and lauric acid 11‐hydroxylase (CYP2E1) activities. Mean Ki (SD) for CYP2C9/10 and CYP2E1 were 69.0 (24.3) and 426 (60)µM, respectively. Incubations of [14C]DEX with pooled human liver microsomes produced one major phase I metabolic fraction, with Vmax=131 pmol/min/mg protein and Km=23.7µM. Further incubations with (i) liver microsomes from 16 individual donors (correlation analysis), (ii) Supersomes™ and (iii) selective chemical inhibitors, implicated CYP3A4/5, CYP2B6 and CYP2C9 in the formation of this component. Thus, DEX interacts with CYP2C9 both as inhibitor (Ki=69.0µM) and as substrate in vitro. However, based on the maximum concentration (27µM) after repeated oral doses of 200mg t.i.d. and the unbound fraction (0.03) of DEX in human plasma, no clinically relevant metabolic interactions with other CYP substrates are predicted. Copyright © 2004 John Wiley & Sons, Ltd.
Pharmacokinetics of mebudipine, a new calcium antagonist, following single intravenous and oral administrations in rats
Authors: Bohlooli Shahab , Keyhanfar Fariborz , Mahmoudian Massoud
Published: March 2004

The pharmacokinetics of a new calcium antagonist, mebudipine, was studied after a single intravenous (0.5 mg/kg) and oral (10 mg/kg) administration to rats. After intravenous dosing, the plasma concentration of mebudipine declined biexponentially with a terminal half‐life of 2.84 h. The blood clearance was 1.67 l/h/kg and the volume of distribution at steady state was found to be 6.26 l/kg. After oral dosing (10 mg/kg), the Cmax of mebudipine was 25.9±9.79 ng/ml. The oral bioavailability was low (< 2%) suggesting a marked first‐pass effect. The distribution of mebudipine into some tissues such as brain, heart, liver and kidney following intravenous administration (0.5 mg/kg) was studied and a rapid distribution of mebudipine into these tissues was found. It was concluded that brain, heart, liver and kidney are in the same compartment as plasma (central). Copyright © 2004 John Wiley & Sons, Ltd.
Decision framing: moderating effects of individual differences and cognitive processing
Authors: Simon Andrew F. , Fagley N. S. , Halleran Jennifer G.
Published: March 2004

Two studies examined the effect of an individual difference variable, need for cognition (NC), and processing of the options on the occurrence of risky choice framing effects. In Study 1 (N=206), frame interacted with NC and math skill such that no framing effect was observed among those high in both NC and math skill. No effect was found for the processing manipulation of requesting a reason for one's choices. Study 2 (N=257) enhanced the processing of the problems by asking participants to write out the options as they would describe them to a friend. Results showed that frame interacted with NC and depth of processing such that no framing effect was observed among those high in NC who were in the deep processing condition. These findings suggest that NC and depth of processing need to be considered in concert in order to understand their moderating effects on framing. Copyright © 2004 John Wiley & Sons, Ltd.
Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster as an experimental model
Authors: Palermo Ana María , Reynoso A.S. , López Nigro M. , Carballo M.A. , Mudry M.D.
Published: April 2004

BACKGROUND

Drosophila and vertebrates show similarities that suggest that the mechanisms involved in the induction of developmental defects may be similar in both. Therefore, Drosophila has been proposed as a useful, rapid, and economical model in the preliminary screening for teratology studies. The objective of the present study was to investigate the effect of metronidazole (MTZ) and ornidazole (ONZ) on the developmental stages of Drosophila melanogaster.

METHODS

Samarkand wild‐type females were allowed to lay eggs for 24 hr in media containing MTZ or ONZ at concentrations of 0, 500, 1000, and 2000 μg/ml. When larvae completed their development, the emerging flies were counted and examined for morphological abnormalities.

RESULTS

After the analysis of 400–1000 flies for each concentration, ONZ‐treated flies did not show an incidence of malformations above control values, although a significant high number of individuals with reduced body size was observed (p < 0.005, χ2 test). On the other hand, the 1000‐ and 2000‐μg/ml MTZ‐treated series presented higher frequencies of total abnormalities than did concurrent and historic controls (p < 0.05, χ2 test), indicating an MTZ effect during developmental morphogenesis.

CONCLUSIONS

These findings contribute to the characterization of both nitroimidazoles, which are widely used, especially in underdeveloped countries. At the same time, this Drosophila bioassay is sensitive enough to detect differential effects of MTZ and ONZ (abnormalities vs. growth effects), showing specificity and selectivity. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Student rights, safety, and codes of conduct
Authors: Mawdsley Ralph D.
Published: April 2004

Community college students, like students in all of higher education, find their relationship with the college defined by contract. However, this contract is shaped and influenced by rights granted under state and federal constitutions and statutes. Knowing what these rights are can assist college officials in avoiding unnecessary litigation.
Legal resources for community colleges
Authors: Kozeracki Carol A.
Published: April 2004

This chapter provides a description of additional resources on legal issues at community colleges.
Enantioselective HPLC determination of E‐6087, a new COX‐2 inhibitor, in human plasma: Validation and pharmacokinetic application
Authors: Salgado Leonardo , Encina Gregorio , Farran Ramón , Puig Santiago , Martínez Luis
Published: April 2004

E‐6087 is a nonsteroidal anti‐inflammatory compound that selectively inhibits cyclooxygenase‐2. Because E‐6087 has a chiral center, this compound is a racemic mixture of two stereoisomers, (+)‐(R)‐E‐6087 (E‐6231) and (−)‐(S)‐E‐6087 (E‐6232). A normal‐phase liquid‐chromatographic method for the enantioselective determination of E‐6087 in human plasma was developed and validated. The samples were extracted using solid‐phase extraction cartridges containing C18 sorbent, and the extracts were redissolved in absolute ethanol and injected into the chromatographic system. The enantiomeric separation was achieved on a chiral stationary‐phase column of derivatized amylose, and the enantiomers were quantified by fluorescence detection. The method was validated for drug concentrations ranging from 5 to 400 ng/ml for both enantiomers. No peaks interfering with the quantification of enantiomers were observed. The limit of quantification was 5 ng/ml, with precision expressed as a coefficient of variation lower than 10.6% and accuracy expressed as relative error lower than 12.2%. The utility of this method was demonstrated by analysis of plasma samples from healthy volunteers given an oral dose of rac‐E‐6087. Peak plasma levels of E‐6231 were higher than levels obtained for E‐6232. Results were consistent with those obtained with a conventional reversed‐phase method used for determination of the racemic compound. Chirality 16:302–308, 2004. © 2004 Wiley‐Liss, Inc.
Enantiomeric resolution of kielcorin derivatives by HPLC on polysaccharide stationary phases using multimodal elution
Authors: Sousa Emília P. , Tiritan M.E. , Oliveira Regina V. , Afonso C.M.M. , Cass Q.B. , Pinto Madalena M.M.
Published: April 2004

Analytical HPLC methods using carbamate chiral stationary phases of polysaccharide derivatives were developed for the enantiomeric resolution of five racemic mixtures of xanthonolignoids: rac‐trans‐kielcorin C, rac‐cis‐kielcorin C, rac‐trans‐kielcorin D, rac‐trans‐isokielcorin D, and rac‐trans‐kielcorin E. The separations were evaluated with the stationary phases cellulose tris‐3,5‐dimethylphenylcarbamate, amylose tris‐3,5‐dimethylphenylcarbamate, amylose tris‐(S)‐1‐phenylethylcarbamate, and amylose tris‐3,5‐dimethoxyphenylcarbamate under normal, reversed‐phase, and polar organic elution conditions. Chiral recognition of those chiral stationary phases, the influence of mobile phases on the enantiomers separation, and the effects of structural features of the solutes on the chiral discrimination observed are discussed. The best performance was achieved on an amylose tris‐3,5‐dimethylphenylcarbamate phase. Polar organic conditions gave shorter retention factors and better resolutions and were a valuable alternative to the alcohol‐hexane or reversed‐phase conditions. Chirality 16:279–285, 2004. © 2004 Wiley‐Liss, Inc.
The never‐ending controversies of screening mammography
Authors: Brem Rachel F.
Published: March 2004

Controversies regarding the recommendations for screening mammography seen to be never ending. In this issue of Cancer, Gur et al. report their findings that breast cancer diagnosis improves with increasing recall rate above 10% in a study of experienced, high‐volume radiologists. This editorial discusses the implication of this well designed and executed study with bold and important conclusions.

See also pages 000–000.
Oral topotecan in children with recurrent or progressive high‐grade glioma
Authors: Wagner Sabine , Erdlenbruch Bernhard , Längler Alfred , Gnekow Astrid , Kühl Joachim , Albani Michael , Völpel Sigrid , Bucsky Peter , Emser Angela , Peters Ove , Wolff Johannes E. A.
Published: March 2004

BACKGROUND

Continuous oral treatment with topotecan may be more effective than the typical 1‐day and 5‐day treatment schedules. In previous studies of continuous treatment with topotecan, increased intestinal side effects were reported in adult patients; however, the experience in pediatric patients and patients with high‐grade glioma is quite limited.

METHODS

Thirty‐two pediatric patients with recurrent high‐grade glioma (16 females and 16 males; median age, 9.5 years) were enrolled in the current Phase I/II study. Tumor locations included the cerebral cortex (n = 5), pons (n = 18), and other sites (n = 9). An injectable formulation of topotecan was administered orally, in ice‐cold orange juice, once daily. The starting dose of 0.4 mg/m2 per day was escalated on a patient‐by‐patient basis. At each patient's maximum dose, blood samples were obtained for the determination of plasma hydroxytopotecan and topotecan lactone concentrations and for the calculation of pharmacokinetic quantities.

RESULTS

The toxicity criteria for a maximum tolerated topotecan dose were met in only 19 patients. The primary toxicity type was hematologic. The median maximum tolerated dose was 0.9 mg/m2 per day (n = 19). The calculated maximum total plasma topotecan concentration was 3.8 ng/mL (n = 7), with an area under the concentration‐time curve of 38.4 ng · hours/mL and a half‐life of 4.1 hours, which would result in the complete disappearance of topotecan from the plasma after 12 hours. Objective responses were observed in 2 of 13 evaluable patients and lasted for 2.5 and 9 months, respectively (continuous clinical remission, 1 of 14 patients; partial response, 2 of 14 patients; stable disease, 7 of 14 patients; progressive disease, 4 of 14 patients).

CONCLUSIONS

Oral topotecan (median dose, 0.9 mg/m2 per day) administered once daily was well tolerated and somewhat effective in children with recurrent high‐grade glioma. A schedule in which the daily dose is split so that dosing is performed twice daily may be superior to the current schedule. Cancer 2004. © 2004 American Cancer Society.
Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma
Authors: Shapira Ma'anit , Ben‐Izhak Ofer , Bishara Bishara , Futerman Boris , Minkov Ira , Krausz Michael M. , Pagano Michele , Hershko Dan D.
Published: March 2004

BACKGROUND

Low levels of p27Kip1 are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27Kip1 for degradation, was overexpressed and was inversely related to p27Kip1 levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2‐dependent p27 degradation was recently discovered, but its role in human malignancies is unknown.

METHODS

Quick‐frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate–polyacrylamide gels, transferred to nitrocellulose, and probed with highly specific monoclonal antibodies directed against Cks1, Skp2, and p27Kip1. The expression of Cks1 was also examined by immunohistochemistry using formalin‐fixed, paraffin‐embedded tissue sections from the same patients.

RESULTS

A strong correlation was found between Cks1 levels and Skp2 expression and loss of tumor differentiation. A significant inverse relation was also observed between levels of Cks1 and p27Kip1 and overall survival.

CONCLUSIONS

The results of the current study suggest that increased expression of Cks1 may have an important causative role in decreasing levels of p27 in patients with aggressive colorectal carcinoma. Cancer 2004. © 2004 American Cancer Society.
The natural history of breast carcinoma in the elderly
Authors: Singh Rachana , Hellman Samuel , Heimann Ruth
Published: March 2004

BACKGROUND

The authors evaluated the two indicators of metastatic proclivity (namely, virulence [V; the rate of appearance of distant metastases] and metastagenicity [M; the ultimate likelihood of developing distant metastases]) of breast carcinoma in elderly women. The authors then compared these characteristics with the corresponding characteristics in a cohort of younger women to determine whether breast carcinoma was more indolent in women age > 70 years, as is commonly believed in the medical community.

METHODS

The authors examined 2136 women who underwent mastectomy without adjuvant systemic therapy at The University of Chicago Hospitals (Chicago, IL) between 1927 and 1987. The median follow‐up period was 12.3 years. Distant disease–free survival (DDFS) was determined for women who did not receive systemic therapy. V and M were obtained from log‐linear plots of DDFS.

RESULTS

No significant difference in tumor size at presentation was observed among women age < 40 years, women ages 40–70 years, and women age > 70 years (P = 0.86), whereas significantly fewer women age > 70 years presented with positive lymph nodes compared with younger women (P = 0.05). In women with negative lymph node status, there was a higher DDFS rate among patients ages 40–70 years (81% at 10 years) compared with patients age > 70 years (65% at 10 years; P = 0.018). There was no significant age‐related difference among women with lymph node–positive disease (P = 0.2). For example, the 10‐year DDFS rate for women ages 40–70 years was 33%, compared with 38% for women age > 70 years. Among those with lymph node–negative disease, V was 3% per year for women ages 40–70 years as well as women age > 70 years. Among women with lymph node–negative disease, M was 0.20 for patients ages 40–70 years and 0.35 for patients age > 70 years. In women with positive lymph node status, both V (11% per year vs. 10% per year) and M (0.70 vs. 0.65) were similar in both age groups.

CONCLUSIONS

Fewer women age > 70 years had lymph node involvement at presentation. However, when this finding was taken into account, the authors found no evidence that breast carcinoma was more indolent in women age > 70 years. These results support the use of similar diagnostic and therapeutic efforts for elderly women and younger women, with modification for elderly women based only on comorbidity. Cancer 2004. © 2004 American Cancer Society.
Parallel program debugging by specification
Authors: Huband Simon , McDonald Chris
Published: April 2004

Most message passing parallel programs employ logical process topologies with regular characteristics to support their computation. Since process topologies define the relationship between processes, they present an excellent opportunity for debugging. The primary benefit is that process behaviours can be correlated, allowing expected behaviour to be abstracted and identified, and undesirable behaviour reported. However, topology support is inadequate in most message passing parallel programming environments, including the popular Message Passing Interface (MPI) and the Parallel Virtual Machine (PVM). Programmers are forced to implement topology support themselves, increasing the possibility of introducing errors.

This paper proposes a trace‐ and topology‐based approach to parallel program debugging, driven by four distinct types of specifications. Trace specifications allow trace data from a variety of sources and message passing libraries to be interpreted in an abstract manner, and topology specifications address the lack of explicit topology knowledge, whilst also facilitating the construction of user‐consistent views of the debugging activity. Loop specifications express topology‐consistent patterns of expected trace events, allowing conformance testing of associated trace data, and error specifications specify undesirable event interactions, including mismatched message sizes and mismatched communication pairs. Both loop and error specifications are simplified by having knowledge of the actual topologies being debugged.

The proposed debugging framework enables a wealth of potential debugging views and techniques. Copyright © 2004 John Wiley & Sons, Ltd.
A comparison of the efficacy and acceptability of group versus individual cognitive behaviour therapy in the treatment of panic disorder and agoraphobia in primary care
Authors: Sharp D. M. , Power K. G. , Swanson V.
Published: March 2004

Panic disorder and agoraphobia is a prevalent clinical condition which places heavy demands on treatment resources in primary care. The efficient delivery of evidence‐based psychological treatment for this disorder is therefore important. Previous research has investigated both individual and group treatment formats for cognitive behaviour therapy (CBT) for panic disorder and agoraphobia. These two modalities of treatment delivery are, however, rarely compared within the same study format. Also little is known of patients' preferences regarding treatment delivery formats. The present study investigated the relative efficacy of a group treatment CBT and an individual treatment CBT in comparison with a waiting list control group in the treatment of panic disorder with or without agoraphobia in primary care. Ninety‐seven patients suffering from DSM‐IV panic disorder with or without agoraphobia were randomly allocated to receive either group CBT, individual CBT, or waiting list control. All patients were seen by the same therapist and all received an identical treatment manual. Treatment response was measured by blind assessor, therapist and patient‐rated measures of anxiety, depression, and agoraphobic avoidance, and was analysed in terms of both traditional statistical significance and clinical significance of outcome. At treatment end‐point, in terms of traditional statistical significance, both the group and individual CBT were significantly superior to waiting list control but did not differ significantly from each other. When clinical significance of outcome at treatment end‐point was considered, individual CBT showed a significant advantage over both group CBT and waiting list control. At 3‐month follow‐up, however, the individual CBT treatment group showed significant superiority to the group CBT treatment on clinical significance of outcome on one outcome measure only. This was principally due to a reduction in the proportion of patients achieving criteria of clinically significant change in the individual CBT treatment group over the 3‐month follow‐up period. When given a free choice of group or individual CBT at the end of the waiting list period, the overwhelming majority (95%) of the waiting list patients chose individual CBT. The implications of these findings for future research and for wider clinical practice are discussed. Copyright © 2004 John Wiley & Sons, Ltd.